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Wang YC, Zhu Y, Meng WT, Zheng Y, Guan XQ, Shao CL, Li XY, Hu D, Wang MZ, Guo HD. Dihydrotanshinone I improves cardiac function by promoting lymphangiogenesis after myocardial ischemia-reperfusion injury. Eur J Pharmacol 2025; 989:177245. [PMID: 39753160 DOI: 10.1016/j.ejphar.2024.177245] [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: 07/11/2024] [Revised: 12/26/2024] [Accepted: 12/30/2024] [Indexed: 01/11/2025]
Abstract
Dihydrotanshinone I (DHT) is an active ingredient derived from Salvia miltiorrhiza. Previous studies have demonstrated that DHT can improve cardiac function in rats with myocardial ischemia-reperfusion injury (IR). However, the mechanism by which DHT improves myocardial injury in rats still requires further research. Lymphangiogenesis can reduce myocardial edema, inflammation, and fibrosis after myocardial infarction in rats, and improve cardiac function. In this study, the changes in cardiac functions, collagen fiber deposition in the infarcted area and the level of relevant indicators of lymphangiogenesis were examined by echocardiography, Masson's trichrome staining, immunohistochemistry and Western blot, respectively. Human lymphatic endothelial cells (HLECs) were transfected with siVE-cadherin and siVEGFR-3, and the effects of DHT on HLEC cell viability, migration and tube formation were detected through CCK8, TUNEL, transwell, wound healing and tube formation assay. We found that in myocardial IR rats treated with DHT, the levels of LYVE-1, PROX1, VEGF-C, VEGFR-3, IGF-1, podoplanin and IGF-1R, which are associated with lymphangiogenesis, were increased, as well as the level of VE-cadherin, which maintains endothelial cell function. DHT reduced the levels of inflammatory factors and myocardial cell apoptosis, thereby improving cardiac function after I/R. To explore the mechanism of DHT promoting lymphangiogenesis, H2O2 and OGD/R injury models of HLECs were constructed to simulate the microenvironment of myocardial IR in vitro. The results proved that DHT could reduce the damage and apoptosis of HLECs. On the other hand, DHT enhanced the expression of VEGFR-3 and VE-cadherin in HLECs, promoted cell migration and tube formation. The effects of DHT on the tube formation and migration of HLECs were significantly decreased after knocking down VEGFR-3 or VE-cadherin. Our research proposed that DHT could improve the heart function after IR through the enhancement of lymphangiogenesis and contributed to the development of the treatment methods for myocardial IR.
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Affiliation(s)
- Ya-Chao Wang
- Academy of Integrated Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yan Zhu
- Department of Neurological Rehabilitation, The Second Rehabilitation Hospital of Shanghai, Shanghai, China
| | - Wan-Ting Meng
- Academy of Integrated Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yan Zheng
- Jiading Hospital of Traditional Chinese Medicine, Shanghai, China
| | - Xiao-Qi Guan
- Academy of Integrated Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chang-le Shao
- Academy of Integrated Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiu-Ya Li
- Academy of Integrated Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Dan Hu
- Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China.
| | - Ming-Zhu Wang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
| | - Hai-Dong Guo
- Academy of Integrated Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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Long Y, Lei F, Hu J, Zheng Z, Gui S, He N. Design and Evaluation of Ophthalmic Thermosensitive In Situ Gel of Compound Salvia. AAPS PharmSciTech 2024; 25:191. [PMID: 39164556 DOI: 10.1208/s12249-024-02913-8] [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: 04/04/2024] [Accepted: 08/01/2024] [Indexed: 08/22/2024] Open
Abstract
The compound Salvia Recipe has been shown to have a relatively significant curative effect in management of cardiovascular and cerebrovascular diseases. This work aimed to prepare a thermosensitive in situ gel (ISG) delivery system that utilizes Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose for ocular administration of the compound Salvia recipe to treat cardiovascular and cerebrovascular diseases. The central composite design-response surface method was utilized to improve the prescription of the gel. The formulated gel was characterized and assessed in terms of stability, retention time, in vitro release, rheology, ocular irritation, pharmacokinetics studies, and tissue distribution. The gel was a liquid solution at room temperature and became semisolid at physiological temperature, prolonging its stay time in the eye. Pharmacokinetics and tissue distribution experiments indicated that thermosensitive ISG had enhanced targeting of heart and brain tissues. Additionally, it could lower drug toxicity and side effects in the lungs and kidneys. The compound Salvia ophthalmic thermosensitive ISG is a promising drug delivery system for the management of cardiovascular and cerebrovascular illnesses.
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Affiliation(s)
- Yanqiu Long
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Hefei, AnHui, People's Republic of China
| | - Fang Lei
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Hefei, AnHui, People's Republic of China
| | - Jie Hu
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Hefei, AnHui, People's Republic of China
| | - Zhiyun Zheng
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Hefei, AnHui, People's Republic of China
- Institute of Pharmaceutics, Anhui Academy of Chinese Medical Sciences, Hefei, 230012, People's Republic of China
- Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Hefei, 230012, China
- Institute of Pharmaceutics, Anhui Academy of Chinese Medical Sciences, Hefei, 230012, China
| | - Shuangying Gui
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Hefei, AnHui, People's Republic of China
- Institute of Pharmaceutics, Anhui Academy of Chinese Medical Sciences, Hefei, 230012, People's Republic of China
- Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Hefei, 230012, China
- Institute of Pharmaceutics, Anhui Academy of Chinese Medical Sciences, Hefei, 230012, China
| | - Ning He
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Hefei, AnHui, People's Republic of China.
- Institute of Pharmaceutics, Anhui Academy of Chinese Medical Sciences, Hefei, 230012, People's Republic of China.
- Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Hefei, 230012, China.
- Institute of Pharmaceutics, Anhui Academy of Chinese Medical Sciences, Hefei, 230012, China.
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Hai Y, Ren K, Hou WQ, Cao HS, Zhang YR, Li ZM, Wang SQ, Yang W, Liu DL. Hypoglycemic TCM formulas (Huangqi-Gegen drug pair) have the potential as an Alzheimer's disease. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 130:155723. [PMID: 38815405 DOI: 10.1016/j.phymed.2024.155723] [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: 06/29/2023] [Revised: 12/28/2023] [Accepted: 05/07/2024] [Indexed: 06/01/2024]
Abstract
BACKGROUND Alzheimer's disease (AD) is a neurological disorder. There is a considerable unmet medical need among those suffering from it. HYPOTHESIS AND PURPOSE Given the link between type-2 diabetes mellitus (T2DM) and AD, hypoglycemic traditional Chinese medicine formulas (TCMFs) may be a treatment for AD. We investigated the possibility of identifying anti-AD medicines in hypoglycemic TCMFs and presented another option for the screening of AD medications. STUDY DESIGN AND METHODS Paralysis of the transgenic Caenorhabditis elegans (C. elegans) strain CL4176 (caused by amyloid beta (Aβ)1-42 aggregates) was used to evaluate the anti-AD effect. The toxicity and neurodegeneration induced by neuronal expression of Aβ in the transgenic C. elegans strain CL2355 were determined using a 5-hydroxytryptamine (5-HT) assay. The transgenic Aβ-expressing strain CL 2006 and transgenic tau-expressing strain BR5270 were used to explore the effect of TCMFs on protein expression in C. elegans using ELISAs. Then, network pharmacology was used to determine the mechanism of action. The Traditional Chinese Medicine Inheritance Support System platform was used to investigate prescription patterns, core drugs, and optimum combinations of hypoglycemic TCMFs for AD. RESULTS Sixteen hypoglycemic TCMFs prolonged the PT50 (half paralysis time) of the CL4176 strain of C. elegans, reduced the percentage of worms paralyzed. The results of network pharmacology showed that prostaglandin-endoperoxide synthase 2 (PTGS2) and acetylcholine esterase (AChE) are main targets of hypoglycemic TCMFs. Enriched pathway analysis showed that the cholinergic receptor-related pathway was the core pathway of hypoglycemic TCMFs. According to the "four qi and five flavors" system of TCM theory, the main pharmacological qualities were "cold" and "sweet." Through the analysis by TCMISS, we found that Huangqi-Gegen drug pair as the significant Chinese herbs of hypoglycemic TCMFs. The Huangqi-Gegen pairing had the most robust therapeutic effect when delivered at a 2:1 (v/v) ratio. It reduced the paralysis caused by 5-HT, decreased protein expression of AChE and PTGS2, and reduced Aβ deposition in the brain of the CL2006 strain of C. elegans. CONCLUSIONS Huangqi-Gegen is a promising treatment of AD, and its mechanism may be induced by suppressing the protein production of AChE and PTGS2, reducing 5-HT intake, and then decreasing Aβ deposition.
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Affiliation(s)
- Yang Hai
- Scientific Research and Experimental Center, Gansu University of Chinese Medicine, Gansu Province, Lanzhou 730000, PR China; Key Laboratory of Dunhuang Medicine, Gansu University of Chinese Medicine, Gansu Province, Lanzhou 730000, PR China.
| | - Ke Ren
- School of Pharmacy, Gansu University of Chinese Medicine, Gansu Province, Lanzhou 730000, PR China
| | - Wen-Qian Hou
- School of Pharmacy, Gansu University of Chinese Medicine, Gansu Province, Lanzhou 730000, PR China
| | - Hao-Shi Cao
- School of Pharmacy, Gansu University of Chinese Medicine, Gansu Province, Lanzhou 730000, PR China
| | - Ya-Rong Zhang
- School of Pharmacy, Gansu University of Chinese Medicine, Gansu Province, Lanzhou 730000, PR China
| | - Zi-Mu Li
- School of Pharmacy, Gansu University of Chinese Medicine, Gansu Province, Lanzhou 730000, PR China
| | - Si-Qi Wang
- School of Pharmacy, Gansu University of Chinese Medicine, Gansu Province, Lanzhou 730000, PR China
| | - Wen Yang
- School of Pharmacy, Gansu University of Chinese Medicine, Gansu Province, Lanzhou 730000, PR China
| | - Dong-Ling Liu
- School of Pharmacy, Gansu University of Chinese Medicine, Gansu Province, Lanzhou 730000, PR China; Gansu Pharmaceutical Industry Innovation Research Institute, Gansu Province, Lanzhou 730000, PR China.
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Shi W, Xu G, Gao Y, Yang H, Liu T, Zhao J, Li H, Wei Z, Hou X, Chen Y, Wen J, Li C, Zhao J, Zhang P, Wang Z, Xiao X, Bai Z. Compound Danshen Dripping Pill effectively alleviates cGAS-STING-triggered diseases by disrupting STING-TBK1 interaction. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 128:155404. [PMID: 38507852 DOI: 10.1016/j.phymed.2024.155404] [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: 10/17/2023] [Revised: 01/13/2024] [Accepted: 01/31/2024] [Indexed: 03/22/2024]
Abstract
BACKGROUND The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (IFN) genes (STING) pathway is critical in the innate immune system and can be mobilized by cytosolic DNA. The various inflammatory and autoimmune diseases progression is highly correlated with aberrant cGAS-STING pathway activation. While some cGAS-STING pathway inhibitor were identified, there are no drugs that can be applied to the clinic. Compound Danshen Dripping Pill (CDDP) has been successfully used in clinic around the world, but the most common application is limited to cardiovascular disease. Therefore, the purpose of the present investigation was to examine whether CDDP inhibits the cGAS-STING pathway and could be used as a therapeutic agent for multiple cGAS-STING-triggered diseases. METHODS BMDMs, THP1 cells or Trex1-/- BMDMs were stimulated with various cGAS-STING-agonists after pretreatment with CDDP to detect the function of CDDP on IFN-β and ISGs productionn. Next, we detect the influence on IRF3 and P65 nuclear translocation, STING oligomerization and STING-TBK1-IRF3 complex formation of CDDP. Additionally, the DMXAA-mediated activation mice model of cGAS-STING pathway was used to study the effects of CDDP. Trex1-/- mice model and HFD-mediated obesity model were established to clarify the efficacy of CDDP on inflammatory and autoimmune diseases. RESULTS CDDP efficacy suppressed the IRF3 phosphorylation or the generation of IFN-β, ISGs, IL-6 and TNF-α. Mechanistically, CDDP did not influence the STING oligomerization and IRF3-TBK1 and STING-IRF3 interaction, but remarkably eliminated the STING-TBK1 interaction, ultimately blocking the downstream responses. In addition, we also clarified that CDDP could suppress cGAS-STING pathway activation triggered by DMXAA, in vivo. Consistently, CDDP could alleviate multi-organ inflammatory responses in Trex1-/- mice model and attenuate the inflammatory disorders, incleding obesity-induced insulin resistance. CONCLUSION CDDP is a specifically cGAS-STING pathway inhibitor. Furthermore, we provide novel mechanism for CDDP and discovered a clinical agent for the therapy of cGAS-STING-triggered inflammatory and autoimmune diseases.
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Affiliation(s)
- Wei Shi
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Guang Xu
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Yuan Gao
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Huijie Yang
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Tingting Liu
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jia Zhao
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Hui Li
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Ziying Wei
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xiaorong Hou
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yuanyuan Chen
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jincai Wen
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Chengwei Li
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jun Zhao
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ping Zhang
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhongxia Wang
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xiaohe Xiao
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; Military Institute of Chinese Materia, the Fifth Medical Centre, General Hospital of PLA, Beijing, China; National Key Laboratory of Kidney Diseases, China.
| | - Zhaofang Bai
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; Military Institute of Chinese Materia, the Fifth Medical Centre, General Hospital of PLA, Beijing, China; National Key Laboratory of Kidney Diseases, China.
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Kurepa J, Bruce KA, Gerhardt GA, Smalle JA. A Plant Model of α-Synucleinopathy: Expression of α-Synuclein A53T Variant in Hairy Root Cultures Leads to Proteostatic Stress and Dysregulation of Iron Metabolism. APPLIED BIOSCIENCES 2024; 3:233-249. [PMID: 38835931 PMCID: PMC11149894 DOI: 10.3390/applbiosci3020016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2024]
Abstract
Synucleinopathies, typified by Parkinson's disease (PD), entail the accumulation of α-synuclein (αSyn) aggregates in nerve cells. Various αSyn mutants, including the αSyn A53T variant linked to early-onset PD, increase the propensity for αSyn aggregate formation. In addition to disrupting protein homeostasis and inducing proteostatic stress, the aggregation of αSyn in PD is associated with an imbalance in iron metabolism, which increases the generation of reactive oxygen species and causes oxidative stress. This study explored the impact of αSyn A53T expression in transgenic hairy roots of four medicinal plants (Lobelia cardinalis, Artemisia annua, Salvia miltiorrhiza, and Polygonum multiflorum). In all tested plants, αSyn A53T expression triggered proteotoxic stress and perturbed iron homeostasis, mirroring the molecular profile observed in human and animal nerve cells. In addition to the common eukaryotic defense mechanisms against proteostatic and oxidative stresses, a plant stress response generally includes the biosynthesis of a diverse set of protective secondary metabolites. Therefore, the hairy root cultures expressing αSyn A53T offer a platform for identifying secondary metabolites that can ameliorate the effects of αSyn, thereby aiding in the development of possible PD treatments and/or treatments of synucleinopathies.
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Affiliation(s)
- Jasmina Kurepa
- Department of Plant and Soil Sciences, Martin-Gatton College of Agriculture Food and Environment, Kentucky Tobacco Research & Development Center, University of Kentucky, Lexington, KY 40546, USA
| | - Kristen A. Bruce
- Naprogenix, Inc., UK-AsTeCC, 145 Graham Avenue, Lexington, KY 40506, USA
| | - Greg A. Gerhardt
- Brain Restoration Center, University of Kentucky, Lexington, KY 40536, USA
- Department of Neurosurgery, University of Kentucky, Lexington, KY 40536, USA
- Department of Neuroscience, University of Kentucky, Lexington, KY 40536, USA
- Department of Neurology, University of Kentucky, Lexington, KY 40536, USA
| | - Jan A. Smalle
- Department of Plant and Soil Sciences, Martin-Gatton College of Agriculture Food and Environment, Kentucky Tobacco Research & Development Center, University of Kentucky, Lexington, KY 40546, USA
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Li X, Liu L, Chu J, Wei G, Li J, Sun X, Fan H. Functional characterization of terpene synthases SmTPS1 involved in floral scent formation in Salvia miltiorrhiza. PHYTOCHEMISTRY 2024; 221:114045. [PMID: 38460781 DOI: 10.1016/j.phytochem.2024.114045] [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: 12/02/2023] [Revised: 02/29/2024] [Accepted: 02/29/2024] [Indexed: 03/11/2024]
Abstract
Plants attract beneficial insects and promote pollination by releasing floral scents. Salvia miltiorrhiza, as an insect-pollinated flowering plant, which has been less studied for its floral aroma substances. This study revealed that S. miltiorrhiza flowers produce various volatile terpenoids, including five monoterpenes and ten sesquiterpenes, with the sesquiterpene compound (E)-β-caryophyllene being the most abundant, accounting for 28.1% of the total volatile terpenoids. Y-tube olfactometer experiments were conducted on the primary pollinator of S. miltiorrhiza, the Apis ceranas. The results indicated that (E)-β-caryophyllene compound had an attractive effect on the Apis ceranas. By comparing the homologous sequences with the genes of (E)-β-caryophyllene terpene synthases in other plants, the SmTPS1 gene was selected for further experiment. Subcellular localization experiments showed SmTPS1 localized in the cytoplasm, and its in vitro enzyme assay revealed that it could catalyze FPP into β-Elemene, (E)-β-caryophyllene and α-Humulene. Overexpression of SmTPS1 in S. miltiorrhiza resulted in a 5.29-fold increase in gene expression. The GC-MS analysis revealed a significant increase in the concentration of (E)-β-caryophyllene in the transgenic plants, with levels 2.47-fold higher compared to the empty vector plants. Furthermore, Y-tube olfactometer experiments showed that the transgenic plants were significantly more attractive to Apis ceranas compared to the empty vector plants. Co-expression analysis suggested that four SmMYCs (SmMYC1, SmMYC5, SmMYC10, and SmMYC11) may be involved in the transcriptional regulation of SmTPS1. The yeast one-hybrid screen and the Dual luciferase assay indicated that SmMYC10 positively regulates the expression of SmTPS1. In conclusion, this study lays a foundation for the functional analysis and transcriptional regulation of terpene synthase genes in S. miltiorrhiza.
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Affiliation(s)
- Xiaohong Li
- School of Life Sciences, Anhui Agricultural University, Hefei, 230036, China
| | - Lin Liu
- School of Life Sciences, Anhui Agricultural University, Hefei, 230036, China
| | - Jin Chu
- School of Life Sciences, Anhui Agricultural University, Hefei, 230036, China
| | - Guo Wei
- College of Horticulture and Landscape Architecture, Yangzhou University, Yangzhou, 225009, China
| | - Jiaxue Li
- School of Life Sciences, Anhui Agricultural University, Hefei, 230036, China
| | - Xu Sun
- School of Life Sciences, Anhui Agricultural University, Hefei, 230036, China.
| | - Honghong Fan
- School of Life Sciences, Anhui Agricultural University, Hefei, 230036, China.
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Zhu K, Pu PM, Li G, Zhou LY, Li ZY, Shi Q, Wang YJ, Cui XJ, Yao M. Shenqisherong pill ameliorates neuronal apoptosis by inhibiting the JNK/caspase-3 signaling pathway in a rat model of cervical cord compression. JOURNAL OF ETHNOPHARMACOLOGY 2024; 318:116901. [PMID: 37437792 DOI: 10.1016/j.jep.2023.116901] [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: 04/17/2023] [Revised: 07/01/2023] [Accepted: 07/08/2023] [Indexed: 07/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Shenqisherong (SQSR) pill is an empirical prescription of traditional Chinese medicine (TCM), which originated from the National Chinese Medical Science Master, Shi Qi. It has been widely used in the treatment of cervical spondylotic myelopathy (CSM) and promote the recovery of spinal cord function, but underlying molecular mechanism remains unclear. AIM OF THE STUDY The objective of this study was to confirm the neuroprotective effects of the SQSR pill. MATERIALS AND METHODS A rat model of chronic compression at double-level cervical cord was used in vivo. The protective role of SQSR pill on CSM rats was measured by Basso, Beattie, and Bresnahan (BBB) locomotor scale, inclined plane test, forelimb grip strength assessment, hindlimb pain threshold assessment, and gait analysis. The levels of reactive oxygen species (ROS) were examined by Dihydroethidium (DHE) staining and 2',7'-Dichlorofluorescein (DCF) assay, and apoptosis was detected by TdT-mediated dUTP nick-end labeling (TUNEL) assay. The expression of apoptosis proteins was evaluated by immunofluorescence staining and Western blot. RESULTS SQSR pill could facilitate locomotor function recovery in rats with chronic cervical cord compression, reduce local ROS in the spinal cord and downregulate the c-Jun-N-terminal kinase (JNK)/caspase-3 signaling pathway. In addition, the SQSR pill could protect primary rat cortical neurons from glutamate-treated toxicity in vitro by reducing the ROS and downregulating the phosphorylation of JNK and its downstream factors related to neuronal apoptosis meditated by the caspase cascade. Then, the neuroprotective effect was counteracted by a JNK activator. CONCLUSIONS Together, SQSR pill could ameliorate neuronal apoptosis by restraining ROS accumulation and inhibiting the JNK/caspase-3 signaling pathway, indicating that SQSR pill could be a candidate drug for CSM.
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Affiliation(s)
- Ke Zhu
- Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
| | - Pei-Min Pu
- Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
| | - Gan Li
- Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
| | - Long-Yun Zhou
- Rehabilitation Medicine Center, Jiangsu Provincial People's Hospital, Jiangsu, 210029, China.
| | - Zhuo-Yao Li
- Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
| | - Qi Shi
- Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
| | - Yong-Jun Wang
- Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
| | - Xue-Jun Cui
- Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
| | - Min Yao
- Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
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Liu XQ, Hu T, Wu GL, Qiao LJ, Cai YF, Wang Q, Zhang SJ. Tanshinone IIA, the key compound in Salvia miltiorrhiza, improves cognitive impairment by upregulating Aβ-degrading enzymes in APP/PS1 mice. Int J Biol Macromol 2024; 254:127923. [PMID: 37944734 DOI: 10.1016/j.ijbiomac.2023.127923] [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: 09/29/2022] [Revised: 11/04/2023] [Accepted: 11/04/2023] [Indexed: 11/12/2023]
Abstract
In Alzheimer's disease (AD), amyloid-beta (Aβ) plays a crucial role in pathogenesis. Clearing Aβ from the brain is considered as a key therapeutic strategy. Previous studies indicated that Salvia miltiorrhiza (Danshen) could protect against AD. However, the main anti-AD components in Danshen and their specific mechanisms are not clear. In this study, pharmacological network analysis indicated that Tanshinone IIA (Tan IIA) was identified as the key active compound in Danshen contributing to protect against AD. Then, APP/PS1 double transgenic mice were employed to examine the neuroprotective effect of Tan IIA. APP/PS1 mice (age, 6 months) were administered (10 and 20 mg/kg) for 8 weeks. Tan IIA improved learning and anxiety behaviors in APP/PS1 mice. Furthermore, Tan IIA reduced oxidative stress, inhibited neuronal apoptosis, improved cholinergic nervous system and decreased endoplasmic reticulum stress in the brain of APP/PS1 mice. Moreover, Tan IIA treatment reduced the level of Aβ. Molecular docking result showed that Tan IIA might block AD by upregulating Aβ-degrading enzymes. Western blot results confirmed that the expressions of insulin degrading enzymes (IDE) and neprilysin (NEP) were significantly increased after Tan IIA treatment, which demonstrated that Tan IIA improved AD by increasing Aβ-degrading enzymes.
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Affiliation(s)
- Xiao-Qi Liu
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510405, China; Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Tian Hu
- Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510405, China
| | - Guang-Liang Wu
- Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510405, China
| | - Li-Jun Qiao
- Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510405, China
| | - Ye-Feng Cai
- Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510405, China.
| | - Qi Wang
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
| | - Shi-Jie Zhang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510405, China.
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9
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Zhang T, Chen X, Ju X, Yuan J, Zhou J, Zhang Z, Ju G, Xu D. PPARG is a potential target of Tanshinone IIA in prostate cancer treatment: a combination study of molecular docking and dynamic simulation based on transcriptomic bioinformatics. Eur J Med Res 2023; 28:487. [PMID: 37932808 PMCID: PMC10626789 DOI: 10.1186/s40001-023-01477-w] [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: 10/05/2023] [Accepted: 10/26/2023] [Indexed: 11/08/2023] Open
Abstract
Tanshinone IIA is a lipophilic organic compound from the root of Danshen (Salvia miltiorrhiza) and is one of the most well-known Tanshinone molecules by pharmacologists. In recent years, in addition to effects of anti-cardiovascular and neurological diseases, Tanshinone IIA has also shown some degrees of anti-prostate cancer potential. Although they do have some studies focusing on the molecular mechanism of Tanshinone IIA's anti-prostate cancer effects, a further understanding on the transcriptomic and structural level is still lacking. In this study, transcriptomic sequencing technology and computer technology were employed to illustrate the effects of Tanshinone IIA on prostate cancer through bioinformatic analysis and molecular dynamics simulation, and PPARG was considered to be one of the targets for Tanshinone IIA according to docking scoring and dynamic calculation. Our study provides a novel direction to further understand the mechanism of the effects of Tanshinone IIA on prostate cancer, and further molecular biological studies need to be carried on to further investigate the molecular mechanism of Tanshinone IIA's anti-prostate cancer effect through PPARG.
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Affiliation(s)
- Tongtong Zhang
- Urology Centre, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
- Institute of Surgery of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
| | - Xinglin Chen
- Urology Centre, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
- Institute of Surgery of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
| | - Xiran Ju
- Urology Centre, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
- Institute of Surgery of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
| | - Jixiang Yuan
- Urology Centre, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
- Institute of Surgery of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
| | - Jielong Zhou
- Urology Centre, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
- Institute of Surgery of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
| | - Zhihang Zhang
- Urology Centre, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
- Institute of Surgery of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China
| | - Guanqun Ju
- Urology Centre, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China.
- Institute of Surgery of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China.
| | - Dongliang Xu
- Urology Centre, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China.
- Institute of Surgery of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China.
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10
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Carpi S, Quarta S, Doccini S, Saviano A, Marigliano N, Polini B, Massaro M, Carluccio MA, Calabriso N, Wabitsch M, Santorelli FM, Cecchini M, Maione F, Nieri P, Scoditti E. Tanshinone IIA and Cryptotanshinone Counteract Inflammation by Regulating Gene and miRNA Expression in Human SGBS Adipocytes. Biomolecules 2023; 13:1029. [PMID: 37509065 PMCID: PMC10377153 DOI: 10.3390/biom13071029] [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: 05/11/2023] [Revised: 06/14/2023] [Accepted: 06/21/2023] [Indexed: 07/30/2023] Open
Abstract
Inflammation of the adipose tissue contributes to the onset and progression of several chronic obesity-related diseases. The two most important lipophilic diterpenoid compounds found in the root of Salvia milthorrhiza Bunge (also called Danshen), tanshinone IIA (TIIA) and cryptotanshinone (CRY), have many favorable pharmacological effects. However, their roles in obesity-associated adipocyte inflammation and related sub-networks have not been fully elucidated. In the present study, we investigated the gene, miRNAs and protein expression profile of prototypical obesity-associated dysfunction markers in inflamed human adipocytes treated with TIIA and CRY. The results showed that TIIA and CRY prevented tumor necrosis factor (TNF)-α induced inflammatory response in adipocytes, by counter-regulating the pattern of secreted cytokines/chemokines associated with adipocyte inflammation (CCL2/MCP-1, CXCL10/IP-10, CCL5/RANTES, CXCL1/GRO-α, IL-6, IL-8, MIF and PAI-1/Serpin E1) via the modulation of gene expression (as demonstrated for CCL2/MCP-1, CXCL10/IP-10, CCL5/RANTES, CXCL1/GRO-α, and IL-8), as well as related miRNA expression (miR-126-3p, miR-223-3p, miR-124-3p, miR-155-5p, and miR-132-3p), and by attenuating monocyte recruitment. This is the first demonstration of a beneficial effect by TIIA and CRY on adipocyte dysfunction associated with obesity development and complications, offering a new outlook for the prevention and/or treatment of metabolic diseases.
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Affiliation(s)
- Sara Carpi
- Science of Health Department, Magna Græcia University, 88100 Catanzaro, Italy
- NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, 56100 Pisa, Italy
- Department of Pharmacy, University of Pisa, 56100 Pisa, Italy
| | - Stefano Quarta
- Department of Biological and Environmental Sciences and Technologies (DISTEBA), University of Salento, 73100 Lecce, Italy
| | - Stefano Doccini
- IRCCS Fondazione Stella Maris, Calambrone, 56128 Pisa, Italy
| | - Anella Saviano
- ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
| | - Noemi Marigliano
- ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
| | - Beatrice Polini
- Department of Pharmacy, University of Pisa, 56100 Pisa, Italy
- Department of Pathology, University of Pisa, 56100 Pisa, Italy
| | - Marika Massaro
- National Research Council (CNR), Institute of Clinical Physiology (IFC), 73100 Lecce, Italy
| | | | - Nadia Calabriso
- National Research Council (CNR), Institute of Clinical Physiology (IFC), 73100 Lecce, Italy
| | - Martin Wabitsch
- Division of Pediatric Endocrinology, Diabetes and Obesity, Department of Pediatrics and Adolescent Medicine, University of Ulm, 89075 Ulm, Germany
| | | | - Marco Cecchini
- NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, 56100 Pisa, Italy
| | - Francesco Maione
- ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
| | - Paola Nieri
- Department of Pharmacy, University of Pisa, 56100 Pisa, Italy
| | - Egeria Scoditti
- National Research Council (CNR), Institute of Clinical Physiology (IFC), 73100 Lecce, Italy
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11
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Astragaloside IV: A promising natural neuroprotective agent for neurological disorders. Biomed Pharmacother 2023; 159:114229. [PMID: 36652731 DOI: 10.1016/j.biopha.2023.114229] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/05/2023] [Accepted: 01/05/2023] [Indexed: 01/18/2023] Open
Abstract
Neurological disorders are characterized by high morbidity, disability, and mortality rates, which seriously threaten human health. However, clinically satisfactory agents for treatment are still currently lacking. Therefore, finding neuroprotective agents with minimum side effects and better efficacy is a challenge. Chinese herbal medicine, particularly natural preparations extracted from herbs or plants, has become an unparalleled resource for discovering new agent candidates. Astragali Radix is an important Qi tonic drug in traditional Chinese medicine and has a long medicinal history. As a natural medicine, it has a good prevention and treatment effect on neurological disorders. Here, the role and mechanism of astragaloside IV in the treatment of neurological disorders were evaluated and discussed through previous research results. Related information from major scientific databases, such as PubMed, MEDLINE, Web of Science, ScienceDirect, Embase, BIOSIS Previews, and the Cochrane Central Register of Controlled Trials and Cochrane Library, covering between 2001 and 2021 was compiled, using "Astragaloside IV" and "Neurological disorders," "Astragaloside IV," and "Neurodegenerative diseases" as reference terms. By summarizing previous research results, we found that astragaloside IV may play a neuroprotective role through various mechanisms: anti-inflammatory, anti-oxidative, anti-apoptotic protection of nerve cells and regulation of nerve growth factor, as well as by inhibiting neurodegeneration and promoting nerve regeneration. Astragaloside IV is a promising natural neuroprotective agent. By determining its pharmacological mechanism, astragaloside IV may be a new candidate drug for the treatment of neurological disorders.
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12
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Acero N, Ortega T, Villagrasa V, Leon G, Muñoz-Mingarro D, Castillo E, González-Rosende ME, Borrás S, Rios JL, Bosch-Morell F, Martínez-Solís I. Phytotherapeutic alternatives for neurodegenerative dementias: Scientific review, discussion and therapeutic proposal. Phytother Res 2023; 37:1176-1211. [PMID: 36690605 DOI: 10.1002/ptr.7727] [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: 07/20/2022] [Revised: 11/16/2022] [Accepted: 12/27/2022] [Indexed: 01/25/2023]
Abstract
The incidence and prevalence of age-related neurodegenerative dementias have been increasing. There is no curative therapy and conventional drug treatment can cause problems for patients. Medicinal plants traditionally used for problems associated with ageing are emerging as a therapeutic resource. The main aim is to give a proposal for use and future research based on scientific knowledge and tradition. A literature search was conducted in several searchable databases. The keywords used were related to neurodegenerative dementias, ageing and medicinal plants. Boolean operators and filters were used to focus the search. As a result, there is current clinical and preclinical scientific information on 49 species used in traditional medicine for ageing-related problems, including neurodegenerative dementias. There are preclinical and clinical scientific evidences on their properties against protein aggregates in the central nervous system and their effects on neuroinflammation, apoptosis dysregulation, mitochondrial dysfunction, gabaergic, glutamatergic and dopaminergic systems alterations, monoamine oxidase alterations, serotonin depletion and oestrogenic protection. In conclusion, the potential therapeutic effect of the different medicinal plants depends on the type of neurodegenerative dementia and its stage of development, but more clinical and preclinical research is needed to find better, safer and more effective treatments.
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Affiliation(s)
- Nuria Acero
- Pharmaceutical and Health Sciences Department, Pharmacy Faculty, San Pablo-CEU University, CEU Universities, Boadilla del Monte, Madrid, Spain
| | - Teresa Ortega
- Pharmacology, Pharmacognosy and Botany Department, Pharmacy Faculty, Complutense University of Madrid, Madrid, Spain
| | - Victoria Villagrasa
- Department of Pharmacy, Faculty of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
| | - Gemma Leon
- Department of Pharmacy, Faculty of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
| | - Dolores Muñoz-Mingarro
- Chemistry and Biochemistry Department, Pharmacy Faculty, San Pablo-CEU University, CEU Universities, Boadilla del Monte, Madrid, Spain
| | - Encarna Castillo
- Department of Pharmacy, Faculty of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
| | - M Eugenia González-Rosende
- Department of Pharmacy, Faculty of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
| | - Silvia Borrás
- Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Valencia, Spain
| | - Jose Luis Rios
- Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Valencia, Spain
| | - Francisco Bosch-Morell
- Biomedical Sciences Institute, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain.,Department of Biomedical Sciences, Faculty of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain
| | - Isabel Martínez-Solís
- Department of Pharmacy, Faculty of Health Sciences, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Valencia, Spain.,ICBiBE-Botanical Garden, University of Valencia, Valencia, Valencia, Spain
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13
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Fang J, He Y, Cao Y, Shi Y, Wang H, Hong Z, Chai Y. Effect of P-Glycoprotein on the Blood-Brain Barrier Transport of the Major Active Constituents of Salvia miltiorrhiza Based on the MDCK-MDR1 Cell Model. ACS Chem Neurosci 2023; 14:766-772. [PMID: 36704945 DOI: 10.1021/acschemneuro.2c00757] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Salvia miltiorrhiza Bunge (S. miltiorrhiza) is a traditional Chinese medicine that has been widely used in the treatment of various central nervous system (CNS) diseases. However, the mechanism of active components of S. miltiorrhiza crossing the blood-brain barrier (BBB) stays unclear. The purpose of this study was to clarify the mechanism of four ingredients of S. miltiorrhiza, i.e., cryptotanshinone (CTS), dihydrotanshinone I (DTS I), tanshinone IIA (TS IIA), and protocatechuic acid (PCTA) crossing the BBB using the in vitro model. The bidirectional transport of detectable components was tested using the MDCK-MDR1 monolayers. High performance liquid chromatography coupled to triple-quadrupole mass spectrometry (HPLC-QQQ/MS) was used to detect the content changes of S. miltiorrhiza monomer components transported through the BBB. Papp of CTS, DTS I, and TS IIA in the absorption direction were lower than 1.0 × 10-6 cm/s, suggesting that these components were poorly absorbed, while PCTA was moderately absorbed through the BBB. The efflux ratio (ER) of CTS, DTS I, TS IIA, and PCTA were 1.65, 0.92, 4.27, and 1.48, respectively. After treatment with P-gp inhibitor tariquidar, the efflux ratio (ER) of CTS, DTS I, and TS IIA significantly decreased from 1.65 to 1.27, 0.92 to 0.36, and 4.27 to 0.86 (P < 0.05), respectively, while the efflux ratio of PCTA decreased without significance from 1.48 to 0.80. This indicated that the transport of CTS, DTS I, and TS IIA might be related to P-gp. TS IIA and CTS were verified as the substrates of P-gp among the four components since the ER of TS IIA and CTS is greater than 1.5. For PCTA and DTS I, their transport mechanism may be related to other transport proteins or passive transport. The results were confirmed by molecular docking in our current work. In this study, an in vitro BBB model was established and applied to the trans-BBB study of active components in S. miltiorrhiza for the first time, which may provide a basis for further research on the mechanisms of other TCMs in treating CNS diseases and is of great significance in promoting the rational and effective use of TCMs.
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Affiliation(s)
- Jiahao Fang
- School of Pharmacy, Second Military Medical University, Shanghai200433, China
| | - Yuzhen He
- School of Pharmacy, Second Military Medical University, Shanghai200433, China
| | - Yuhong Cao
- Zhejiang Institute for Food and Drug Control, Hangzhou310057, China
| | - Yiwei Shi
- School of Pharmacy, Second Military Medical University, Shanghai200433, China
| | - Hui Wang
- School of Pharmacy, Second Military Medical University, Shanghai200433, China
| | - Zhanying Hong
- School of Pharmacy, Second Military Medical University, Shanghai200433, China
| | - Yifeng Chai
- School of Pharmacy, Second Military Medical University, Shanghai200433, China
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14
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An Q, Wu M, Yang C, Feng Y, Xu X, Su H, Zhang G. Salviae miltiorrhiza against human lung cancer: A review of its mechanism (Review). Exp Ther Med 2023; 25:139. [PMID: 36845955 PMCID: PMC9947574 DOI: 10.3892/etm.2023.11838] [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: 08/23/2022] [Accepted: 01/10/2023] [Indexed: 02/15/2023] Open
Abstract
Lung cancer is one of the commonest malignant tumors in the world today, causing millions of mortalities every year. New methods to treat lung cancer are urgently needed. Salviae miltiorrhiza Bunge is a common Chinese medicine, often used for promoting blood circulation. In the past 20 years, Salviae miltiorrhiza has made significant progress in the treatment of lung cancer and is considered to be one of the most promising methods to fight against the disease. A great amount of research has shown that the mechanism of Salviae miltiorrhiza against human lung cancer mainly includes inhibiting the proliferation of lung cancer cells, promoting lung cancer cell apoptosis, inducing cell autophagy, regulating immunity and resisting angiogenesis. Research has shown that Salviae miltiorrhiza has certain effects on the resistance to chemotherapy drugs. The present review discussed the status and prospects of Salviae miltiorrhiza against human lung cancer.
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Affiliation(s)
- Qingwen An
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China,Key Laboratory of Blood-Stasis-Toxin Syndrome of Zhejiang Province, Hangzhou, Zhejiang 310053, P.R. China
| | - Mengting Wu
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China,Key Laboratory of Blood-Stasis-Toxin Syndrome of Zhejiang Province, Hangzhou, Zhejiang 310053, P.R. China
| | - Chuqi Yang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China,Key Laboratory of Blood-Stasis-Toxin Syndrome of Zhejiang Province, Hangzhou, Zhejiang 310053, P.R. China
| | - Yewen Feng
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China,Key Laboratory of Blood-Stasis-Toxin Syndrome of Zhejiang Province, Hangzhou, Zhejiang 310053, P.R. China
| | - Xuefei Xu
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China,Key Laboratory of Blood-Stasis-Toxin Syndrome of Zhejiang Province, Hangzhou, Zhejiang 310053, P.R. China
| | - Hang Su
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China,Key Laboratory of Blood-Stasis-Toxin Syndrome of Zhejiang Province, Hangzhou, Zhejiang 310053, P.R. China
| | - Guangji Zhang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China,Key Laboratory of Blood-Stasis-Toxin Syndrome of Zhejiang Province, Hangzhou, Zhejiang 310053, P.R. China,Traditional Chinese Medicine ‘Preventing Disease’ Wisdom Health Project Research Center of Zhejiang, Hangzhou, Zhejiang 310053, P.R. China,Correspondence to: Professor Guangji Zhang, School of Basic Medical Sciences, Zhejiang Chinese Medical University, 526 Binwen Road, Hangzhou, Zhejiang 310053, P.R. China
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15
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Cedeño-Pinos C, Jiménez-Monreal AM, Quílez M, Bañón S. Polyphenol Extracts from Sage ( Salvia lavandulifolia Vahl) By-Products as Natural Antioxidants for Pasteurised Chilled Yoghurt Sauce. Antioxidants (Basel) 2023; 12:364. [PMID: 36829923 PMCID: PMC9952586 DOI: 10.3390/antiox12020364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 01/30/2023] [Accepted: 02/01/2023] [Indexed: 02/05/2023] Open
Abstract
Sage by-product extracts (SE) are a valuable source of phenolic acids and flavonoids for food applications. The objective was to test two SE as antioxidants in pasteurised chilled yoghurt sauces against oxidation. Two SE of different polyphenol total content and profile were selected: SE38 (37.6 mg/g) and SE70 (69.8 mg/g), with salvianic and rosmarinic acid as the main polyphenols, respectively. Four experimental low-fat yoghurt sauces were formulated: untreated; SE70/2 (0.16 g/kg); SE38 (0.3 g/kg); and SE70 (0.3 g/kg). The stability of phenolic acids, microbiological quality (mesophilic bacteria, moulds and yeasts, and L. monocytogenes), and oxidative stability (lipids, colour, and pH) were studied in the sauces after pasteurisation at 70 °C for 30 min (day 0) and stored by refrigeration (day 42). Pasteurisation and further chilling ensured the microbiological quality and inhibition of microbial growth could not be evidenced, although SE70 showed some antimicrobial potential. Both SE showed good properties as antioxidants for yoghurt sauces. This finding was based on two results: (i) their main polyphenols, salvianic and rosmarinic acids, resisted to mild pasteurisation and remained quite stable during shelf life; and (ii) SE improved radical scavenging capacity, delayed primary and secondary lipid oxidation, and increased colour stability, contributing to sauce stabilisation. SE38 had a better antioxidant profile than SE70; therefore, the selection criteria for SE should be based on both quantity and type of polyphenols. Due to their stability and antioxidant properties, sage polyphenols can be used as natural antioxidants for clean-label yoghurt sauces.
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Affiliation(s)
- Cristina Cedeño-Pinos
- Department of Food Technology and Science and Nutrition, Veterinary Faculty, Regional Campus of International Excellence “Campus Mare Nostrum”, University of Murcia, 30100 Murcia, Spain
| | - Antonia María Jiménez-Monreal
- Department of Food Technology and Science and Nutrition, Veterinary Faculty, Regional Campus of International Excellence “Campus Mare Nostrum”, University of Murcia, 30100 Murcia, Spain
- CIBER: CB12/03/30038 Pathophysiology of Obesity and Nutrition, CIBERobn, Carlos III Health Institute (ISCIII), 28013 Madrid, Spain
| | - María Quílez
- Research Group on Rainfed Crops for the Rural Development, Murcia Institute of Agri-Food Research and Development (IMIDA), 30150 Murcia, Spain
| | - Sancho Bañón
- Department of Food Technology and Science and Nutrition, Veterinary Faculty, Regional Campus of International Excellence “Campus Mare Nostrum”, University of Murcia, 30100 Murcia, Spain
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16
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Sun JM, Agarwal S, Desai TD, Ju DT, Chang YM, Liao SC, Ho TJ, Yeh YL, Kuo WW, Lin YJ, Huang CY. Cryptotanshinone protects against oxidative stress in the paraquat-induced Parkinson's disease model. ENVIRONMENTAL TOXICOLOGY 2023; 38:39-48. [PMID: 36124540 DOI: 10.1002/tox.23660] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 08/29/2022] [Accepted: 08/30/2022] [Indexed: 06/15/2023]
Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder associated with striatal dopaminergic neuronal loss in the Substantia nigra. Oxidative stress plays a significant role in several neurodegenerative diseases. Paraquat (PQ) is considered a potential neurotoxin that affects the brain leading to the death of dopaminergic neurons mimicking the PD phenotype. Various scientific reports have proven that cryptotanshinone possesses antioxidant and anti-inflammatory properties. We hypothesized that cryptotanshinone could extend its neuroprotective activity by exerting antioxidant effects. This study was designed to evaluate the effects of cryptotanshinone in both cellular and animal models of PQ-induced PD. Annexin V-PI double staining and immunoblotting were used to detect apoptosis and oxidative stress proteins, respectively. Reactive oxygen species kits were used to evaluate oxidative stress in cells. For in vivo studies, 18 B6 mice were divided into three groups. The rotarod data revealed the motor function and immunostaining showed the survival of TH+ neurons in SNpc region. Our study showed that cryptotanshinone attenuated paraquat-induced oxidative stress by upregulating anti-oxidant markers in vitro, and restored behavioral deficits and survival of dopaminergic neurons in vivo, demonstrating its therapeutic potential.
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Affiliation(s)
- Jui-Ming Sun
- Section of Neurosurgery, Department of Surgery, Chia-Yi Christian Hospital, Chia-Yi City, Taiwan
- Department of Biotechnology, Asia University, Taichung City, Taiwan
| | - Surbhi Agarwal
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Tushar Dnyaneshwar Desai
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Da-Tong Ju
- Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yung-Ming Chang
- The School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan
- Chinese Medicine Department, E-DA Hospital, Kaohsiung, Taiwan
- 1PT Biotechnology Co., Ltd., Taichung, Taiwan
| | - Shih-Chieh Liao
- Department of Social Medicine, School of Medicine, China Medical University, Taichung, Taiwan
| | - Tsung-Jung Ho
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Post-Baccalaureate Chinese Medicine, College of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Yu-Lan Yeh
- Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
- Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
| | - Wei-Wen Kuo
- Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
| | - Yu-Jung Lin
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Chih-Yang Huang
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- Department of Biological Science and Technology, Asia University, Taichung, Taiwan
- Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
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17
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Fan Q, Lu Q, Wang G, Zhu W, Teng L, Chen W, Bi L. Optimizing component formula suppresses lung cancer by blocking DTL-mediated PDCD4 ubiquitination to regulate the MAPK/JNK pathway. JOURNAL OF ETHNOPHARMACOLOGY 2022; 299:115546. [PMID: 35850313 DOI: 10.1016/j.jep.2022.115546] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 07/02/2022] [Accepted: 07/11/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Salvia miltiorrhiza Bunge and Panax ginseng C. A. Meyer have special curative effect on cancer treatment. The optimizing component formula (OCF) extracted from those two herbs was in line with the anti-lung cancer treatment principle of activating blood and supplementing 'Qi'. However, the study on the mechanism of component formula has always been an insurmountable challenge. Nowadays, the application of network pharmacology and artificial intelligence (AI) in the field of TCM provides new ideas for the study of new targets and mechanisms of TCM, which promotes the modernization of TCM. AIM OF THE STUDY This study aims to further explore the anti-lung cancer mechanism of OCF by using an integrated strategy of network pharmacology and AI technology. MATERIALS AND METHODS Bioinformatic analysis was used to analyze the expression levels, prognosis and survival of DTL and PDCD4 in cancer patients. The binding strength of OCF and DTL was simulated by molecular docking, and the affinity between them was detected by Bio-layer interferometry. Network pharmacology was used to predict the active components, potential targets and pathways of OCF. The association between key targets and their corresponding components and DTL was analyzed by Ingenuity Pathway Analysis (IPA). MTT assay, colony formation assay, wound-healing assay and transwell assay were used to verify the inhibitory effects of OCF on lung cancer cells in vitro. qRT-PCR and Western blot assay were used to detect the effects of OCF on mRNA and protein expression of DTL, PDCD4 and key genes in MAPK/JNK pathways. RESULTS Bioinformatics analysis showed that DTL was significantly up-regulated in lung cancer, which was associated with high malignancy rate, high metastasis rate and poor prognosis of primary tumor. PDCD4 was down-regulated in lung cancer, and associated with high metastasis rate and poor prognosis. The good affinity between OCF and DTL was predicted and verified by molecular docking and Bio-layer interferometry. Based on the network pharmacological databases, 40 active components and 220 corresponding targets of OCF were screened out. KEGG analysis showed that OCF component targets were mainly enriched in MAPK signaling pathway. IPA results showed the interrelationship between DTL, PDCD4, MAPK pathway genes and their corresponding OCF components. In addition, in vitro experiments demonstrated anti-lung cancer activity of OCF, as validated, via impairing cell viability and cell proliferation, as well as inhibiting migration and invasion abilities in lung cancer cells. qRT-PCR showed that OCF down-regulated the mRNA expression of DTL, MAP4K1, JNK, c-Jun and c-Myc, and up-regulated the mRNA expression of PDCD4 and P53 genes in A549 lung cancer cells. Western blot suggested that OCF suppressed the protein level of DTL and blocked the ubiquitination of PDCD4 in A549 lung cancer cells, and down-regulated the protein levels of MAP4K1, p-JNK and p-c-Jun while up-regulated the proteins expression level of P53. CONCLUSIONS OCF might elicit an anti-lung cancer effect by blocking DTL-mediated PDCD4 ubiquitination and suppression of the MAPK/JNK pathway. Meanwhile, our work revealed that network pharmacology and AI technology strategy are cogent means of studying the active components and mechanism of TCM.
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Affiliation(s)
- Qianqian Fan
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Qinwei Lu
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Guiyang Wang
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Wenjing Zhu
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Linxin Teng
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Weiping Chen
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Lei Bi
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
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Liu R, Zou P, Yan ZY, Chen X. Identification, classification, and expression profile analysis of heat shock transcription factor gene family in Salvia miltiorrhiza. PeerJ 2022; 10:e14464. [PMID: 36523473 PMCID: PMC9745953 DOI: 10.7717/peerj.14464] [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: 08/16/2022] [Accepted: 11/03/2022] [Indexed: 12/09/2022] Open
Abstract
In response to abiotic stresses, transcription factors are essential. Heat shock transcription factors (HSFs), which control gene expression, serve as essential regulators of plant growth, development, and stress response. As a model medicinal plant, Salvia miltiorrhiza is a crucial component in the treatment of cardiovascular illnesses. But throughout its growth cycle, S.miltiorrhiza is exposed to a series of abiotic challenges, including heat and drought. In this study, 35 HSF genes were identified based on genome sequencing of Salvia miltiorrhiza utilizing bioinformatics techniques. Additionally, 35 genes were classified into three groups by phylogeny and gene structural analysis, comprising 22 HSFA, 11 HSFB, and two HSFC. The distribution and sequence analysis of motif showed that SmHSFs were relatively conservative. In SmHSF genes, analysis of the promoter region revealed the presence of many cis-acting elements linked to stress, hormones, and growth and development, suggesting that these factors have regulatory roles. The majority of SmHSFs were expressed in response to heat and drought stress, according to combined transcriptome and real-time quantitative PCR (qRT-PCR) analyses. In conclusion, this study looked at the SmHSF gene family using genome-wide identification, evolutionary analysis, sequence characterization, and expression analysis. This research serves as a foundation for further investigations into the role of HSF genes and their molecular mechanisms in plant stress responses.
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Affiliation(s)
- Rui Liu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China,Key Laboratory of Characteristic Chinese Medicinal Resources in Southwest, Chengdu, Sichuan, China
| | - Peijin Zou
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China,Key Laboratory of Characteristic Chinese Medicinal Resources in Southwest, Chengdu, Sichuan, China
| | - Zhu-Yun Yan
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China,Key Laboratory of Characteristic Chinese Medicinal Resources in Southwest, Chengdu, Sichuan, China
| | - Xin Chen
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China,Key Laboratory of Characteristic Chinese Medicinal Resources in Southwest, Chengdu, Sichuan, China
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Yuan P, Qin HY, Wei JY, Chen G, Li X. Proteomics reveals the potential mechanism of Tanshinone IIA in promoting the Ex Vivo expansion of human bone marrow mesenchymal stem cells. Regen Ther 2022; 21:560-573. [DOI: 10.1016/j.reth.2022.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 11/03/2022] [Accepted: 11/08/2022] [Indexed: 11/25/2022] Open
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Tan W, Qi L, Hu X, Tan Z. Research progress in traditional Chinese medicine in the treatment of Alzheimer's disease and related dementias. Front Pharmacol 2022; 13:921794. [PMID: 36506569 PMCID: PMC9729772 DOI: 10.3389/fphar.2022.921794] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 11/09/2022] [Indexed: 11/25/2022] Open
Abstract
Alzheimer's disease (AD) is the world's leading cause of dementia and has become a huge economic burden on nations and families. However, the exact etiology of AD is still unknown, and there are no efficient medicines or methods to prevent the deterioration of cognition. Traditional Chinese medicine (TCM) has made important contributions in the battle against AD based on the characteristics of multiple targets of TCM. This study reviewed the treatment strategies and new discoveries of traditional Chinese medicine in current research, which may be beneficial to new drug researchers.
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Affiliation(s)
- Wanying Tan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Lingjun Qi
- Sichuan Academy of Traditional Chinese Medicine, Chengdu, China
| | - Xiaoyu Hu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhenghuai Tan
- Sichuan Academy of Traditional Chinese Medicine, Chengdu, China
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21
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A Review on the Pharmacological Activities of Salvia Miltiorrhizae Radix Using International Classification of Disease, 10th Revision (ICD-10) Codes. Processes (Basel) 2022. [DOI: 10.3390/pr10091860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Salvia Miltiorrhizae Radix (SMR) is a widely-used herbal medicine for the treatment of various blood stasis-related diseases (mainly circulatory system). It has been extensively studied in the field of pharmacology over the last few decades. In addition, several reviews concerning the effect of SMR are available. The purpose of this study was to review the pharmacological activities of SMC based on the 10th revision of the international disease classification (ICD-10). After an analysis of the literatures in the Medline database between January 1988 and August 2018, 691 eligible articles were chosen and 971 results were obtained (395 in vitro, 536 in vivo, and 40 human). The extracted data were categorized into the disease chapters of the ICD-10 and the major chapters were: IX Diseases of the circulatory system, II Neoplasms, XI Diseases of the digestive system, XIX Injury, poisoning and certain other consequences of external causes, IV Endocrine, nutritional, and metabolic diseases, VI Diseases of the nervous system, V Mental and behavioral disorders, etc. The major diseases and the pharmacological results of each chapter of the ICD-10 were described assiduously, along with the statistical details. The current study provided a comprehensive understanding and insight of SMR in terms of pharmacological activities.
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22
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Guo X, Ma R, Wang M, Wui-Man Lau B, Chen X, Li Y. Novel perspectives on the therapeutic role of cryptotanshinone in the management of stem cell behaviors for high-incidence diseases. Front Pharmacol 2022; 13:971444. [PMID: 36046823 PMCID: PMC9420941 DOI: 10.3389/fphar.2022.971444] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 07/18/2022] [Indexed: 11/22/2022] Open
Abstract
Cryptotanshinone (CTS), a diterpenoid quinone, is found mostly in Salvia miltiorrhiza Bunge (S. miltiorrhiza) and plays a crucial role in many cellular processes, such as cell proliferation/self-renewal, differentiation and apoptosis. In particular, CTS’s profound physiological impact on various stem cell populations and their maintenance and fate determination could improve the efficiency and accuracy of stem cell therapy for high-incidence disease. However, as much promise CTS holds, these CTS-mediated processes are complex and multifactorial and many of the underlying mechanisms as well as their clinical significance for high-incidence diseases are not yet fully understood. This review aims to shed light on the impact and mechanisms of CTS on the actions of diverse stem cells and the involvement of CTS in the many processes of stem cell behavior and provide new insights for the application of CTS and stem cell therapy in treating high-incidence diseases.
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Affiliation(s)
- Xiaomeng Guo
- State Key Laboratory of Component-Based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ruishuang Ma
- State Key Laboratory of Component-Based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Meng Wang
- State Key Laboratory of Component-Based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Benson Wui-Man Lau
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
| | - Xiaopeng Chen
- State Key Laboratory of Component-Based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- *Correspondence: Xiaopeng Chen, ; Yue Li,
| | - Yue Li
- State Key Laboratory of Component-Based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- *Correspondence: Xiaopeng Chen, ; Yue Li,
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Guo X, Meng X, Li Y, Qu C, Liu Y, Cao M, Yao X, Meng F, Wu J, Peng H, Peng D, Xing S, Jiang W. Comparative proteomics reveals biochemical changes in Salvia miltiorrhiza Bunge during sweating processing. JOURNAL OF ETHNOPHARMACOLOGY 2022; 293:115329. [PMID: 35490901 DOI: 10.1016/j.jep.2022.115329] [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: 12/26/2021] [Revised: 03/31/2022] [Accepted: 04/25/2022] [Indexed: 06/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Salvia miltiorrhiza Bunge is a bulk medicinal material used in traditional Chinese medicine, that can cure cardiovascular diseases, neurasthenia, and other conditions. Sweating is a frequently used method of processing S. miltiorrhiza for medical applications. We previously demonstrated changes to the metabolic profile of linoleic acid, glyoxylate, and dicarboxylate after Sweating. However, this alteration has not been explained at the molecular level. MATERIALS AND METHODS Fresh roots of Salvia miltiorrhiza Bunge were treated by the Sweating processing, and then the tandem mass tag technique was used to compare the proteome difference between Sweating S. miltiorrhiza and non-Sweating S. miltiorrhiza. RESULTS We identified a total of 850 differentially expressed proteins after Sweating treatment in S. miltiorrhiza, including 529 upregulated proteins and 321 downregulated proteins. GO enrichment analysis indicated that these differentially expressed proteins are involved in external encapsulating structure, cell wall, oxidoreductase activity, ligase activity, and others. Further analysis showed that CYP450, the pathogenesis-related protein Bet v 1 family, and the peroxidase domain were the major protein domains. KEGG enrichment identified 18 pathways, of which phenylpropanoid biosynthesis is the most important one related to the metabolite profile and is the principal chemical component of S. miltiorrhiza. CONCLUSION This study addressed potential molecular mechanisms in S. miltiorrhiza after Sweating, and the findings provide reasons for the changes in biochemical properties and metabolites changes which might cause pharmacological variation at the proteome level.
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Affiliation(s)
- Xiaohu Guo
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China
| | - Xiaoxi Meng
- Department of Horticultural Science, University of Minnesota, MN, 55108, USA
| | - Yan Li
- Hunan Key Laboratory for Conservation and Utilization of Biological Resources in the Nanyue Mountainous Region, College of Life Sciences and Environment, Hengyang Normal University, Hengyang, 421008, China
| | - Changqing Qu
- Engineering Technology Research Center of Anti-aging, Chinese Herbal Medicine, Fuyang Normal University, Fuyang, 236037, China
| | - Yingying Liu
- College of Humanities and International Education Exchange, Anhui University of Chinese Medicine, Hefei, 230012, China
| | - Mengyang Cao
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China
| | - Xiaoyan Yao
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China
| | - Fei Meng
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China
| | - Jing Wu
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China
| | - Huasheng Peng
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China
| | - Daiyin Peng
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, 230012, China; Synergetic Innovation Center of Anhui Authentic Chinese Medicine Quality Improvement, Hefei, 230038, China
| | - Shihai Xing
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Synergetic Innovation Center of Anhui Authentic Chinese Medicine Quality Improvement, Hefei, 230038, China; Anhui Province Key Laboratory of Research & Development of Chinese Medicine, Hefei, 230012, China.
| | - Weimin Jiang
- Hunan Key Laboratory for Conservation and Utilization of Biological Resources in the Nanyue Mountainous Region, College of Life Sciences and Environment, Hengyang Normal University, Hengyang, 421008, China.
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A Novel Based-Network Strategy to Identify Phytochemicals from Radix Salviae Miltiorrhizae (Danshen) for Treating Alzheimer's Disease. Molecules 2022; 27:molecules27144463. [PMID: 35889336 PMCID: PMC9317794 DOI: 10.3390/molecules27144463] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 07/07/2022] [Accepted: 07/07/2022] [Indexed: 12/14/2022] Open
Abstract
Alzheimer’s disease (AD) is a common age-related neurodegenerative disease that strikes millions worldwide. Herein, we demonstrate a new approach based on network target to identify anti-AD compounds from Danshen. Network pharmacology and molecular docking were employed to establish the DS-AD network, which mainly involved apoptosis of neuron cells. Then network scoring was confirmed via Connectivity Map analysis. M308 (Danshenxinkun D) was an anti-AD candidate with a high score (p < 0.01). Furthermore, we conducted ex vivo experiments with H2O2-treated PC12 cells to verify the neuroprotective effect of Salvia miltiorrhiza-containing plasma (SMP), and UPLC-Q-TOF/MS and RT-qPCR were performed to demonstrate the anti-AD activity of M308 from SMP. Results revealed that SMP could enhance cell viability and level of acetylcholine. AO/EB staining and Mitochondrial membrane potential (MMP) analysis showed that SMP significantly suppressed apoptosis, which may be due to anti-oxidative stress activity. Moreover, the effects of M308 and SMP on expressions of PSEN1, DRD2, and APP mRNA were consistent, and M308 can significantly reverse the expression of PSEN1 and DRD2 mRNA in H2O2-treated PC12 cells. The strategy based on the network could be employed to identify anti-AD compounds from Chinese herbs. Notably, M308 stands out as a promising anti-AD candidate for development.
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Xu W, Jiang Y, Wang N, Bai H, Xu S, Xia T, Xin H. Traditional Chinese Medicine as a Promising Strategy for the Treatment of Alzheimer's Disease Complicated With Osteoporosis. Front Pharmacol 2022; 13:842101. [PMID: 35721142 PMCID: PMC9198449 DOI: 10.3389/fphar.2022.842101] [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: 12/23/2021] [Accepted: 03/21/2022] [Indexed: 11/13/2022] Open
Abstract
Alzheimer’s disease (AD) and osteoporosis (OP) are progressive degenerative diseases caused by multiple factors, placing a huge burden on the world. Much evidence indicates that OP is a common complication in AD patients. In addition, there is also evidence to show that patients with OP have a higher risk of AD than those without OP. This suggests that the association between the two diseases may be due to a pathophysiological link rather than one disease causing the other. Several in vitro and in vivo studies have also proved their common pathogenesis. Based on the theory of traditional Chinese medicine, some classic and specific natural Chinese medicines are widely used to effectively treat AD and OP. Current evidence also shows that these treatments can ameliorate both brain damage and bone metabolism disorder and further alleviate AD complicated with OP. These valuable therapies might provide effective and safe alternatives to major pharmacological strategies.
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Affiliation(s)
- Weifan Xu
- Department of Pharmacognosy, School of Pharmacy, Naval Medical University, Shanghai, China.,Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Yiping Jiang
- Department of Pharmacognosy, School of Pharmacy, Naval Medical University, Shanghai, China
| | - Nani Wang
- Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Huanhuan Bai
- Department of Pharmacognosy, School of Pharmacy, Naval Medical University, Shanghai, China
| | - Shengyan Xu
- Department of Pharmacognosy, School of Pharmacy, Naval Medical University, Shanghai, China
| | - Tianshuang Xia
- Department of Pharmacognosy, School of Pharmacy, Naval Medical University, Shanghai, China
| | - Hailiang Xin
- Department of Pharmacognosy, School of Pharmacy, Naval Medical University, Shanghai, China
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Medication Rules in Herbal Medicine for Mild Cognitive Impairment: A Network Pharmacology and Data Mining Study. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:2478940. [PMID: 35646138 PMCID: PMC9132671 DOI: 10.1155/2022/2478940] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 04/18/2022] [Indexed: 11/17/2022]
Abstract
Background Although traditional Chinese medicine (TCM) has good efficacy in the treatment of mild cognitive impairment (MCI), especially memory improvement and safety, its substance basis and intervention mechanism are particularly complex and unknown. Therefore, based on network pharmacology and data mining, this study aims to explore the rules, active ingredients and mechanism of TCM in the treatment of MCI. Methods By searching the GeneCard, OMIM, DisGeNET and DrugBank databases, we obtained the critical targets associated with MCI. We matched the components and herbs corresponding to the important targets in the TCMSP platform. Using Cytoscape 3.7.2 software, we constructed a target-component-herb network and conducted a network topology analysis to obtain the core components and herbs. Molecular docking was used to preliminarily analyze and predict the binding activities and main binding combinations of the core targets and components. Based on the analysis of the properties, flavor and meridian distribution of herbs, the rules of herbal therapy for MCI were summarized. Results Twenty-eight critical targets were obtained after the screening. Using the TCMSP platform, 492 components were obtained. After standardization, we obtained 387 herbs. Based on the target-composition-herb network analysis, the core targets were ADRB2, ADRA1B, DPP4, ACHE and ADRA1D. According to the screening, the core ingredients were beta-sitosterol, quercetin, kaempferol, stigmasterol and luteolin. The core herbs were matched to Danshen, Yanhusuo, Gancao, Gouteng and Jiangxiang. It was found that the herbs were mainly warm in nature, pungent in taste and liver and lung in meridian. The molecular docking results showed that most core components exhibited strong binding activity to the target combination regardless of the in or out of network combination. Conclusion The results of this study indicate that herbs have great potential in the treatment of MCI. This study provides a reference and basis for clinical application, experimental research and new drug development of herbal therapy for MCI.
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Panda SP, Soni U. A review of dementia, focusing on the distinct roles of viral protein corona and MMP9 in dementia: Potential pharmacotherapeutic priorities. Ageing Res Rev 2022; 75:101560. [PMID: 35031512 DOI: 10.1016/j.arr.2022.101560] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 12/27/2021] [Accepted: 01/07/2022] [Indexed: 02/08/2023]
Abstract
Dementia, in particular, is a defining feature of Alzheimer's and Parkinson's diseases. Because of the combination of motor and cognitive impairments, Parkinson's disease dementia (PDD) has a greater impact on affected people than Alzheimer's disease dementia (ADD) and others. If one family member develops dementia, the other members will suffer greatly in terms of social and occupational functioning. Currently, no relevant treatment is available based on an examination of the absolute pathophysiology of dementia. As a result, our objective of current review encouraged to look for dementia pharmacotherapy based on their pathogenesis. We systematically searched electronic databases such as PubMed, Scopus, and ESCI for information on the pathophysiology of demetia, as well as their treatment with allopathic and herbal medications. By modulating intermediate proteins, oxidative stress, viral protein corona, and MMP9 are etiological factors that cause dementia. The pathophysiology of ADD was described by two hypotheses: the amyloid cascade hypothesis and the tau and tangle hypothesis. ADD is caused by an increase in amyloid-beta (Aβ) and neurofibrillary tangles in the cerebrum. The viral protein corona (VPC) is more contagious and helps to form amyloid-beta (Aβ) plaques and neurofibrillary tangles in the cerebrum. Thioredoxin interacting protein (TXNIP) inside the BBB encourages Aβ to become more engaged. PDD is caused by decreased or absent dopamine secretion from nerve cells in the substantia nigra, as well as PRKN gene deletion/duplication mutations, and shift in the PRKN-PACRG organisation, all of which are linked to ageing. This article discussed the pathophysiology of dementia, as well as a list of herbal medications that can easily cross the BBB and have a therapeutic effect on dementia.
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Uncommon Terpenoids from Salvia Species: Chemistry, Biosynthesis and Biological Activities. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27031128. [PMID: 35164392 PMCID: PMC8838292 DOI: 10.3390/molecules27031128] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 02/05/2022] [Accepted: 02/06/2022] [Indexed: 11/20/2022]
Abstract
The search for new bioactive compounds from plant sources has been and continues to be one of the most important fields of research in drug discovery. However, Natural Products research has continuously evolved, and more and more has gained a multidisciplinary character. Despite new developments of methodologies and concepts, one intriguing aspect still persists, i.e., different species belonging to the same genus can produce different secondary metabolites, whereas taxonomically different genera can produce the same compounds. The genus Salvia L. (Family Lamiaceae) comprises myriad distinct medicinal herbs used in traditional medicine worldwide that show different pharmacological activities due to the presence of a variety of interesting specialized metabolites, including mono-, sesqui-, di-, sester-, tri-, tetra-, and higher terpenoids as well as phenylpropanoids, phenolic acid derivatives, lignans, flavonoids, and alkaloids. We herein summarize the research progress on some uncommon terpenoids, isolated from members of the genus Salvia, which are well recognized for their potential pharmacological activities. This review also provides a current knowledge on the biosynthesis and occurrence of some interesting phytochemicals from Salvia species, viz. C23-terpenoids, sesterterpenoids (C25), dammarane triterpenoids (C30), and uncommon triterpenoids (C20+C10). The study was carried out by searching various scientific databases, including Elsevier, ACS publications, Taylor and Francis, Wiley Online Library, MDPI, Springer, Thieme, and ProQuest. Therefore, 106 uncommon terpenoids were identified and summarized. Some of these compounds possessed a variety of pharmacological properties, such as antibacterial, antiviral, antiparasitic, cytotoxic and tubulin tyrosine ligase inhibitory activities. Due to the lack of pharmacological information for the presented compounds gathered from previous studies, biological investigation of these compounds should be reinvestigated.
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Simultaneous Determination of Seven Lipophilic and Hydrophilic Components in Salvia miltiorrhiza Bunge by LC-MS/MS Method and Its Application to a Transport Study in a Blood-Brain-Barrier Cell Model. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27030657. [PMID: 35163922 PMCID: PMC8838936 DOI: 10.3390/molecules27030657] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/14/2022] [Accepted: 01/18/2022] [Indexed: 01/15/2023]
Abstract
Salvia miltiorrhiza Bunge (SM) has been extensively used in Alzheimer’s disease treatment, the permeability through the blood-brain barrier (BBB) determining its efficacy. However, the transport mechanism of SM components across the BBB remains to be clarified. A simple, precise, and sensitive method using LC-MS/MS was developed for simultaneous quantification of tanshinone I (TS I), dihydrotanshinone I (DTS I), tanshinone IIA (TS IIA), cryptotanshinone (CTS), protocatechuic aldehyde (PAL), protocatechuic acid (PCTA), and caffeic acid (CFA) in transport samples. The analytes were separated on a C18 column by gradient elution. Multiple reaction monitoring mode via electrospray ionization source was used to quantify the analytes in positive mode for TS I, DTS I, TS IIA, CTS, and negative mode for PAL, PCTA, and CFA. The linearity ranges were 0.1–8 ng/mL for TS I and DTS I, 0.2–8 ng/mL for TS IIA, 1–80 ng/mL for CTS, 20–800 ng/mL for PAL and CFA, and 10–4000 ng/mL for PCTA. The developed method was accurate and precise for the compounds. The relative matrix effect was less than 15%, and the analytes were stable for analysis. The established method was successfully applied for transport experiments on a BBB cell model to evaluate the apparent permeability of the seven components.
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Zhang S, Luo H, Sun S, Zhang Y, Ma J, Lin Y, Yang L, Tan D, Fu C, Zhong Z, Wang Y. Salvia miltiorrhiza Bge. (Danshen) for Inflammatory Bowel Disease: Clinical Evidence and Network Pharmacology-Based Strategy for Developing Supplementary Medical Application. Front Pharmacol 2022; 12:741871. [PMID: 35126100 PMCID: PMC8807566 DOI: 10.3389/fphar.2021.741871] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 12/28/2021] [Indexed: 01/30/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a non-specific colorectal disease caused by multifaceted triggers. Although conventional treatments are effective in the management of IBD, high cost and frequent side effects limit their applications and have turned sufferers toward alternative and complementary approaches. Salvia miltiorrhiza Bge (Danshen) is an herbal medicine that reportedly alleviates the symptoms of IBD. A large body of research, including clinical trials in which Danshen-based products or botanical compounds were used, has unmasked its multiple mechanisms of action, but no review has focused on its efficacy as a treatment for IBD. Here, we discussed triggers of IBD, collected relevant clinical trials and analyzed experimental reports, in which bioactive compounds of Danshen attenuated rodent colitis in the management of intestinal integrity, gut microflora, cell death, immune conditions, cytokines, and free radicals. A network pharmacology approach was applied to describe sophisticated mechanisms in a holistic view. The safety of Danshen was also discussed. This review of evidence will help to better understand the potential benefits of Danshen for IBD treatment and provide insights for the development of innovative applications of Danshen.
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Affiliation(s)
- Siyuan Zhang
- Macau Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China
| | - Hua Luo
- Macau Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China
| | - Shiyi Sun
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yating Zhang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jiaqi Ma
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuting Lin
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Lin Yang
- Macau Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China
| | - Dechao Tan
- Macau Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China
| | - Chaomei Fu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhangfeng Zhong
- Macau Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China
- *Correspondence: Zhangfeng Zhong, ; Yitao Wang,
| | - Yitao Wang
- Macau Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China
- *Correspondence: Zhangfeng Zhong, ; Yitao Wang,
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Zhou J, Liu R, Shuai M, Yan ZY, Chen X. Comparative transcriptome analyses of different Salvia miltiorrhiza varieties during the accumulation of tanshinones. PeerJ 2021; 9:e12300. [PMID: 34721983 PMCID: PMC8541307 DOI: 10.7717/peerj.12300] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 09/22/2021] [Indexed: 01/07/2023] Open
Abstract
Salvia miltiorrhiza (Labiatae) is an important medicinal plant in traditional Chinese medicine. Tanshinones are one of the main active components of S. miltiorrhiza. It has been found that the intraspecific variation of S. miltiorrhiza is relatively large and the content of tanshinones in its roots of different varieties is also relatively different. To investigate the molecular mechanisms that responsible for the differences among these varieties, the tanshinones content was determined and comparative transcriptomics analysis was carried out during the tanshinones accumulation stage. A total of 52,216 unigenes were obtained from the transcriptome by RNA sequencing among which 23,369 genes were differentially expressed among different varieties, and 2,016 genes including 18 diterpenoid biosynthesis-related genes were differentially expressed during the tanshinones accumulation stage. Functional categorization of the differentially expressed genes (DEGs) among these varieties revealed that the pathway related to photosynthesis, oxidative phosphorylation, secondary metabolite biosynthesis, diterpenoid biosynthesis, terpenoid backbone biosynthesis, sesquiterpenoid and triterpenoid biosynthesis are the most differentially regulated processes in these varieties. The six tanshinone components in these varieties showed different dynamic changes in tanshinone accumulation stage. In addition, combined with the analysis of the dynamic changes, 277 DEGs (including one dehydrogenase, three CYP450 and 24 transcription factors belonging to 12 transcription factor families) related to the accumulation of tanshinones components were obtained. Furthermore, the KEGG pathway enrichment analysis of these 277 DEGs suggested that there might be an interconnection between the primary metabolic processes, signaling processes and the accumulation of tanshinones components. This study expands the vision of intraspecific variation and gene regulation mechanism of secondary metabolite biosynthesis pathways in medicinal plants from the “omics” perspective.
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Affiliation(s)
- Jingwen Zhou
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.,Key Laboratory of Characteristic Chinese Medicinal Resources in Southwest, Chengdu, Sichuan, China
| | - Rui Liu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.,Key Laboratory of Characteristic Chinese Medicinal Resources in Southwest, Chengdu, Sichuan, China
| | - Min Shuai
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.,Key Laboratory of Characteristic Chinese Medicinal Resources in Southwest, Chengdu, Sichuan, China
| | - Zhu-Yun Yan
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.,Key Laboratory of Characteristic Chinese Medicinal Resources in Southwest, Chengdu, Sichuan, China
| | - Xin Chen
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.,Key Laboratory of Characteristic Chinese Medicinal Resources in Southwest, Chengdu, Sichuan, China
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32
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Zhou W, Hu M, Hu J, Du Z, Su Q, Xiang Z. Luteolin Suppresses Microglia Neuroinflammatory Responses and Relieves Inflammation-Induced Cognitive Impairments. Neurotox Res 2021; 39:1800-1811. [PMID: 34655374 DOI: 10.1007/s12640-021-00426-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 09/30/2021] [Accepted: 10/01/2021] [Indexed: 12/13/2022]
Abstract
Microglia-mediated neuroinflammation in response to injurious self and non-self-stimuli exerts detrimental effects on neurons, which may lead to cognitive impairment. Luteolin, a typical kind of natural flavonoid in honeysuckle, chrysanthemum, and Herba Schizonepetae, is widely recognized to be anti-inflammatory and antioxidant against peripheral inflammation. However, its protective effect against inflammation-induced cognitive impairment is currently unknown. In this paper, we investigated the relief potential of luteolin against lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation and its possible anti-inflammatory mechanisms in lipopolysaccharide-stimulated BV2 microglia cells. In this study, luteolin ameliorated LPS-induced cognitive impairments, indicated by behavioral performance of neuroinflammatory model mice in Morris water maze tests. Protein analyses and histological examination also revealed protective effect of luteolin against neuronal damage, through inhibiting overproduction of inflammatory cytokines in both hippocampus and cortex of mice. We also observed luteolin in vitro significantly suppressed the levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 β (IL-1β), and inflammatory mediators like nitric oxide. Taken together, these results demonstrated luteolin was effective in alleviating cognitive impairment and limited neuronal damage via inhibiting the release of inflammatory mediators, suggesting luteolin is potential for further therapeutic research of neuroinflammation-related neurodegenerative diseases.
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Affiliation(s)
- Wei Zhou
- School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, 100 Waihuanxi Road, Guangzhou, 510006, PR China
| | - Mengmeng Hu
- School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, 100 Waihuanxi Road, Guangzhou, 510006, PR China
| | - Jingrong Hu
- School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, 100 Waihuanxi Road, Guangzhou, 510006, PR China
| | - Zhiyun Du
- School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, 100 Waihuanxi Road, Guangzhou, 510006, PR China
| | - Qing Su
- School of Computers, Guangdong University of Technology, 100 Waihuanxi Road, Guangzhou, 510006, PR China.
| | - Zhangmin Xiang
- Guangdong Provincial Key Laboratory of Emergency Test for Dangerous Chemicals, Guangdong Institute of Analysis, Guangzhou, 510070, PR China.
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Qi MM, He PZ, Zhang L, Dong WG. STAT3-mediated activation of mitochondrial pathway contributes to antitumor effect of dihydrotanshinone I in esophageal squamous cell carcinoma cells. World J Gastrointest Oncol 2021; 13:893-914. [PMID: 34457194 PMCID: PMC8371523 DOI: 10.4251/wjgo.v13.i8.893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/17/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with a poor prognosis, and its treatment remains a great challenge. Dihydrotanshinone I (DHTS) has been reported to exert antitumor effect in many cancers. However, the role of DHTS in ESCC remains unclear.
AIM To investigate the antitumor effect of DHTS in ESCC and the underlying mechanisms.
METHODS CCK-8 assay and cell cycle analysis were used to detect proliferation and cell cycle in ESCC cells. Annexin V-PE/7-AAD double staining assay and Hoechst 33258 staining were used to detect apoptosis in ESCC cells. Western blot was used to detect the expression of proteins associated with the mitochondrial pathway. Immunofluorescence was used to detect the expression of phosphorylated STAT3 (pSTAT3) in DHTS-treated ESCC cells. ESCC cells with STAT3 knockdown and overexpression were constructed to verify the role of STAT3 in DHTS induced apoptosis. A xenograft tumor model in nude mice was used to evaluate the antitumor effect of DHTS in vivo.
RESULTS After treatment with DHTS, the proliferation of ESCC cells was inhibited in a dose- and time-dependent manner. Moreover, DHTS induced cell cycle arrest in the G0/1 phase. Annexin V-PE/7-AAD double staining assay and Hoechst 33258 staining revealed that DHTS induced obvious apoptosis in KYSE30 and Eca109 cells. At the molecular level, DHTS treatment reduced the expression of pSTAT3 and anti-apoptotic proteins, while increasing the expression of pro-apoptotic proteins in ESCC cells. STAT3 knockdown in ESCC cells markedly promoted the activation of the mitochondrial pathway while STAT3 overexpression blocked the activation of the mitochondrial pathway. Additionally, DHTS inhibited tumor cell proliferation and induced apoptosis in a xenograft tumor mouse model.
CONCLUSION DHTS exerts antitumor effect in ESCC via STAT3-mediated activation of the mitochondrial pathway. DHTS may be a novel therapeutic agent for ESCC.
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Affiliation(s)
- Ming-Ming Qi
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
- Central Laboratory of Renmin Hospital, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Peng-Zhan He
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
- Central Laboratory of Renmin Hospital, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Lan Zhang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
- Central Laboratory of Renmin Hospital, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Wei-Guo Dong
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
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34
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Guan L, Peng D, Zhang L, Jia J, Jiang H. Design, synthesis, and cholinesterase inhibition assay of liquiritigenin derivatives as anti-Alzheimer's activity. Bioorg Med Chem Lett 2021; 52:128306. [PMID: 34371131 DOI: 10.1016/j.bmcl.2021.128306] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 07/28/2021] [Accepted: 07/31/2021] [Indexed: 12/30/2022]
Abstract
The marine environment is a rich resource for discovering functional materials, and seaweed is recognized for its potential use in biology and medicine. Liquiritigenin has been isolated and identified from Sargassum pallidum. To find new anti-Alzheimer's activity, we designed and synthesized thirty-two 7-prenyloxy-2,3-dihydroflavanone derivatives (3a-3p) and 5-hydroxy-7-prenyloxy-2,3-dihydro- flavanone derivatives (4a-4p) as cholinesterases inhibitors based on liquiritigenin as the lead compound. Inhibition screening against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) indicated that all synthesized compounds possessed potent AChE inhibitory activity and moderated to weak BuChE inhibitory activity in vitro. Kinetic studies demonstrated that compound 4o inhibited AChE via a dual binding site ability. In addition, all compounds displayed the radical scavenging effects. Finally, the molecular docking simulation of 4o in AChE active site displayed good agreement with the obtained the pharmacological results.
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Affiliation(s)
- Liping Guan
- Food and Pharmacy College, Zhejiang Ocean University, Zhejiang, Zhoushan 316022, PR China
| | - Dingxin Peng
- Food and Pharmacy College, Zhejiang Ocean University, Zhejiang, Zhoushan 316022, PR China
| | - Li Zhang
- Food and Pharmacy College, Zhejiang Ocean University, Zhejiang, Zhoushan 316022, PR China
| | - Jinjing Jia
- Department of Physiology and Pathophysiology, Jiaxing University Medical College, Jiaxing 314001, China
| | - Haiying Jiang
- Department of Physiology and Pathophysiology, Jiaxing University Medical College, Jiaxing 314001, China.
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35
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Zhang B, Zhao J, Wang Z, Guo P, Liu A, Du G. Identification of Multi-Target Anti-AD Chemical Constituents From Traditional Chinese Medicine Formulae by Integrating Virtual Screening and In Vitro Validation. Front Pharmacol 2021; 12:709607. [PMID: 34335272 PMCID: PMC8322649 DOI: 10.3389/fphar.2021.709607] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 06/29/2021] [Indexed: 12/18/2022] Open
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens the health of the elderly. At present, no drugs have been proven to cure or delay the progression of the disease. Due to the multifactorial aetiology of this disease, the multi-target-directed ligand (MTDL) approach provides an innovative and promising idea in search for new drugs against AD. In order to find potential multi-target anti-AD drugs from traditional Chinese medicine (TCM) formulae, a compound database derived from anti-AD Chinese herbal formulae was constructed and predicted by the anti-AD multi-target drug prediction platform established in our laboratory. By analyzing the results of virtual screening, 226 chemical constituents with 3 or more potential AD-related targets were collected, from which 16 compounds that were predicted to combat AD through various mechanisms were chosen for biological validation. Several cell models were established to validate the anti-AD effects of these compounds, including KCl, Aβ, okadaic acid (OA), SNP and H2O2 induced SH-SY5Y cell model and LPS induced BV2 microglia model. The experimental results showed that 12 compounds including Nonivamide, Bavachromene and 3,4-Dimethoxycinnamic acid could protect model cells from AD-related damages and showed potential anti-AD activity. Furthermore, the potential targets of Nonivamide were investigated by molecular docking study and analysis with CDOCKER revealed the possible binding mode of Nonivamide with its predicted targets. In summary, 12 potential multi-target anti-AD compounds have been found from anti-AD TCM formulae by comprehensive application of computational prediction, molecular docking method and biological validation, which laid a theoretical and experimental foundation for in-depth study, also providing important information and new research ideas for the discovery of anti-AD compounds from traditional Chinese medicine.
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Affiliation(s)
- Baoyue Zhang
- Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Zhao
- Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhe Wang
- Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Pengfei Guo
- Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ailin Liu
- Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Guanhua Du
- Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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36
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Wang GK, Yang JS, Huang YF, Liu JS, Tsai CW, Bau DAT, Chang WS. Culture Separation, Identification and Unique Anti-pathogenic Fungi Capacity of Endophytic Fungi from Gucheng Salvia Miltiorrhiza. In Vivo 2021; 35:325-332. [PMID: 33402481 DOI: 10.21873/invivo.12263] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 10/21/2020] [Accepted: 10/27/2020] [Indexed: 11/10/2022]
Abstract
BACKGROUND Salvia miltiorrhiza is a medical herb for human disorders including cardiovascular diseases and cancer. However, the interactions between Salvia miltiorrhiza and its endophytes are largely unknown. The current study aimed at identifying its endophytic fungi and examining their inhibitory effects on anti-pathogenic fungus. MATERIALS AND METHODS Distinct species of endophytic fungi were isolated from the roots of Salvia miltiorrhiza, cultured, sequenced, aiming to predict their taxonomical structures. Meanwhile, extracts from each endophytic fungus fermentations were isolated, compared and evaluated on the inhibitory efficacies on five pathological fungi, Cercospora nicotianae, Phoma arachnidicola, Staphylococcus, Phytophthora eggplant, and Rhizoctonia cerealis. RESULTS A total of 34 strains of endophytic fungi were obtained from Salvia miltiorrhiza. Among them, SX19 and C. Gloeosporioids exhibited the most effective inhibitions on five pathogenic fungi. CONCLUSION The anti-fungal activities of the endophytic fungus from Salvia miltiorrhiza were confirmed for the first time, and this may benefit crop quality and production in the future.
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Affiliation(s)
- Guo-Kai Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, P.R. China.,Anhui Province Key Laboratory of Research and Development of Chinese Medicine, Hefei, P.R. China
| | - Jai-Sing Yang
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C
| | - Yu-Fei Huang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, P.R. China
| | - Jin-Song Liu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, P.R. China.,Anhui Province Key Laboratory of Research and Development of Chinese Medicine, Hefei, P.R. China
| | - Chia-Wen Tsai
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C
| | - DA-Tian Bau
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.; .,Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, R.O.C
| | - Wen-Shin Chang
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.;
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37
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Chen X, Drew J, Berney W, Lei W. Neuroprotective Natural Products for Alzheimer's Disease. Cells 2021; 10:1309. [PMID: 34070275 PMCID: PMC8225186 DOI: 10.3390/cells10061309] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/17/2021] [Accepted: 05/22/2021] [Indexed: 12/22/2022] Open
Abstract
Alzheimer's disease (AD) is the number one neurovegetative disease, but its treatment options are relatively few and ineffective. In efforts to discover new strategies for AD therapy, natural products have aroused interest in the research community and in the pharmaceutical industry for their neuroprotective activity, targeting different pathological mechanisms associated with AD. A wide variety of natural products from different origins have been evaluated preclinically and clinically for their neuroprotective mechanisms in preventing and attenuating the multifactorial pathologies of AD. This review mainly focuses on the possible neuroprotective mechanisms from natural products that may be beneficial in AD treatment and the natural product mixtures or extracts from different sources that have demonstrated neuroprotective activity in preclinical and/or clinical studies. It is believed that natural product mixtures or extracts containing multiple bioactive compounds that can work additively or synergistically to exhibit multiple neuroprotective mechanisms might be an effective approach in AD drug discovery.
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Affiliation(s)
- Xin Chen
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, USA
| | - Joshua Drew
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, USA
| | - Wren Berney
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, USA
| | - Wei Lei
- Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, Presbyterian College, Clinton, SC 29325, USA
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38
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Dhage PA, Sharbidre AA, Dakua SP, Balakrishnan S. Leveraging hallmark Alzheimer's molecular targets using phytoconstituents: Current perspective and emerging trends. Biomed Pharmacother 2021; 139:111634. [PMID: 33965726 DOI: 10.1016/j.biopha.2021.111634] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Revised: 04/19/2021] [Accepted: 04/19/2021] [Indexed: 01/04/2023] Open
Abstract
Alzheimer's disease (AD), a type of dementia, severely distresses different brain regions. Characterized by various neuropathologies, it interferes with cognitive functions and neuropsychiatrical controls. This progressive deterioration has negative impacts not only on an individual's daily activity but also on social and occupational life. The pharmacological approach has always remained in the limelight for the treatment of AD. However, this approach is condemned with several side effects. Henceforth, a change in treatment approach has become crucial. Plant-based natural products are garnering special attention due to lesser side effects associated with their use. The current review emphasizes the anti-AD properties of phytoconstituents, throws light on those under clinical trials, and compiles information on their specific mode of actions against AD-related different neuropathologies. The phytoconstituents alone or in combinations will surely help discover new potent drugs for the effective treatment of AD with lesser side effects than the currently available pharmacological treatment.
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Affiliation(s)
- Prajakta A Dhage
- Department of Zoology, K.R.T. Arts, B.H. Commerce and A.M. Science College (KTHM College), Nashik 422002, MS, India
| | - Archana A Sharbidre
- Department of Zoology, Savitribai Phule Pune University, Pune 411007, MS, India.
| | - Sarada P Dakua
- Department of Surgery, Hamad Medical Corporation (HMC), 3050 Doha, Qatar
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Chen YW, Huang YP, Wu PC, Chiang WY, Wang PH, Chen BY. The Functional Vision Protection Effect of Danshensu via Dopamine D1 Receptors: In Vivo Study. Nutrients 2021; 13:nu13030978. [PMID: 33803057 PMCID: PMC8002943 DOI: 10.3390/nu13030978] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/09/2021] [Accepted: 03/15/2021] [Indexed: 12/22/2022] Open
Abstract
Danshensu, a traditional herb-based active component (Salvia miltiorrhiza Bunge), has garnered attention, due to its safety, nutritional value, and antioxidant effects, along with cardiovascular-protective and neuroprotective abilities; however, its effect on the retinal tissues and functional vision has not been fully studied. The objective of this study was to analyze the protective effect of danshensu on retinal tissues and functional vision in vivo in a mouse model of light-induced retinal degeneration. High energy light-evoked visual damage was confirmed by the loss in structural tissue integrity in the retina accompanied by a decline in visual acuity and visual contrast sensitivity function (VCSF), whereas the retina tissue exhibited severe Müller cell gliosis. Although danshensu treatment did not particularly reduce light-evoked damage to the photoreceptors, it significantly prevented Müller cell gliosis. Danshensu exerted protective effects against light-evoked deterioration on low spatial frequency-based VCSF as determined by the behavioral optomotor reflex method. Additionally, the protective effect of danshensu on VCSF can be reversed and blocked by the injection of a dopamine D1 receptor antagonist (SCH 23390). This study demonstrated that the major functional vision promotional effect of danshensu in vivo was through the dopamine D1 receptors enhancement pathway, rather than the structural protection of the retinas.
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Affiliation(s)
- Yun-Wen Chen
- Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 88301, Taiwan; (Y.-W.C.); (P.-C.W.); (W.-Y.C.)
| | - Yun-Ping Huang
- Department of Optometry, Chung Shan Medical University, Taichung 40201, Taiwan; (Y.-P.H.); (P.-H.W.)
| | - Pei-Chang Wu
- Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 88301, Taiwan; (Y.-W.C.); (P.-C.W.); (W.-Y.C.)
| | - Wei-Yu Chiang
- Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 88301, Taiwan; (Y.-W.C.); (P.-C.W.); (W.-Y.C.)
| | - Ping-Hsun Wang
- Department of Optometry, Chung Shan Medical University, Taichung 40201, Taiwan; (Y.-P.H.); (P.-H.W.)
| | - Bo-Yie Chen
- Department of Optometry, Chung Shan Medical University, Taichung 40201, Taiwan; (Y.-P.H.); (P.-H.W.)
- Department of Ophthalmology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- Correspondence: ; Tel.: +886-4-2473-0022 (ext. 12319)
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40
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Yuen CW, Murugaiyah V, Najimudin N, Azzam G. Danshen (Salvia miltiorrhiza) water extract shows potential neuroprotective effects in Caenorhabditis elegans. JOURNAL OF ETHNOPHARMACOLOGY 2021; 266:113418. [PMID: 32991971 DOI: 10.1016/j.jep.2020.113418] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 09/21/2020] [Accepted: 09/23/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Danshen, is a traditional Chinese medicine obtained from the dried root and rhizome of Salvia miltiorrhiza Bunge. It is known to be used for neurological disorder including for Alzheimer's disease (AD). This study uncovers the effect of Danshen water extract on the Alzheimer's disease model of C.elegans. MATERIAL AND METHODS The composition of Danshen water extract was determined using (High Performance Liquid Chromatography (HPLC). Then Thioflavin T assay was used to determined if Danshen water extract could prevent the aggregation of amyloid-β peptide (Aβ). Alzheimer's disease C.elegans model was used to determine the effect of Danshen water extract. Finally, the reactive oxygen species (ROS) was determined using the 2,7-dichlorofuorescein diacetate method. RESULTS In this study, we found that standardized Danshen water extract that contains danshensu (1.26%), salvianolic acid A (0.35%) and salvianolic acid B (2.21%) are able to bind directly to Aβ and prevents it from aggregating. The IC50 for the inhibition of Aβ aggregation by Danshen water extract was 0.5 mg/ml. In the AD model of C.elegans, Danshen water extract managed to alleviates the paralysis phenotype. Furthermore, the administration of Danshen water extract displayed antioxidant properties toward the Aβ-induced oxidative stress. CONCLUSIONS AD is a widespread neurodegenerative disease attributed to the accumulation of extracellular plaques comprising Aβ. Danshen water extract could significantly reduce the progress of paralysis in the AD model of C. elegans, showing promising results with its antioxidant properties. It can be concluded that Danshen water extract could potentially serve as a therapeutic for AD.
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Affiliation(s)
- Chee Wah Yuen
- School of Biological Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia
| | - Vikneswaran Murugaiyah
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia
| | - Nazalan Najimudin
- School of Biological Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia; USM-RIKEN International Centre for Ageing Science (URICAS), Universiti Sains Malaysia, 11800, Penang, Malaysia.
| | - Ghows Azzam
- School of Biological Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia; USM-RIKEN International Centre for Ageing Science (URICAS), Universiti Sains Malaysia, 11800, Penang, Malaysia.
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In vitro biological activity of Salvia fruticosa Mill. infusion against amyloid β-peptide-induced toxicity and inhibition of GSK-3 β, CK-1 δ, and BACE-1 enzymes relevant to Alzheimer's disease. Saudi Pharm J 2021; 29:236-243. [PMID: 33981172 PMCID: PMC8084717 DOI: 10.1016/j.jsps.2021.01.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 01/20/2021] [Indexed: 12/17/2022] Open
Abstract
Salvia species have been traditionally used to improve cognition and have been proved to be a potential natural treatment for Alzheimer’s disease. Salvia fruticosa Mill. (Turkish sage or Greek sage) demonstrated to have anticholinergic effects in vitro. The aim of this study was to understand the mechanism underlying the neuroprotective effects of S. fruticosa infusion and its representative compound rosmarinic acid, which was detected by LC-DAD-ESI-MS/MS. The protective effects of the S. fruticosa infusion (SFINF) and its major substance rosmarinic acid (RA) on amyloid beta 1–42 -induced cytotoxicity on SH-SY5Y cells together with p-GSK-3β activation were investigated. Their in vitro inhibitory effects against glycogen synthase kinase 3β, β-secretase, and casein kinase 1δ enzymes were also evaluated. The results showed that treatment with the all tested concentrations, SFINF significantly decreased Aβ 1–42-induced cytotoxicity and exhibited promising in vitro glycogen synthase kinase 3β inhibitory activity below 10 µg/mL (IC50 6.52 ± 1.14 µg/mL), in addition to β-secretase inhibition (IC50 86 ± 2.9 µg/mL) and casein kinase 1δ inhibition (IC50 121.57 ± 4.00). The SFINF (100 µg/mL and 250 µg/mL) also activated the expression of p-GSK-3β in amyloid beta 1–42 treated SH-SY5Y cells. The outcomes of this study demonstrated that the S. fruticosa infusion possessed activity to prevent amyloid beta 1–42 -induced neurotoxicity and provided proof that its mechanism may involve regulation of p-GSK-3β protein.
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Soheili M, Karimian M, Hamidi G, Salami M. Alzheimer's disease treatment: The share of herbal medicines. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2021; 24:123-135. [PMID: 33953850 PMCID: PMC8061323 DOI: 10.22038/ijbms.2020.50536.11512] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Accepted: 11/07/2020] [Indexed: 11/25/2022]
Abstract
One of the most frequent forms of dementia in neurological disorders is Alzheimer's disease (AD). It is a chronic neurodegenerative disease characterized by impaired learning and memory. Pathological symptoms as extracellular amyloid-beta (Aβ) plaques and intracellular accumulation of neurofibrillary tangles occur in AD. Due to the aging of the population and increased prevalence of AD, discovery of new therapeutic agents with the highest effectiveness and fewer side effect seems to be necessary. Numerous synthetic medicines such as tacrine, donepezil, galantamine, rivastigmine, memantine, glutathione, ascorbic acid, ubiquinone, ibuprofen, and ladostigil are routinely used for reduction of the symptoms and prevention of disease progression. Nowadays, herbal medicines have attracted popular attention for numerous beneficial effects with little side effects. Lavandula angustifolia, Ginkgo biloba, Melissa officinalis, Crocus sativus, Ginseng, Salvia miltiorrhiza, and Magnolia officinalis have been widely used for relief of symptoms of some neurological disorders. This paper reviews the therapeutic effects of phytomedicines with prominent effects against various factors implicated in the emergence and progression of AD.
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Affiliation(s)
- Masoud Soheili
- Physiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Karimian
- Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran
| | - Gholamali Hamidi
- Physiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Mahmoud Salami
- Physiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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Tung MC, Tsai KC, Fung KM, Don MJ, Tseng TS. Characterizing the structure-activity relationships of natural products, tanshinones, reveals their mode of action in inhibiting spleen tyrosine kinase. RSC Adv 2021; 11:2453-2461. [PMID: 35424194 PMCID: PMC8693659 DOI: 10.1039/d0ra08769f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 01/05/2021] [Indexed: 11/21/2022] Open
Abstract
The cytosolic non-receptor protein kinase, spleen tyrosine kinase (SYK), is an attractive drug target in autoimmune, inflammatory disorder, and cancers indications. Here, we employed pharmacophore-based drug screening combined with biochemical assay and molecular dynamics (MD) simulations to identify and characterize inhibitors targeting SYK. The built pharmacophore model, phar-TanI, successfully identified tanshinone (TanI (IC50 = 1.72 μM)) and its analogs (TanIIA (IC50 = 3.2 μM), ST32da (IC50 = 46 μM), and ST32db (IC50 = 51 μM)) which apparently attenuated the activities of SYK in vitro. Additionally, the MD simulations followed by Ligplot analyses revealed that TanI and TanIIA interfered SYK activity through binding deeply into the active site. Besides, TanI and TanIIA mainly interact with residues L377, A400, V433, M448, M450, A451, E452, L453, G454, P455, and L501, which are functional hotspots for structure-based inhibitor optimization against SYK. The structure-activity relationships (SAR) study of the identified SYK inhibitors demonstrated that the pharmacophore model, phar-TanI is reliable and precise in screening inhibitors against SYK. This study disclosed the structure-function relationships of tanshinones from Traditional Chinese Medicine (Danshen), revealing their binding site and mode of action in inhibiting SYK and provides applicability in developing new therapeutic agents.
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Affiliation(s)
- Min-Che Tung
- Department of Stomatology, Tung's MetroHarbor Hospital Taichung Taiwan
| | - Keng-Chang Tsai
- National Research Institute of Chinese Medicine, Ministry of Health and Welfare Taipei Taiwan
- PhD Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University Taipei Taiwan
| | - Kit-Man Fung
- Institute of Biological Chemistry, Academia Sinica Taipei 115 Taiwan
| | - Ming-Jaw Don
- National Research Institute of Chinese Medicine, Ministry of Health and Welfare Taipei Taiwan
| | - Tien-Sheng Tseng
- Institute of Molecular Biology, National Chung Hsing University Taichung Taiwan
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Ansari MA, Khan FB, Safdari HA, Almatroudi A, Alzohairy MA, Safdari M, Amirizadeh M, Rehman S, Equbal MJ, Hoque M. Prospective therapeutic potential of Tanshinone IIA: An updated overview. Pharmacol Res 2020; 164:105364. [PMID: 33285229 DOI: 10.1016/j.phrs.2020.105364] [Citation(s) in RCA: 95] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/29/2020] [Accepted: 11/29/2020] [Indexed: 01/03/2023]
Abstract
In the past decades, the branch of complementary and alternative medicine based therapeutics has gained considerable attention worldwide. Pharmacological efficacy of various traditional medicinal plants, their products and/or product derivatives have been explored on an increasing scale. Tanshinone IIA (Tan IIA) is a pharmacologically active lipophilic component of Salvia miltiorrhiza extract. Tan IIA shares a history of high repute in Traditional Chinese Medicine. Reckoning with these, the present review collates the pharmacological properties of Tan IIA with a special emphasis on its therapeutic potential against diverse diseases including cardiovascular diseases, cerebrovascular diseases, cancer, diabetes, obesity and neurogenerative diseases. Further, possible applications of various therapeutic preparations of Tan IIA were discussed with special emphasis on nano-based drug delivery formulations. Considering the tremendous advancement in the field of nanomedicine and the therapeutic potential of Tan IIA, the convergence of these two aspects can be foreseen with great promise in clinical application.
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Affiliation(s)
- Mohammad Azam Ansari
- Department of Epidemic Disease Research, Institutes for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1881, Dammam 31441, Saudi Arabia
| | - Farheen Badrealam Khan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 404, Taiwan
| | - Haaris Ahsan Safdari
- New Technology Center, University of Warsaw, Stefana Banacha 2c, 02-097 Warszawa, Poland
| | - Ahmad Almatroudi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Qassim 51431, Saudi Arabia
| | - Mohammad A Alzohairy
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Qassim 51431, Saudi Arabia
| | - Mohammadreza Safdari
- Imam Ali Hospital, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Mehran Amirizadeh
- Department of Pharmacotherapy, Faculty of Pharmacy, University of Medical Sciences, Khorramabad, Lorestan, Iran
| | - Suriya Rehman
- Department of Epidemic Disease Research, Institutes for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1881, Dammam 31441, Saudi Arabia
| | - Mohammad Javed Equbal
- Biomedical Institute for Regenerative Research, Texas A&M University Commerce, Commerce, TX 75429, United States.
| | - Mehboob Hoque
- Department of Biological Sciences, Aliah University, Kolkata 700 160, India.
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UPLC/MS-based untargeted metabolomics reveals the changes of metabolites profile of Salvia miltiorrhiza bunge during Sweating processing. Sci Rep 2020; 10:19524. [PMID: 33177654 PMCID: PMC7658355 DOI: 10.1038/s41598-020-76650-w] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 10/29/2020] [Indexed: 02/07/2023] Open
Abstract
Salvia miltiorrhiza has numerous compounds with extensive clinical application. "Sweating", a processing method of Traditional Chinese Medicine (TCM), results in great changes in pharmacology and pharmacodynamics. Previously, chromatogram of 10 characteristic metabolites in S. miltiorrhiza showed a significant difference after "Sweating". Due to the complexity of TCM, changes in metabolites should be investigated metabolome-wide after "Sweating". An untargeted UPLC/MS-based metabolomics was performed to discover metabolites profile variation of S. miltiorrhiza after "Sweating". Multivariate analysis was conducted to screen differential metabolites. Analysis indicated distinct differences between sweated and non-sweated samples. 10,108 substance peaks had been detected altogether, and 4759 metabolites had been identified from negative and positive ion model. 287 differential metabolites were screened including 112 up-regulated and 175 down-regulated and they belong to lipids and lipid-like molecules, and phenylpropanoid and polyketides. KEGG analysis showed the pathway of linoleic acid metabolism, and glyoxylate and dicarboxylate metabolism were mainly enriched. 31 and 49 identified metabolites were exclusively detected in SSM and NSSM, respectively, which mainly belong to carboxylic acids and derivatives, polyketides and fatty acyls. By mapping tanshinones and salvianolic acids to 4759 identified metabolites library, 23 characteristic metabolites had been identified, among which 11 metabolites changed most. We conclude that "Sweating'' has significant effect on metabolites content and composition of S. miltiorrhiza.
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Overview of Salvia miltiorrhiza as a Potential Therapeutic Agent for Various Diseases: An Update on Efficacy and Mechanisms of Action. Antioxidants (Basel) 2020; 9:antiox9090857. [PMID: 32933217 PMCID: PMC7555792 DOI: 10.3390/antiox9090857] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 09/08/2020] [Accepted: 09/11/2020] [Indexed: 02/06/2023] Open
Abstract
Salvia miltiorrhiza Bunge (S. miltiorrhiza) is a medicinal herb that has been used for the treatment for various diseases such as cardiovascular and cerebrovascular diseases in East Asia including Korea. Considering its extensive usage as a therapeutic agent for multiple diseases, there is a need to review previous research regarding its therapeutic benefits and their mechanisms. Therefore, we searched PubMed and PubMed Central for articles reporting its therapeutic effects on certain disease groups including cancers, cardiovascular, liver, and nervous system diseases. This review provides an overview of therapeutic benefits and targets of S. miltiorrhiza, including inflammation, fibrosis, oxidative stress, and apoptosis. The findings on multi-functional properties of S. miltiorrhiza discussed in this article support the efficacy of S. miltiorrhiza extract on various diseases, but also call for further research on the multiple mechanisms that mediate its therapeutic effects.
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The oxygenated products of cryptotanshinone by biotransformation with Cunninghamella elegans exerting anti-neuroinflammatory effects by inhibiting TLR 4-mediated MAPK signaling pathway. Bioorg Chem 2020; 104:104246. [PMID: 32911197 DOI: 10.1016/j.bioorg.2020.104246] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 08/03/2020] [Accepted: 08/28/2020] [Indexed: 12/11/2022]
Abstract
Cryptotanshinone (1), a major bioactive constituent in the traditional Chinese medicinal herb Dan-Shen Salvia miltiorrhiza Bunge, has been reported to possess remarkable pharmacological activities. To improve its bioactivities and physicochemical properties, in the present study, cryptotanshinone (1) was biotransformed with the fungus Cunninghamella elegans AS3.2028. Three oxygenated products (2-4) at C-3 of cryptotanshinone (1) were obtained, among them 2 was a new compound. Their structures were elucidated by comprehensive spectroscopic analysis including HRESIMS, NMR and ECD data. All of the biotransformation products (2-4) were found to inhibit significantly lipopolysaccharide-induced nitric oxide production in BV2 microglia cells with the IC50 values of 0.16-1.16 μM, approximately 2-20 folds stronger than the substrate (1). These biotransformation products also displayed remarkably improved inhibitory effects on the production of inflammatory cytokines (IL-1β, IL-6, TNF-α, COX-2 and iNOS) in BV-2 cells via targeting TLR4 compared to substrate (1). The underlying mechanism of 2 was elucidated by comparative transcriptome analysis, which suggested that it reduced neuroinflammatory mainly through mitogen-activated protein kinase (MAPK) signaling pathway. Western blotting results revealed that 2 downregulated LPS-induced phosphorylation of JNK, ERK, and p38 in MAPK signaling pathway. These findings provide a basal material for the discovery of candidates in treating Alzheimer's disease.
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Qiu JM, Qin CF, Wu SG, Ji TY, Tang GT, Lei XY, Cao X, Xie ZZ. A novel salvianolic acid A analog with resveratrol structure and its antioxidant activities in vitro and in vivo. Drug Dev Res 2020; 82:108-114. [PMID: 32780460 DOI: 10.1002/ddr.21734] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 07/16/2020] [Accepted: 07/22/2020] [Indexed: 12/13/2022]
Abstract
E-DRS is a novel salvianolic acid A (SAA) analog, which was synthesized from resveratrol (RES) and methyldopate. Its structure is similar to that of SAA, but the 3',4'-dihydroxy-trans-stilbene group and the ester structure in SAA were replaced by the RES structure and an amine group, respectively. E-DRS scavenged free oxygen radicals effectively, including superoxide anion (ascorbic acid > E-DRS > SAA ≥ rutin > RES) and DPPH radical (rutin > E-DRS ≥ ascorbic acid > SAA > RES), and exhibited powerful total antioxidant capacity (ascorbic acid > E-DRS > SAA ≥ rutin > RES) in vitro. Furthermore, oral administration of E-DRS dose-dependently and significantly decreased CCl4 -induced oxidative stress in mice as indicated by the decreased content of hepatic malondialdehyde (MDA). In addition, oral administration of E-DRS also increased the content of nonenzymatic antioxidant glutathione (GSH) and the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) in the liver of mice. All these results demonstrated that E-DRS had good antioxidant activities both in vitro and in vivo, and could be a potential antioxidant agent after further optimization and evaluation.
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Affiliation(s)
- Jin-Mei Qiu
- Hunan Provincial Key Laboratory of Tumour Microenvironment Responsive Drug Research, University of South China, Hengyang, China
| | - Chang-Feng Qin
- Hunan Provincial Key Laboratory of Tumour Microenvironment Responsive Drug Research, University of South China, Hengyang, China
| | - Shen-Gen Wu
- Hunan Provincial Key Laboratory of Tumour Microenvironment Responsive Drug Research, University of South China, Hengyang, China
| | - Tong-Ying Ji
- Hunan Provincial Key Laboratory of Tumour Microenvironment Responsive Drug Research, University of South China, Hengyang, China
| | - Guo-Tao Tang
- Hunan Provincial Key Laboratory of Tumour Microenvironment Responsive Drug Research, University of South China, Hengyang, China
| | - Xiao-Yong Lei
- Hunan Provincial Key Laboratory of Tumour Microenvironment Responsive Drug Research, University of South China, Hengyang, China
| | - Xuan Cao
- Hunan Provincial Key Laboratory of Tumour Microenvironment Responsive Drug Research, University of South China, Hengyang, China
| | - Zhi-Zhong Xie
- Hunan Provincial Key Laboratory of Tumour Microenvironment Responsive Drug Research, University of South China, Hengyang, China.,Hunan Provincial Cooperative Innovation Centre for Molecular Target New Drug Study, University of South China, Hengyang, China
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Protective Effects of Active Compounds from Salviae miltiorrhizae Radix against Glutamate-Induced HT-22 Hippocampal Neuronal Cell Death. Processes (Basel) 2020. [DOI: 10.3390/pr8080914] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Oxidative stress is considered one of the factors that cause dysfunction and damage of neurons, causing diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), and Parkinson’s disease (PD).Recently, natural antioxidant sources have emerged as one of the main research areas for the discovery of potential neuroprotectants that can be used to treat neurological diseases. In this research, we assessed the neuroprotective effect of a 70% ethanol Salvia miltiorrhiza Radix (SMR) extract and five of its constituent compounds (tanshinone IIA, caffeic acid, salvianolic acid B, rosmarinic acid, and salvianic acid A) in HT-22 hippocampal cells. The experimental data showed that most samples were effective in attenuating the cytotoxicity caused by glutamate in HT-22 cells, except for rosmarinic acid and salvianolic acid B. Of the compounds tested, tanshinone IIA (TS-IIA) exerted the strongest effect in protecting HT-22 cells against glutamate neurotoxin. Treatment with 400 nM TS-IIA restored HT-22 cell viability almost completely. TS-IIA prevented glutamate-induced oxytosis by abating the accumulation of calcium influx, reactive oxygen species, and phosphorylation of mitogen-activated protein kinases. Moreover, TS-IIA inhibited glutamate-induced cytotoxicity by reducing the activation and phosphorylation of p53, as well as by stimulating Akt expression. This research suggested that TS-IIA is a potential neuroprotective component of SMR, with the ability to protect against neuronal cell death induced by excessive amounts of glutamate.
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Jiang T, Zhang M, Wen C, Xie X, Tian W, Wen S, Lu R, Liu L. Integrated metabolomic and transcriptomic analysis of the anthocyanin regulatory networks in Salvia miltiorrhiza Bge. flowers. BMC PLANT BIOLOGY 2020; 20:349. [PMID: 32703155 PMCID: PMC7379815 DOI: 10.1186/s12870-020-02553-7] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 07/15/2020] [Indexed: 05/05/2023]
Abstract
BACKGROUND The objectives of this study were to reveal the anthocyanin biosynthesis metabolic pathway in white and purple flowers of Salvia miltiorrhiza using metabolomics and transcriptomics, to identify different anthocyanin metabolites, and to analyze the differentially expressed genes involved in anthocyanin biosynthesis. RESULTS We analyzed the metabolomics and transcriptomics data of S. miltiorrhiza flowers. A total of 1994 differentially expressed genes and 84 flavonoid metabolites were identified between the white and purple flowers of S. miltiorrhiza. Integrated analysis of transcriptomics and metabolomics showed that cyanidin 3,5-O-diglucoside, malvidin 3,5-diglucoside, and cyanidin 3-O-galactoside were mainly responsible for the purple flower color of S. miltiorrhiza. A total of 100 unigenes encoding 10 enzymes were identified as candidate genes involved in anthocyanin biosynthesis in S. miltiorrhiza flowers. Low expression of the ANS gene decreased the anthocyanin content but enhanced the accumulation of flavonoids in S. miltiorrhiza flowers. CONCLUSIONS Our results provide valuable information on the anthocyanin metabolites and the candidate genes involved in the anthocyanin biosynthesis pathways in S. miltiorrhiza.
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Affiliation(s)
- Tao Jiang
- Institute of Cash Crops, Hebei Academy of Agricultural and Forestry Sciences, Shijiazhuang, 050051, Hebei, China
| | - Meidi Zhang
- Institute of Chinese Herbal Medicines, Hubei Academy of Agricultural Sciences, Enshi, 445000, Hubei, China
| | - Chunxiu Wen
- Institute of Cash Crops, Hebei Academy of Agricultural and Forestry Sciences, Shijiazhuang, 050051, Hebei, China
| | - Xiaoliang Xie
- Institute of Cash Crops, Hebei Academy of Agricultural and Forestry Sciences, Shijiazhuang, 050051, Hebei, China
| | - Wei Tian
- Institute of Cash Crops, Hebei Academy of Agricultural and Forestry Sciences, Shijiazhuang, 050051, Hebei, China
| | - Saiqun Wen
- Institute of Cash Crops, Hebei Academy of Agricultural and Forestry Sciences, Shijiazhuang, 050051, Hebei, China
| | - Ruike Lu
- Institute of Cash Crops, Hebei Academy of Agricultural and Forestry Sciences, Shijiazhuang, 050051, Hebei, China
| | - Lingdi Liu
- Institute of Cash Crops, Hebei Academy of Agricultural and Forestry Sciences, Shijiazhuang, 050051, Hebei, China.
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