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Zhong M, Xu QQ, Huang MQ, Zhan RT, Huang XQ, Yang W, Lin ZX, Xian YF. Rhynchophylline alleviates cognitive deficits in multiple transgenic mouse models of Alzheimer's disease via modulating neuropathology and gut microbiota. Acta Pharmacol Sin 2025:10.1038/s41401-025-01475-0. [PMID: 40011632 DOI: 10.1038/s41401-025-01475-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 01/02/2025] [Indexed: 02/28/2025] Open
Abstract
Amyloid-beta (Aβ) aggregation, phosphorylated tau accumulation and neuroinflammation are considered as three hallmarks of Alzheimer's disease (AD). Rhynchophylline (RN), the major alkaloid of a Chinese medicinal plant Uncaria rhynchophylla, has been shown to possess potent anti-AD effects. This study explored the effects of RN on Aβ pathology, tauopathy, and neuroinflammation using three AD mouse models, including TgCRND8, 3×Tg-AD, and 5×FAD, with RN treatment lasting for 4, 6, and 6 months, respectively, followed by behavioral tests and biological assays. In addition, BV2 cells were employed to further evaluate the biological effects of RN. RN treatment improved cognitive functions by reducing anxiety-like behaviors, enhancing recognition ability, and ameliorating learning impairments. It modulated Aβ processing through reducing the Aβ-producing enzyme activities and enhancing degradation enzyme activities, thereby diminishing Aβ accumulation. RN also decreased hyperphosphorylated tau proteins at Thr181, Thr205, Ser396, and Ser404 sites. Moreover, RN diminished neuroinflammation by reducing microglia and astrocyte activation and lowering the release of inflammatory cytokines. Furthermore, RN treatment could restore gut microbiota dysbiosis in 5×FAD mice. In BV2 cells, knockdown of p53, HDAC2, and Galectin-3 markedly enhanced the anti-inflammatory effects of RN. Overall, the anti-AD properties of RN were attributed to its regulation of multiple biological pathways, including regulation of the p53/PINK1 signaling pathway, inhibition of the HDAC2/AMPK signaling pathway, suppression of the Galectin-3/C/EBPβ/AEP signaling pathway, and modulation of gut microflora dysbiosis. This pioneering study unambiguously revealed the effects of RN on cognitive impairments, APP processing, tauopathy, and neuroinflammation in different transgenic mouse models with differing AD burdens, highlighting its potential as an anti-AD therapeutic agent and enhancing the scientific basis for its clinical use in treating AD.
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Affiliation(s)
- Mei Zhong
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China
- Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, International Joint Research Center of Human-machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province, Hainan Provincial Key Laboratory of Research and Development on Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou, 571199, China
| | - Qing-Qing Xu
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China
| | - Ming-Qing Huang
- College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China
| | - Ruo-Ting Zhan
- Key Laboratory of Chinese Medicinal Resource from Lingnan (Ministry of Education), School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Xiao-Qi Huang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Wen Yang
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China
| | - Zhi-Xiu Lin
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
- Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong, Shatin, N.T., Hong Kong SAR, China.
- Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
| | - Yan-Fang Xian
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
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Chen Y, Zhang D, Chen T, Zhao L, Wen L, Hou R. Traditional Chinese Medicine for Alzheimer's Disease: A Systematic Review and Meta-Analysis. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2025; 53:1-15. [PMID: 40000385 DOI: 10.1142/s0192415x25500016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/27/2025]
Abstract
The treatment of Alzheimer's Disease (AD) remains a challenge for modern medicine due to its complex pathogenesis. Traditional Chinese Medicine (TCM) has demonstrated significant success in the prevention and treatment of variable medical conditions. For AD pharmacological management, TCM could provide promising approaches. This study aimed to systematically evaluate the current evidence of the effects of TCM therapies on AD. A systematic search of the literature was performed on electronic databases including PubMed, the Cochrane Library, the Chinese National Knowledge Infrastructure (CNKI), and Web of Science. Thirteen studies were included in this review, subject to inclusion and exclusion criteria. Screening, data extraction, and quality assessment were undertaken following the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Our results show that TCM offered a significant improvement in cognitive functioning compared to the control group, measured on both MMSE and ADAS-CoG scales, suggesting its potential utility in slowing cognitive decline and improving cognitive function as compared to conventional drug treatments and placebos. No significant difference was found for scores of neuropsychiatric symptoms (NPI) or ability to perform daily living activities (ADCS-ADL). These findings highlight TCM as a potential adjuvant therapy, in combination with conventional medicine, to improve the effectiveness and reduce the limitations of conventional AD drug regimes. Studies with larger sample sizes, rigorous study designs, accurate long-term reporting, and correlation to neuropathological markers are needed in the future to enhance the evidence base for the use of TCM in AD patients, and to further confirm its efficacy.
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Affiliation(s)
- Yuqing Chen
- School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
| | - Danning Zhang
- Shandong Mental Health Center, Shandong University, Jinan, Shandong, P. R. China
| | - Teng Chen
- Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China
| | - Lixia Zhao
- Department of Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong, P. R. China
| | - Lei Wen
- Xiamen Key Laboratory for Traditional Chinese Medicine, Neurology & Immunology Research, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, School of Medicine, Xiamen University, Xiamen, P. R. China
| | - Ruihua Hou
- Department of Psychiatry, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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Zheng Y, Gao X, Tang J, Gao L, Cui X, Liu K, Zhang X, Jin M. Exploring the Efficacy and Target Genes of Atractylodes Macrocephala Koidz Against Alzheimer's Disease Based on Multi-Omics, Computational Chemistry, and Experimental Verification. Curr Issues Mol Biol 2025; 47:118. [PMID: 39996839 PMCID: PMC11853862 DOI: 10.3390/cimb47020118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 02/03/2025] [Accepted: 02/05/2025] [Indexed: 02/26/2025] Open
Abstract
OBJECTIVE To unveil the efficacy and ferroptosis-related mechanisms of Atractylodes Macrocephala Koidz (AMK) against Alzheimer's disease (AD), which is the most widespread neurodegenerative disease. METHODS Gene set variation analysis (GSVA) scores were used to investigate the relationship between ferroptosis and AD. Logistic regression with seven feature selections and a deep learning model were utilized to identify potential targets of AMK based on transcriptomic data from multiple tissues. A transcriptome-wide association study (TWAS), summary-data-based mendelian randomization (SMR), and mendelian randomization (MR) were utilized to validate the causal relationship between target genes and AD risk. A single-gene gene set enrichment analysis (GSEA) was employed to investigate the biological pathways associated with the target genes. Three molecular docking strategies and a molecular dynamics simulation were employed to verify the binding domains interacting with AMK. Furthermore, the anti-AD effects of AMK were validated in a zebrafish AD model by testing behavior responses, apoptosis, and the deposition of beta-amyloid (Aβ) in the brain. Ultimately, real-time qPCR was used to verify the ferroptosis-related targets, which was identified via multi-omics. RESULTS Ferroptosis is an important pathogenic mechanism of AD, as suggested by the GSVA scores. AMK may exert its anti-AD activity through targets genes identified in the brain (ATP5MC3, GOT1, SAT1, EGFR, and MAPK9) and blood (G6PD, PGD, ALOX5, HMOX1, and ULK1). EGFR and HMOX1 were further confirmed as target genes mediating the anti-AD activity of AMK through TWAS, SMR, and MR analyses. The GSEA results indicated that EGFR may be involved in oxidative phosphorylation-related pathways, while HMOX1 may be associated with lysosome and phagosome pathways. The results of three molecular docking strategies and molecular dynamics simulations implied that the kinase domain of EGFR and the catalytic domain of HMOX1 played pivotal roles in the interaction between AMK and the targets. In a zebrafish model, AD-like symptoms including motor slowness and delayed responses, neuronal apoptosis, and plaque deposition in the brain, were significantly improved after AMK treatment. Accordingly, AMK reversed the abnormal expression of egfra and hmox1a, two core targets genes involved in ferroptosis. CONCLUSIONS AMK significantly alleviated AD-like symptoms through the modulation of EGFR and HMOX1, which might reduce lipid peroxidation, thereby suppressing ferroptosis. This study provided evidence supporting the efficacy and therapeutic targets associated with ferroptosis in AMK-treated AD, which aid in the development of therapeutic interventions.
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Affiliation(s)
- Yuanteng Zheng
- Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China
- Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China
- School of Psychology, North China University of Science and Technology, 21 Bohai Road, Tangshan 063210, China
- School of Public Health, North China University of Science and Technology, 21 Bohai Road, Tangshan 063210, China
| | - Xin Gao
- Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China
- Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China
| | - Jiyang Tang
- Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China
- Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China
| | - Li Gao
- Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China
- Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China
- School of Psychology, North China University of Science and Technology, 21 Bohai Road, Tangshan 063210, China
- School of Public Health, North China University of Science and Technology, 21 Bohai Road, Tangshan 063210, China
| | - Xiaotong Cui
- Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China
- Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China
| | - Kechun Liu
- Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China
- Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China
| | - Xiujun Zhang
- School of Psychology, North China University of Science and Technology, 21 Bohai Road, Tangshan 063210, China
- School of Public Health, North China University of Science and Technology, 21 Bohai Road, Tangshan 063210, China
| | - Meng Jin
- Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan 250103, China
- Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, China
- School of Public Health, North China University of Science and Technology, 21 Bohai Road, Tangshan 063210, China
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Cacabelos R, Martínez-Iglesias O, Cacabelos N, Carrera I, Corzo L, Naidoo V. Therapeutic Options in Alzheimer's Disease: From Classic Acetylcholinesterase Inhibitors to Multi-Target Drugs with Pleiotropic Activity. Life (Basel) 2024; 14:1555. [PMID: 39768263 PMCID: PMC11678002 DOI: 10.3390/life14121555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 11/20/2024] [Accepted: 11/21/2024] [Indexed: 01/11/2025] Open
Abstract
Alzheimer's disease (AD) is a complex/multifactorial brain disorder involving hundreds of defective genes, epigenetic aberrations, cerebrovascular alterations, and environmental risk factors. The onset of the neurodegenerative process is triggered decades before the first symptoms appear, probably due to a combination of genomic and epigenetic phenomena. Therefore, the primary objective of any effective treatment is to intercept the disease process in its presymptomatic phases. Since the approval of acetylcholinesterase inhibitors (Tacrine, Donepezil, Rivastigmine, Galantamine) and Memantine, between 1993 and 2003, no new drug was approved by the FDA until the advent of immunotherapy with Aducanumab in 2021 and Lecanemab in 2023. Over the past decade, more than 10,000 new compounds with potential action on some pathogenic components of AD have been tested. The limitations of these anti-AD treatments have stimulated the search for multi-target (MT) drugs. In recent years, more than 1000 drugs with potential MT function have been studied in AD models. MT drugs aim to address the complex and multifactorial nature of the disease. This approach has the potential to offer more comprehensive benefits than single-target therapies, which may be limited in their effectiveness due to the intricate pathology of AD. A strategy still unexplored is the combination of epigenetic drugs with MT agents. Another option could be biotechnological products with pleiotropic action, among which nosustrophine-like compounds could represent an attractive, although not definitive, example.
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Affiliation(s)
- Ramón Cacabelos
- EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, Bergondo, 15165 Corunna, Spain; (O.M.-I.); (N.C.); (I.C.); (L.C.); (V.N.)
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Xia Y, Wang X, Lin S, Dong TTX, Tsim KWK. Berberine and palmatine, acting as allosteric potential ligands of α7 nAChR, synergistically regulate inflammation and phagocytosis of microglial cells. FASEB J 2024; 38:e70094. [PMID: 39373933 DOI: 10.1096/fj.202302538rrrr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 09/10/2024] [Accepted: 09/23/2024] [Indexed: 10/08/2024]
Abstract
Berberine and palmatine are isoquinoline quaternary alkaloids derived from Chinese medicinal herbs. These alkaloids have shown promising synergy in inhibiting acetylcholinesterase (AChE), indicating their potential in treating Alzheimer's disease (AD). Besides, the anti-inflammatory effects of berberine and palmatine have been widely reported, although the underlying mechanism remains unclear. Here, we found that berberine and palmatine could induce calcium ion (Ca2+) influx via activating α7 nicotinic acetylcholine receptor (α7 nAChR) in cultured microglial cells, possibly serving as its allosteric potential ligands. Furthermore, we examined the synergistic anti-inflammatory effects of berberine and palmatine in the LPS-induced microglia, that significantly suppressed the production of TNF-α and iNOS. Notably, this suppression was reversed by co-treatment with a selective antagonist of α7 nAChR. Moreover, the alkaloid-induced microglial phagocytosis was shown to be mediated by the induction of Ca2+ influx through α7 nAChR and subsequent CaMKII-Rac1-dependent pathway. Additionally, the combination of berberine and palmatine, at low concentration, protected against the LPS-induced endoplasmic reticulum stress and mitochondrial dysfunction in microglia. These findings indicate the potential of berberine and palmatine, either individually or in combination, in contributing to anti-AD drug development, which provide valuable insights into the mechanisms by which natural products, such as plant alkaloids, exert their anti-AD effects.
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Affiliation(s)
- Yingjie Xia
- Division of Life Science, Center for Chinese Medicine and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, SRI, The Hong Kong University of Science and Technology, Shenzhen, China
| | - Xiaoyang Wang
- Division of Life Science, Center for Chinese Medicine and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, SRI, The Hong Kong University of Science and Technology, Shenzhen, China
| | - Shengying Lin
- Division of Life Science, Center for Chinese Medicine and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, SRI, The Hong Kong University of Science and Technology, Shenzhen, China
| | - Tina T X Dong
- Division of Life Science, Center for Chinese Medicine and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, SRI, The Hong Kong University of Science and Technology, Shenzhen, China
| | - Karl W K Tsim
- Division of Life Science, Center for Chinese Medicine and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, SRI, The Hong Kong University of Science and Technology, Shenzhen, China
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Yan C, Yang S, Shao S, Zu R, Lu H, Chen Y, Zhou Y, Ying X, Xiang S, Zhang P, Li Z, Yuan Y, Zhang Z, Wang P, Xie Z, Wang W, Ma H, Sun Y. Exploring the anti-ferroptosis mechanism of Kai-Xin-San against Alzheimer's disease through integrating network pharmacology, bioinformatics, and experimental validation strategy in vivo and in vitro. JOURNAL OF ETHNOPHARMACOLOGY 2024; 326:117915. [PMID: 38360383 DOI: 10.1016/j.jep.2024.117915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/29/2024] [Accepted: 02/13/2024] [Indexed: 02/17/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Kai Xin San (KXS), first proposed by Sun Simiao during the Tang Dynasty, has been utilized to treat dementia by tonifying qi and dispersing phlegm. AIM OF THE STUDY This study aimed to elucidate the mechanism by which KXS exerts its therapeutic effects on Alzheimer's disease (AD) by targeting ferroptosis, using a combination of network pharmacology, bioinformatics, and experimental validation strategies. MATERIALS AND METHODS The active target sites and the further potential mechanisms of KXS in protecting against AD were investigated through molecular docking, molecular dynamics simulation, and network pharmacology, and combined with the validation of animal experiments. RESULTS Computational and experimental findings provide the first indication that KXS significantly improves learning and memory defects and inhibits neuronal ferroptosis by repairing mitochondria damage and upregulating the protein expression of ferroptosis suppressor protein 1 (FSP1) in vivo APP/PS1 mice AD model. According to bioinformatics analysis, the mechanism by which KXS inhibits ferroptosis may involve SIRT1. KXS notably upregulated the mRNA and protein expression of SIRT1 in both vivo APP/PS1 mice and in vitro APP-overexpressed HT22 cells. Additionally, KXS inhibited ferroptosis induced by APP-overexpression in HT22 cells through activating the SIRT1-FSP1 signal pathway. CONCLUSIONS Collectively, our findings suggest that KXS may inhibit neuronal ferroptosis through activating the SIRT1/FSP1 signaling pathway. This study reveals the scientific basis and underlying modern theory of replenishing qi and eliminating phlegm, which involves the inhibition of ferroptosis. Moreover, it highlights the potential application of SIRT1 or FSP1 activators in the treatment of AD and other ferroptosis-related diseases.
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Affiliation(s)
- Chenchen Yan
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Song Yang
- Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, PR China
| | - Simai Shao
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Runru Zu
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Hao Lu
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Yuanzhao Chen
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Yangang Zhou
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Xiran Ying
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Shixie Xiang
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Peixu Zhang
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Zhonghua Li
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Ye Yuan
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Zhenqiang Zhang
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Pan Wang
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Zhishen Xie
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China.
| | - Wang Wang
- School of basic medicine, Nanchang Medical College, Nanchang, 330052, Jiangxi, PR China.
| | - Huifen Ma
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases with Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China.
| | - Yiran Sun
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China.
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Parashar A, Jha D, Mehta V, Chauhan B, Ghosh P, Deb PK, Jaiswal M, Prajapati SK. Sonic hedgehog signalling pathway contributes in age-related disorders and Alzheimer's disease. Ageing Res Rev 2024; 96:102271. [PMID: 38492808 DOI: 10.1016/j.arr.2024.102271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 03/10/2024] [Accepted: 03/11/2024] [Indexed: 03/18/2024]
Abstract
Alzheimer's disease (AD) is caused by the aging process and manifested by cognitive deficits and progressive memory loss. During aging, several conditions, including hypertension, diabetes, and cholesterol, have been identified as potential causes of AD by affecting Sonic hedgehog (Shh) signalling. In addition to being essential for cell differentiation and proliferation, Shh signalling is involved in tissue repair and the prevention of neurodegeneration. Neurogenesis is dependent on Shh signalling; inhibition of this pathway results in neurodegeneration. Several protein-protein interactions that are involved in Shh signalling are implicated in the pathophysiology of AD like overexpression of the protein nexin-1 inhibits the Shh pathway in AD. A protein called Growth Arrest Specific-1 works with another protein called cysteine dioxygenase (CDO) to boost Shh signalling. CDO is involved in the development of the central nervous system (CNS). Shh signalling strengthened the blood brain barrier and therefore prevent the entry of amyloid beta and other toxins to the brain from periphery. Further, several traditional remedies used for AD and dementia, including Epigallocatechin gallate, yokukansan, Lycium barbarum polysaccharides, salvianolic acid, and baicalin, are known to stimulate the Shh pathway. In this review, we elaborated that the Shh signalling exerts a substantial influence on the pathogenesis of AD. In this article, we have tried to explore the various possible connections between the Shh signalling and various known pathologies of AD.
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Affiliation(s)
- Arun Parashar
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology & Management Sciences, Solan 173 212, India.
| | - Dhruv Jha
- Birla Institute of Technology, India
| | - Vineet Mehta
- Department of Pharmacology, Government College of Pharmacy, Rohru, District Shimla, Himachal Pradesh 171207, India
| | - Bonney Chauhan
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology & Management Sciences, Solan 173 212, India
| | - Pappu Ghosh
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology & Management Sciences, Solan 173 212, India
| | - Prashanta Kumar Deb
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology & Management Sciences, Solan 173 212, India
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He S, Shi J, Chai H, Ma L, Pei H, Zhang P, Shi D, Li H. Mechanisms with network pharmacology approach of Ginsenosides in Alzheimer's disease. Heliyon 2024; 10:e26642. [PMID: 38434355 PMCID: PMC10906400 DOI: 10.1016/j.heliyon.2024.e26642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 01/23/2024] [Accepted: 02/16/2024] [Indexed: 03/05/2024] Open
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss, cognitive disorder, language dysfunction, and mental disability. The main neuropathological changes in AD mainly include amyloid plaque deposition, neurofibrillary tangles, synapse loss, and neuron reduction. However, the current anti-AD drugs do not demonstrate a favorable effect in altering the pathological course of AD. Moreover, long-term use of these drugs is usually accompanied with various side effects. Ginsenosides are the major active constituents of ginseng and have protective effects on AD through various mechanisms in both in vivo and in vitro studies. In this review, we focused on discussing the therapeutic potential effects and the mechanisms of pharmacological activities of ginsenosides in AD, to provide new insight for further research and clinical application of ginsenosides in the future. Recent studies on the pharmacological effects and mechanisms of ginsenosides were retrieved from Chinese National Knowledge Infrastructure, National Science and Technology Library, Wanfang Data, Elsevier, ScienceDirect, PubMed, SpringerLink, and the Web of Science database up to April 2023 using relevant keywords. Network pharmacology and bioinformatics analysis were used to predict the therapeutic effects and mechanisms of ginsenosides against AD. Ginsenosides presented a wide range of therapeutic and biological activities, including alleviating Aβ deposition, decreasing tau hyperphosphorylation, regulating the cholinergic system, resisting oxidative stress, modulating Ca2+ homeostasis, as well as anti-inflammation and anti-apoptosis in neurons, respectively. For further developing the therapeutic potential as well as clinical applications, the network pharmacology approach was combined with a summary of published studies.
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Affiliation(s)
- Shan He
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Junhe Shi
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hua Chai
- Hepingli Hospital, Beijing, China
| | - Lina Ma
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hui Pei
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ping Zhang
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Dazhuo Shi
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hao Li
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Teng Y, Gao J, Tan T, Zhang X, Wang Y, Zhang J, Ni L. Chemical components and against alzheimer's disease effects of the calyxes of Physalis alkekengi L. var. franchetii (Mast.) Makino. J Chem Neuroanat 2024; 136:102390. [PMID: 38228242 DOI: 10.1016/j.jchemneu.2024.102390] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 01/08/2024] [Accepted: 01/08/2024] [Indexed: 01/18/2024]
Abstract
Physalis alkekengi L. var. franchetii (Mast.) Makino (PA), a traditional Chinese medicine, is utilised for treating dermatitis, sore throat, dysuria, and cough. This research aimed to identify the main constituents in the four extracted portions from the calyces of PA (PAC) utilising ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The Alzheimer's disease (AD) mice model was induced by D-galactose (D-gal) combined with aluminium chloride (AlCl3). Subsequent investigation into the underlying mechanisms involved behavioural and histopathological observations. The results demonstrated that four extracted portions of PAC (PACE) significantly enhanced memory and learning abilities in the Morris water maze. The concentrations of Aβ, tau and p-tau in brain tissue exhibited a significant decrease relative to the model group. Moreover, the four PACE treatment groups increased the glutathione (GSH) and superoxide dismutase (SOD) levels, while concurrently reducing malondialdehyde (MDA), interleukin-1β (IL-1β) and interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) levels. In summary, the current study demonstrates that the four PACE formulations exhibit beneficial anti-AD properties, with the most pronounced efficacy observed in the EA group. Additionally, PAC shows potential in mitigating neuroinflammation and oxidative damage by inhibiting the TLR4/NF-κB signalling pathway. This research lays a theoretical groundwork for the future clinical development and utilisation of PAC in treating AD.
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Affiliation(s)
- Yang Teng
- Department of Pharmacy, Jiamusi University, Jiamusi, China; Department of Vocational Education Group, Jiamusi, China
| | - Jia Gao
- Department of Pharmacy, Jiamusi University, Jiamusi, China
| | - Tian Tan
- Department of Vocational Education Group, Jiamusi, China
| | | | - Yuliang Wang
- Department of Pharmacy, Jiamusi University, Jiamusi, China
| | - Jiaguang Zhang
- Department of Vocational Education Group, Jiamusi, China
| | - Lei Ni
- Department of Clinical Medicine, Jiamusi University, Jiamusi, China.
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Abubakar M, Nama L, Ansari MA, Ansari MM, Bhardwaj S, Daksh R, Syamala KLV, Jamadade MS, Chhabra V, Kumar D, Kumar N. GLP-1/GIP Agonist as an Intriguing and Ultimate Remedy for Combating Alzheimer's Disease through its Supporting DPP4 Inhibitors: A Review. Curr Top Med Chem 2024; 24:1635-1664. [PMID: 38803170 DOI: 10.2174/0115680266293416240515075450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 04/14/2024] [Accepted: 04/22/2024] [Indexed: 05/29/2024]
Abstract
BACKGROUND Alzheimer's disease (AD) is a widespread neurological illness in the elderly, which impacted about 50 million people globally in 2020. Type 2 diabetes has been identified as a risk factor. Insulin and incretins are substances that have various impacts on neurodegenerative processes. Preclinical research has shown that GLP-1 receptor agonists decrease neuroinflammation, tau phosphorylation, amyloid deposition, synaptic function, and memory formation. Phase 2 and 3 studies are now occurring in Alzheimer's disease populations. In this article, we present a detailed assessment of the therapeutic potential of GLP-1 analogues and DPP4 inhibitors in Alzheimer's disease. AIM This study aimed to gain insight into how GLP-1 analogues and associated antagonists of DPP4 safeguard against AD. METHODS This study uses terms from search engines, such as Scopus, PubMed, and Google Scholar, to explore the role, function, and treatment options of the GLP-1 analogue for AD. RESULTS The review suggested that GLP-1 analogues may be useful for treating AD because they have been linked to anti-inflammatory, neurotrophic, and neuroprotective characteristics. Throughout this review, we discuss the underlying causes of AD and how GLP signaling functions. CONCLUSION With a focus on AD, the molecular and pharmacological effects of a few GLP-1/GIP analogs, both synthetic and natural, as well as DPP4 inhibitors, have been mentioned, which are in the preclinical and clinical studies. This has been demonstrated to improve cognitive function in Alzheimer's patients.
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Affiliation(s)
- Mohammad Abubakar
- Department of Pharmacology and Toxicology, National Institution of Pharmaceutical Education and Research, Hajipur, Vaishali, 844102, Bihar, India
| | - Lokesh Nama
- Department of Pharmacology and Toxicology, National Institution of Pharmaceutical Education and Research, Hajipur, Vaishali, 844102, Bihar, India
| | - Mohammad Arif Ansari
- Department of Pharmacology and Toxicology, National Institution of Pharmaceutical Education and Research, Hajipur, Vaishali, 844102, Bihar, India
| | - Mohammad Mazharuddin Ansari
- Department of Pharmacology and Toxicology, National Institution of Pharmaceutical Education and Research, Hajipur, Vaishali, 844102, Bihar, India
| | - Shivani Bhardwaj
- Department of Pharmacology and Toxicology, National Institution of Pharmaceutical Education and Research, Hajipur, Vaishali, 844102, Bihar, India
| | - Rajni Daksh
- Department of Pharmacology and Toxicology, National Institution of Pharmaceutical Education and Research, Hajipur, Vaishali, 844102, Bihar, India
| | - Katta Leela Venkata Syamala
- Department of Regulatory and Toxicology, National Institution of Pharmaceutical Education and Research, Hajipur, Vaishali, 844102, Bihar, India
| | - Mohini Santosh Jamadade
- Department of Pharmacology and Toxicology, National Institution of Pharmaceutical Education and Research, Hajipur, Vaishali, 844102, Bihar, India
| | - Vishal Chhabra
- Department of Pharmacology and Toxicology, National Institution of Pharmaceutical Education and Research, Hajipur, Vaishali, 844102, Bihar, India
| | - Dileep Kumar
- Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Pune, Maharashtra, 411038, India
- Department of Entomology, University of California, Davis, One Shields Ave, Davis, CA, 95616, USA
| | - Nitesh Kumar
- Department of Pharmacology and Toxicology, National Institution of Pharmaceutical Education and Research, Hajipur, Vaishali, 844102, Bihar, India
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Wu X, Cao S, Zou Y, Wu F. Traditional Chinese Medicine studies for Alzheimer's disease via network pharmacology based on entropy and random walk. PLoS One 2023; 18:e0294772. [PMID: 38019798 PMCID: PMC10686466 DOI: 10.1371/journal.pone.0294772] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Accepted: 11/08/2023] [Indexed: 12/01/2023] Open
Abstract
Alzheimer's disease (AD) is a common neurodegenerative disease having complex pathogenesis, approved drugs can only alleviate symptoms of AD for a period of time. Traditional Chinese medicine (TCM) contains multiple active ingredients that can act on multiple targets simultaneously. In this paper, a novel algorithm based on entropy and random walk with the restart of heterogeneous network (RWRHE) is proposed for predicting active ingredients for AD and screening out the effective TCMs for AD. First, Six TCM compounds containing 20 herbs from the AD drug reviews in the CNKI (China National Knowledge Internet) are collected, their active ingredients and targets are retrieved from different databases. Then, comprehensive similarity networks of active ingredients and targets are constructed based on different aspects and entropy weight, respectively. A comprehensive heterogeneous network is constructed by integrating the known active ingredient-target association information and two comprehensive similarity networks. Subsequently, bi-random walks are applied on the heterogeneous network to predict active ingredient-target associations. AD related targets are selected as the seed nodes, a random walk is carried out on the target similarity network to predict the AD-target associations, and the associations of AD-active ingredients are inferred and scored. The effective herbs and compounds for AD are screened out based on their active ingredients' scores. The results measured by machine learning and bioinformatics show that the RWRHE algorithm achieves better prediction accuracy, the top 15 active ingredients may act as multi-target agents in the prevention and treatment of AD, Danshen, Gouteng and Chaihu are recommended as effective TCMs for AD, Yiqitongyutang is recommended as effective compound for AD.
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Affiliation(s)
- Xiaolu Wu
- School of Mathematical Sciences, Tiangong University, Tianjin, China
| | - Shujuan Cao
- School of Mathematical Sciences, Tiangong University, Tianjin, China
| | - Yongming Zou
- Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China
| | - Fangxiang Wu
- Division of Biomedical Engineering, Department of Mechanical Engineering and Department of Computer Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
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Liu LW, Yue HY, Zou J, Tang M, Zou FM, Li ZL, Jia QQ, Li YB, Kang J, Zuo LH. Comprehensive metabolomics and lipidomics profiling uncovering neuroprotective effects of Ginkgo biloba L. leaf extract on Alzheimer's disease. Front Pharmacol 2022; 13:1076960. [PMID: 36618950 PMCID: PMC9810818 DOI: 10.3389/fphar.2022.1076960] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 12/12/2022] [Indexed: 12/24/2022] Open
Abstract
Introduction: Ginkgo biloba L. leaf extract (GBLE) has been reported to be effective for alleviating cognitive and memory impairment in Alzheimer's disease (AD). Nevertheless, the potential mechanism remains unclear. Herein, this study aimed to explore the neuroprotective effects of GBLE on AD and elaborate the underlying therapeutic mechanism. Methods: Donepezil, the most widely prescribed drug for AD, was used as a positive control. An integrated metabolomics and lipidomics approach was adopted to characterize plasma metabolic phenotype of APP/PS1 double transgenic mice and describe the metabolomic and lipidomic fingerprint changes after GBLE intervention. The Morris water maze test and immunohistochemistry were applied to evaluate the efficacy of GBLE. Results: As a result, administration of GBLE significantly improved the cognitive function and alleviated amyloid beta (Aβ) deposition in APP/PS1 mice, showing similar effects to donepezil. Significant alterations were observed in metabolic signatures of APP/PS1 mice compared with wild type (WT) mice by metabolomic analysis. A total of 60 markedly altered differential metabolites were identified, including 28 lipid and lipid-like molecules, 13 organic acids and derivatives, 11 organic nitrogen compounds, and 8 other compounds, indicative of significant changes in lipid metabolism of AD. Further lipidomic profiling showed that the differential expressed lipid metabolites between APP/PS1 and WT mice mainly consisted of phosphatidylcholines, lysophosphatidylcholines, triglycerides, and ceramides. Taking together all the data, the plasma metabolic signature of APP/PS1 mice was primarily characterized by disrupted sphingolipid metabolism, glycerophospholipid metabolism, glycerolipid metabolism, and amino acid metabolism. Most of the disordered metabolites were ameliorated after GBLE treatment, 19 metabolites and 24 lipids of which were significantly reversely regulated (adjusted-p<0.05), which were considered as potential therapeutic targets of GBLE on AD. The response of APP/PS1 mice to GBLE was similar to that of donepezil, which significantly reversed the levels of 23 disturbed metabolites and 30 lipids. Discussion: Our data suggested that lipid metabolism was dramatically perturbed in the plasma of APP/PS1 mice, and GBLE might exert its neuroprotective effects by restoring lipid metabolic balance. This work provided a basis for better understanding the potential pathogenesis of AD and shed new light on the therapeutic mechanism of GBLE in the treatment of AD.
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Affiliation(s)
- Li-Wei Liu
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou, Henan Province, China,Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, Henan Province, China
| | - He-Ying Yue
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou, Henan Province, China,Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, Henan Province, China
| | - Jing Zou
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou, Henan Province, China,Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, Henan Province, China
| | - Meng Tang
- The First Department of Orthopaedics, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province, China
| | - Fan-Mei Zou
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou, Henan Province, China,Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, Henan Province, China
| | - Zhuo-Lun Li
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou, Henan Province, China,Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, Henan Province, China
| | - Qing-Quan Jia
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou, Henan Province, China,Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, Henan Province, China
| | - Yu-Bo Li
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jian Kang
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou, Henan Province, China,Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, Henan Province, China
| | - Li-Hua Zuo
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China,Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou, Henan Province, China,Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, Henan Province, China,*Correspondence: Li-Hua Zuo,
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Briskey D, Rao A. A double-blind, randomised cross-over study to evaluate the absorption of a commercially available Ginkgo biloba extract compared to the liposomal extract Ginkgosome. BMC Complement Med Ther 2022; 22:206. [PMID: 35922794 PMCID: PMC9347086 DOI: 10.1186/s12906-022-03679-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 06/27/2022] [Indexed: 11/10/2022] Open
Abstract
Background Ginkgo biloba extracts (GBE) have been used in traditional medicines for centuries. GBE has been shown to deliver protective effects against symptoms of age-related cognitive decline. Despite there being standardised extractions for GBE, there is still variability in the absorption and efficacy of different extracts. Following the development of a liposomal GBE (Ginkgosome™), the aim of this study is to investigate the absorption of the liposomal formulation compared to a comparator formulation of equal dose. Methods Thirteen healthy male and female volunteers completed this single equivalent dose, randomised, double-blind crossover study. Plasma concentrations were determined at baseline and at regular intervals over a 24-h period following ingestion of 120 mg of either a liposomal or comparator formulation. Results The liposomal formulation was able to increase plasma concentration of ginkgolide B and C by 1.9 and 2.2-fold compared to the comparator formulation. Conclusion The novel liposomal formulation is safe in humans and demonstrates superior absorption for the supply of GBE constituents compared to a comparator standardised formulation.
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Ethnomedicinal Plants with Protective Effects against Beta-Amyloid Peptide (Aβ)1-42 Indicate Therapeutic Potential in a New In Vivo Model of Alzheimer's Disease. Antioxidants (Basel) 2022; 11:antiox11101865. [PMID: 36290588 PMCID: PMC9598277 DOI: 10.3390/antiox11101865] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 09/08/2022] [Accepted: 09/17/2022] [Indexed: 11/25/2022] Open
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with unmet medical need. This investigation consisted of testing a range of ethanolic ethnomedicinal plant extracts (n = 18) traditionally used in the treatment of disorders such as anxiety, delirium, and memory loss. They were then screened for in vitro inhibitory activity against acetylcholinesterase (AChE), butylcholinesterase (BuChE), beta-secretase 1/beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), and antioxidant activities. Plants with potent activities were further characterised using a recently developed in vivo model of AD, Globodera pallida. The ability of phytoextracts to protect this organism against amyloid-beta Aβ (1-42) exposure was assessed by measuring chemosensing, survival rate, production of reactive oxygen species (ROS), and antioxidant responses. Extracts (n = 5) from Juglans regia (leaves), Ellettaria cardamomum (seeds), Cinnamomum zeylanicum (bark), Salvia officinalis (leaves/flowers), and Hypericum perforatum (flowers) exerted concentration-dependent inhibitory activities against AChE and BuChE. Three of these plant extracts (i.e., J. regia, E. cardamomum, and S. officinalis) possessed strong concentration-dependent inhibitory activity against BACE1. Furthermore, the five selected medicinal plant extracts not only enhanced significantly (p < 0.05) the nematode’s chemosensing, survival rate, and antioxidant responses (i.e., anti-ROS production, mitochondrial reductase activity, oxidized glutathione (GSSG) to reduced glutathione (GSH) ratio), but also greatly restored (p < 0.05) in a concentration-dependent manner the Aβ (1-42)-induced deleterious changes in these same parameters. In brief, this investigation highlights plant extracts with strong anti-AD activities which could be trialled as novel therapeutic supplements or undergo further biodiscovery research.
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Elyasi L, Rosenholm JM, Jesmi F, Jahanshahi M. The Antioxidative Effects of Picein and Its Neuroprotective Potential: A Review of the Literature. Molecules 2022; 27:molecules27196189. [PMID: 36234724 PMCID: PMC9571929 DOI: 10.3390/molecules27196189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 09/14/2022] [Accepted: 09/15/2022] [Indexed: 11/16/2022] Open
Abstract
Neurodegenerative diseases (NDDs) are the main cause of dementia in the elderly, having no cure to date, as the currently available therapies focus on symptom remission. Most NDDs will progress despite treatment and eventually result in the death of the patient after several years of a burden on both the patient and the caregivers. Therefore, it is necessary to investigate agents that tackle the disease pathogenesis and can efficiently slow down or halt disease progression, with the hope of curing the patients and preventing further burden and mortality. Accordingly, recent research has focused on disease-modifying treatments with neuroregenerative or neuroprotective effects. For this purpose, it is necessary to understand the pathogenesis of NDDs. It has been shown that oxidative stress plays an important role in the damage to the central nervous system and the progression of neurodegenerative disorders. Furthermore, mitochondrial dysfunction and the accumulation of unfolded proteins, including beta-amyloid (Aβ), tau proteins, and α-synuclein, have been suggested. Accordingly, cellular and molecular studies have investigated the efficacy of several natural compounds (herbs and nutritional agents) for their neuroprotective and antioxidative properties. The most popular herbs suggested for the treatment and/or prevention of NDDs include Withania somnifera (ashwagandha), ginseng, curcumin, resveratrol, Baccopa monnieri, and Ginkgo biloba. In some herbs, such as ginseng, preclinical and clinical evidence are available for supporting its effectiveness; however, in some others, only cellular and animal studies are available. In line with the scant literature in terms of the effectiveness of herbal compounds on NDDs, there are also other herbal agents that have been disregarded. Picein is one of the herbal agents that has been investigated in only a few studies. Picein is the active ingredient of several herbs and can be thus extracted from different types of herbs, which makes it more available. It has shown to have anti-inflammatory properties in cellular and plant studies; however, to date, only one study has suggested its neuroprotective properties. Furthermore, some cellular studies have shown no anti-inflammatory effect of picein. Therefore, a review of the available literature is required to summarize the results of studies on picein. To date, no review study seems to have addressed this issue. Thus, in the present study, we gather the available information about the antioxidative and potential neuroprotective properties of picein and its possible effectiveness in treating NDDs. We also summarize the plants from which picein can be extracted in order to guide researchers for future investigations.
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Affiliation(s)
- Leila Elyasi
- Neuroscience Research Center, Department of Anatomy, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan 4917955315, Iran
- Correspondence: ; Tel./Fax: +98-17-32453515
| | - Jessica M. Rosenholm
- Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20500 Turku, Finland
| | - Fatemeh Jesmi
- Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran 1415944911, Iran
| | - Mehrdad Jahanshahi
- Neuroscience Research Center, Department of Anatomy, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan 4917955315, Iran
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Bandyopadhyay A, Dey A. Medicinal pteridophytes: ethnopharmacological, phytochemical, and clinical attributes. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2022. [DOI: 10.1186/s43088-022-00283-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Almost from the very beginning of human existence, man has been interacting with plants. Throughout human history, plants have provided humans with basic needs such as sustenance, firewood, livestock feed, and wood. The world has approximately 3 million vascular plants. The treatment of primary health problems is provided primarily by traditional medicines by around 80% of the world's population. Compared to other vascular plants, pteridophytes remain underexplored in ethnobotanical aspects, despite being regarded as a valuable component of healthcare for centuries. As an alternative medicine, pteridophytes are being investigated for their pharmacological activity. Almost 2000 years ago, humans were exploring and using plant species from this lineage because of its beneficial properties since pteridophytes were the first vascular plants.
Main body of the abstract
All popular search engines such as PubMed, Google Scholar, ScienceDirect, and Scopus were searched to retrieve the relevant literature using various search strings relevant to the topic. Pteridophytes belonging to thirty different families have been documented as medicinal plants. For instance, Selaginella sp. has been demonstrated to have numerous therapeutic properties, including antioxidative, inflammation-reducing, anti-carcinogenic, diabetes-fighting, virucidal, antibacterial, and anti-senile dementia effects. In addition, clinical trials and studies performed on pteridophytes and derived compounds are also discussed in details.
Short conclusion
This review offers a compilation of therapeutically valuable pteridophytes utilized by local ethnic groups, as well as the public.
Graphical Abstract
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Current Progress on Neuroprotection Induced by Artemisia, Ginseng, Astragalus, and Ginkgo Traditional Chinese Medicines for the Therapy of Alzheimer's Disease. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:3777021. [PMID: 35746960 PMCID: PMC9213169 DOI: 10.1155/2022/3777021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 05/20/2022] [Indexed: 11/17/2022]
Abstract
Aging is associated with the occurrence of diverse degenerative changes in various tissues and organs and with an increased incidence of neurological disorders, especially neurodegenerative diseases such as Alzheimer's disease (AD). In recent years, the search for effective components derived from medicinal plants in delaying aging and preventing and treating neurodegenerative diseases has been increasing and the number of related publications shows a rising trend. Here, we present a concise, updated review on the preclinical and clinical research progress in the assessment of the therapeutic potential of different traditional Chinese medicines and derived active ingredients and their effect on the signaling pathways involved in AD neuroprotection. Recognized by their multitargeting ability, these natural compounds hold great potential in developing novel drugs for AD.
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Francesca F, Caitlin A, Sarah L, Robyn GL. Antroquinonol administration in animal preclinical studies for Alzheimer's disease (AD): A new avenue for modifying progression of AD pathophysiology. Brain Behav Immun Health 2022; 21:100435. [PMID: 35252893 PMCID: PMC8892093 DOI: 10.1016/j.bbih.2022.100435] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 01/28/2022] [Accepted: 02/22/2022] [Indexed: 11/28/2022] Open
Abstract
Despite the rise of Alzheimer's disease (AD) in an ageing population, no cure is currently available for this disorder. This study assessed the role of a natural compound, Antroquinonol, in modifying the progression of AD when administered at the start and/or before appearance of symptoms and when the disease was well established, in a transgenic animal model. Antroquinonol was administered daily for 8 weeks, in 11 week (early stage) and 9 month (late stage) male transgenic mice (3 times Transgenic mice PS1M146V, APPSwe, and tauP301L, 3 Tg XAD) and their respective aged controls. Behavioural testing (including Elevated Plus Maze Watermaze, Recognition object testing and Y maze) was performed at the end of the drug administration. In addition AD biomarkers (Amyloid beta 42 (Aβ42), tau and phospho-tau levels), oxidative stress and inflammatory markers, were assessed in tested mice brains after their sacrifice at the end of the treatment. When administered before the start of symptoms at 11 weeks, Antroquinonol treatment at 34 mg/kg (D2) and more consistently at 75 mg/kg (D3), had a significant effect on reducing systemic inflammatory markers (Interleukin 1, IL-1β and TNF-α) and AD biomarker (Amyloid Beta 42, Aβ42 and tau) levels in the brain. The reduction of behavioural impairment reported for 3TgXAD mice was observed significantly for the D3 drug dose only and for all behavioural tests, when administered at 11 weeks. Similarly, beneficial effects of Antroquinonol (at higher dose D3) were noted in the transgenic mice in terms of AD biomarkers (tau and phosphorylated-tau), systemic inflammatory (IL-1β), brain anti-inflammatory (Nrf2) and oxidative (3-Nitrotyrosine, 3NT) markers. Improvement of memory impairment was also reported when Antroquinonol (D3) was administered at late stage (9 months). Since Antroquinonol has been used without adverse effects in previous successful clinical trials, this drug may offer a new avenue of treatment to modify AD development and progression.
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Affiliation(s)
- Fernandez Francesca
- School of Behavioural and Health Sciences, Faculty of Health Sciences, Australian Catholic University, 1100 Nudgee Rd, Banyo, Queensland, 4014, Australia
- Centre for Genomics and Personalised Medicine, Genomics Research Centre, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD, 4059, Australia
| | - Aust Caitlin
- School of Behavioural and Health Sciences, Faculty of Health Sciences, Australian Catholic University, 1100 Nudgee Rd, Banyo, Queensland, 4014, Australia
- Centre for Genomics and Personalised Medicine, Genomics Research Centre, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD, 4059, Australia
| | - Lye Sarah
- School of Behavioural and Health Sciences, Faculty of Health Sciences, Australian Catholic University, 1100 Nudgee Rd, Banyo, Queensland, 4014, Australia
- Centre for Genomics and Personalised Medicine, Genomics Research Centre, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD, 4059, Australia
| | - Griffiths Lyn Robyn
- Centre for Genomics and Personalised Medicine, Genomics Research Centre, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD, 4059, Australia
- Corresponding author. Centre for Genomics and Personalised Health Genomics Research Centre, Queensland University of Technology, Australia.
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Li DQ, Jiang F, Zhang HS, Zheng LJ, Wang QJ, Fu R, Liu XG, Gao PY. Network pharmacology-based approach to investigate the mechanisms of Zingiber officinale Roscoe in the treatment of neurodegenerative diseases. J Food Biochem 2022; 46:e14068. [PMID: 35128682 DOI: 10.1111/jfbc.14068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 12/01/2021] [Accepted: 12/06/2021] [Indexed: 11/28/2022]
Abstract
Neurodegenerative diseases (NDDs) are chronic neurological disorders associated with cognitive or motor dysfunction. As a common spice, Zingiber officinale Roscoe has been used as a medicine to treat a variety of NDDs. However, at the molecular level, the mechanisms of Z. officinale in treating of NDDs have not been deeply investigated. In this study, network pharmacology method, molecular docking, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to predict the mechanisms of Z. officinale in the treatment of NDDs. After a series of biological information analyses, five core targets were obtained, including heme oxygenase 1 (HMOX1), acetylcholinesterase (AChE), nitric oxide synthase (NOS), catechol-O-methyl-transferase (COMT), and metabotropic glutamate receptor 5 (mGluR5). Compounds 75, 68, 46, 67, 69, 49, 66, 50, 34, and 64 were identified as the main components of Z. officinale in the treatment of NDDs. The crucial pathways mainly include neuroactive ligand-receptor signaling pathways, cyclic adenosine monophosphate signaling pathways, dopamine synaptic signaling pathways, and so on. Besides, in vitro experiments by AChE inhibitory activities assay and neuroprotective activities against H2 O2 -induced injury in human neuroblastoma SH-SY5Y cells validated the reliability of the results of network analysis. PRACTICAL APPLICATIONS: Zingiber officinale Roscoe is widely used as a traditional spice and herbal medicine. It contains a number of active ingredients, which have shown activities on anti-neurodegenerative diseases (NDDs). In this paper, the potential mechanism of Z. officinale in the treatment of NDDs is explored through network pharmacology, and it was verified by in vitro experiments. The mechanism was not only clarified at the system level but also proved to be effective at the biological level. The results can be used as a reference for Z. officinale in the treating of NDDs.
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Affiliation(s)
- Dan-Qi Li
- Institute of Functional Molecules, Shenyang University of Chemical Technology, Shenyang, PR China
- Liaoning Province Key Laboratory of Green Functional Molecular Design and Development, Shenyang University of Chemical Technology, Shenyang, PR China
| | - Fan Jiang
- College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, PR China
| | - Han-Shuo Zhang
- College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, PR China
| | - Lian-Jun Zheng
- College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, PR China
| | - Qing-Jie Wang
- College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, PR China
| | - Ran Fu
- College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, PR China
| | - Xue-Gui Liu
- Institute of Functional Molecules, Shenyang University of Chemical Technology, Shenyang, PR China
- National-Local Joint Engineering Laboratory for Development of Boron and Magnesium Resources and Fine Chemical Technology, Shenyang University of Chemical Technology, Shenyang, PR China
| | - Pin-Yi Gao
- Liaoning Province Key Laboratory of Green Functional Molecular Design and Development, Shenyang University of Chemical Technology, Shenyang, PR China
- College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, PR China
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Onaolapo OJ, Olofinnade AT, Ojo FO, Onaolapo AY. Neuroinflammation and Oxidative Stress in Alzheimer's Disease; Can Nutraceuticals and Functional Foods Come to the Rescue? Antiinflamm Antiallergy Agents Med Chem 2022; 21:75-89. [PMID: 36043770 DOI: 10.2174/1871523021666220815151559] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 06/17/2022] [Accepted: 06/29/2022] [Indexed: 06/15/2023]
Abstract
Alzheimer's disease (AD), the most prevalent form of age-related dementia, is typified by progressive memory loss and spatial awareness with personality changes. The increasing socioeconomic burden associated with AD has made it a focus of extensive research. Ample scientific evidence supports the role of neuroinflammation and oxidative stress in AD pathophysiology, and there is increasing research into the possible role of anti-inflammatory and antioxidative agents as disease modifying therapies. While, the result of numerous preclinical studies has demonstrated the benefits of anti-inflammatory agents, these benefits however have not been replicated in clinical trials, necessitating a further search for more promising anti-inflammatory agents. Current understanding highlights the role of diet in the development of neuroinflammation and oxidative stress, as well as the importance of dietary interventions and lifestyle modifications in mitigating them. The current narrative review examines scientific literature for evidence of the roles (if any) of dietary components, nutraceuticals and functional foods in the prevention or management of AD. It also examines how diet/ dietary components could modulate oxidative stress/inflammatory mediators and pathways that are crucial to the pathogenesis and/or progression of AD.
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Affiliation(s)
- Olakunle J Onaolapo
- Department of Pharmacology, Behavioural Neuroscience Unit, Neuropharmacology Subdivision, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - Anthony T Olofinnade
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Clinical Sciences, College of Medicine, Lagos State University, Ikeja, Lagos State, Nigeria
| | - Folusho O Ojo
- Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - Adejoke Y Onaolapo
- Department of Anatomy, Behavioural Neuroscience Unit, Neurobiology Subdivision, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
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21
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Nguyen P, Kim KY, Kim AY, Kang S, Osabutey AF, Jin H, Guo Y, Park H, Suh JW, Koh YH. The additive memory and healthspan enhancement effects by the combined treatment of mature silkworm powders and Korean angelica extracts. JOURNAL OF ETHNOPHARMACOLOGY 2021; 281:114520. [PMID: 34391862 DOI: 10.1016/j.jep.2021.114520] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 08/02/2021] [Accepted: 08/11/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Silkworm (Bombyx mori) and Korean angelica (KoAg; Angelica gigas Nakai) have been widely used as traditional oriental medicines in Korea, China, and Japan to treat various diseases such as anemia, cold, diabetes, palsy, stroke, etc. Steamed and freeze-dried mature silkworm powder, also known as HongJam (HJ), and extracts of KoAg root (KoAgE) are currently sold in Korea as functional foods to improve memory, cognition, and liver functions. However, the molecular and pharmacological basis for the improvement of brain functions of HJ and KoAgE has not yet been elucidated. AIM OF STUDY This study aimed to elucidate the molecular basis underlying the memory-enhancing effects of HJ and KoAgE and determine whether administration of HJ and KoAgE complexes (HJ+KoAgC) has additive memory and healthspan-enhancing effects. MATERIALS AND METHODS The MCI mouse models generated by intraperitoneal injection of Scopolamine (Sco-IP) were orally administered with HJ and KoAgE alone or as complexes. Their memory-enhancing effects were examined on spatial, fear-aggravated, and social memories and compared with control or Donepezil (Dp) treatment. The activities of mitochondria complex (MitoCom) I-IV and acetylcholinesterase (AChE) and the amounts of ATP in the mouse brains were examined. The Drosophila model was used to investigate lifespan- and healthspan-promoting effects of HJ+KoAgC. RESULTS Administration of HJ+KoAgC produced more memory-enhancing effects than administration of HJ or KoAgE alone or Dp. The increase in MitoCom I-IV activities and ATP amounts and the decrease in AChE activities in the mouse brains were the molecular basis for the memory enhancement. The greatest improvement in memory and mitochondrial function was observed when the mice were administered the 1:0.8 ratio of HJ+KoAgC. Administration of HJ+KoAgC to Drosophila prolonged the lifespan and the healthspan and increased the amounts of ATP. CONCLUSION HJ+KoAgC had superior effects on memory improvement and healthspan extension by increasing mitochondrial activities and ATP amounts in treated animal models.
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Affiliation(s)
- Phuong Nguyen
- Ilsong Institute of Life Sciences, Hallym University, Anyang, Gyeonggi-do, Republic of Korea.
| | - Kee-Young Kim
- Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration, Wanju, Jeollabuk-do, Republic of Korea.
| | - A-Young Kim
- Ilsong Institute of Life Sciences, Hallym University, Anyang, Gyeonggi-do, Republic of Korea.
| | - SangKook Kang
- Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration, Wanju, Jeollabuk-do, Republic of Korea.
| | - Angelica F Osabutey
- Ilsong Institute of Life Sciences, Hallym University, Anyang, Gyeonggi-do, Republic of Korea; Department of Biomedical Gerontology, Hallym University Graduate School, Chuncheon, Gangwon-do, Republic of Korea.
| | - Hui Jin
- Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi-do, South Korea.
| | - Yuanri Guo
- Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi-do, South Korea.
| | - Hyunwoo Park
- HealthPark. 2502ho, Gangnamdaero 305, Seoul, South Korea.
| | - Joo-Won Suh
- Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi-do, South Korea.
| | - Young Ho Koh
- Ilsong Institute of Life Sciences, Hallym University, Anyang, Gyeonggi-do, Republic of Korea; Department of Biomedical Gerontology, Hallym University Graduate School, Chuncheon, Gangwon-do, Republic of Korea.
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Alzobaidi N, Quasimi H, Emad NA, Alhalmi A, Naqvi M. Bioactive Compounds and Traditional Herbal Medicine: Promising Approaches for the Treatment of Dementia. Degener Neurol Neuromuscul Dis 2021; 11:1-14. [PMID: 33880073 PMCID: PMC8051957 DOI: 10.2147/dnnd.s299589] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 03/23/2021] [Indexed: 12/13/2022] Open
Abstract
Dementia is a term that encompasses a group of clinical symptoms affecting memory, thinking and social abilities, characterized by progressive impairment of memory performance and cognitive functions. There are several factors involved in the pathogenesis and progression of dementia, such as old age, brain ischemia, toxin exposure, and oxidative stress. There are extensive similarities between dementia and Alzheimer's disease (AD) either in clinical manifestations or experimental animal models. AD is the most dominant form of dementia, characterized by the accumulation of beta-amyloid protein and cholinergic neurotransmission deficits in the brain. Currently available medications for the treatment of dementia, such as choline esterase inhibitors, N-methyl-D-aspartate (NMDA) antagonists (memantine), have short-term efficacy and only relieve symptoms rather than targeting the main underlying pathogenesis. Several animal studies and clinical trials are being conducted to provide a rational approach to these medicinal plants in the prevention or treatment of memory deficits. This review highlights the potential effects of medicinal plants and their derived lead molecules, and explains the related mechanisms and effects reviewed from published literature as major thrust aspects and hopeful strategies in the prevention or treatment of dementia.
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Affiliation(s)
- Nafaa Alzobaidi
- Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard, New Delhi, India
| | - Huma Quasimi
- Department of Physiology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard, New Delhi, India
| | - Nasr A Emad
- Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India
| | - Abdulsalam Alhalmi
- Department of Pharmaceutics, College of Pharmacy, Aden University, Aden, Yemen
| | - Maaz Naqvi
- Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard, New Delhi, India
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23
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Xia Y, Shi LSB, Chang JH, Miao HZ, Wang D. Impact of the COVID-19 pandemic on intention to use traditional Chinese medicine: A cross-sectional study based on the theory of planned behavior. JOURNAL OF INTEGRATIVE MEDICINE-JIM 2021; 19:219-225. [PMID: 33547011 PMCID: PMC7826027 DOI: 10.1016/j.joim.2021.01.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Accepted: 12/11/2020] [Indexed: 12/11/2022]
Abstract
Objective Coronavirus disease 2019 (COVID-19) has become an increasingly severe public health emergency. Although traditional Chinese medicine (TCM) has helped to combat COVID-19, public perception of TCM remains controversial. We used the theory of planned behavior (TPB) to identify factors that affect the intention to use TCM. Methods A cross-sectional web-based survey of 10,824 individuals from the general public was conducted between March 16 and April 2, 2020. The participants were recruited using a snowball sampling method. Data were collected using a self-administered questionnaire, based on the TPB. The questionnaire consisted of demographic characteristics and TPB structures. Structural equation modeling was used to identify predictors of intention. Results The results indicated the model explained 77.5% and 71.9% of intention and attitude variance. Intention to use TCM had the strongest relationship with attitude (P < 0.001), followed by past behavior (P < 0.001), subjective norms (P < 0.001) and perceived behavioral control (P < 0.001). Attitudes toward TCM were significantly affected by perceived behavioral control (P < 0.001), subjective norms (P < 0.001) and cognition of TCM (P < 0.001). Conclusion Attitude is a key factor in determining the intention to use TCM, followed by past behaviors, subjective norms and perceived behavioral control. Our results offer important implications for health policy makers to promote the use of TCM.
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Affiliation(s)
- Yi Xia
- School of Public Health, Southern Medical University, Guangzhou 510515, Guangdong Province, China; School of Health Management, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Lu-Shao-Bo Shi
- School of Health Management, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Jing-Hui Chang
- School of Health Management, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Hua-Zhang Miao
- School of Health Management, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Dong Wang
- School of Health Management, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
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24
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Lye S, Aust CE, Griffiths LR, Fernandez F. Exploring new avenues for modifying course of progression of Alzheimer's disease: The rise of natural medicine. J Neurol Sci 2021; 422:117332. [PMID: 33607542 DOI: 10.1016/j.jns.2021.117332] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 01/07/2021] [Accepted: 01/22/2021] [Indexed: 12/01/2022]
Abstract
With a constantly growing elderly population worldwide, a focus on developing efficient prevention and therapy for Alzheimer's disease (AD) seems timely and topical. Emphasis on natural medicine is increasingly popular in the search for drug candidates that are capable of preventing and treating AD related pathology, particularly where suppression of amyloid accumulation, neurofibrillary tangle formation, neuroinflammation and oxidative stress are equally significant. A number of phytochemical compounds have been shown to collectively reduce these AD hallmarks with the progression of natural drug candidates into human clinical trials. This review focuses on current research surrounding the therapies emerging within natural medicines and their related therapeutic potential for AD treatment.
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Affiliation(s)
- Sarah Lye
- School of Health and Behavioural Science, Faculty of Health Sciences, 1100 Nudgee Road, Australian Catholic University, Brisbane, QLD, Australia
| | - Caitlin E Aust
- School of Health and Behavioural Science, Faculty of Health Sciences, 1100 Nudgee Road, Australian Catholic University, Brisbane, QLD, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia
| | - Lyn R Griffiths
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia
| | - Francesca Fernandez
- School of Health and Behavioural Science, Faculty of Health Sciences, 1100 Nudgee Road, Australian Catholic University, Brisbane, QLD, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia.
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25
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The Cholinesterase Inhibitory Properties of Stephaniae Tetrandrae Radix. Molecules 2020; 25:molecules25245914. [PMID: 33327436 PMCID: PMC7764916 DOI: 10.3390/molecules25245914] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 12/08/2020] [Accepted: 12/10/2020] [Indexed: 11/18/2022] Open
Abstract
Stephaniae tetrandrae radix (STR) is a commonly used traditional Chinese medicine in alleviating edema by inducing diuresis. In the clinic, STR extracts or its components are widely used in the treatment of edema, dysuria, and rheumatism for the regulation of water metabolism. Furthermore, STR has been used in treating emotional problems for years by combining with other Chinese herbs. However, the material basis and mechanism of STR on the nervous system have not been revealed. Here, the main components of STR extracts with different extracting solvents were identified, including three major alkaloids, i.e., cyclanoline, fangchinoline, and tetrandrine. The cholinesterase inhibitory activity of STR extracts and its alkaloids was determined using the Ellman assay. Both cyclanoline and fangchinoline showed acetylcholinesterase (AChE) inhibitory activity, demonstrating noncompetitive enzyme inhibition. In contrast, tetrandrine did not show enzymatic inhibition. The synergism of STR alkaloids with huperzine A or donepezil was calculated by the median-effect principle. The drug combination of fangchinoline–huperzine A or donepezil synergistically inhibited AChE, having a combination index (CI) < 1 at Fa = 0.5. Furthermore, the molecular docking results showed that fangchinoline bound with AChE residues in the peripheral anionic site, and cyclanoline bound with AChE residues in the peripheral anionic site, anionic site, and catalytic site. In parallel, cyclanoline bound with butyrylcholinesterase (BChE) residues in the anionic site, catalytic site, and aromatic site. The results support that fangchinoline and cyclanoline, alkaloids derived from STR, could account for the anti-AChE function of STR. Thus, STR extract or its alkaloids may potentially be developed as a therapeutic strategy for Alzheimer’s patients.
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Song Z, Li F, He C, Yu J, Li P, Li Z, Yang M, Cheng S. In-depth transcriptomic analyses of LncRNA and mRNA expression in the hippocampus of APP/PS1 mice by Danggui-Shaoyao-San. Aging (Albany NY) 2020; 12:23945-23959. [PMID: 33221745 PMCID: PMC7762474 DOI: 10.18632/aging.104068] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 08/17/2020] [Indexed: 12/21/2022]
Abstract
Alzheimer’s disease (AD) is an age-related neurodegenerative disease with a high incidence worldwide, and with no medications currently able to prevent the progression of AD. Danggui-Shaoyao-San (DSS) is widely used in traditional Chinese medicine (TCM) and has been proven to be effective for memory and cognitive dysfunction, yet its precise mechanism remains to be delineated. The present study was designed to investigate the genome-wide expression profile of long non-coding RNAs (LncRNAs) and messenger RNAs (mRNAs) in the hippocampus of APP/PS1 mice after DSS treatment by RNA sequencing. A total of 285 differentially expressed LncRNAs and 137 differentially expressed mRNAs were identified (fold-change ≥2.0 and P < 0.05). Partial differentially expressed LncRNAs and mRNAs were selected to verify the RNA sequencing results by quantitative polymerase chain reaction (qPCR). A co-expression network was established to analyze co-expressed LncRNAs and genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to evaluate the biological functions related to the differentially co-expressed LncRNAs, and the results showed that the co-expressed LncRNAs were mainly involved in AD development from distinct origins, such as APP processing, neuron migration, and synaptic transmission. Our research describes the lncRNA and mRNA expression profiles and functional networks involved in the therapeutic effect of DSS in APP/PS1 mice model. The results suggest that the therapeutic effect of DSS on AD involves the expression of LncRNAs. Our findings provide a new perspective for research on the treatment of complex diseases using traditional Chinese medicine prescriptions.
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Affiliation(s)
- Zhenyan Song
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China
| | - Fuzhou Li
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China
| | - Chunxiang He
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China
| | - Jingping Yu
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China
| | - Ping Li
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China
| | - Ze Li
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China
| | - Miao Yang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China
| | - Shaowu Cheng
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China
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Network Pharmacology Analysis and Molecular Characterization of the Herbal Medicine Formulation Qi-Fu-Yin for the Inhibition of the Neuroinflammatory Biomarker iNOS in Microglial BV-2 Cells: Implication for the Treatment of Alzheimer's Disease. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:5780703. [PMID: 32952851 PMCID: PMC7481926 DOI: 10.1155/2020/5780703] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 08/12/2020] [Indexed: 12/23/2022]
Abstract
Aberrant microglial activation drives neuroinflammation and neurodegeneration in Alzheimer's disease (AD). The present study is aimed at investigating whether the herbal formula Qi-Fu-Yin (QFY) could inhibit the inflammatory activation of cultured BV-2 microglia. A network pharmacology approach was employed to predict the active compounds of QFY, protein targets, and affected pathways. The representative pathways and molecular functions of the targets were analyzed by Gene Ontology (GO) and pathway enrichment. A total of 145 active compounds were selected from seven herbal ingredients of QFY. Targets (e.g., MAPT, APP, ACHE, iNOS, and COX-2) were predicted for the selected active compounds based on the relevance to AD and inflammation. As a validation, fractions were sequentially prepared by aqueous extraction, ethanolic precipitation, and HPLC separation, and assayed for downregulating two key proinflammatory biomarkers iNOS and COX-2 in lipopolysaccharide- (LPS-) challenged BV-2 cells by the Western blotting technique. Moreover, the compounds of QFY in 90% ethanol downregulated iNOS in BV-2 cells but showed no activity against COX-2 induction. Among the herbal ingredients of QFY, Angelicae Sinensis Radix and Ginseng Radix et Rhizoma contributed to the selective inhibition of iNOS induction. Furthermore, chemical analysis identified ginsenosides, especially Rg3, as antineuroinflammatory compounds. The herbal formula QFY may ameliorate neuroinflammation via downregulating iNOS in microglia.
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Klimova B, Kuca K, Valis M, Hort J. Traditional Chinese Medicine as an Effective Complementary Non-Pharmacological Approach to Mild Cognitive Impairment: A Call for Collaboration. J Alzheimers Dis 2020; 68:1185-1192. [PMID: 30909244 DOI: 10.3233/jad-181281] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Currently, there is an increase in the number of older people worldwide. Unfortunately, this demographic trend causes a rise in aging diseases, one of which is dementia. Recent research studies have indicated that mild cognitive impairment (MCI) may serve as a predictor of dementia in many patients. At present, there is no pharmacological treatment against MCI. Therefore, there is constant search for novel alternative non-pharmacological approaches to improve MCI. One of the effective complementary emerging approaches seems to be Traditional Chinese Medicine (TCM), which is nowadays becoming quite popular in the treatment of different disorders. The purpose of this study is to explore the efficacy of TCM as an effective complementary non-pharmacological tool for the improvement and treatment of MCI in older adults. The methods used for this review study included a literature search in the world's databases: Web of Science, Scopus, PubMed, and Springer. Afterwards, methods of comparison and evaluation of the findings from the selected studies were applied. The results of this review study indicate that TCM might be a beneficial complementary non-pharmacological approach to the improvement and treatment of MCI in older individuals. Nevertheless, more rigorously designed quality randomized clinical trials should be conducted in order to conclusively prove efficacy of TCM on the improvement of MCI among older population groups. In addition, there is an urgent call for a functional collaboration between western and eastern medicinal approaches, which could contribute to the enhancement of the overall quality of life of these aging population groups.
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Affiliation(s)
- Blanka Klimova
- Department of Neurology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
| | - Kamil Kuca
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic
| | - Martin Valis
- Department of Neurology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
| | - Jakub Hort
- Department of Neurology, Memory Disorders Clinic, Charles University in Prague, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.,International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic
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Guan H, Li J, Tan X, Luo S, Liu Y, Meng Y, Wu B, Zhou Y, Yang Y, Chen H, Hou L, Qiu Y, Li J. Natural Xanthone α-Mangostin Inhibits LPS-Induced Microglial Inflammatory Responses and Memory Impairment by Blocking the TAK1/NF-κB Signaling Pathway. Mol Nutr Food Res 2020; 64:e2000096. [PMID: 32506806 DOI: 10.1002/mnfr.202000096] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 05/14/2020] [Indexed: 12/18/2022]
Abstract
SCOPE The effect of α-mangostin (α-M), a polyphenolic xanthone isolated from mangostin, on lipopolysaccharide (LPS)-induced microglial activation and memory impairment is explored. The possible underlying mechanisms are also investigated. METHODS AND RESULTS Cytokine production and activation of transforming growth factor activated kinase-1 (TAK1) and nuclear factor-κB (NF-κB) are detected by enzyme-linked immunosorbent assay (ELISA) or Western blot. Microglial migration and phagocytosis are evaluated with scratch wound-healing assay and phagocytosis of fluorescent latex beads, respectively. Learning and memory abilities of mice are evaluated with the Morris water maze test. The nanomolar (100-500 nm) α-M suppresses LPS-induced pro-inflammatory cytokine production and inducible nitric oxide synthase (iNOS) expression in microglia. It also inhibits LPS-induced microglial migration and phagocytosis. α-M rescues LPS-caused, microglia-mediated neuronal dendritic damage. Moreover, α-M represses LPS-induced toll-like receptor 4 (TLR4) expression and activation of TAK1 and NF-κB. In a mouse neuroinflammation model, α-M (50 mg kg-1 day-1 ) shows obvious anti-neuroinflammatory, neuroprotective, and memory-improving effects in vivo. CONCLUSION α-M inhibits microglia-mediated neuroinflammation and prevents neurotoxicity and memory impairment from inflammatory damage. These results indicate that α-M has great potential to be used as a nutritional preventive strategy for neuroinflammation-related neurodegenerative disorders such as Alzheimer's disease.
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Affiliation(s)
- Huifeng Guan
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P. R. China
| | - Jiabing Li
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P. R. China
| | - Xiaofang Tan
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P. R. China
| | - Shenying Luo
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P. R. China
| | - Yangdan Liu
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P. R. China
| | - Yiwen Meng
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P. R. China
| | - Baichuan Wu
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P. R. China
| | - Yan Zhou
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P. R. China
| | - Yang Yang
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P. R. China
| | - Hongzhuan Chen
- Institute of Interdisciplinary Integrative Biomedical Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201210, P. R. China
| | - Lina Hou
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P. R. China
| | - Yu Qiu
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P. R. China
| | - Juan Li
- Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, P. R. China
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Feng YN, Zhang XF. Polysaccharide extracted from Huperzia serrata using response surface methodology and its biological activity. Int J Biol Macromol 2020; 157:267-275. [PMID: 32339584 DOI: 10.1016/j.ijbiomac.2020.04.134] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Revised: 03/07/2020] [Accepted: 04/18/2020] [Indexed: 12/15/2022]
Abstract
In this study, Huperzia serrata polysaccharide (HSP) fraction was isolated using response surface methodology (RSM) and Box-Behnken design (BBD). The extraction time, temperature and ratio of water to raw material were employed effects. And properties of four polysaccharide (60%-HSP, 70%-HSP, 80%-HSP and 90%-HSP) were evaluated. The results indicated that the optimal extraction conditions were the following: 3.07 h, 49.46 °C and a liquid material ratio of 20.73:1. The four HSP presented irregular aggregation of shape. And all HSP exhibited antioxidant and anticancer activities.
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Affiliation(s)
- Yan-Ni Feng
- College of Veterinary medicine, Qingdao Agricultural University, Qingdao 266100, China
| | - Xi-Feng Zhang
- College of Veterinary medicine, Qingdao Agricultural University, Qingdao 266100, China.
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Piwowar A, Rembiałkowska N, Rorbach-Dolata A, Garbiec A, Ślusarczyk S, Dobosz A, Długosz A, Marchewka Z, Matkowski A, Saczko J. Anemarrhenae asphodeloides rhizoma Extract Enriched in Mangiferin Protects PC12 Cells against a Neurotoxic Agent-3-Nitropropionic Acid. Int J Mol Sci 2020; 21:ijms21072510. [PMID: 32260390 PMCID: PMC7177269 DOI: 10.3390/ijms21072510] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 03/31/2020] [Accepted: 04/01/2020] [Indexed: 02/06/2023] Open
Abstract
The rhizome of Anemarrhena asphodeloides Bunge, used in Traditional Chinese Medicine as a brain function-improving herb, is a promising source of neuroprotective substances. The aim of this study was to evaluate the protective action of xanthones from A. asphodeloides rhizomes on the PC12 cell line exposed to the neurotoxic agent—3-nitropropionic acid (3-NP). The xanthone-enriched fraction of the ethanolic extract of A. asphodeloides (abbreviated from now on as XF, for the Xanthone Fraction), rich in polyphenolic xanthone glycosides, in concentrations from 5 to 100 μg/mL, and 3-NP in concentrations from 2.5 to 15 mM, were examined. After 8, 16, 24, 48, and 72 h of exposure of cells to various combinations of 3-NP and XF, the MTT viability assay was performed and morphological changes were estimated by confocal fluorescence microscopy. The obtained results showed a significant increase in the number of cells surviving after treatment with XF with exposure to neurotoxic 3-NP and decreased morphological changes in PC12 cells in a dose and time dependent manner. The most effective protective action was observed when PC12 cells were pre-incubated with the XF. This effect may contribute to the traditional indications of this herb for neurological and cognitive complaints. However, a significant cytotoxicity observed at higher XF concentrations (over 10 µg/mL) and longer incubation time (48 h) requires caution in future research and thorough investigation into potential adverse effects.
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Affiliation(s)
- Agnieszka Piwowar
- Department of Toxicology, Wroclaw Medical University, 211 50556 Borowska, Poland; (A.P.); (A.R.-D.); (A.D.); (Z.M.)
| | - Nina Rembiałkowska
- Department of Molecular and Cellular Biology, Wroclaw Medical University, 211A 50556 Borowska, Poland; (N.R.); (J.S.)
| | - Anna Rorbach-Dolata
- Department of Toxicology, Wroclaw Medical University, 211 50556 Borowska, Poland; (A.P.); (A.R.-D.); (A.D.); (Z.M.)
| | - Arnold Garbiec
- Department of Developmental Biology, Institute of Experimental Biology, University of Wroclaw, ul. H. 21 50335 Sienkiewicza, Poland;
| | - Sylwester Ślusarczyk
- Department of Pharmaceutical Biology and Botany, Wroclaw Medical University, 211 50556 Borowska, Poland;
| | - Agnieszka Dobosz
- Department of Basic Medical Sciences, Wroclaw Medical University, 211 50556 Borowska, Poland;
| | - Anna Długosz
- Department of Toxicology, Wroclaw Medical University, 211 50556 Borowska, Poland; (A.P.); (A.R.-D.); (A.D.); (Z.M.)
| | - Zofia Marchewka
- Department of Toxicology, Wroclaw Medical University, 211 50556 Borowska, Poland; (A.P.); (A.R.-D.); (A.D.); (Z.M.)
| | - Adam Matkowski
- Department of Pharmaceutical Biology and Botany, Wroclaw Medical University, 211 50556 Borowska, Poland;
- Correspondence: ; Tel.: +48-71-784-0001; Fax: +48-71-784-0452
| | - Jolanta Saczko
- Department of Molecular and Cellular Biology, Wroclaw Medical University, 211A 50556 Borowska, Poland; (N.R.); (J.S.)
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Lin L, Li C, Zhang D, Yuan M, Chen CH, Li M. Synergic Effects of Berberine and Curcumin on Improving Cognitive Function in an Alzheimer's Disease Mouse Model. Neurochem Res 2020; 45:1130-1141. [PMID: 32080784 DOI: 10.1007/s11064-020-02992-6] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 02/07/2020] [Accepted: 02/17/2020] [Indexed: 12/17/2022]
Abstract
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, and no effective therapies have been found to prevent or cure AD to date. Berberine and curcumin are extracts from traditional Chinese herbs that have a long history of clinical benefits for AD. Here, using a transgenic AD mouse model, we found that the combined berberine and curcumin treatment had a much better effect on improving the cognitive function of mice than the single-drug treatment, suggesting synergic effects of the combined berberine and curcumin treatment. In addition, we found that the combined berberine and curcumin treatment had significant synergic effects on reducing soluble amyloid-β-peptide(1-42) production. Furthermore, the combination treatment also had remarkable synergic effects on decreasing inflammatory responses and oxidative stress in both the cortex and hippocampus of AD mice. We also found that the combination treatment performed much better than the single drugs in reducing the APP and BACE1 levels and increasing AMPKα phosphorylation and cell autophagy, which might be the underlying mechanism of the synergic effects. Taken together, the result of this study reveal the synergic effects and potential underlying mechanisms of the combined berberine and curcumin treatment in improving the symptoms of AD in mice. This study sheds light on a new strategy for exploring new phytotherapies for AD and also emphasizes that more research should focus on the synergic effects of herbal drugs in the future.
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Affiliation(s)
- Lin Lin
- Collaborative Innovation Center of Sichuan for Elderly Care and Health, Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Cheng Li
- Department of Public Health, Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Deyi Zhang
- Department of Anesthesiology, Mianyang People's Hospital, Mianyang, 621000, Sichuan, China
| | - Mingxiang Yuan
- Department of Gynaecology and Obstetrics, Mianyang People's Hospital, Mianyang, 621000, Sichuan, China
| | - Chun-Hai Chen
- Department of Occupational Health, Amy Medical University, Chongqing, 400038, China.
| | - Maoquan Li
- Affiliated Traditional Chinese Medicine Hospital of Chengdu Medical College, Chengdu, 610300, Sichuan, China. .,Chengdu Qingbaijiang District Traditional Chinese Medicine Hospital, Chengdu, 610300, Sichuan, China. .,Department of Public Health, Chengdu Medical College, Chengdu, 610500, Sichuan, China.
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Reale M, Costantini E, Jagarlapoodi S, Khan H, Belwal T, Cichelli A. Relationship of Wine Consumption with Alzheimer's Disease. Nutrients 2020; 12:E206. [PMID: 31941117 PMCID: PMC7019227 DOI: 10.3390/nu12010206] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 01/07/2020] [Accepted: 01/08/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Alzheimer's disease (AD), the most threatening neurodegenerative disease, is characterized by the loss of memory and language function, an unbalanced perception of space, and other cognitive and physical manifestations. The pathology of AD is characterized by neuronal loss and the extensive distribution of senile plaques and neurofibrillary tangles (NFTs). The role of environment and the diet in AD is being actively studied, and nutrition is one of the main factors playing a prominent role in the prevention of neurodegenerative diseases. In this context, the relationship between dementia and wine use/abuse has received increased research interest, with varying and often conflicting results. Scope and Approach: With this review, we aimed to critically summarize the main relevant studies to clarify the relationship between wine drinking and AD, as well as how frequency and/or amount of drinking may influence the effects. Key Findings and Conclusions: Overall, based on the interpretation of various studies, no definitive results highlight if light to moderate alcohol drinking is detrimental to cognition and dementia, or if alcohol intake could reduce risk of developing AD.
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Affiliation(s)
- Marcella Reale
- Dept. of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 65100 Chieti, Italy; (E.C.); (S.J.); (A.C.)
| | - Erica Costantini
- Dept. of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 65100 Chieti, Italy; (E.C.); (S.J.); (A.C.)
| | - Srinivas Jagarlapoodi
- Dept. of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 65100 Chieti, Italy; (E.C.); (S.J.); (A.C.)
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan;
| | - Tarun Belwal
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310027, China;
| | - Angelo Cichelli
- Dept. of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 65100 Chieti, Italy; (E.C.); (S.J.); (A.C.)
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Kong XP, Liu EY, Chen ZC, Xu ML, Yu AX, Wu QY, Xia YJ, Duan R, Dong TT, Tsim KW. Synergistic Inhibition of Acetylcholinesterase by Alkaloids Derived from Stephaniae Tetrandrae Radix, Coptidis Rhizoma and Phellodendri Chinensis Cortex. Molecules 2019; 24:molecules24244567. [PMID: 31847089 PMCID: PMC6943709 DOI: 10.3390/molecules24244567] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 11/30/2019] [Accepted: 12/10/2019] [Indexed: 12/28/2022] Open
Abstract
Alkaloids having acetylcholinesterase (AChE) inhibitory activity are commonly found in traditional Chinese medicine (TCM); for example, berberine from Coptis chinensis, galantamine from Lycoris radiata, and huperzine A from Huperzia serrata. In practice of TCM, Stephaniae Tetrandrae Radix (STR) is often combined with Coptidis Rhizoma (CR) or Phellodendri Chinensis Cortex (PCC) as paired herbs during clinical application. Fangchinoline from STR and coptisine and/or berberine from CR and/or PCC are active alkaloids in inhibiting AChE. The traditional usage of paired herbs suggests the synergistic effect of fangchinoline–coptisine or fangchinoline–berberine pairing in AChE inhibition. HPLC was applied to identify the main components in herbal extracts of STR, CR, and PCC, and the AChE inhibition of their main components was determined by Ellman assay. The synergism of herb combination and active component combination was calculated by median-effect principle. Molecular docking was applied to investigate the underlying binding mechanisms of the active components with the AChE protein. It was found that fangchinoline showed AChE inhibitory potency; furthermore, fangchinoline–coptisine/berberine pairs (at ratios of 1:5, 1:2, 1:1, and 2:1) synergistically inhibited AChE; the combination index (CI) at different ratios was less than one when Fa = 0.5, suggesting synergistic inhibition of AChE. Furthermore, the molecular docking simulation supported this enzymatic inhibition. Therefore, fangchinoline–coptisine/berberine pairs, or their parental herbal mixtures, may potentially be developed as a possible therapeutic strategy for Alzheimer’s patients.
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Affiliation(s)
- Xiang-Peng Kong
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, China; (X.-P.K.); (Z.-C.C.); (M.L.X.); (Q.-Y.W.); (Y.-J.X.); (R.D.)
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong 030619, China
| | - Etta Y.L. Liu
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, China; (X.-P.K.); (Z.-C.C.); (M.L.X.); (Q.-Y.W.); (Y.-J.X.); (R.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
| | - Zhi-Cong Chen
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, China; (X.-P.K.); (Z.-C.C.); (M.L.X.); (Q.-Y.W.); (Y.-J.X.); (R.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
| | - Miranda Li Xu
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, China; (X.-P.K.); (Z.-C.C.); (M.L.X.); (Q.-Y.W.); (Y.-J.X.); (R.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
| | - Anna X.D. Yu
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, China; (X.-P.K.); (Z.-C.C.); (M.L.X.); (Q.-Y.W.); (Y.-J.X.); (R.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
| | - Qi-Yun Wu
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, China; (X.-P.K.); (Z.-C.C.); (M.L.X.); (Q.-Y.W.); (Y.-J.X.); (R.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
| | - Ying-Jie Xia
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, China; (X.-P.K.); (Z.-C.C.); (M.L.X.); (Q.-Y.W.); (Y.-J.X.); (R.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
| | - Ran Duan
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, China; (X.-P.K.); (Z.-C.C.); (M.L.X.); (Q.-Y.W.); (Y.-J.X.); (R.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
| | - Tina T.X. Dong
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, China; (X.-P.K.); (Z.-C.C.); (M.L.X.); (Q.-Y.W.); (Y.-J.X.); (R.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
- Correspondence: (T.T.X.D.); (K.W.K.T.); Tel.: +86-755-8671-5683 (T.T.X.D.); +852-2358-7332 (K.W.K.T.)
| | - Karl W.K. Tsim
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Shenzhen 518057, China; (X.-P.K.); (Z.-C.C.); (M.L.X.); (Q.-Y.W.); (Y.-J.X.); (R.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
- Correspondence: (T.T.X.D.); (K.W.K.T.); Tel.: +86-755-8671-5683 (T.T.X.D.); +852-2358-7332 (K.W.K.T.)
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Ma Y, Yang MW, Li XW, Yue JW, Chen JZ, Yang MW, Huang X, Zhu LL, Hong FF, Yang SL. Therapeutic Effects of Natural Drugs on Alzheimer's Disease. Front Pharmacol 2019; 10:1355. [PMID: 31866858 PMCID: PMC6904940 DOI: 10.3389/fphar.2019.01355] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 10/25/2019] [Indexed: 12/28/2022] Open
Abstract
Alzheimer disease (AD) is characterized as a chronic neurodegenerative disease associated with aging. The clinical manifestations of AD include latent episodes of memory and cognitive impairment, psychiatric symptoms and behavioral disorders, as well as limited activities in daily life. In developed countries, AD is now acknowledged as the third leading cause of death, following cardiovascular disease and cancer. The pathogenesis and mechanism of AD remain unclear, although some theories have been proposed to explain AD, such as the theory of β-amyloid, the theory of the abnormal metabolism of tau protein, the theory of free radical damage, the theory of the inflammatory response, the theory of cholinergic damage, etc. Effective methods to predict, prevent or reverse AD are unavailable, and thus the development of new, efficient therapeutic drugs has become a current research hot spot worldwide. The isolation and extraction of active components from natural drugs have great potential in treating AD. These drugs possess the advantages of multiple targets in multiple pathways, fewer side effects and a long duration of curative effects. This article summaries the latest research progress regarding the mechanisms of natural drugs in the treatment of AD, providing a review of the literature and a theoretical basis for improving the clinical treatment of AD.
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Affiliation(s)
- Yuan Ma
- Department of Physiology, College of Medicine, Nanchang University, Nanchang, China
| | - Man-Wen Yang
- Department of Physiology, College of Medicine, Nanchang University, Nanchang, China
| | - Xin-Wei Li
- Department of Physiology, College of Medicine, Nanchang University, Nanchang, China
| | - Jian-Wei Yue
- Department of Physiology, College of Medicine, Nanchang University, Nanchang, China
| | - Jun-Zong Chen
- Department of Physiology, College of Medicine, Nanchang University, Nanchang, China
| | - Mei-Wen Yang
- Department of Nurse, Nanchang University Hospital, Nanchang, China
| | - Xuan Huang
- Department of Physiology, College of Medicine, Nanchang University, Nanchang, China
| | - Lian-Lian Zhu
- Department of Physiology, College of Medicine, Nanchang University, Nanchang, China
| | - Fen-Fang Hong
- Department of Experimental Teaching Center, Nanchang University, Nanchang, China
| | - Shu-Long Yang
- Department of Physiology, College of Medicine, Nanchang University, Nanchang, China
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Yu J, Qiu LX, Qing GP, Zhao BW, Wang H. Modified Cortex Mori Capsules improving the successful rate of functional filtering blebs after reclinical glaucoma filtering surgery. World J Clin Cases 2019; 7:3436-3445. [PMID: 31750327 PMCID: PMC6854417 DOI: 10.12998/wjcc.v7.i21.3436] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 09/27/2019] [Accepted: 10/05/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The major reason for filtering bleb failure or scarring of the bleb site is due to excessive scarring after glaucoma filtration surgery in the clinic. Traditional Chinese medicine has preeminence in the prevention of fibrosis formation through the regulation of systemic circulation and improvement of the properties of the inflammatory cells in the blood.
AIM To examine the clinical efficacy of using the Modified Cortex Mori Capsules (MCMC; Chinese name: Jiawei Sangbaipi Capsules) in the success rate of functional filtering blebs after glaucoma filtering surgery in clinical patients.
METHODS Sixty resurgery glaucoma patients were randomly divided into two groups: 30 patients in surgery with the placebo group and 30 patients in surgery with the MCMC group. Patients took either the placebo or the MCMC 2 wk before and after surgery. Postoperative morphology and function filtering bleb, visual acuity, intraocular pressure, postoperative complications, the success rate of filtration surgery and clinical efficacy were observed.
RESULTS Fifty patients completed the study. The percentage of functional filtering blebs in the surgery plus MCMC group was 84% at 6 mo after surgery, which was higher than surgery plus placebo group (64%, P < 0.05). The surgical success rate in the MCMC and placebo groups were 79% ± 8.3% and 57% ± 10.6% respectively (P < 0.05). The visual acuity, intraocular pressure and the postoperative complications in the two groups had no significant differences.
CONCLUSION Glaucoma filtering surgery while taking MCMC not only reduced excessive scar formation and increased the success rate of functional filtering blebs but also improved the success of glaucoma filtration operations.
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Affiliation(s)
- Jing Yu
- Beijing Tongren Eye Center, Laboratory of Ophthalmology and Visual Science in Beijing, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Li-Xin Qiu
- Beijing Tongren Eye Center, Laboratory of Ophthalmology and Visual Science in Beijing, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Guo-Ping Qing
- Beijing Tongren Eye Center, Laboratory of Ophthalmology and Visual Science in Beijing, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Bo-Wen Zhao
- Beijing Tongren Eye Center, Laboratory of Ophthalmology and Visual Science in Beijing, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Hui Wang
- Beijing Tongren Eye Center, Laboratory of Ophthalmology and Visual Science in Beijing, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
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Shetty AK, Upadhya R, Madhu LN, Kodali M. Novel Insights on Systemic and Brain Aging, Stroke, Amyotrophic Lateral Sclerosis, and Alzheimer's Disease. Aging Dis 2019; 10:470-482. [PMID: 31011489 PMCID: PMC6457051 DOI: 10.14336/ad.2019.0330] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 03/30/2019] [Indexed: 12/11/2022] Open
Abstract
The mechanisms that underlie the pathophysiology of aging, amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and stroke are not fully understood and have been the focus of intense and constant investigation worldwide. Studies that provide insights on aging and age-related disease mechanisms are critical for advancing novel therapies that promote successful aging and prevent or cure multiple age-related diseases. The April 2019 issue of the journal, "Aging & Disease" published a series of articles that confer fresh insights on numerous age-related conditions and diseases. The age-related topics include the detrimental effect of overweight on energy metabolism and muscle integrity, senoinflammation as the cause of neuroinflammation, the link between systemic C-reactive protein and brain white matter loss, the role of miR-34a in promoting healthy heart and brain, the potential of sirtuin 3 for reducing cardiac and pulmonary fibrosis, and the promise of statin therapy for ameliorating asymptomatic intracranial atherosclerotic stenosis. Additional aging-related articles highlighted the involvement of miR-181b-5p and high mobility group box-1 in hypertension, Yes-associated protein in cataract formation, multiple miRs and long noncoding RNAs in coronary artery disease development, the role of higher meat consumption on sleep problems, and the link between glycated hemoglobin and depression. The topics related to ALS suggested that individuals with higher education and living in a rural environment have a higher risk for developing ALS, and collagen XIX alpha 1 is a prognostic biomarker of ALS. The topics discussed on AD implied that extracellular amyloid β42 is likely the cause of intraneuronal neurofibrillary tangle accumulation in familial AD and traditional oriental concoctions may be useful for slowing down the progression of AD. The article on stroke suggested that inhibition of the complement system is likely helpful in promoting brain repair after ischemic stroke. The significance of the above findings for understanding the pathogenesis in aging, ALS, AD, and stroke, slowing down the progression of aging, ALS and AD, and promoting brain repair after stroke are discussed.
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Affiliation(s)
- Ashok K. Shetty
- Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center College of Medicine, College Station, Texas, USA
| | - Raghavendra Upadhya
- Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center College of Medicine, College Station, Texas, USA
| | - Leelavathi N. Madhu
- Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center College of Medicine, College Station, Texas, USA
| | - Maheedhar Kodali
- Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center College of Medicine, College Station, Texas, USA
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Jeon SG, Song EJ, Lee D, Park J, Nam Y, Kim JI, Moon M. Traditional Oriental Medicines and Alzheimer's Disease. Aging Dis 2019; 10:307-328. [PMID: 31435482 PMCID: PMC6667206 DOI: 10.14336/ad.2018.0328] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 03/28/2018] [Indexed: 12/27/2022] Open
Abstract
Alzheimer’s disease (AD), which is the most major cause of dementia, is a progressive neurodegenerative disease that affects cognitive functions. Even though the prevalence of AD is continuously increasing, few drugs including cholinesterase inhibitors and N-methyl D-aspartate-receptor antagonists were approved to treat AD. Because the clinical trials of AD drugs with single targets, such as β-amyloid and tau, have failed, the development of multi-target drugs that ameliorate many of the symptoms of AD is needed. Thus, recent studies have investigated the effects and underlying mechanisms of herbal formulae consisting of various herb combinations used to treat AD. This review discusses the results of clinical and nonclinical studies of the therapeutic efficacy in AD and underlying mechanisms of the herbal formulae of traditional Oriental medicines and bioactive compounds of medicinal plants.
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Affiliation(s)
- Seong Gak Jeon
- 1Department of Biochemistry, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea
| | - Eun Ji Song
- 1Department of Biochemistry, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea
| | - Dongje Lee
- 1Department of Biochemistry, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea
| | - Junyong Park
- 1Department of Biochemistry, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea
| | - Yunkwon Nam
- 2Center for Organic Devices and Advanced Materials, Kyungsung University, Busan 48434, Republic of Korea
| | - Jin-Il Kim
- 3Department of Nursing, College of Nursing, Jeju National University, Jeju-si 63243, Republic of Korea
| | - Minho Moon
- 1Department of Biochemistry, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea
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Zhu Y, Shi Y, Cao C, Han Z, Liu M, Qi M, Huang R, Zhu Z, Qian D, Duan JA. Jia-Wei-Kai-Xin-San, an Herbal Medicine Formula, Ameliorates Cognitive Deficits via Modulating Metabolism of Beta Amyloid Protein and Neurotrophic Factors in Hippocampus of Aβ 1-42 Induced Cognitive Deficit Mice. Front Pharmacol 2019; 10:258. [PMID: 30941041 PMCID: PMC6433786 DOI: 10.3389/fphar.2019.00258] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 02/28/2019] [Indexed: 12/20/2022] Open
Abstract
Jia-Wei-Kai-Xin-San (JWKXS) is a Chinese medicine formula applied for treating morbid forgetfulness in ancient China. Today, this formula is frequently applied for Alzheimer's disease and vascular dementia (VD) in clinic. Here, we developed it as granules and aimed to evaluate its anti-AD effect on β amyloid protein 1-42 (Aβ1-42) induced cognitive deficit mice and reveal the possible molecular mechanisms. Firstly, daily intra-gastric administration of chemically standardized of JWKXS granules for 7 days significantly ameliorated the cognitive deficit symptoms and inhibited cell apoptosis in hippocampus on Aβ1-42 injection mice. JWKXS granules significantly decreased Aβ level, increased superoxide dismutase activity and decreased malondialdehyde level in hippocampus of model mice. It also restored acetylcholine amounts, inhibited acetylcholinesterase activities and increased choline acetyltransferase activities. In addition, JWKXS granules enabled the transformation of precursors of NGF and BDNF into mature forms. Furthermore, JWKXS granules could regulate gene expressions related to Aβ production, transportation, degradation and neurotrophic factor transformation, which led to down-regulation of Aβ and up-regulation of NGF and BDNF. These findings suggested that JWKXS granules ameliorated cognitive deficit via decreasing Aβ levels, protecting neuron from oxidation damages and nourishing neuron, which could serve as alternative medicine for patients suffering from AD.
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Affiliation(s)
- Yue Zhu
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yiwei Shi
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Cheng Cao
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhenxiang Han
- Department of Neurology and Rehabilitation, Shanghai Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Mengqiu Liu
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mingzhu Qi
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Renjie Huang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Ziqiang Zhu
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Dawei Qian
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jin-ao Duan
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
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Ahmad Azam A, Ismail IS, Shaikh MF, Shaari K, Abas F. Effects of Clinacanthus nutans leaf extract on lipopolysaccharide -induced neuroinflammation in rats: A behavioral and 1H NMR-based metabolomics study. AVICENNA JOURNAL OF PHYTOMEDICINE 2019; 9:164-186. [PMID: 30984581 PMCID: PMC6448548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 08/09/2018] [Accepted: 08/23/2018] [Indexed: 11/06/2022]
Abstract
OBJECTIVE This research revealed the biochemical outcomes of metabolic dysregulation in serum associated with physiological sickness behavior following lipopolysaccharide (LPS)-induced neuroinflammation in rats, and treatment with Clinacanthus nutans (CN). Verification of 1H NMR analysis of the CN aqueous extract proved the existence of bioactive phytochemical constituents' in extract. MATERIALS AND METHODS Twenty-five rats were subjected to unilateral stereotaxic injection of 10 µL LPS (1 mg/mL), while another ten rats were injected with phosphate-buffered saline (PBS, 10 µL) as control. Then, 29 parameters of rat behavior related to sickness were tracked by a device software (SMART 3.0.1) on days 0 and 14 of CN treatment. The acquired and accumulated data were analyzed using multivariate data analysis with the SIMCA Software package (version 13, Umetrics AB; Umeå, Sweden). The pattern trends of related groups were documented using PCA and OPLS analysis. RESULTS A similar ameliorated correlation pattern was detected between improvement in physiological sickness behavior and anti-inflammatory biomarkers by the 1H NMR spectra of the sera following treatment with CN (500 and 1000 mg/kg body weight (bw)) and the control drug (dextromethorphan hydrobromide, 5 mg/kg of rats bw) in rats. Here, 21 biomarkers were detected for neuroinflammation. Treatment with the aqueous CN extract resulted in a statistically significant alteration in neuroinflammation metabolite biomarkers, including ethanol, choline, and acetate. CONCLUSION This result denotes that the metabolomics approach is a reliable tool to disclose the relationship between central neuroinflammation, and systemic metabolic and physiological disturbances which could be used for future ethno-pharmacological assessments.
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Affiliation(s)
- Amalina Ahmad Azam
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
| | - Intan Safinar Ismail
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
| | - Mohd Farooq Shaikh
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, Malaysia
| | - Khozirah Shaari
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
| | - Faridah Abas
- Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
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Castañeda R, Natarajan S, Jeong SY, Hong BN, Kang TH. Traditional oriental medicine for sensorineural hearing loss: Can ethnopharmacology contribute to potential drug discovery? JOURNAL OF ETHNOPHARMACOLOGY 2019; 231:409-428. [PMID: 30439402 DOI: 10.1016/j.jep.2018.11.016] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 11/06/2018] [Accepted: 11/06/2018] [Indexed: 06/09/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE In Traditional Oriental Medicine (TOM), the development of hearing pathologies is related to an inadequate nourishment of the ears by the kidney and other organs involved in regulation of bodily fluids and nutrients. Several herbal species have historically been prescribed for promoting the production of bodily fluids or as antiaging agents to treat deficiencies in hearing. AIM OF REVIEW The prevalence of hearing loss has been increasing in the last decade and is projected to grow considerably in the coming years. Recently, several herbal-derived products prescribed in TOM have demonstrated a therapeutic potential for acquired sensorineural hearing loss and tinnitus. Therefore, the aims of this review are to provide a comprehensive overview of the current known efficacy of the herbs used in TOM for preventing different forms of acquired sensorineural hearing loss and tinnitus, and associate the traditional principle with the demonstrated pharmacological mechanisms to establish a solid foundation for directing future research. METHODS The present review collected the literature related to herbs used in TOM or related compounds on hearing from Chinese, Korean, and Japanese herbal classics; library catalogs; and scientific databases (PubMed, Scopus, Google Scholar; and Science Direct). RESULTS This review shows that approximately 25 herbal species and 40 active compounds prescribed in TOM for hearing loss and tinnitus have shown in vitro or in vivo beneficial effects for acquired sensorineural hearing loss produced by noise, aging, ototoxic drugs or diabetes. The inner ear is highly vulnerable to ischemia and oxidative damage, where several TOM agents have revealed a direct effect on the auditory system by normalizing the blood supply to the cochlea and increasing the antioxidant defense in sensory hair cells. These strategies have shown a positive impact on maintaining the inner ear potential, sustaining the production of endolymph, reducing the accumulation of toxic and inflammatory substances, preventing sensory cell death and preserving sensory transmission. There are still several herbal species with demonstrated therapeutic efficacy whose mechanisms have not been deeply studied and others that have been traditionally used in hearing loss but have not been tested experimentally. In clinical studies, Ginkgo biloba, Panax ginseng, and Astragalus propinquus have demonstrated to improve hearing thresholds in patients with sensorineural hearing loss and alleviated the symptoms of tinnitus. However, some of these clinical studies have been limited by small sample sizes, lack of an adequate control group or contradictory results. CONCLUSIONS Current therapeutic strategies have proven that the goal of the traditional oriental medicine principle of increasing bodily fluids is a relevant approach for reducing the development of hearing loss by improving microcirculation in the blood-labyrinth barrier and increasing cochlear blood flow. The potential benefits of TOM agents expand to a multi-target approach on different auditory structures of the inner ear related to increased cochlear blood flow, antioxidant, anti-inflammatory, anti-apoptotic and neuroprotective activities. However, more research is required, given the evidence is very limited in terms of the mechanism of action at the preclinical in vivo level and the scarce number of clinical studies published.
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Affiliation(s)
- Rodrigo Castañeda
- Graduate School of Biotechnology, Kyung Hee University, Republic of Korea; Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Global Campus, Gyeonggi, Republic of Korea.
| | - Sathishkumar Natarajan
- Graduate School of Biotechnology, Kyung Hee University, Republic of Korea; Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Global Campus, Gyeonggi, Republic of Korea.
| | - Seo Yule Jeong
- Graduate School of Biotechnology, Kyung Hee University, Republic of Korea; Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Global Campus, Gyeonggi, Republic of Korea.
| | - Bin Na Hong
- Graduate School of Biotechnology, Kyung Hee University, Republic of Korea.
| | - Tong Ho Kang
- Graduate School of Biotechnology, Kyung Hee University, Republic of Korea; Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Global Campus, Gyeonggi, Republic of Korea.
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Hu XL, Guo C, Hou JQ, Feng JH, Zhang XQ, Xiong F, Ye WC, Wang H. Stereoisomers of Schisandrin B Are Potent ATP Competitive GSK-3β Inhibitors with Neuroprotective Effects against Alzheimer's Disease: Stereochemistry and Biological Activity. ACS Chem Neurosci 2019; 10:996-1007. [PMID: 29944335 DOI: 10.1021/acschemneuro.8b00252] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Glycogen synthase kinase-3β (GSK-3β) is a key enzyme in hyperphosphorylation of tau proteins and is a promising therapeutic target in Alzheimer's disease (AD). Here, we reported, for the first time, that the stereoisomers of Schisandrin B (Sch B), (+)-1, (-)-1, (+)-2, and (-)-2, were potent GSK-3β inhibitors. They were demonstrated to selectively target GSK-3β in an orthosteric binding mode, with IC50 values of 340, 290, 80, and 70 nM, respectively. Further study showed that these stereoisomers can significantly increase the expression of p-GSK-3β (Ser9) and decrease the expressions of p-GSK-3β (Tyr216) and p-GSK-3β (Tyr279). Finally, these compounds can alleviate the cell injury induced by Aβ, and the cognitive disorders in AD mice, especially (+)-2 and (-)-2. Collectively, the stereoisomers of Sch B, especially (+)-2 and (-)-2, were found to be potential selective ATP-competitive GSK-3β inhibitors, which further affected their anti-AD effects. These promising findings explained the biological target of Sch B in AD, and bring a new understanding in the stereochemistry and bioactivities of Sch B.
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Affiliation(s)
- Xiao-Long Hu
- State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy. China Pharmaceutical University, Nanjing 210009, People’s Republic of China
| | - Cui Guo
- State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy. China Pharmaceutical University, Nanjing 210009, People’s Republic of China
| | - Ji-Qin Hou
- State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy. China Pharmaceutical University, Nanjing 210009, People’s Republic of China
| | - Jia-Hao Feng
- State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy. China Pharmaceutical University, Nanjing 210009, People’s Republic of China
| | - Xiao-Qi Zhang
- Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou 510632, People’s Republic of China
| | - Fei Xiong
- State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, Southeast University, Nanjing 210009, People’s Republic of China
| | - Wen-Cai Ye
- Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou 510632, People’s Republic of China
| | - Hao Wang
- State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy. China Pharmaceutical University, Nanjing 210009, People’s Republic of China
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Wu DJ, Dong HC, Tang TN, Zhu SF. Acupressure for insomnia: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2018; 97:e13180. [PMID: 30407352 PMCID: PMC6250509 DOI: 10.1097/md.0000000000013180] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 10/17/2018] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Insomnia is a public sleep disorder defined as a deficiency of sleep quantity or quality. Acupressure is a low-cost treatment that has potential as an insomnia therapy. METHODS Four databases will be searched from inception to date. The researchers will screen clinical randomized trials of acupressure and auricular acupuncture for insomnia. The screening of the study, data extraction will be carried out independently by 2 researchers. The specific process will refer to the Cochrane Handbook for Systematic Review. RESULTS The results of the study will be published in a scientific journal after peer-review. We integrate the latest study about acupressure for insomnia. CONCLUSION This systematic review will provide evidence for assessing the improvement of acupressure for insomnia. ETHICS AND DISSEMINATION The systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print.PROSPERO registration: CRD42018104155.
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Affiliation(s)
- Dong-Jie Wu
- Graduate School, Zhejiang Chinese Medical University, Hangzhou, Zhejiang
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
| | - Hai-Cheng Dong
- Department of Tradition Chinese Medicine, Children's Hospital, Zhejiang University School of Medicine, Hangzhou
| | - Tsz-Nga Tang
- Graduate School, Zhejiang Chinese Medical University, Hangzhou, Zhejiang
| | - Shi-Feng Zhu
- Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China
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Xu Y, Patel DN, Ng SLP, Tan SH, Toh D, Poh J, Lim AT, Chan CL, Low MY, Koh HL. Retrospective Study of Reported Adverse Events Due to Complementary Health Products in Singapore From 2010 to 2016. Front Med (Lausanne) 2018; 5:167. [PMID: 29946545 PMCID: PMC6006675 DOI: 10.3389/fmed.2018.00167] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Accepted: 05/14/2018] [Indexed: 01/16/2023] Open
Abstract
The objective of this study is to collate and analyse adverse event reports associated with the use of complementary health products (CHP) submitted to the Health Sciences Authority (HSA) of Singapore for the period 2010-2016 to identify various trends and signals for pharmacovigilance purposes. A total of 147,215 adverse event reports suspected to be associated with pharmaceutical products and CHP were received by HSA between 2010 and 2016. Of these, 143,191 (97.3%) were associated with chemical drugs, 1,807 (1.2%) with vaccines, 1,324 (0.9%) with biological drugs (biologics), and 893 (0.6%) with CHP. The number of adverse event reports associated with Chinese Proprietary Medicine, other complementary medicine and health supplements are presented. Eight hundred and ninety three adverse event reports associated with CHP in the 7-year period have been successfully collated and analyzed. In agreement with other studies, adverse events related to the "skin and appendages disorders" were the most commonly reported. Most of the cases involved dermal allergies (e.g., rashes) associated with the use of glucosamine products and most of the adulterated products were associated with the illegal addition of undeclared drugs for pain relief. Dexamethasone, chlorpheniramine, and piroxicam were the most common adulterants detected. Reporting suspected adverse events is strongly encouraged even if the causality is not confirmed because any signs of clustering will allow rapid regulatory actions to be taken. The findings from this study help to create greater awareness on the health risks, albeit low, when consuming CHP and dispelling the common misconception that "natural" means "safe." In particular, healthcare professionals and the general public should be aware of potential adulteration of CHP. The analysis of spontaneously reported adverse events is an important surveillance system in monitoring the safety of CHP and helps in the understanding of the risk associated with the use of such products. Greater collaboration and communication between healthcare professionals, regulators, patients, manufacturers, researchers, and the general public are important to ensure the quality and safety of CHP.
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Affiliation(s)
- Yimin Xu
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore
- Applied Sciences Group, Pharmaceutical Division, Health Sciences Authority, Singapore, Singapore
| | - Dhavalkumar N. Patel
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore
| | - Suet-Leng P. Ng
- Vigilance, Compliance and Enforcement Cluster, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore
| | - Siew-Har Tan
- Vigilance, Compliance and Enforcement Cluster, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore
| | - Dorothy Toh
- Vigilance, Compliance and Enforcement Cluster, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore
| | - Jalene Poh
- Vigilance, Compliance and Enforcement Cluster, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore
| | - Adena Theen Lim
- Vigilance, Compliance and Enforcement Cluster, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore
| | - Cheng-Leng Chan
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore
- Vigilance, Compliance and Enforcement Cluster, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore
| | - Min-Yong Low
- Applied Sciences Group, Pharmaceutical Division, Health Sciences Authority, Singapore, Singapore
| | - Hwee-Ling Koh
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore
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Lu Y, Liu Q, Yu Q. Quercetin enrich diet during the early-middle not middle-late stage of alzheimer's disease ameliorates cognitive dysfunction. Am J Transl Res 2018; 10:1237-1246. [PMID: 29736217 PMCID: PMC5934583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Accepted: 03/16/2018] [Indexed: 06/08/2023]
Abstract
The aim of this study was to evaluate the protective effects of dietary flavonoid quercetin against Alzheimer's disease (AD) and detect the explicit administration of quercetin in early-middle or middle-late stage of AD pathology could play the effect as well as its mechanism of action. In this study, APP/PS1 mice were used to investigate cognitive impairment and related pathologies. The results showed that quercetin enrich diet could play an ameliorated pathology development of AD in APP/PS1 mice. And then we next determined administration of quercetin in early-middle and middle-late stage of AD pathology, which exerted that only quercetin enrich diet during the early-middle stage of AD pathological development period ameliorates cognitive dysfunction and the protection effect was mainly related to increased Aβ clearance and reduced astrogliosis. These findings suggest a possible new protective role for dietary flavonoids on AD. This new role might expand the preventive and/or therapeutic use of AD in conditions.
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Affiliation(s)
- Yaqin Lu
- The First Clinical Medical College of Lanzhou UniversityLanzhou 730000, P. R. China
- Department of Rehabilitation, The First Hospital of Lanzhou UniversityLanzhou 730000, P. R. China
| | - Qi Liu
- The First Clinical Medical College of Lanzhou UniversityLanzhou 730000, P. R. China
- Department of Rehabilitation, The First Hospital of Lanzhou UniversityLanzhou 730000, P. R. China
| | - Qin Yu
- The First Clinical Medical College of Lanzhou UniversityLanzhou 730000, P. R. China
- Department of Respiration, The First Hospital of Lanzhou UniversityLanzhou 730000, P. R. China
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Nogami-Hara A, Nagao M, Takasaki K, Egashira N, Fujikawa R, Kubota K, Watanabe T, Katsurabayashi S, Hatip FB, Hatip-Al-Khatib I, Iwasaki K. The Japanese Angelica acutiloba root and yokukansan increase hippocampal acetylcholine level, prevent apoptosis and improve memory in a rat model of repeated cerebral ischemia. JOURNAL OF ETHNOPHARMACOLOGY 2018; 214:190-196. [PMID: 29269276 DOI: 10.1016/j.jep.2017.12.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2017] [Revised: 12/16/2017] [Accepted: 12/16/2017] [Indexed: 05/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Japanese Angelica acutiloba root (Angelica root) is included in several Kampo medicines including Yokukansan (YKS). Angelica root and YKS are used for the treatment of a variety of psychological and neurodegenerative disorders. Development of safe and effective therapeutic agents against cerebrovascular disorders will improve the treatment of patients with dementia. AIM OF THE STUDY The effect of Angelica root and YKS on ischemia-impaired memory has not yet been fully investigated. The present study investigated whether Angelica root is also involved in memory improving and neuroprotective effect of YKS in a model of cerebrovascular ischemia. MATERIALS AND METHODS Male Wistar rats grouped into sham rats received saline, and other three groups subjected to repeated cerebral ischemia induced by 4-vessel occlusion (4-VO), received a 7-day oral administration of either saline, Angelica root or YKS. Memory was evaluated by eight-arm radial maze task. Acetylcholine release (ACh) in the dorsal hippocampus was investigated by microdialysis-HPLC. Apoptosis was determined by terminal deoxynucleotidyl transferase (TdT)-mediated fluorescein-deoxyuridine triphosphate (dUTP) nick-end labeling. RESULTS Ischemia induced apoptosis, reduced release of ACh, and impaired the memory (increased error choices and decreased correct choices). Angelica root and YKS improved the memory deficits, upregulated the release of ACh and prevented 4-VO-induced hippocampal apoptosis. CONCLUSION The dual ACh-increasing and neuroprotective effect of Angelica root could make it a promising therapeutic agent useful for the treatment of symptoms of cerebrovascular dementia. Angelica root could be one of the components contributing to the memory-improving and neuroprotective effects of YKS.
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Affiliation(s)
- Ai Nogami-Hara
- Department of Neuropharmacology, Faculty of Pharmaceutical Science, Japan
| | - Masaki Nagao
- A.I.G. Collaborative Research Institute for Aging and Brain Sciences, Japan
| | - Kotaro Takasaki
- Department of Neuropharmacology, Faculty of Pharmaceutical Science, Japan
| | - Nobuaki Egashira
- Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan
| | - Risako Fujikawa
- Department of Neuropharmacology, Faculty of Pharmaceutical Science, Japan
| | - Kaori Kubota
- Department of Neuropharmacology, Faculty of Pharmaceutical Science, Japan; A.I.G. Collaborative Research Institute for Aging and Brain Sciences, Japan
| | - Takuya Watanabe
- Department of Neuropharmacology, Faculty of Pharmaceutical Science, Japan; A.I.G. Collaborative Research Institute for Aging and Brain Sciences, Japan
| | | | - Funda Bolukbasi Hatip
- Department of Medical Pharmacology, Faculty of Medicine, Pamukkale University, Denizli 22070, Turkey
| | - Izzettin Hatip-Al-Khatib
- Department of Medical Pharmacology, Faculty of Medicine, Pamukkale University, Denizli 22070, Turkey.
| | - Katsunori Iwasaki
- Department of Neuropharmacology, Faculty of Pharmaceutical Science, Japan; A.I.G. Collaborative Research Institute for Aging and Brain Sciences, Japan
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Manthey AL, Chiu K, So KF. Demystifying traditional Chinese medicines: Lycium barbarum as a model therapeutic. TRADITIONAL MEDICINE AND MODERN MEDICINE 2018. [DOI: 10.1142/s2575900018300011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
The practice of Traditional Chinese Medicine (TCM) focuses on holistic treatment of the body. This often includes preparation and application of medicinal herbs, either alone or in combination with other supplements. Lycium barbarum (LB), for example, is a commonly used herbal supplement in many Asian countries, being most well-known for improving kidney, liver, and eye health. It is also one of the most widely scientifically researched TCMs and a large body of literature is available describing its effects on various tissues and organ systems. In this perspective, we briefly expand upon how LB can be used as a model TCM in the systematic study of other herbal medicines, highlighting two of the primary barriers to their use in modern medicine worldwide.
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Affiliation(s)
- Abby Leigh Manthey
- Department of Ophthalmology, The University of Hong Kong, Hong Kong SAR, P. R. China
| | - Kin Chiu
- Department of Ophthalmology, The University of Hong Kong, Hong Kong SAR, P. R. China
- State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, P. R. China
| | - Kwok-Fai So
- Department of Ophthalmology, The University of Hong Kong, Hong Kong SAR, P. R. China
- State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, P. R. China
- Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, P. R. China
- Guangdong Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, P. R. China
- Ministry of Education Joint International Research, Laboratory of CNS Regeneration, Jinan University, Guangzhou, P. R. China
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Tewari D, Stankiewicz AM, Mocan A, Sah AN, Tzvetkov NT, Huminiecki L, Horbańczuk JO, Atanasov AG. Ethnopharmacological Approaches for Dementia Therapy and Significance of Natural Products and Herbal Drugs. Front Aging Neurosci 2018; 10:3. [PMID: 29483867 PMCID: PMC5816049 DOI: 10.3389/fnagi.2018.00003] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2017] [Accepted: 01/08/2018] [Indexed: 12/21/2022] Open
Abstract
Dementia is a clinical syndrome wherein gradual decline of mental and cognitive capabilities of an afflicted person takes place. Dementia is associated with various risk factors and conditions such as insufficient cerebral blood supply, toxin exposure, mitochondrial dysfunction, oxidative damage, and often coexisting with some neurodegenerative disorders such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD). Although there are well-established (semi-)synthetic drugs currently used for the management of AD and AD-associated dementia, most of them have several adverse effects. Thus, traditional medicine provides various plant-derived lead molecules that may be useful for further medical research. Herein we review the worldwide use of ethnomedicinal plants in dementia treatment. We have explored a number of recognized databases by using keywords and phrases such as “dementia”, “Alzheimer's,” “traditional medicine,” “ethnopharmacology,” “ethnobotany,” “herbs,” “medicinal plants” or other relevant terms, and summarized 90 medicinal plants that are traditionally used to treat dementia. Moreover, we highlight five medicinal plants or plant genera of prime importance and discuss the physiological effects, as well as the mechanism of action of their major bioactive compounds. Furthermore, the link between mitochondrial dysfunction and dementia is also discussed. We conclude that several drugs of plant origin may serve as promising therapeutics for the treatment of dementia, however, pivotal evidence for their therapeutic efficacy in advanced clinical studies is still lacking.
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Affiliation(s)
- Devesh Tewari
- Department of Pharmaceutical Sciences, Faculty of Technology, Kumaun University, Nainital, India
| | - Adrian M Stankiewicz
- Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland
| | - Andrei Mocan
- Department of Pharmaceutical Botany, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.,ICHAT and Institute for Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania
| | - Archana N Sah
- Department of Pharmaceutical Sciences, Faculty of Technology, Kumaun University, Nainital, India
| | - Nikolay T Tzvetkov
- Department of Molecular Biology and Biochemical Pharmacology, Institute of Molecular Biology Roumen Tsanev, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Lukasz Huminiecki
- Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland
| | - Jarosław O Horbańczuk
- Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland
| | - Atanas G Atanasov
- Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland.,Department of Pharmacognosy, University of Vienna, Vienna, Austria
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Ting HC, Chang CY, Lu KY, Chuang HM, Tsai SF, Huang MH, Liu CA, Lin SZ, Harn HJ. Targeting Cellular Stress Mechanisms and Metabolic Homeostasis by Chinese Herbal Drugs for Neuroprotection. Molecules 2018; 23:E259. [PMID: 29382106 PMCID: PMC6017457 DOI: 10.3390/molecules23020259] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Revised: 01/25/2018] [Accepted: 01/26/2018] [Indexed: 12/14/2022] Open
Abstract
Traditional Chinese medicine has been practiced for centuries in East Asia. Herbs are used to maintain health and cure disease. Certain Chinese herbs are known to protect and improve the brain, memory, and nervous system. To apply ancient knowledge to modern science, some major natural therapeutic compounds in herbs were extracted and evaluated in recent decades. Emerging studies have shown that herbal compounds have neuroprotective effects or can ameliorate neurodegenerative diseases. To understand the mechanisms of herbal compounds that protect against neurodegenerative diseases, we summarize studies that discovered neuroprotection by herbal compounds and compound-related mechanisms in neurodegenerative disease models. Those compounds discussed herein show neuroprotection through different mechanisms, such as cytokine regulation, autophagy, endoplasmic reticulum (ER) stress, glucose metabolism, and synaptic function. The interleukin (IL)-1β and tumor necrosis factor (TNF)-α signaling pathways are inhibited by some compounds, thus attenuating the inflammatory response and protecting neurons from cell death. As to autophagy regulation, herbal compounds show opposite regulatory effects in different neurodegenerative models. Herbal compounds that inhibit ER stress prevent neuronal death in neurodegenerative diseases. Moreover, there are compounds that protect against neuronal death by affecting glucose metabolism and synaptic function. Since the progression of neurodegenerative diseases is complicated, and compound-related mechanisms for neuroprotection differ, therapeutic strategies may need to involve multiple compounds and consider the type and stage of neurodegenerative diseases.
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Affiliation(s)
- Hsiao-Chien Ting
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
| | - Chia-Yu Chang
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan
| | - Kang-Yun Lu
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan
| | - Hong-Meng Chuang
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Agricultural Biotechnology Center, Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan
| | - Sheng-Feng Tsai
- Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan;
| | - Mao-Hsuan Huang
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan;
| | - Ching-Ann Liu
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan
| | - Shinn-Zong Lin
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan
| | - Horng-Jyh Harn
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Department of Pathology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien 970, Taiwan
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Yuk-Mi-Jihwang-Tang, a Traditional Korean Multiple Herbal Formulae, Improves Hippocampal Memory on Scopolamine Injection-Induced Amnesia Model of C57BL/6 Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:2821040. [PMID: 29507588 PMCID: PMC5817211 DOI: 10.1155/2018/2821040] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Revised: 03/25/2017] [Accepted: 06/27/2017] [Indexed: 11/23/2022]
Abstract
We evaluated neuropharmacological properties of Yuk-Mi-Jihwang-Tang (YJT) against scopolamine injection-induced memory impairment mice model. Mice were orally administered with YJT (50, 100, or 200 mg/kg) or tacrine (TAC, 12.5 mg/kg) for 10 days. At the first day of Morris water maze task, scopolamine (2 mg/kg) was intraperitoneally injected before 30 min of it. The hippocampal memory function was determined by the Morris water maze task for 5 days consecutively. Scopolamine drastically increased escape latency and decreased time spent in target quadrant. Pretreatment YJT properly improved them. Regarding the redox status, YJT significantly reduced the oxidative stress and it also exerted much effort to improve both superoxide dismutase and catalase activities in hippocampal gene expression and protein levels. These effects were well coincided with immunohistochemical analysis of 4-hydroxyneal-positive signals in hippocampal areas. Additionally, acetylcholine esterase activities and brain-derived neurotrophic factor abnormalities in the hippocampal protein levels were significantly normalized by YJT, and their related molecules were also improved. The neuronal proliferation in hippocampal regions was markedly inhibited by scopolamine, whereas YJT notably recovered them. Collectively, YJT exerts much effort to enhance memorial functions through improving redox status homeostasis and partially regulates acetylcholine esterase activities as well as neuronal cell proliferation.
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