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Qin L, Fan B, Zhou Y, Zheng J, Diao R, Wang F, Liu J. Targeted gut microbiome therapy: Applications and prospects of probiotics, fecal microbiota transplantation and natural products in the management of type 2 diabetes. Pharmacol Res 2025; 213:107625. [PMID: 39875017 DOI: 10.1016/j.phrs.2025.107625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/21/2024] [Accepted: 01/21/2025] [Indexed: 01/30/2025]
Abstract
Type 2 diabetes mellitus (T2DM) is considered as one of the most pressing public health challenges worldwide. Studies have shown significant differences in the gut microbiota between healthy individuals and T2DM patients, suggesting that gut microorganisms may play a key role in the onset and progression of T2DM. This review systematically summarizes the relationship between gut microbiota and T2DM, and explores the mechanisms through which gut microorganisms may alleviate T2DM. Additionally, it evaluates the potential of probiotics, fecal microbiota transplantation (FMT)/virome transplantation (FVT), and natural products in modulating gut microbiota to treat T2DM. Although existing studies have suggested that these interventions may delay or even halt the progression of T2DM, most research remained limited to animal models and observational clinical studies, with a lack of high-quality clinical data. This has led to an imbalance between theoretical research and clinical application. Although some studies have explored the regulatory role of the gut virome on the gut microbiota, research in this area remains in its early stages. Based on these current studies, future research should be focused on large-scale, long-term clinical studies and further investigation on the potential role of the gut virome in T2DM. In conclusion, this review aims to summarize the current evidence and explore the applications of gut microbiota in T2DM treatment, as well as providing recommendations for further investigation in this field.
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Affiliation(s)
- Luqi Qin
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China
| | - Bei Fan
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China
| | - Yixia Zhou
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China
| | - Jiahuan Zheng
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China
| | - Rao Diao
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China
| | - Fengzhong Wang
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China.
| | - Jiameng Liu
- Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No.2, Yuanmingyuan West Road, Haidian District, Beijing 100193, PR China.
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Džidić Krivić A, Begagić E, Hadžić S, Bećirović A, Bećirović E, Hibić H, Tandir Lihić L, Kadić Vukas S, Bečulić H, Kasapović T, Pojskić M. Unveiling the Important Role of Gut Microbiota and Diet in Multiple Sclerosis. Brain Sci 2025; 15:253. [PMID: 40149775 PMCID: PMC11939953 DOI: 10.3390/brainsci15030253] [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: 12/27/2024] [Revised: 02/23/2025] [Accepted: 02/25/2025] [Indexed: 03/29/2025] Open
Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by neurodegeneration, axonal damage, demyelination, and inflammation. Recently, gut dysbiosis has been linked to MS and other autoimmune conditions. Namely, gut microbiota has a vital role in regulating immune function by influencing immune cell development, cytokine production, and intestinal barrier integrity. While balanced microbiota fosters immune tolerance, dysbiosis disrupts immune regulation, damages intestinal permeability, and heightens the risk of autoimmune diseases. The critical factor in shaping the gut microbiota and modulating immune response is diet. Research shows that high-fat diets rich in saturated fats are associated with disease progression. Conversely, diets rich in fruits, yogurt, and legumes may lower the risk of MS onset and progression. Specific dietary interventions, such as the Mediterranean diet (MD) and ketogenic diet, have shown potential to reduce inflammation, support neuroprotection, and promote CNS repair. Probiotics, by restoring microbial balance, may also help mitigate immune dysfunction noted in MS. Personalized dietary strategies targeting the gut microbiota hold promise for managing MS by modulating immune responses and slowing disease progression. Optimizing nutrient intake and adopting anti-inflammatory diets could improve disease control and quality of life. Understanding gut-immune interactions is essential for developing tailored nutritional therapies for MS patients.
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Affiliation(s)
- Amina Džidić Krivić
- Department of Neurology, Cantonal Hospital Zenica, Crkvice 67, 72000 Zenica, Bosnia and Herzegovina; (A.D.K.); (L.T.L.)
- Department of Physiology, School of Medicine, University of Zenica, Travnička 1, 72000 Zenica, Bosnia and Herzegovina
| | - Emir Begagić
- Department of Neurosurgery, Cantonal Hospital Zenica, Crkvice 67, 72000 Zenica, Bosnia and Herzegovina; (E.B.)
- Department of Doctoral Studies, School of Medicine, University of Tuzla, 75000 Tuzla, Bosnia and Herzegovina
| | - Semir Hadžić
- Internal Medicine Clinic, University Clinical Center of Tuzla, Ulica prof. dr. Ibre Pašića, 75000 Tuzla, Bosnia and Herzegovina (E.B.)
- Department of Physiology, School of Medicine, University of Tuzla, Univerzitetska 1, 75000 Tuzla, Bosnia and Herzegovina
| | - Amir Bećirović
- Internal Medicine Clinic, University Clinical Center of Tuzla, Ulica prof. dr. Ibre Pašića, 75000 Tuzla, Bosnia and Herzegovina (E.B.)
| | - Emir Bećirović
- Internal Medicine Clinic, University Clinical Center of Tuzla, Ulica prof. dr. Ibre Pašića, 75000 Tuzla, Bosnia and Herzegovina (E.B.)
| | - Harisa Hibić
- Department of Maxillofacial Surgery, Cantonal Hospital Zenica, Crkvice 67, 72000 Zenica, Bosnia and Herzegovina
| | - Lejla Tandir Lihić
- Department of Neurology, Cantonal Hospital Zenica, Crkvice 67, 72000 Zenica, Bosnia and Herzegovina; (A.D.K.); (L.T.L.)
- Department of Neurology, School of Medicine, University of Zenica, Travnička 1, 72000 Zenica, Bosnia and Herzegovina
| | - Samra Kadić Vukas
- Department of Neurology, Cantonal Hospital Zenica, Crkvice 67, 72000 Zenica, Bosnia and Herzegovina; (A.D.K.); (L.T.L.)
- Department of Neurology, School of Medicine, University of Zenica, Travnička 1, 72000 Zenica, Bosnia and Herzegovina
| | - Hakija Bečulić
- Department of Neurosurgery, Cantonal Hospital Zenica, Crkvice 67, 72000 Zenica, Bosnia and Herzegovina; (E.B.)
- Department of Anatomy, School of Medicine, University of Zenica, Travnička 1, 72000 Zenica, Bosnia and Herzegovina
| | - Tarik Kasapović
- Internal Medicine Clinic, University Clinical Center of Tuzla, Ulica prof. dr. Ibre Pašića, 75000 Tuzla, Bosnia and Herzegovina (E.B.)
| | - Mirza Pojskić
- Department of Neurosurgery, University Hospital Marburg, Baldingerstr., 35033 Marburg, Germany
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Singh AK, Kumar P, Mishra SK, Rajput VD, Tiwari KN, Singh AK, Minkina T, Pandey AK, Upadhyay P. A Dual Therapeutic Approach to Diabetes Mellitus via Bioactive Phytochemicals Found in a Poly Herbal Extract by Restoration of Favorable Gut Flora and Related Short-Chain Fatty Acids. Appl Biochem Biotechnol 2024; 196:6690-6715. [PMID: 38393580 DOI: 10.1007/s12010-024-04879-6] [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] [Accepted: 02/12/2024] [Indexed: 02/25/2024]
Abstract
Diabetes mellitus (DM), a metabolic and endocrine condition, poses a serious threat to human health and longevity. The emerging role of gut microbiome associated with bioactive compounds has recently created a new hope for DM treatment. UHPLC-HRMS methods were used to identify these compounds in a poly herbal ethanolic extract (PHE). The effects of PHE on body weight (BW), fasting blood glucose (FBG) level, gut microbiota, fecal short-chain fatty acids (SCFAs) production, and the correlation between DM-related indices and gut microbes, in rats were investigated. Chebulic acid (0.368%), gallic acid (0.469%), andrographolide (1.304%), berberine (6.442%), and numerous polysaccharides were the most representative constituents in PHE. A more significant BW gain and a reduction in FBG level towards normal of PHE 600 mg/kg treated rats group were resulted at the end of 28th days of the study. Moreover, the composition of the gut microbiota corroborated the study's hypothesis, as evidenced by an increased ratio of Bacteroidetes to Firmicutes and some beneficial microbial species, including Prevotella copri and Lactobacillus hamster. The relative abundance of Bifidobacterium pseudolongum, Ruminococcus bromii, and Blautia producta was found to decline in PHE treatment groups as compared to diabetic group. The abundance of beneficial bacteria in PHE 600 mg/kg treatment group was concurrently associated with increased SCFAs concentrations of acetate and propionate (7.26 nmol/g and 4.13 nmol/g). The findings of this study suggest a promising approach to prevent DM by demonstrating that these naturally occurring compounds decreased FBG levels by increasing SCFAs content and SCFAs producing gut microbiota.
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Affiliation(s)
- Amit Kumar Singh
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India
| | - Pradeep Kumar
- Department of Botany, MMV, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India
| | - Sunil Kumar Mishra
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.
| | - Vishnu D Rajput
- Academy of Biology and Biotechnology, Southern Federal University, Rostov On Don, Russia
| | - Kavindra Nath Tiwari
- Department of Botany, MMV, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India
| | - Anand Kumar Singh
- Department of Chemistry, Mariahu PG College, VBS Purvanchal University, Jaunpur, Uttar Pradesh, 222161, India
| | - Tatiana Minkina
- Academy of Biology and Biotechnology, Southern Federal University, Rostov On Don, Russia
| | - Ajay Kumar Pandey
- Department of Kaychikitsa, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India
| | - Prabhat Upadhyay
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA
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Tian YQ, Ren X, Wang J, Li X, Yin YS, Guo ZH, Qin ZL, Zeng XY. Berberine hydrochloride alleviates chronic prostatitis/chronic pelvic pain syndrome by modifying gut microbiome signaling. Asian J Androl 2024; 26:500-509. [PMID: 39012524 PMCID: PMC11449416 DOI: 10.4103/aja202427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Accepted: 04/16/2024] [Indexed: 07/17/2024] Open
Abstract
ABSTRACT Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is highly prevalent worldwide and poses a significant threat to men's health, particularly affecting young men. However, the exact causes and mechanisms behind CP/CPPS remain unclear, leading to challenges in its treatment. In this research, a CP/CPPS rat model was established with complete Freund's adjuvant (CFA), and berberine hydrochloride was administered through daily gavage to assess its therapeutic effects. The alterations in the gut microbiome induced by CP/CPPS and berberine hydrochloride were investigated through 16S ribosomal RNA sequencing of cecum content and colonic epithelial cells. To investigate the impact of the gut microbiome on CP/CPPS, a pseudo germ-free rat model was established, and fecal microbiome transplantation (FMT) was performed on these rats. In all, berberine hydrochloride demonstrated effective reduction of inflammation and oxidative stress in the prostate, offering significant therapeutic advantages for CP/CPPS. Through analysis of the gut microbiome using 16S ribosome RNA sequencing, distinct differences were observed between CP/CPPS rats and control rats, and Clostridium butyricum was identified as a key bacteria. Pseudo germ-free rats that underwent FMT from CP/CPPS rats or rats treated with berberine hydrochloride displayed varying levels of inflammatory cytokine production, oxidative stress, and activity of associated signaling pathways. In conclusion, the therapeutic potential of berberine hydrochloride in addressing CP/CPPS is highly significant. The gut microbiome has emerged as a critical factor in the development of CP/CPPS and plays a pivotal role in mediating the therapeutic effects of berberine hydrochloride.
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Affiliation(s)
- Yi-Qun Tian
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Institute of Urology of Hubei Province, Wuhan 430000, China
| | - Xiang Ren
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Institute of Urology of Hubei Province, Wuhan 430000, China
| | - Jing Wang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Institute of Urology of Hubei Province, Wuhan 430000, China
| | - Xing Li
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Institute of Urology of Hubei Province, Wuhan 430000, China
| | - Yi-Sheng Yin
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Institute of Urology of Hubei Province, Wuhan 430000, China
| | - Zi-Hao Guo
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Institute of Urology of Hubei Province, Wuhan 430000, China
| | - Zhen-Liang Qin
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Institute of Urology of Hubei Province, Wuhan 430000, China
| | - Xiao-Yong Zeng
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Institute of Urology of Hubei Province, Wuhan 430000, China
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Chang C, Roh YS, Du M, Kuo YC, Zhang Y, Hardy M, Gahler R, Solnier J. Differences in Metabolite Profiles of Dihydroberberine and Micellar Berberine in Caco-2 Cells and Humans-A Pilot Study. Int J Mol Sci 2024; 25:5625. [PMID: 38891813 PMCID: PMC11171481 DOI: 10.3390/ijms25115625] [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: 04/15/2024] [Revised: 05/17/2024] [Accepted: 05/20/2024] [Indexed: 06/21/2024] Open
Abstract
We investigated the pharmacokinetic pathway of berberine and its metabolites in vitro, in Caco-2 cells, and in human participants following the administration of dihydroberberine (DHB) and micellar berberine (LipoMicel®, LMB) formulations. A pilot trial involving nine healthy volunteers was conducted over a 24 h period; blood samples were collected and subjected to Ultra High-Performance Liquid Chromatography-High Resolution Mass Spectrometry (UHPLC-HRMS) analyses to quantify the concentrations of berberine and its metabolites. Pharmacokinetic correlations indicated that berberrubine and thalifendine follow distinct metabolic pathways. Additionally, jatrorrhizine sulfate appeared to undergo metabolism differently compared to the other sulfated metabolites. Moreover, berberrubine glucuronide likely has a unique metabolic pathway distinct from other glucuronides. The human trial revealed significantly higher blood concentrations of berberine metabolites in participants of the DHB treatment group compared to the LMB treatment group-except for berberrubine glucuronide, which was only detected in the LMB treatment group. Similarly, results from in vitro investigations showed significant differences in berberine metabolite profiles between DHB and LMB. Dihydroberberine, dihydroxy-berberrubine/thalifendine and jatrorrhizine sulfate were detected in LMB-treated cells, but not in DHB-treated cells; thalifendine and jatrorrhizine-glucuronide were detected in DHB-treated cells only. While DHB treatment provided higher blood concentrations of berberine and most berberine metabolites, both in vitro (Caco-2 cells) and in vivo human studies showed that treatment with LMB resulted in a higher proportion of unmetabolized berberine compared to DHB. These findings suggest potential clinical implications that merit further investigation in future large-scale trials.
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Affiliation(s)
- Chuck Chang
- ISURA, Clinical Research, Burnaby, BC V3N 4S9, Canada; (C.C.); (Y.S.R.); (M.D.); (Y.C.K.); (Y.Z.)
| | - Yoon Seok Roh
- ISURA, Clinical Research, Burnaby, BC V3N 4S9, Canada; (C.C.); (Y.S.R.); (M.D.); (Y.C.K.); (Y.Z.)
| | - Min Du
- ISURA, Clinical Research, Burnaby, BC V3N 4S9, Canada; (C.C.); (Y.S.R.); (M.D.); (Y.C.K.); (Y.Z.)
| | - Yun Chai Kuo
- ISURA, Clinical Research, Burnaby, BC V3N 4S9, Canada; (C.C.); (Y.S.R.); (M.D.); (Y.C.K.); (Y.Z.)
| | - Yiming Zhang
- ISURA, Clinical Research, Burnaby, BC V3N 4S9, Canada; (C.C.); (Y.S.R.); (M.D.); (Y.C.K.); (Y.Z.)
| | - Mary Hardy
- Academy of Integrative and Holistic Medicine, San Diego, CA 92037, USA;
| | | | - Julia Solnier
- ISURA, Clinical Research, Burnaby, BC V3N 4S9, Canada; (C.C.); (Y.S.R.); (M.D.); (Y.C.K.); (Y.Z.)
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Yan M, Liu S, Zeng W, Guo Q, Mei Y, Shao X, Su L, Liu Z, Zhang Y, Wang L, Diao H, Rong X, Guo J. The Chinese herbal medicine Fufang Zhenzhu Tiaozhi ameliorates diabetic cardiomyopathy by regulating cardiac abnormal lipid metabolism and mitochondrial dynamics in diabetic mice. Biomed Pharmacother 2023; 164:114919. [PMID: 37302318 DOI: 10.1016/j.biopha.2023.114919] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 05/03/2023] [Accepted: 05/18/2023] [Indexed: 06/13/2023] Open
Abstract
Diabetic cardiomyopathy (DCM) is an important complication leading to the death of patients with diabetes, but there is no effective strategy for clinical treatments. Fufang Zhenzhu Tiaozhi (FTZ) is a patent medicine that is a traditional Chinese medicine compound preparation with comprehensive effects for the prevention and treatment of glycolipid metabolic diseases under the guidance of "modulating liver, starting pivot and cleaning turbidity". FTZ was proposed by Professor Guo Jiao and is used for the clinical treatment of hyperlipidemia. This study was designed to explore the regulatory mechanisms of FTZ on heart lipid metabolism dysfunction and mitochondrial dynamics disorder in mice with DCM, and it provides a theoretical basis for the myocardial protective effect of FTZ in diabetes. In this study, we demonstrated that FTZ protected heart function in DCM mice and downregulated the overexpression of free fatty acids (FFAs) uptake-related proteins cluster of differentiation 36 (CD36), fatty acid binding protein 3 (FABP3) and carnitine palmitoyl transferase 1 (CPT1). Moreover, FTZ treatment showed a regulatory effect on mitochondrial dynamics by inhibiting mitochondrial fission and promoting mitochondrial fusion. We also identified in vitro that FTZ could restore lipid metabolism-related proteins, mitochondrial dynamics-related proteins and mitochondrial energy metabolism in PA-treated cardiomyocytes. Our study indicated that FTZ improves the cardiac function of diabetic mice by attenuating the increase in fasting blood glucose levels, inhibiting the decrease in body weight, alleviating disordered lipid metabolism, and restoring mitochondrial dynamics and myocardial apoptosis in diabetic mouse hearts.
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Affiliation(s)
- Meiling Yan
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China
| | - Suping Liu
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China
| | - Wenru Zeng
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China
| | - Qiaoling Guo
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China
| | - Yu Mei
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China
| | - Xiaoqi Shao
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China
| | - Liyan Su
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China
| | - Zhou Liu
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China
| | - Yue Zhang
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China
| | - Lexun Wang
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China
| | - Hongtao Diao
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China
| | - Xianglu Rong
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China
| | - Jiao Guo
- Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangzhou, China; Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, China; Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangzhou 510006, China.
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Liu J, Chen H, Yu T, Fu X, Qian C, Feng X. Berberine mitigates intracerebral hemorrhage-induced neuroinflammation in a gut microbiota-dependent manner in mice. Aging (Albany NY) 2023; 15:2705-2720. [PMID: 37036515 PMCID: PMC10120891 DOI: 10.18632/aging.204642] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Accepted: 03/24/2023] [Indexed: 04/11/2023]
Abstract
BACKGROUND Neuroinflammation is a frequent cause of brain damage after intracerebral hemorrhage (ICH). Gut microbiota are reported to regulate neuroinflammation. Berberine has been found to have anti-inflammatory actions, including in the central nervous system. However, it is not known whether berberine regulates neuroinflammation after ICH, nor is the relationship between the antineuroinflammatory actions of berberine and the gut microbiota after ICH understood. METHODS ICH was induced in male mice by collagenase injection. Immunofluorescent staining and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect microglia/macrophage phenotypes. Immunofluorescent staining, ELISA, and FITC-dextran were conducted to determine gut function. 16S rRNA sequencing of the fecal material was conducted to determine alterations in the gut microbiota. Antibiotic cocktail treatment and fecal microbiota transplantation (FMT) were used to deplete or restore the gut microbiota, respectively. Cylinder, forelimb placement and wire hanging tests were conducted to evaluate neurobehavioral function. RESULTS Berberine significantly reduced neuroinflammation and alleviated neurological dysfunction by preventing microglial/macrophage proinflammatory polarization in ICH mice. Berberine also enhanced the function of the intestinal barrier, as shown by reductions in the levels of lipopolysaccharide-binding protein. Neuroinflammation in ICH mice was markedly reduced after transplantation of microbiota from berberine-treated mice, similar to treatment with oral berberine. In addition, a reduction in the microbiota reversed the neuroprotective effect of berberine. CONCLUSIONS Berberine is a potential treatment for ICH-induced neuroinflammation, and its effects are at least partially dependent on the gut microbiota.
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Affiliation(s)
- Jing Liu
- Department of Nursing, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang, China
| | - Haotian Chen
- Department of Nursing, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang, China
| | - Ting Yu
- Department of Neurosurgery, Tiantai People’s Hospital of Zhejiang Province, Taizhou 317299, Zhejiang, China
| | - Xiongjie Fu
- Department of Neurosurgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang, China
| | - Cong Qian
- Department of Neurosurgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang, China
| | - Xiuqin Feng
- Department of Nursing, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang, China
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Cortez-Navarrete M, Pérez-Rubio KG, Escobedo-Gutiérrez MDJ. Role of Fenugreek, Cinnamon, Curcuma longa, Berberine and Momordica charantia in Type 2 Diabetes Mellitus Treatment: A Review. Pharmaceuticals (Basel) 2023; 16:ph16040515. [PMID: 37111272 PMCID: PMC10145167 DOI: 10.3390/ph16040515] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 03/25/2023] [Accepted: 03/28/2023] [Indexed: 04/03/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a complex disease that has become a major global health concern. Given the efficacy of antidiabetic drugs, pharmacological therapy is considered the first-line treatment of T2DM; however, due to their potential side effects and high costs, new and cost-effective treatments with minimal side effects are needed. Medicinal plants have been used for centuries as part of traditional medicine to treat T2DM. Among these, fenugreek, cinnamon, Curcuma longa, berberine, and Momordica charantia have demonstrated different degrees of hypoglycemic activity in clinical studies and animal models. Therefore, the aim of this review is to synthesize the mechanisms of action of five medicinal plants, as well as the experimental and clinical evidence of their hypoglycemic activity from the published literature.
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Affiliation(s)
- Marisol Cortez-Navarrete
- Institute of Experimental and Clinical Therapeutics, Department of Physiology, Health Science University Center, University of Guadalajara, Sierra Mojada 950, Col. Independencia, Guadalajara 44340, Jalisco, Mexico
| | - Karina G. Pérez-Rubio
- Institute of Experimental and Clinical Therapeutics, Department of Physiology, Health Science University Center, University of Guadalajara, Sierra Mojada 950, Col. Independencia, Guadalajara 44340, Jalisco, Mexico
| | - Miriam de J. Escobedo-Gutiérrez
- Institute of Experimental and Clinical Therapeutics, Department of Physiology, Health Science University Center, University of Guadalajara, Sierra Mojada 950, Col. Independencia, Guadalajara 44340, Jalisco, Mexico
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9
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Deng B, Tao L, Wang Y. Natural products against inflammation and atherosclerosis: Targeting on gut microbiota. Front Microbiol 2022; 13:997056. [PMID: 36532443 PMCID: PMC9751351 DOI: 10.3389/fmicb.2022.997056] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 10/25/2022] [Indexed: 09/29/2023] Open
Abstract
The gut microbiota (GM) has become recognized as a crucial element in preserving human fitness and influencing disease consequences. Commensal and pathogenic gut microorganisms are correlated with pathological progress in atherosclerosis (AS). GM may thus be a promising therapeutic target for AS. Natural products with cardioprotective qualities might improve the inflammation of AS by modulating the GM ecosystem, opening new avenues for researches and therapies. However, it is unclear what components of natural products are useful and what the actual mechanisms are. In this review, we have summarized the natural products relieving inflammation of AS by regulating the GM balance and active metabolites produced by GM.
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Affiliation(s)
- Bing Deng
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Liyu Tao
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yiru Wang
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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10
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Zamani M, Zarei M, Nikbaf-Shandiz M, Hosseini S, Shiraseb F, Asbaghi O. The effects of berberine supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis. Front Nutr 2022; 9:1013055. [PMID: 36313096 PMCID: PMC9614282 DOI: 10.3389/fnut.2022.1013055] [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: 08/06/2022] [Accepted: 09/20/2022] [Indexed: 11/25/2022] Open
Abstract
Cardiovascular disease (CVD) is a major concern today. Herbal medicine is one helping way to control CVD risks. One conclusive of herbal medicine is Berberine (BBR) and converse about it still exists, to clarify this issue, this meta-analysis was performed. PubMed/Medline, Scopus, and Web of Science were searched for RCTs in adults on the effect of BBR supplementation on CVD risk factors up to July 2022. The pooled results showed BBR significantly reduced triglyceride (WMD = -23.70 mg/dl; 95%CI -30.16, -17.25; P < 0.001), total cholesterol (WMD = -20.64 mg/dl; 95%CI -23.65, -17.63; P < 0.001), low-density lipoprotein WMD = -9.63 mg/dl; 95%CI, -13.87, -5.39; P < 0.001), fasting blood glucose (FBG) (WMD = -7.74 mg/dl; 95%CI -10.79, -4.70; P < 0.001), insulin (WMD = -3.27 mg/dl; 95%CI -4.46,-2.07; P < 0.001), HbA1c (WMD = -0.45%; 95%CI -0.68, -0.23; P < 0.001), HOMA-IR (WMD = -1.04; 95%CI -1.55, -0.52; P < 0.001), systolic blood pressure (WMD = -5.46 mmHg; 95%CI -8.17, -2.76; P < 0.001), weight (WMD = -0.84; 95%CI -1.34,-0.34; P < 0.001), body mass index (WMD = -0.25 kg/m2; 95%CI -0.46, -0.04; P = 0.020), while increased high-density lipoprotein (HDL) (WMD = 1.37 mg/dl; 95%CI 0.41,2.23; P = 0.005). The optimal dose of BBR was 1 g/day for TG, TC, and weight, 1.8 g/day for insulin and HOMA-IR, and 5 g/day for HDL. FBG's most efficient time frame was 40 weeks from the beginning of supplementation, whereas DBP and waist circumference was 50 weeks. In conclusion, the lipid profile, FBG balance, obesity parameters, and SBP were improved with BBR supplementation. Systematic review registration CRD42022347004.
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Affiliation(s)
- Mohammad Zamani
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahtab Zarei
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | | | - Shabnam Hosseini
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farideh Shiraseb
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Omid Asbaghi
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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11
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Law SK, Wang Y, Lu X, Au DCT, Chow WYL, Leung AWN, Xu C. Chinese medicinal herbs as potential prodrugs for obesity. Front Pharmacol 2022; 13:1016004. [PMID: 36263142 PMCID: PMC9573959 DOI: 10.3389/fphar.2022.1016004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 09/14/2022] [Indexed: 11/13/2022] Open
Abstract
Obesity is a leading worldwide health threat with ever-growing prevalence, it promotes the incidence of various diseases, particularly cardiovascular disease, metabolic syndrome, diabetes, hypertension, and certain cancers. Traditional Chinese Medicine (TCM) has been used to control body weight and treat obesity for thousands of years, Chinese medicinal herbs provide a rich natural source of effective agents against obesity. However, some problems such as complex active ingredients, poor quality control, and unclear therapeutic mechanisms still need to be investigated and resolved. Prodrugs provide a path forward to overcome TCM deficiencies such as absorption, distribution, metabolism, excretion (ADME) properties, and toxicity. This article aimed to review the possible prodrugs from various medicinal plants that demonstrate beneficial effects on obesity and seek to offer insights on prodrug design as well as a solution to the global obesity issues.
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Affiliation(s)
- Siu Kan Law
- Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
- Faculty of Science and Technology, The Technological and Higher Education Institute of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Yanping Wang
- School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, Hong Kong SAR, China
| | - Xinchen Lu
- Faculty of Science and Technology, The Technological and Higher Education Institute of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Dawn Ching Tung Au
- Faculty of Science and Technology, The Technological and Higher Education Institute of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Wesley Yeuk Lung Chow
- Faculty of Science and Technology, The Technological and Higher Education Institute of Hong Kong, Hong Kong, Hong Kong SAR, China
| | | | - Chuanshan Xu
- Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
- *Correspondence: Chuanshan Xu,
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12
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Yang S, Hao S, Wang Q, Lou Y, Jia L, Chen D. The interactions between traditional Chinese medicine and gut microbiota: Global research status and trends. Front Cell Infect Microbiol 2022; 12:1005730. [PMID: 36171760 PMCID: PMC9510645 DOI: 10.3389/fcimb.2022.1005730] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 08/22/2022] [Indexed: 11/15/2022] Open
Abstract
Background There is a crosstalk between traditional Chinese medicine (TCM) and gut microbiota (GM), many articles have studied and discussed the relationship between the two. The purpose of this study is to use bibliometric analysis to explore the research status and development trends of the TCM/GM research, identify and analyze the highly cited papers relating to the TCM/GM. Methods A literature search regarding TCM/GM publications from 2004 to 2021 was undertaken on August 13, 2022. The main information (full record and cited references) of publications was extracted from the Science Citation Index Expanded (SCI-E) of Web of Science Core Collection (WoSCC). The Bibliometrix of R package, CiteSpace and VOSviewer were used for bibliometric analysis. Results A total of 830 papers were included. The publication years of papers were from 2004 to 2021. The number of papers had increased rapidly since 2018. China had the most publications and made most contributions to this field. Nanjing University of Chinese Medicine and Beijing University of Chinese Medicine were in the leading productive position in TCM/GM research, Chinese Academy of Chinese Medical Sciences had the highest total citations (TC). Duan Jin-ao from Nanjing University of Chinese Medicine had the largest number of publications, and Tong Xiao-lin from China Academy of Chinese Medical Sciences had the most TC. The Journal of Ethnopharmacology had the most published papers and the most TC. The main themes in TCM/GM included the role of GM in TCM treatment of glucolipid metabolism diseases and lower gastrointestinal diseases; the mechanism of interactions between GM and TCM to treat diseases; the links between TCM/GM and metabolism; and the relationship between GM and oral bioavailability of TCM. Conclusion This study gained insight into the research status, hotspots and trends of global TCM/GM research, identified the most cited articles in TCM/GM and analyzed their characteristics, which may inform clinical researchers and practitioners’ future directions.
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Affiliation(s)
- Shanshan Yang
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Shaodong Hao
- Sixth Clinical School of Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Qin Wang
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Yanni Lou
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Liqun Jia
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
- *Correspondence: Liqun Jia, ; Dongmei Chen,
| | - Dongmei Chen
- Oncology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
- *Correspondence: Liqun Jia, ; Dongmei Chen,
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13
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Nematollahi S, Pishdad GR, Zakerkish M, Namjoyan F, Ahmadi Angali K, Borazjani F. The effect of berberine and fenugreek seed co-supplementation on inflammatory factor, lipid and glycemic profile in patients with type 2 diabetes mellitus: a double-blind controlled randomized clinical trial. Diabetol Metab Syndr 2022; 14:120. [PMID: 35999562 PMCID: PMC9395822 DOI: 10.1186/s13098-022-00888-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 08/07/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Type 2 Diabetes mellitus is one of the most common chronic diseases in the world and has many complications. Due to the importance of using alternative therapies in managing symptoms of this disease, the present study was designed and conducted to investigate the effect of co-supplementation of berberine and fenugreek in patients with type 2 diabetes mellitus. METHODS A randomized controlled clinical trial was conducted on 50 patients with type 2 diabetes mellitus. Participants were randomized in the intervention group, which received 3 capsules/day of 500 mg (300 mg of berberine + 200 mg of fenugreek seed powder) or placebo for 12 weeks. Biochemical and anthropometric variables were measured at the beginning and end of the study. RESULTS We observed that fasting insulin, HbA1C, and hs-CRP significantly decreased in the intervention group compared to the baseline. The mean difference in insulin resistance (-0.32 vs. 0.15), fasting blood sugar (-14.40 vs. 1.68), and fasting insulin (- 2.18 vs. 1.34) were clinically significant in comparison to the control group. Almost all domains of SF-12 scores were significantly higher in the intervention group than in the placebo group. CONCLUSIONS The combination of berberine and fenugreek seed can improve cardio-metabolic status in patients with diabetes and support the anti-diabetic and anti-inflammatory role of herb in the improvement of quality of life.
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Affiliation(s)
- Shima Nematollahi
- Nutrition and Metabolic Diseases Research Center and Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Gholam Reza Pishdad
- Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehrnoosh Zakerkish
- Health Research Institute, Diabetes Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Foroogh Namjoyan
- Research center for Traditional Medicine and History of Medicine, Shiraz University of medical sciences, Shiraz, Iran
| | - Kambiz Ahmadi Angali
- Department of Statistics and Epidemiology, School of Health Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Fatemeh Borazjani
- Nutrition and Metabolic Disease Research Center and Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
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14
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He L, Yang FQ, Tang P, Gao TH, Yang CX, Tan L, Yue P, Hua YN, Liu SJ, Guo JL. Regulation of the intestinal flora: A potential mechanism of natural medicines in the treatment of type 2 diabetes mellitus. Biomed Pharmacother 2022; 151:113091. [PMID: 35576662 DOI: 10.1016/j.biopha.2022.113091] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 04/24/2022] [Accepted: 05/04/2022] [Indexed: 11/02/2022] Open
Abstract
Diabetes mellitus comprises a group of heterogeneous disorders, which are usually subdivided into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Both genetic and environmental factors have been implicated in the onset of diabetes. Type 1 diabetes primarily involves autoimmune insulin deficiency. In comparison, type 2 diabetes is contributed by the pathological state of insulin deficiency and insulin resistance. In recent years, significant differences were found in the abundance of microflora, intestinal barrier, and intestinal metabolites in diabetic subjects when compared to normal subjects. To further understand the relationship between diabetes mellitus and intestinal flora, this paper summarizes the interaction mechanism between diabetes mellitus and intestinal flora. Furthermore, the natural compounds found to treat diabetes through intestinal flora were classified and summarized. This review is expected to provide a valuable resource for the development of new diabetic drugs and the applications of natural compounds.
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Affiliation(s)
- Liying He
- Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Fang-Qing Yang
- Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Pan Tang
- Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Ting-Hui Gao
- Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Cai-Xia Yang
- Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Li Tan
- Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Pan Yue
- Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Ya-Nan Hua
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Si-Jing Liu
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Jin-Lin Guo
- Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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15
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Expatiating the Pharmacological and Nanotechnological Aspects of the Alkaloidal Drug Berberine: Current and Future Trends. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27123705. [PMID: 35744831 PMCID: PMC9229453 DOI: 10.3390/molecules27123705] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 06/03/2022] [Accepted: 06/07/2022] [Indexed: 12/12/2022]
Abstract
Traditionally, herbal compounds have been the focus of scientific interest for the last several centuries, and continuous research into their medicinal potential is underway. Berberine (BBR) is an isoquinoline alkaloid extracted from plants that possess a broad array of medicinal properties, including anti-diarrheal, anti-fibrotic, antidiabetic, anti-inflammatory, anti-obesity, antihyperlipidemic, antihypertensive, antiarrhythmic, antidepressant, and anxiolytic effects, and is frequently utilized as a traditional Chinese medicine. BBR promotes metabolisms of glucose and lipids by activating adenosine monophosphate-activated protein kinase, stimulating glycolysis and inhibiting functions of mitochondria; all of these ameliorate type 2 diabetes mellitus. BBR has also been shown to have benefits in congestive heart failure, hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, Alzheimer’s disease, and polycystic ovary syndrome. BBR has been investigated as an interesting pharmacophore with the potential to contribute significantly to the research and development of novel therapeutic medicines for a variety of disorders. Despite its enormous therapeutic promise, the clinical application of this alkaloid was severely limited because of its unpleasant pharmacokinetic characteristics. Poor bioavailability, limited absorption, and poor water solubility are some of the obstacles that restricted its use. Nanotechnology has been suggested as a possible solution to these problems. The present review aims at recent updates on important therapeutic activities of BBR and different types of nanocarriers used for the delivery of BBR in different diseases.
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16
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Cai Y, Li S, Zhang X, Cao X, Liu D, Zhu Y, Ye S, Xu Z, Liao Q, Hong Y, Xie Z. Integrated microbiome-metabolomics analysis reveals the potential therapeutic mechanism of Zuo-Jin-Wan in ulcerative colitis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 98:153914. [PMID: 35104755 DOI: 10.1016/j.phymed.2021.153914] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 12/02/2021] [Accepted: 12/24/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND Dysregulation in gut microbiota and host cometabolome contributes to the complicated pathology of ulcerative colitis (UC), while Zuo-Jin-Wan (ZJW), a traditional Chinese medicine has shown therapeutic effects against UC with its underlying mechanism remains elusive. PURPOSE This study utilized an integrated analysis combining gut microbiome and host cometabolism to disclose the potential therapeutic mechanism of ZJW on dextran sulfate sodium (DSS)-induced UC in rats. METHODS We first evaluated the therapeutic effects of ZJW treatment in DSS-induced rat model. 16S rRNA sequencing, 1H NMR spectroscopy-based metabolomics and Spearman correlation analysis were conducted to explore the potential therapeutic mechanism during the treatment. RESULTS Our results showed that UC symptoms in ZJW rats were significantly attenuated. Marked decline in microbial diversity in ZJW group was accompanied by its correspondent function adjustment. Specific enrichment of genus Bacteroides, Sutterella, Akkermansia and Roseburia along with the major varying amino acid metabolism and lipid metabolism were observed meantime. Metabolic data further corroborated that ZJW-related metabolic changes were basically gathered in amino acid metabolism, carbohydrate/energy metabolism and lipid metabolism. Of note, some biochemical parameters were deeply implicated with the discriminative microbial genera and metabolites involved in tricarboxylic acid (TCA) cycle and amino acid metabolism, indicating the microbiome-metabolome association in gut microbiota-metabolite-phenotype axis during UC treatment of ZJW. CONCLUSION For the first time, integrated microbiome-metabolome analysis depicted that ZJW could alleviate DSS-induced UC in rats via a crosstalk between gut microbiota and host cometabolites.
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Affiliation(s)
- Ying Cai
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510006, China
| | - Siju Li
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510006, China
| | - Xiaojun Zhang
- Department of Pharmacy, Maternal and Child Health Hospital of Yingde City, Qingyuan, 513000, China
| | - Xueqin Cao
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510006, China
| | - Deliang Liu
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510006, China
| | - Yanglu Zhu
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510006, China
| | - Simin Ye
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510006, China
| | - Zengmei Xu
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510006, China
| | - Qiongfeng Liao
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
| | - Yanjun Hong
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510006, China.
| | - Zhiyong Xie
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510006, China.
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17
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Berberine, a Herbal Metabolite in the Metabolic Syndrome: The Risk Factors, Course, and Consequences of the Disease. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27041351. [PMID: 35209140 PMCID: PMC8874997 DOI: 10.3390/molecules27041351] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 02/11/2022] [Accepted: 02/13/2022] [Indexed: 12/13/2022]
Abstract
In recent years, the health of patients exposed to the consequences of the metabolic syndrome still requires the search for new solutions, and plant nutraceuticals are currently being intensively investigated. Berberine is a plant alkaloid possessing scientifically determined mechanisms of the prevention of the development of atherosclerosis, type 2 diabetes, and obesity, as well as cardiovascular complications and cancer. It positively contributes to elevated levels of fasting, postprandial blood glucose, and glycosylated hemoglobin, while decreasing insulin resistance. It stimulates glycolysis, improving insulin secretion, and inhibits gluconeogenesis and adipogenesis in the liver; by reducing insulin resistance, berberine also improves ovulation. The anti-obesity action of berberine has been also well-documented. Berberine acts as an anti-sclerotic, lowering the LDL and testosterone levels. The alkaloid exhibits an anti-inflammatory property by stalling the expression of cyclooxygenase 2 (COX-2) and prostaglandin E2. Berberine is neuroprotective and acts as an antidepressive. However, the outcomes in psychiatric patients are nonspecific, as it has been shown that berberine improves metabolic parameters in schizophrenic patients, acting as an adjuvant during antipsychotic treatment. Berberine acts as an anticancer option by inducing apoptosis, the cell cycle arrest, influencing MAPK (mitogen-activated protein kinase), and influencing transcription regulation. The inhibition of carcinogenesis is also combined with lipid metabolism.
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18
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Zhao Y, Huang J, Li T, Zhang S, Wen C, Wang L. Berberine ameliorates aGVHD by gut microbiota remodelling, TLR4 signalling suppression and colonic barrier repairment for NLRP3 inflammasome inhibition. J Cell Mol Med 2022; 26:1060-1070. [PMID: 34984827 PMCID: PMC8831946 DOI: 10.1111/jcmm.17158] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/22/2021] [Accepted: 12/17/2021] [Indexed: 02/05/2023] Open
Abstract
Berberine (BBR), an isoquinoline alkaloid, is used to treat gastrointestinal disorders as an herbal medicine in China. The aim of this study was to investigate the anti‐inflammatory activities of BBR in a mouse model with acute graft‐versus‐host disease (aGVHD). Mice were intravenously injected with bone marrow cells from donors combined with splenocytes to develop aGVHD. The body weight, survival rate and clinical scores were monitored. Then the levels of inflammatory cytokines, histological changes (lung, liver and colon), colonic mucosal barrier and gut microbiota were analysed. Moreover, the toll‐like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (Myd88)/nuclear factor‐κB signalling pathway, NLRP3 inflammasome and its cytokines’ expressions were determined. The results showed that the gavage of BBR lessened GVHD‐induced weight loss, high mortality and clinical scores, inhibited inflammation and target organs damages and prevented GVHD‐indued colonic barrier damage. Additionally, BBR modulated gut microbiota, suppressed the activation of the TLR4 signaling pathway and inhibited NLRP3 inflammasome and its cytokine release. This study indicated that BBR might be a potential therapy for aGVHD through NLRP3 inflammasome inhibition.
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Affiliation(s)
- Yanna Zhao
- College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China.,Institute of Hematology Research, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiefeng Huang
- Institute of Hematology Research, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Tianyi Li
- College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shuijuan Zhang
- College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Chengping Wen
- College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Lipei Wang
- College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
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Wang S, Yong H, He XD. Multi-omics: Opportunities for research on mechanism of type 2 diabetes mellitus. World J Diabetes 2021; 12:1070-1080. [PMID: 34326955 PMCID: PMC8311486 DOI: 10.4239/wjd.v12.i7.1070] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 03/22/2021] [Accepted: 05/22/2021] [Indexed: 02/06/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a burdensome global disease. In-depth understanding of its mechanism will help to optimize diagnosis and treatment, which reduces the burden. Multi-omics research has unparalleled advantages in contributing to the overall understanding of the mechanism of this chronic metabolic disease. In the past two decades, the study of multi-omics on T2DM-related intestinal flora perturbation and plasma dyslipidemia has shown tremendous potential and is expected to achieve major breakthroughs. The regulation of intestinal flora in diabetic patients has been confirmed by multiple studies. The use of metagenomics, 16S RNA sequencing, and metabolomics has comprehensively identified the overall changes in the intestinal flora and the metabolic disturbances that could directly or indirectly participate in the intestinal flora-host interactions. Lipidomics combined with other “omics” has characterized lipid metabolism disorders in T2DM. The combined application and cross-validation of multi-omics can screen for dysregulation in T2DM, which will provide immense opportunities to understand the mechanisms behind T2DM.
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Affiliation(s)
- Shuai Wang
- Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Hui Yong
- Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Xiao-Dong He
- Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
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20
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Effect of a New Formulation of Nutraceuticals as an Add-On to Metformin Monotherapy for Patients with Type 2 Diabetes and Suboptimal Glycemic Control: A Randomized Controlled Trial. Nutrients 2021; 13:nu13072373. [PMID: 34371883 PMCID: PMC8308828 DOI: 10.3390/nu13072373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 06/29/2021] [Accepted: 07/09/2021] [Indexed: 11/16/2022] Open
Abstract
The aim of the study was to evaluate the overall biohumoral and metabolic effects of a 12-week add-on therapy consisting of a new nutraceutical formulation (BHC) based on berberine, hesperidin, and chromium picolinate in type 2 diabetes mellitus (T2D) patients with suboptimal glycemic compensation receiving metformin. After 12 weeks, participants in the group receiving metformin plus BHC, compared to the group receiving metformin only, saw a significant improvement in their glucose profile, in terms of both glycated hemoglobin (HbA1c) and fasting blood glucose (FBG). Their FBG dropped from 145 ± 20 mg/dL to 128 ± 23 mg/dL (p < 0.01), a decrease of 11.7% compared with the baseline. This decrease differed significantly from the situation in the control arm (p < 0.05). HbA1c decreased by 7.5% from the baseline, from 53.5 ± 4.3 mmol/mol to 49.5 ± 5.1 mmol/mol (p < 0.01), in the group given BHC, while no difference was seen in the control group. Advanced glycation end products (AGEs) and malondialdehyde (MDA) were found to be significantly reduced (p < 0.01) only in the BHC group, from 9.34 ± 7.61 μg/mL to 6.75 ± 6.13 μg/mL, and from 1.7 ± 0.15 μmol/L to 1.4 ± 0.25 μmol/L, respectively. In patients with T2D taking metformin with suboptimal glycemic compensation, adding BHC for 3 months significantly improved glucose control in terms of FBG and HbA1c, and had a positive effect on the lipid peroxidation profile, as indicated by a decrease in AGEs and MDA.
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21
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Zhou H, Li W, Sun L, Li W, Liu Q. A rapid LC-MS/MS method for simultaneous determination of berberine and irbesartan in rat plasma: Application to the drug-drug pharmacokinetic interaction study after oral administration in rats. Biomed Chromatogr 2021; 35:e5144. [PMID: 33880775 DOI: 10.1002/bmc.5144] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 04/06/2021] [Accepted: 04/16/2021] [Indexed: 12/20/2022]
Abstract
A sensitive, reproducible, and specific liquid chromatography tandem mass spectrometry method was developed and validated to simultaneously determine the concentration of berberine (BBR) and irbesartan in Sprague-Dawley rat plasma, and applied to study the pharmacokinetic drug-drug interaction (DDI) between BBR and irbesartan in rats. In this method, diphenhydramine was used as the internal standard, and the liquid-liquid extraction method using ethyl acetate as the extraction agent was used for sample preparation. After extraction, the prepared samples were run on an Agilent Welchrom C18 column with the mobile phase consisting of methanol-acetonitrile-water solution with 0.5% formic acid (45:50:5, v/v/v) at a flow rate of 0.8 mL·min-1 . The analytes BBR, irbesartan, and diphenhydramine (IS) were detected using multiple reactions monitoring mode, with the ion transitions being m/z 336.1 → m/z 320.0, m/z 429.1 → m/z 206.9, and m/z 256.2 → m/z 167.0, respectively. In the rats' plasma, BBR had good linearity in the range of 0.5-100 ng·mL-1 with the lower limit of quantitation of 0.5 ng·mL-1 , and the accuracy, intra-day, and inter-day precision were less than 12.33%. Irbesartan had good linearity in the range of 20-1200 ng·mL-1 with the lower limit of quantification of 20 ng·mL-1 , and the accuracy, intra-day, and inter-day precision were less than 13.55%. The validated method was verified to meet the determination requirements of biological samples. It was the first time to study the pharmacokinetics of DDI between BBR and irbesartan successfully, which would be necessary and beneficial to explore the clinical safety and efficacy of the combination of BBR and irbesartan in the treatment of diabetic nephropathy.
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Affiliation(s)
- Hao Zhou
- Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China
| | - Wenyue Li
- Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China
| | - Ling Sun
- Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China
| | - Wenfang Li
- Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China
| | - Qian Liu
- Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China
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22
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Kong M, Xie K, Lv M, Li J, Yao J, Yan K, Wu X, Xu Y, Ye D. Anti-inflammatory phytochemicals for the treatment of diabetes and its complications: Lessons learned and future promise. Biomed Pharmacother 2021; 133:110975. [PMID: 33212375 DOI: 10.1016/j.biopha.2020.110975] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 10/30/2020] [Accepted: 11/01/2020] [Indexed: 12/13/2022] Open
Abstract
Diabetes mellitus (type 1 and type 2) and its various complications continue to place a huge burden on global medical resources, despite the availability of numerous drugs that successfully lower blood glucose levels. The major challenging issue in diabetes management is the prevention of various complications that remain the leading cause of diabetes-related mortality. Moreover, the limited long-term durability of monotherapy and undesirable side effects of currently used anti-diabetic drugs underlie the urgent need for novel therapeutic approaches. Phytochemicals represent a rich source of plant-derived molecules that are of pivotal importance to the identification of compounds with therapeutic potential. In this review, we aim to discuss recent advances in the identification of a large array of phytochemicals with immense potential in the management of diabetes and its complications. Given that metabolic inflammation has been established as a key pathophysiological event that drives the progression of diabetes, we focus on the protective effects of representative phytochemicals in metabolic inflammation. This paper also discusses the potential of phytochemicals in the development of new drugs that target the inflammation in the management of diabetes and its complications.
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Affiliation(s)
- Mengjie Kong
- Key Laboratory of Glucolipid Metabolic Diseases of the Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
| | - Kang Xie
- Key Laboratory of Glucolipid Metabolic Diseases of the Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
| | - Minghui Lv
- Key Laboratory of Glucolipid Metabolic Diseases of the Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
| | - Jufei Li
- Key Laboratory of Glucolipid Metabolic Diseases of the Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
| | - Jianyu Yao
- Key Laboratory of Glucolipid Metabolic Diseases of the Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
| | - Kaixuan Yan
- Key Laboratory of Glucolipid Metabolic Diseases of the Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
| | - Xiaoqin Wu
- Key Laboratory of Glucolipid Metabolic Diseases of the Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
| | - Ying Xu
- The First Affiliated Hospital/School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, China
| | - Dewei Ye
- Key Laboratory of Glucolipid Metabolic Diseases of the Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
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23
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Gharehnaghadeh S, Salehi P, Bararjanian M, Pecio Ł, Babanezhad‐Harikandei K, Khoramjouy M, Shahhosseini S, Faizi M. Novel Triazole‐Tethered Derivatives of Nor‐codeine: Synthesis, Radioligand Binding Assay, Docking Study and Evaluation of Their Analgesic Properties. ChemistrySelect 2020. [DOI: 10.1002/slct.202003684] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Saman Gharehnaghadeh
- Department of Phytochemistry Medicinal Plants and Drugs Research Institute Shahid Beheshti University via G. C., Evin 1983963113 Tehran Iran
| | - Peyman Salehi
- Department of Phytochemistry Medicinal Plants and Drugs Research Institute Shahid Beheshti University via G. C., Evin 1983963113 Tehran Iran
| | - Morteza Bararjanian
- Department of Phytochemistry Medicinal Plants and Drugs Research Institute Shahid Beheshti University via G. C., Evin 1983963113 Tehran Iran
| | - Łukasz Pecio
- Department of Biochemistry and Crop Quality Institute of Soil Science and Plant Cultivation State Research Institute Puławy Poland
| | - Kosar Babanezhad‐Harikandei
- Department of Phytochemistry Medicinal Plants and Drugs Research Institute Shahid Beheshti University via G. C., Evin 1983963113 Tehran Iran
| | - Mona Khoramjouy
- Department of Pharmacology and Toxicology School of Pharmacy Shahid Beheshti University of Medical Sciences 2660 Vali-e-Asr Ave. Tehran 1991953381 Iran
| | - Soraya Shahhosseini
- Department of Pharmaceutical Chemistry and Radiopharmacy School of Pharmacy Shahid Beheshti University of Medical Sciences 2660 Vali-e-Asr Ave. Tehran 1991953381 Iran
| | - Mehrdad Faizi
- Department of Pharmacology and Toxicology School of Pharmacy Shahid Beheshti University of Medical Sciences 2660 Vali-e-Asr Ave. Tehran 1991953381 Iran
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Zhu C, Huang K, Bai Y, Feng X, Gong L, Wei C, Huang H, Zhang H. Dietary supplementation with berberine improves growth performance and modulates the composition and function of cecal microbiota in yellow-feathered broilers. Poult Sci 2020; 100:1034-1048. [PMID: 33518062 PMCID: PMC7858044 DOI: 10.1016/j.psj.2020.10.071] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 10/13/2020] [Accepted: 10/20/2020] [Indexed: 12/15/2022] Open
Abstract
This study investigated the effect of berberine (BBR) on growth performance and composition and function of cecal microbiota in yellow-feathered broilers. A total of 360 1-day-old female broilers were assigned to 3 dietary treatments, each with 6 replicates of 20 birds. The dietary treatments consisted of a basal diet as negative control (NC), basal plus 200 mg/kg oxytetracycline calcium and 250 mg/kg nasiheptide as an antibiotic positive control (PC), and basal plus 250 mg/kg BBR. On day 21, 42, and 63, one chicken from each replicate was randomly selected for blood collection and cecal sampling. The 16S rRNA sequencing technology was used to analyze the community composition and function of cecal microbiota. Dietary supplementation with antibiotics or BBR increased the final body weight (BW) at day 63 and the average daily gain (ADG) during 1 to 21 d compared with the NC (P < 0.05). Supplementation with BBR improved the average daily feed intake (ADFI) at 22 to 42 d, 43 to 63 d, and 1 to 63 d (P < 0.05). Feed efficiency, indicated by feed to gain ratio (F/G), increased with PC during day 1 to 21 compared with NC (P < 0.05). The plasma concentrations of total protein at 42 d and uric acid at 21 d were increased, whereas creatine concentration at 63 d was decreased by BBR treatment (P < 0.05). The Chao 1 and Shannon index representing microbial α-diversity was reduced by BBR treatment (P < 0.05). The abundances of phylum Firmicutes and genera Lachnospiraceae, Lachnoclostridium, Clostridiales, and Intestinimonas were decreased, whereas the abundances of phylum Bacteroidetes and genus Bacteroides were increased with BBR treatment. Functional prediction of microbiota revealed that BBR treatment enriched pathways related to metabolism, organismal systems, and genetic information processing, especially DNA replication. The abundance of phylum Bacteroidetes, and genera Bacteroides and Lactobacillus in cecal contents were positively correlated with broiler growth performance. These results demonstrated dietary BBR supplementation improved the growth performance of yellow-feathered broilers, and was closely related to the significant changes in cecal microbiota composition.
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Affiliation(s)
- Cui Zhu
- School of Life Science and Engineering, Foshan University, Foshan 528225, China.
| | - Kaiyong Huang
- School of Life Science and Engineering, Foshan University, Foshan 528225, China
| | - Yinshan Bai
- School of Life Science and Engineering, Foshan University, Foshan 528225, China
| | - Xin Feng
- School of Life Science and Engineering, Foshan University, Foshan 528225, China
| | - Li Gong
- School of Life Science and Engineering, Foshan University, Foshan 528225, China
| | - Chuangxin Wei
- School of Life Science and Engineering, Foshan University, Foshan 528225, China
| | - Hanze Huang
- School of Life Science and Engineering, Foshan University, Foshan 528225, China
| | - Huihua Zhang
- School of Life Science and Engineering, Foshan University, Foshan 528225, China.
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25
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Di Bisceglie AM, Watts GF, Lavin P, Yu M, Bai R, Liu L. Pharmacokinetics and pharmacodynamics of HTD1801 (berberine ursodeoxycholate, BUDCA) in patients with hyperlipidemia. Lipids Health Dis 2020; 19:239. [PMID: 33183320 PMCID: PMC7661247 DOI: 10.1186/s12944-020-01406-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 10/19/2020] [Indexed: 12/21/2022] Open
Abstract
Background Reduction in elevated serum cholesterol concentrations is important in the management of individuals at risk of atherosclerotic cardiovascular disease (ASCVD), such as myocardial infarction and thrombotic stroke. Although HMGCoA reductase inhibitors (“statins”) are frequently used for this purpose, a significant proportion of patients remain at increased residual risk of ASCVD as they do not adequately address some of the associated co-morbidities such as diabetes and fatty liver disease. Methods A double-blind, randomized, placebo-controlled, dose ranging study was carried out that compared three doses of berberine ursodeoxycholate (BUDCA) to placebo in a cohort of subjects with a history of hypercholesterolemia and serum LDL cholesterol levels above 2.59 mmol/L (> 99.9 mg/dL). BUDCA was administered in two divided doses each day for 28 days. The primary endpoints of the study were safety and tolerability of this new compound, as well as its effect in lowering serum lipid and lipoprotein concentrations. Results A total of 50 subjects were enrolled into three dose cohorts in this study. BUDCA was generally well tolerated, even at doses of 2000 mg per day (the highest dose group); there were no significant adverse effects reported and this highest dose was associated with significant reductions in LDL cholesterol. By day 28 and with the highest dose of BUDCA, there were significant reductions in the serum concentrations of total cholesterol by 8.2% (P = 0.0004) and LDL cholesterol by 10.4% (P = 0.0006), but no significant changes in triglyceride and HDL cholesterol concentrations. Conclusions BUDCA is a new single molecular entity that has a significant but modest effect in safely lowering serum LDL-cholesterol concentrations in individuals with a history of hypercholesterolemia. It has a potential use for treating hypercholesterolemia in individuals who cannot take statins, and possibly as adjunctive to other agents, such as ezetimibe or bempedoic acid. Trial registration The study was registered on Clinicaltrials.gov (NCT03381287).
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Affiliation(s)
- Adrian M Di Bisceglie
- Department of Internal Medicine, Saint Louis University, St. Louis, USA. .,HighTide Therapeutics, Rockville, MD, USA.
| | - Gerald F Watts
- Department of Cardiology, Royal Perth Hospital, School of Medicine, University of Western Australia, Perth, Australia
| | - Philip Lavin
- Boston Biostatistics Research Foundation, Framingham, MA, USA
| | - Meng Yu
- HighTide Therapeutics, Rockville, MD, USA
| | - Ru Bai
- HighTide Therapeutics, Rockville, MD, USA
| | - Liping Liu
- HighTide Therapeutics, Rockville, MD, USA
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26
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Xu X, Yi H, Wu J, Kuang T, Zhang J, Li Q, Du H, Xu T, Jiang G, Fan G. Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence. Biomed Pharmacother 2020; 133:110984. [PMID: 33186794 DOI: 10.1016/j.biopha.2020.110984] [Citation(s) in RCA: 105] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 11/01/2020] [Accepted: 11/03/2020] [Indexed: 02/07/2023] Open
Abstract
The increased incidence of metabolic diseases (e.g., diabetes and obesity) has seriously affected human health and life safety worldwide. It is of great significance to find effective drugs from natural compounds to treat metabolic diseases. Berberine (BBR), an important quaternary benzylisoquinoline alkaloid, exists in many traditional medicinal plants. In recent years, BBR has received widespread attention due to its good potential in the treatment of metabolic diseases. In order to promote the basic research and clinical application of BBR, this review provides a timely and comprehensive summary of the pharmacological and clinical advances of BBR in the treatment of five metabolic diseases, including type 2 diabetes mellitus, obesity, non-alcoholic fatty liver disease, hyperlipidemia, and gout. Both animal and clinical studies have proved that BBR has good therapeutic effects on these five metabolic diseases. The therapeutic effects of BBR are based on regulating various metabolic aspects and pathophysiological procedures. For example, it can promote insulin secretion, improve insulin resistance, inhibit lipogenesis, alleviate adipose tissue fibrosis, reduce hepatic steatosis, and improve gut microbiota disorders. Collectively, BBR may be a good and promising drug candidate for the treatment of metabolic diseases. More studies, especially clinical trials, are needed to further confirm its molecular mechanisms and targets. In addition, large-scale, long-term and multi-center clinical trials are necessary to evaluate the efficacy and safety of BBR in the treatment of these metabolic diseases.
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Affiliation(s)
- Xinmei Xu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Huan Yi
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Jiasi Wu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Tingting Kuang
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Jing Zhang
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Qi Li
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Huan Du
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Tong Xu
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Guihua Jiang
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Gang Fan
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
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Li M, Zhou W, Dang Y, Li C, Ji G, Zhang L. Berberine compounds improves hyperglycemia via microbiome mediated colonic TGR5-GLP pathway in db/db mice. Biomed Pharmacother 2020; 132:110953. [PMID: 33254441 DOI: 10.1016/j.biopha.2020.110953] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 10/27/2020] [Accepted: 10/27/2020] [Indexed: 02/07/2023] Open
Abstract
Berberine compounds (BC), consisting of berberine (BBR), oryzanol and vitamin B6, have been used to treat diabetes and hyperlipidemia in recent years, but the potential mechanisms under the effects have not been well determined. In this study, we evaluated the effect of BC in db/db mice, and found that BC treatment reversed the increased levels of fasting glucose and hemoglobin A1c in db/db mice, which was superior to BBR treatment. Fecal 16S rRNA gene sequencing indicated that BC increased relative abundance of microbiomes Bacteroidaceae and Clostridiaceae, which may promote conversion of primary bile acid cholic acid (CA) into secondary bile acid deoxycholic acid (DCA). Gas chromatography/mass spectrometry (GC/MS)-based metabolomics revealed that BC treatment increased fecal DCA level. Since DCA processes the potential to activate bile acid receptor-takeda G protein-coupled receptor 5 (TGR5) and induce glucagon-like peptide (GLP) secretion, we detected TGR5 expression, and found that BC-treatment significantly increased the colonic TGR5 and serum GLP-1/-2 levels in db/db mice. Modulation of TGR5-GLP pathway may also affect metabolomic profiles of serum and liver, and BC treatment showed effects on restoring the altered carbohydrate, lipid, amino acid and nucleotide metabolism. Our study suggested that BC improved hyperglycemia, the effect might attribute to the increased microbiome mediated DCA production, which up-regulated colonic TGR5 expression and GLP secretion, and improved glucose, lipid and energy metabolism in db/db mice.
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Affiliation(s)
- Meng Li
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Wenjun Zhou
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Yanqi Dang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Chunlin Li
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Guang Ji
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
| | - Li Zhang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
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Cao H, Li C, Lei L, Wang X, Liu S, Liu Q, Huan Y, Sun S, Shen Z. Stachyose Improves the Effects of Berberine on Glucose Metabolism by Regulating Intestinal Microbiota and Short-Chain Fatty Acids in Spontaneous Type 2 Diabetic KKAy Mice. Front Pharmacol 2020; 11:578943. [PMID: 33192521 PMCID: PMC7642818 DOI: 10.3389/fphar.2020.578943] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 09/21/2020] [Indexed: 01/01/2023] Open
Abstract
Berberine (BBR) has the beneficial effects of anti-inflammation, anti-bacteria, and anti-diabetes. The clinical application of BBR has been hindered by its poor gastrointestinal absorption. Stachyose (Sta), a prebiotic agent, improves the composition of gut microbiota and benefits for diabetes. We therefore investigated whether Sta improves the anti-diabetic actions of BBR using KKAy mice. Here, we find that the combination of BBR and Sta is more effective than BBR alone in blood glucose control, improvement of insulin resistance and islet functions, inflammatory mediators decrease, and maintenance of intestinal barrier integrity. Gut microbiota analysis demonstrates that both BBR and combined administration enhance the abundance of Bacteroidaceae and Akkermansiaceae and decrease Lachnospiraceae levels, whereas Akkermansiaceae elevation due to the administration of BBR with Sta is more significant than BBR alone. Interestingly, the proportion of Lactobacillaceae increases with combination treatment, but is diminished by BBR. Additionally, BBR with Sta significantly reduces the concentrations of fecal short-chain fatty acids compared to BBR. Collectively, these results indicate that the combination of BBR and Sta imparts better effects on the maintenance of glycemia and intestinal homeostasis than BBR alone by modulating gut microbiota and short-chain fatty acids, thereby providing a novel approach for the treatment of type 2 diabetes mellitus.
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Affiliation(s)
| | - Caina Li
- *Correspondence: Zhufang Shen, , Caina Li,
| | | | | | | | | | | | | | - Zhufang Shen
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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Wei M, Ma Y, Shen L, Xu Y, Liu L, Bu X, Guo Z, Qin H, Li Z, Wang Z, Wu K, Yao L, Li J, Zhang J. NDRG2 regulates adherens junction integrity to restrict colitis and tumourigenesis. EBioMedicine 2020; 61:103068. [PMID: 33099085 PMCID: PMC7581885 DOI: 10.1016/j.ebiom.2020.103068] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 09/26/2020] [Accepted: 09/29/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Paracellular barriers play an important role in the pathogenesis of Inflammatory bowel disease (IBD) and maintain gut homeostasis. N-myc downstream-regulated gene 2 (NDRG2) has been reported to be a tumour suppressor gene and to inhibit colorectal cancer metastasis. However, whether NDRG2 affects colitis initiation and colitis-associated colorectal cancer is unclear. METHODS Intestine-specific Ndrg2 deficiency mice (Ndrg2ΔIEC) were subjected to DSS- or TNBS-induced colitis, and AOM-DSS-induced colitis-associated tumour. HT29 cells, Caco2 cells, primary intestinal epithelial cells (IECs) from Ndrg2ΔIEC mice, mouse embryo fibroblasts (MEFs) from systemic Ndrg2 knockout mice, HEK293 cells and human UC and DC specimens were used to investigate NDRG2 function in colitis and colitis-associated tumour. FINDINGS Ndrg2 loss led to adherens junction (AJ) structure destruction via E-cadherin expression attenuation, resulting in diminished epithelial barrier function and increased intestinal epithelial permeability. Mechanistically, NDRG2 enhanced the interaction of E3 ligase FBXO11 with Snail, the repressor of E-cadherin, to promote Snail degradation by ubiquitination and maintained E-cadherin expression. In human ulcerative colitis patients, reduced NDRG2 expression is positively correlated with severe inflammation. INTERPRETATION These findings demonstrate that NDRG2 is an essential colonic epithelial barrier regulator and plays an important role in gut homeostasis maintenance and colitis-associated tumour development. FUNDING National Natural Science Foundation of China (No. 81770523, 31571437, 81672751), Creative Research Groups of China (No. 81421003), State Key Laboratory of Cancer Biology Project (CBSKL2019ZZ11, CBSKL201406, CBSKL2017Z08 and CBSKL2017Z11), Fund for Distinguished Young Scholars of ShaanXi province (2019JC-22).
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Affiliation(s)
- Mengying Wei
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an 710032, China
| | - Yongzheng Ma
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an 710032, China
| | - Liangliang Shen
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an 710032, China
| | - Yuqiao Xu
- The State Key Laboratory of Cancer Biology, Department of Pathology, the Fourth Military Medical University, Xi'an 710032, China
| | - Lijun Liu
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an 710032, China
| | - Xin Bu
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an 710032, China
| | - Zhihao Guo
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an 710032, China
| | - Hongyan Qin
- State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an 710032, China
| | - Zengshan Li
- The State Key Laboratory of Cancer Biology, Department of Pathology, the Fourth Military Medical University, Xi'an 710032, China
| | - Zhe Wang
- The State Key Laboratory of Cancer Biology, Department of Pathology, the Fourth Military Medical University, Xi'an 710032, China
| | - Kaichun Wu
- State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Disease, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China
| | - Libo Yao
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an 710032, China
| | - Jipeng Li
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032 Xi'an, China; Department of Experimental Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
| | - Jian Zhang
- The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Xi'an 710032, China.
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Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). Nat Commun 2020; 11:5015. [PMID: 33024120 PMCID: PMC7538905 DOI: 10.1038/s41467-020-18414-8] [Citation(s) in RCA: 189] [Impact Index Per Article: 37.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 08/18/2020] [Indexed: 02/07/2023] Open
Abstract
Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], −1.04[−1.19, −0.89]%) and BBR-alone group (−0.99[−1.16, −0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (−0.59[−0.75, −0.44]%, −0.53[−0.68, −0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261). The gut microbiome affects systemic metabolism and is a therapeutic target for type 2 diabetes. Here the authors demonstrate in a randomized controlled trial that effects of berberine, a plant alkaloid known to lower blood glucose, may be explained by the inhibition of Ruminococcus bromii mediated biotransformation of the bile acid deoxycholic acid.
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Abstract
Advances in the understanding of the pathogenesis of type 2 diabetes mellitus (T2D) have revealed a role for gut microbiota dysbiosis in driving this disease. This suggests the possibility that approaches to restore a healthy host-microbiota relationship might be a means of ameliorating T2D. Indeed, recent studies indicate that many currently used treatments for T2D are reported to impact gut microbiota composition. Such changes in gut microbiota may mediate and/or reflect the efficacy of these interventions. This article outlines the rationale for considering the microbiota as a central determent of development of T2D and, moreover, reviews evidence that impacting microbiota might be germane to amelioration of T2D, both in terms of understanding mechanisms that mediate efficacy of exiting T2D therapies and in developing novel treatments for this disorder.
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Affiliation(s)
- Aneseh Adeshirlarijaney
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA,CONTACT Andrew Gewirtz Institute for Biomedical Sciences, Georgia State University, Atlanta, GA30303, USA
| | - Andrew T. Gewirtz
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA
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Amin AR, Kassab RB, Abdel Moneim AE, Amin HK. Comparison Among Garlic, Berberine, Resveratrol,Hibiscus sabdariffa, GenusZizyphus, Hesperidin, Red Beetroot,Catha edulis,Portulaca oleracea, and Mulberry Leaves in the Treatment of Hypertension and Type 2 DM: A Comprehensive Review. Nat Prod Commun 2020. [DOI: 10.1177/1934578x20921623] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Diabetes mellitus (DM) and hypertension are 2 of the most prevalent diseases with poor impact on health status worldwide. In most cases, they coexist with other metabolic disorders as well as cardiac, micro- and macrovascular complications. Many plants are known for their hypotensive, cardioprotective, and/or antidiabetic activities. Their active ingredients either identified and isolated or still utilized as herbal preparations of certain plant parts. The use of medicinal plants comprises the main basis for most of the traditional medicine (TM) systems and procedures. As conventional medicines seem insufficient to control such progressive diseases, herbal agents from TM could be used as adjuvant with good impact on disease control and progression as well as other concomitant health conditions. The aim of this study is to compare the efficacy of 10 different herbal medicines of botanical origin or herbal preparations in the management of hypertension and its cardiovascular complications and type 2 DM along with various coexisting health disorders. These herbal medicines are garlic, berberine, resveratrol, Hibiscus sabdariffa, Zizyphus ( oxyphylla, mucronate, jujube, rugosa), hesperidin, red beetroot, Catha edulis, mulberry leaves, and Portulaca oleracea.
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Affiliation(s)
- Amira R. Amin
- Cardiology and Oncology Section, Nasser Institute for Research and Treatment, Cairo, Egypt
| | - Rami B. Kassab
- Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt
| | - Ahmed E. Abdel Moneim
- Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt
| | - Hatem K. Amin
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Helwan University, Egypt
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Ilyas Z, Perna S, Al-Thawadi S, Alalwan TA, Riva A, Petrangolini G, Gasparri C, Infantino V, Peroni G, Rondanelli M. The effect of Berberine on weight loss in order to prevent obesity: A systematic review. Biomed Pharmacother 2020; 127:110137. [PMID: 32353823 DOI: 10.1016/j.biopha.2020.110137] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 03/30/2020] [Accepted: 03/30/2020] [Indexed: 01/16/2023] Open
Abstract
This study provides a critical overview of experimental studies in vitro, in humans, and in animals that evaluated the efficacy of Berberine and its effect on management of obesity and the related metabolic consequences. As a result of this review, we summarized the effects of Berberine in different models and the related mechanism of actions. In preclinical models, Berberine demonstrates that it affects gut microbiota by reducing diversity of microbes starting at a dosage of 100 mg/kg/day. Moreover, in animal models, Berberine explicates an action on glucose through the inhibition of α-glycosidase at a dose of 200 mh/kg/day. Berberine is also known to be effective against differentiation of adipocytes through a decrease in LXRs, PPARs, and SREBPs expression at 150 mg/kg/day. Other mechanism ascribed to Berberine are related to its inhibition of hepatic gluconeogenesis through the Phospheoenolpyruvate carboxykinase (PEPCK), Glucose-6-phosphate (G6Pase) and AMP-activated protein kinase (AMPK). Furthermore, Berberine (associated to Red Yeast Rice) is effective in decreasing lipid levels in rats, which consequently lowers the change of weight gain at dosage of 40 mg/kg to 380 mg/kg/day. All the above preclinical data are confirmed in human studies where Berberine can modulate the diversity of gut microbes at the dose of 500 mg/day. In addition, Berberine is found to have a beneficial impact on gene regulation for the absorption of cholesterol at a daily dose of 300 mg in humans, an amelioration on glucose accumulation at 1.0 g daily dose was also observed. For all these reasons, this review gives an important good account of the impact of Berberine in obesity treatment and prevention.
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Affiliation(s)
- Zahra Ilyas
- University of Bahrain, Department of Biology, College of Science, Sakhir Campus P. O. Box 32038, Bahrain
| | - Simone Perna
- University of Bahrain, Department of Biology, College of Science, Sakhir Campus P. O. Box 32038, Bahrain
| | - Salwa Al-Thawadi
- University of Bahrain, Department of Biology, College of Science, Sakhir Campus P. O. Box 32038, Bahrain
| | - Tariq A Alalwan
- University of Bahrain, Department of Biology, College of Science, Sakhir Campus P. O. Box 32038, Bahrain
| | - Antonella Riva
- Research and Development Unit, Indena, Milan, 20139, Italy
| | | | - Clara Gasparri
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona "Istituto Santa Margherita'', University of Pavia, Pavia, 27100, Italy.
| | - Vittoria Infantino
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, 27100, Italy
| | - Gabriella Peroni
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona "Istituto Santa Margherita'', University of Pavia, Pavia, 27100, Italy
| | - Mariangela Rondanelli
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, 27100, Italy; IRCCS Mondino Foundation, Pavia, 27100, Italy
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Belwal T, Bisht A, Devkota HP, Ullah H, Khan H, Pandey A, Bhatt ID, Echeverría J. Phytopharmacology and Clinical Updates of Berberis Species Against Diabetes and Other Metabolic Diseases. Front Pharmacol 2020; 11:41. [PMID: 32132921 PMCID: PMC7040237 DOI: 10.3389/fphar.2020.00041] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Accepted: 01/14/2020] [Indexed: 02/05/2023] Open
Abstract
The incidences of diabetic mellitus and other metabolic diseases such as hypertension and hyperlipidemia are increasing worldwide; however, the current treatment is not able to control the rapidly increasing trend in diabetes mortality and morbidity. Studies related to the effectiveness of extracts and pure compounds obtained from plants have shown promising responses in preclinical and clinical studies related to these metabolic diseases. Plants belonging to the genus Berberis (Family: Berberidaceae) are widely distributed with nearly 550 species worldwide. Extracts and compounds obtained from Berberis species, especially Berberine alkaloid, showed effectiveness in the management of diabetes and other metabolic diseases. Various pharmacological experiments have been performed to evaluate the effects of Berberis extracts, berberine, and its natural and chemically synthesized derivatives against various cell and animal disease models with promising results. Various clinical trials conducted so far also showed preventive effects of Berberis extracts and berberine against metabolic diseases. The present review focuses on i) research updates on traditional uses, ii) phytopharmacology and clinical studies on Berberis species, and iii) active metabolites in the prevention and treatment of diabetes and other metabolic diseases with a detailed mechanism of action. Furthermore, the review critically analyzes current research gaps in the therapeutic use of Berberis species and berberine and provides future recommendations.
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Affiliation(s)
- Tarun Belwal
- Centre for Biodiversity Conservation and Management, G. B. Pant National Institute of Himalayan Environment and Sustainable Development (GBPNIHESD), Kosi-Katarmal, Almora, India
| | - Aarti Bisht
- Centre for Biodiversity Conservation and Management, G. B. Pant National Institute of Himalayan Environment and Sustainable Development (GBPNIHESD), Kosi-Katarmal, Almora, India
| | - Hari Prasad Devkota
- Department of Instrumental Analysis, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.,Program for Leading Graduate Schools, Health Life Science: Interdisciplinary and Glocal Oriented (HIGO) Program, Kumamoto University, Kumamoto, Japan
| | - Hammad Ullah
- Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan
| | - Aseesh Pandey
- Centre for Biodiversity Conservation and Management, G.B. Pant National Institute of Himalayan Environment and Sustainable Development, Sikkim Regional Centre, Pangthang, Gangtok, India
| | - Indra Dutt Bhatt
- Centre for Biodiversity Conservation and Management, G. B. Pant National Institute of Himalayan Environment and Sustainable Development (GBPNIHESD), Kosi-Katarmal, Almora, India
| | - Javier Echeverría
- Department of Environmental Sciences, Faculty of Chemistry and Biology, Universidad de Santiago de Chile, Santiago, Chile
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Kong WJ, Vernieri C, Foiani M, Jiang JD. Berberine in the treatment of metabolism-related chronic diseases: A drug cloud (dCloud) effect to target multifactorial disorders. Pharmacol Ther 2020; 209:107496. [PMID: 32001311 DOI: 10.1016/j.pharmthera.2020.107496] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 01/17/2020] [Indexed: 12/23/2022]
Abstract
Berberine (BBR) is a multi-target drug (MTD) that has proven effective in the treatment of metabolism-related chronic diseases (CDs). However, the mode of action (MOA) of BBR remains to be clarified. At a cellular level, the inhibitory effect of BBR on mitochondrial enzymes is probably responsible for many of its biological activities, including the activation of low-density lipoprotein receptor (LDLR), AMP-activated protein kinase (AMPK) and insulin receptor (InsR); these biological activities contribute to ameliorate peripheral blood metabolic profiles, e.g. by reducing plasma lipids and glucose levels, thus improving signs and symptoms of metabolic disorders. In this perspective, BBR acts as a targeted therapy. However, it also exerts pleiotropic systemic activities on some root causes of CDs that include antioxidant / anti-inflammatory effects and modifications of gut microbiota composition and metabolism, which may also contribute to its disease-modifying effects. After reviewing the different MOA of BBR, here we propose that BBR acts through a drug-cloud (dCloud) mechanism, as different to a drug-target effect. The dCloud here is defined as a group of terminal molecular events induced by the drug (or/and related metabolites), as well as the network connections among them. In this scenario, the therapeutic efficacy of BBR is the result of its dCloud effect acting on symptoms/signs as well as on root causes of the diseases. The dCloud concept is applicable to other established MTDs, such as aspirin, metformin, statins as well as to nutrient starvation, thus providing a novel instrument for the design of effective therapies against multifactorial metabolism-related CDs.
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Affiliation(s)
- Wei-Jia Kong
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050 Beijing, China
| | - Claudio Vernieri
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Fondazione Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy
| | - Marco Foiani
- Fondazione Istituto FIRC di Oncologia Molecolare, 20139 Milan, Italy; University of Milan, Italy.
| | - Jian-Dong Jiang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050 Beijing, China; State Key Laboratory of Bioactive Natural Products and Function, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050 Beijing, China.
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Shinjyo N, Parkinson J, Bell J, Katsuno T, Bligh A. Berberine for prevention of dementia associated with diabetes and its comorbidities: A systematic review. JOURNAL OF INTEGRATIVE MEDICINE-JIM 2020; 18:125-151. [PMID: 32005442 DOI: 10.1016/j.joim.2020.01.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 12/04/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND A growing number of epidemiological studies indicate that metabolic syndrome (MetS) and its associated features play a key role in the development of certain degenerative brain disorders, including Alzheimer's disease and vascular dementia. Produced by several different medicinal plants, berberine is a bioactive alkaloid with a wide range of pharmacological effects, including antidiabetic effects. However, it is not clear whether berberine could prevent the development of dementia in association with diabetes. OBJECTIVE To give an overview of the therapeutic potential of berberine as a treatment for dementia associated with diabetes. SEARCH STRATEGY Database searches A and B were conducted using PubMed and ScienceDirect. In search A, studies on berberine's antidementia activities were identified using "berberine" and "dementia" as search terms. In search B, recent studies on berberine's effects on diabetes were surveyed using "berberine" and "diabetes" as search terms. INCLUSION CRITERIA Clinical and preclinical studies that investigated berberine's effects associated with MetS and cognitive dysfunction were included. DATA EXTRACTION AND ANALYSIS Data from studies were extracted by one author, and checked by a second; quality assessments were performed independently by two authors. RESULTS In search A, 61 articles were identified, and 22 original research articles were selected. In search B, 458 articles were identified, of which 101 were deemed relevant and selected. Three duplicates were removed, and a total of 120 articles were reviewed for this study. The results demonstrate that berberine exerts beneficial effects directly in the brain: enhancing cholinergic neurotransmission, improving cerebral blood flow, protecting neurons from inflammation, limiting hyperphosphorylation of tau and facilitating β-amyloid peptide clearance. In addition, evidence is growing that berberine is effective against diabetes and associated disorders, such as atherosclerosis, cardiomyopathy, hypertension, hepatic steatosis, diabetic nephropathy, gut dysbiosis, retinopathy and neuropathy, suggesting indirect benefits for the prevention of dementia. CONCLUSION Berberine could impede the development of dementia via multiple mechanisms: preventing brain damages and enhancing cognition directly in the brain, and indirectly through alleviating risk factors such as metabolic dysfunction, and cardiovascular, kidney and liver diseases. This study provided evidence to support the value of berberine in the prevention of dementia associated with MetS.
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Affiliation(s)
- Noriko Shinjyo
- Department of Infection and Host Defense, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
| | - James Parkinson
- Department of Life Sciences, Faculty of Science and Technology at the University of Westminster, London W1W 6UW, United Kingdom
| | - Jimmy Bell
- Department of Life Sciences, Faculty of Science and Technology at the University of Westminster, London W1W 6UW, United Kingdom.
| | - Tatsuro Katsuno
- Kashiwanoha Clinic of East Asian Medicine, Chiba University Hospital, Kashiwa, Chiba 277-0882, Japan
| | - Annie Bligh
- School of Health Sciences, Caritas Institute of Higher Education, Tseung Kwan O, NT 999077, Hong Kong, China.
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Xu B, Yan Y, Huang J, Yin B, Pan Y, Ma L. Cortex Phellodendri extract's anti-diarrhea effect in mice related to its modification of gut microbiota. Biomed Pharmacother 2019; 123:109720. [PMID: 31884345 DOI: 10.1016/j.biopha.2019.109720] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 11/30/2019] [Accepted: 12/04/2019] [Indexed: 12/20/2022] Open
Abstract
Cortex Phellodendri extract (CPE) has been used in China to treat diarrhea whereas the underlying mechanisms remain poorly understood. Given that dysbiosis of gut microbiota is a potential reason for diarrhea, and that oral CPE has a low absorption rate in intestine, we hypothesized that modification of gut microbiota is an important factor in CPE's anti-diarrhea effect. To test this hypothesis, we established a diarrhea model by challenging post-weaning mice with oral Enterotoxigenic-Escherichia coli (ETEC), and then the mice were treated with two doses of CPE (80 mg/kg bodyweight and 160 mg/kg bodyweight) or the vehicle control (phosphate buffered saline). Diarrhea indices, inflammatory factors, morphology of jejunum, short-chain fatty acids (SCFAs), and serum endocrine were determined. Modification of gut microbiota was analyzed using 16S rDNA high-throughput sequencing. The changes in functional profiles of gut microbiota were predicted using software PICRUSt. We then explored the association between CPE-responding bacteria and the symptoms indices with the spearman's rank correlation coefficient and significance test. Compared with diarrheal mice, CPE decreased Gut/Carcass ratio and water content of stool, increased goblet cell density and villus height/crypt depth of jejunum, as well as decreased inflammatory indices (Tumour Necrosis Factor-α, Myeloperoxidase and Interleukin-1α). CPE shifted the gut microbiota significantly by increasing alpha diversity (observed species, ace, Shannon, and Simpson) and restoring the gut microbiota. CPE increased Firmicutes and decreased Bacteroidetes. The reduced genus Prevotella, Acinetobacter, and Morganella were positively associated with the diarrhea indices, whereas increased genus Odoribacter, Rikenella, and Roseburia were negatively associated with the diarrhea indices. The abundance of carbohydrate metabolism-related gene and SCFAs-producing bacteria were increased, which was evidenced by increased butyric acid and total SCFAs concentration in the caecum. Consequently, endocrine peptides glucagon-like peptide-1, epidermal growth factor, and peptide tyrosine tyrosine in serum were elevated. CONCLUSIONS: CPE shows a shift function on the gut microbiota in alleviating the diarrhea of mice in a dose-dependent manner. In addition, the microbial metabolites SCFAs may mediate CPE's anti-diarrhea effect by enhancing endocrine secretion in mice.
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Affiliation(s)
- Baoyang Xu
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China
| | - Yiqin Yan
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China
| | - Juncheng Huang
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China
| | - Boqi Yin
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China
| | - Yunxin Pan
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China
| | - Libao Ma
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, 430070, Hubei, China.
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Li CN, Wang X, Lei L, Liu MZ, Li RC, Sun SJ, Liu SN, Huan Y, Zhou T, Liu Q, Cao H, Bai GL, Han YW, Shen ZF. Berberine combined with stachyose induces better glycometabolism than berberine alone through modulating gut microbiota and fecal metabolomics in diabetic mice. Phytother Res 2019; 34:1166-1174. [PMID: 31833107 PMCID: PMC7216932 DOI: 10.1002/ptr.6588] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 10/17/2019] [Accepted: 11/24/2019] [Indexed: 01/19/2023]
Abstract
Berberine (BBR), a small alkaloid, is used as a hypoglycemic agent in China. Stachyose (Sta), a Rehmannia glutinosa oligosaccharide, acts as a prebiotic. This study aimed to evaluate whether BBR combined with Sta produced better glycometabolism than BBR alone, and explored the effects on gut microbiota and metabolomics. Type‐2 diabetic db/db mice were administered BBR (100 mg/kg), Sta (200 mg/kg), or both by gavage once daily. Glucose metabolism, the balance of α‐ and β‐cells, and mucin‐2 expression were ameliorated by combined treatment of BBR and Sta, with stronger effects than upon treatment with BBR alone. The microbial diversity and richness were altered after combined treatment and after treatment with BBR alone. The abundance of Akkermansia muciniphila was increased by combined treatment compared to treatment with BBR alone, while the levels of the metabolite all‐trans‐heptaprenyl diphosphate were decreased and the levels of fumaric acid were increased, which both showed a strong correlation with A. muciniphila. In summary, BBR combined with Sta produced better glycometabolism than BBR alone through modulating gut microbiota and fecal metabolomics, and may aid in the development of a novel pharmaceutical strategy for treating Type 2 diabetes mellitus.
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Affiliation(s)
- Cai-Na Li
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Xing Wang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Lei Lei
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Min-Zhi Liu
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Rong-Cui Li
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Su-Juan Sun
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Shuai-Nan Liu
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yi Huan
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Tian Zhou
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Quan Liu
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Hui Cao
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Guo-Liang Bai
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yu-Wei Han
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Zhu-Fang Shen
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
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An X, Bao Q, Di S, Zhao Y, Zhao S, Zhang H, Lian F, Tong X. The interaction between the gut Microbiota and herbal medicines. Biomed Pharmacother 2019; 118:109252. [DOI: 10.1016/j.biopha.2019.109252] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Revised: 07/18/2019] [Accepted: 07/18/2019] [Indexed: 12/14/2022] Open
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Li BY, Xu XY, Gan RY, Sun QC, Meng JM, Shang A, Mao QQ, Li HB. Targeting Gut Microbiota for the Prevention and Management of Diabetes Mellitus by Dietary Natural Products. Foods 2019; 8:E440. [PMID: 31557941 PMCID: PMC6835620 DOI: 10.3390/foods8100440] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 09/20/2019] [Accepted: 09/23/2019] [Indexed: 12/16/2022] Open
Abstract
Diabetes mellitus is one of the biggest public health concerns worldwide, which includes type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and other rare forms of diabetes mellitus. Accumulating evidence has revealed that intestinal microbiota is closely associated with the initiation and progression of diabetes mellitus. In addition, various dietary natural products and their bioactive components have exhibited anti-diabetic activity by modulating intestinal microbiota. This review addresses the relationship between gut microbiota and diabetes mellitus, and discusses the effects of natural products on diabetes mellitus and its complications by modulating gut microbiota, with special attention paid to the mechanisms of action. It is hoped that this review paper can be helpful for better understanding of the relationships among natural products, gut microbiota, and diabetes mellitus.
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Affiliation(s)
- Bang-Yan Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Xiao-Yu Xu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Ren-You Gan
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610213, China.
- Department of Food Science & Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Quan-Cai Sun
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China.
| | - Jin-Ming Meng
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Ao Shang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Qian-Qian Mao
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Hua-Bin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
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Ran Q, Wang J, Wang L, Zeng HR, Yang XB, Huang QW. Rhizoma coptidis as a Potential Treatment Agent for Type 2 Diabetes Mellitus and the Underlying Mechanisms: A Review. Front Pharmacol 2019; 10:805. [PMID: 31396083 PMCID: PMC6661542 DOI: 10.3389/fphar.2019.00805] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Accepted: 06/21/2019] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus, especially type 2 diabetes mellitus (T2DM), has become a significant public health burden. Rhizoma coptidis (RC), known as Huang Lian, is widely used for treating diabetes in China. The bioactive compounds of RC, especially alkaloids, have the potential to suppress T2DM-induced lesions, including diabetic vascular dysfunction, diabetic heart disease, diabetic hyperlipidemia, diabetic nephropathy, diabetic encephalopathy, diabetic osteopathy, diabetic enteropathy, and diabetic retinopathy. This review summarizes the effects of RC and its bioactive compounds on T2DM and T2DM complications. Less research has been conducted on non-alkaloid fractions of RC, which may exert synergistic action with alkaloids. Moreover, we summarized the pharmacokinetic properties and structure-activity relationships of RC on T2DM with reference to extant literature and showed clearly that RC has potential therapeutic effect on T2DM.
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Affiliation(s)
- Qian Ran
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jin Wang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Lin Wang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hai-rong Zeng
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiang-bo Yang
- Ya’an Xun Kang Pharmaceutical Co., Ltd, Ya’an, China
| | - Qin-wan Huang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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42
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Du Y, Li X, Su C, Wang L, Jiang J, Hong B. The human gut microbiome - a new and exciting avenue in cardiovascular drug discovery. Expert Opin Drug Discov 2019; 14:1037-1052. [PMID: 31315489 DOI: 10.1080/17460441.2019.1638909] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction: Over the past decade, numerous research efforts have identified the gut microbiota as a novel regulator of human metabolic syndrome and cardiovascular disease (CVD). With the elucidation of underlying molecular mechanisms of the gut microbiota and its metabolites, the drug-discovery process of CVD therapeutics might be expedited. Areas covered: The authors describe the evidence concerning the impact of gut microbiota on metabolic disorders and CVD and summarize the current knowledge of the gut microbial mechanisms that underlie CVD with a focus on microbial metabolites. In addition, they discuss the potential impact of the gut microbiota on the drug efficacy of available cardiometabolic therapeutic agents. Most importantly, the authors review the role of the gut microbiome as a promising source of potential drug targets and novel therapeutics for the development of new treatment modalities for CVD. This review also presents the various effective strategies to investigate the gut microbiome for CVD drug-discovery approaches. Expert opinion: With the elucidation of its causative role in cardiometabolic disease and atherosclerosis, the human gut microbiome holds promises as a reservoir of novel potential therapeutic targets as well as novel therapeutic agents, paving a new and exciting avenue in cardiovascular drug discovery.
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Affiliation(s)
- Yu Du
- NHC Key Laboratory of Biotechnology of Antibiotics , Beijing , China
| | - Xingxing Li
- NHC Key Laboratory of Biotechnology of Antibiotics , Beijing , China.,CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China
| | - Chunyan Su
- NHC Key Laboratory of Biotechnology of Antibiotics , Beijing , China
| | - Li Wang
- NHC Key Laboratory of Biotechnology of Antibiotics , Beijing , China
| | - Jiandong Jiang
- NHC Key Laboratory of Biotechnology of Antibiotics , Beijing , China
| | - Bin Hong
- NHC Key Laboratory of Biotechnology of Antibiotics , Beijing , China.,CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China
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Zhang Z, Xu H, Zhao H, Geng Y, Ren Y, Guo L, Shi J, Xu Z. Edgeworthia gardneri (Wall.) Meisn. water extract improves diabetes and modulates gut microbiota. JOURNAL OF ETHNOPHARMACOLOGY 2019; 239:111854. [PMID: 30954614 DOI: 10.1016/j.jep.2019.111854] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2018] [Revised: 03/21/2019] [Accepted: 04/01/2019] [Indexed: 06/09/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE In Chinese folk medicine, the flower of Edgeworthia gardneri (Wall.) Meisn. is used to treat various metabolic diseases, such as hyperglycemia, hypertension, and hyperlipidemia. AIM OF THE STUDY This study aimed to explore the antidiabetes potential of the flower of E. gardneri and investigate whether it can benefit the entire gut bacteria community. MATERIALS AND METHODS Chemical constituents of the extract were analyzed by UHPLC-Q Exactive Mass Spectrometer (UHPLC-QE-MS). The antidiabetes effect of the water extract (WAE) of the flower of E. gardneri was evaluated in diabetic mice induced by high-fat diet (HFD) and streptozotocin (STZ) (six groups, n = 8) daily at doses of 1, 2, and 3 g/kg for 4 weeks. The gut microbiota was analyzed using high-throughput 16S rRNA gene sequencing. Short-chain fatty acids (SCFAs) in the fecal were also investigated. RESULTS UHPLC-QE-MS analysis identified 29 compounds, including five alkaloids, six coumarins, four flavonoids, 11 organic acids, and three additional compounds, in the WAE. Results showed that the high dose of WAE considerably decreased the blood glucose level by 30.0%. Furthermore, E. gardneri significantly ameliorated insulin resistance and lipid metabolism dysfunction and repaired islet, hepatic, and white fat and colon histology in diabetic mice. Diabetic mice treated with WAE showed apparent changes in the structure and composition of the gut microbiota. WAE reversed the changes in Clostridiales, Lachnospiraceae, S24-7, Rikenellaceae, and Dorea in diabetic mice. The correlation analysis indicated that key OTUs were related to diabetes indices. The amounts of SCFAs, including acetic, propionic, and valeric acids, were significantly high in WAE-treated diabetic groups. CONCLUSIONS E. gardneri treatment improved the glucose metabolism and reshaped the unbalanced gut microbiota of diabetic mice. Our study provides evidence for application of E. gardneri to treatment of diabetes mellitus.
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Affiliation(s)
- Zhiwen Zhang
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214122, PR China.
| | - Hongyu Xu
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214122, PR China; National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China.
| | - Hui Zhao
- Tiebet Yuewang Pharmacopoeia Ecological Tibetan Medicine Technology Co.,Ltd., Tiebet, 850000, PR China.
| | - Yan Geng
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214122, PR China.
| | - Yilin Ren
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214122, PR China; National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China; Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China.
| | - Lin Guo
- Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China.
| | - Jinsong Shi
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214122, PR China.
| | - Zhenghong Xu
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, 214122, PR China; National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China; Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China.
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Lin L, Luo L, Zhong M, Xie T, Liu Y, Li H, Ni J. Gut microbiota: a new angle for traditional herbal medicine research. RSC Adv 2019; 9:17457-17472. [PMID: 35519900 PMCID: PMC9064575 DOI: 10.1039/c9ra01838g] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Accepted: 05/21/2019] [Indexed: 12/28/2022] Open
Abstract
Traditional Herbal Medicine (THM) has been used for thousands of years, and is popular worldwide due to its effectiveness in a variety of diseases. THM has also formed the basis of the discovery of modern drugs like artemisinin and paclitaxel. However, at present, studies that focus on development in the field of THM are stagnant because currently, the effective ingredients in the herbal formulations and the ambiguity of the underlying mechanisms of action are unknown. In this review, we have investigated the studies available that focused on the efficacy, active ingredients and bioavailability of THM, and the function of gut microbiota in THM-mediated treatment of disease. We hypothesized that most THMs treat diseases via three mechanisms: (1) metabolizing into active metabolites by the action of gut microbiota, (2) regulation of gut microbiota balance, and (3) regulating the fermentation products of the gut microbes. Therefore, focusing on these aspects can help elucidate the pharmacodynamic constituents of THM preparations, and their therapeutic mechanisms of action.
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Affiliation(s)
- Longfei Lin
- Institute Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing China
| | - Liyu Luo
- School of Pharmaceutical Science and Technology, Tianjin University Tianjin China
| | - Ming Zhong
- Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Chinese Medicine and Pharmaceutical Science Nanning 530022 China
| | - Tanggui Xie
- Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Chinese Medicine and Pharmaceutical Science Nanning 530022 China
| | - Yuling Liu
- Institute Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing China
| | - Hui Li
- Institute Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing China
| | - Jian Ni
- School of Chinese Material Medica, Beijing University of Chinese Medicine Beijing China
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Sahebkar-Khorasani M, Jarahi L, Cramer H, Safarian M, Naghedi-Baghdar H, Salari R, Behravanrad P, Azizi H. Herbal medicines for suppressing appetite: A systematic review of randomized clinical trials. Complement Ther Med 2019; 44:242-252. [PMID: 31126562 DOI: 10.1016/j.ctim.2019.04.019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 04/13/2019] [Accepted: 04/23/2019] [Indexed: 01/04/2023] Open
Abstract
The suppression of appetite with herbal medicines has become very popular in recent years. We conducted this systematic review to evaluate the recent scientific evidence regarding herbal medicines that are used to suppress appetite. We retrieved clinical trials from PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Scientific Information Database, and IranMedex from January 1, 2013 to April 24, 2018. English and Persian language randomized clinical trials that used herbal medicines to suppress appetite in healthy or obese or overweight individuals were included. Risk of bias was assessed using Cochrane methodology. Out of 591 articles, 22 trials with 973 participants were included. One study on the Meratrim formulation which contained the Sphaeranthus indicus flower heads extract and Garcinia mangostana fruit, revealed longer-term evidence; while 6 studies on Ilex paraguariensis, Spinacia oleracea, Phaseolus vulgaris, Secale cereale, Sorghum bicolor and Plantago showed short-term evidence for suppressing appetite. No serious adverse events were reported. Despite some methodological concerns in the included studies, there is promising evidence for suppressing appetite with herbal medicines that needs to be confirmed in long-term clinical trials with adequate sample size and higher methodological quality with more attention to safety, effective dose and side effects.
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Affiliation(s)
| | - Lida Jarahi
- Department of Community Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Holger Cramer
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
| | - Mohammad Safarian
- Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamideh Naghedi-Baghdar
- School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Roshanak Salari
- Department of Pharmaceutical Sciences in Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Pardis Behravanrad
- Student of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Hoda Azizi
- Department of Chinese and Complementary Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Anlu W, Dongcheng C, He Z, Qiuyi L, Yan Z, Yu Q, Hao X, Keji C. Using herbal medicine to target the “microbiota-metabolism-immunity” axis as possible therapy for cardiovascular disease. Pharmacol Res 2019; 142:205-222. [DOI: 10.1016/j.phrs.2019.02.018] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Revised: 02/18/2019] [Accepted: 02/18/2019] [Indexed: 02/08/2023]
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47
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Feng X, Sureda A, Jafari S, Memariani Z, Tewari D, Annunziata G, Barrea L, Hassan ST, Šmejkal K, Malaník M, Sychrová A, Barreca D, Ziberna L, Mahomoodally MF, Zengin G, Xu S, Nabavi SM, Shen AZ. Berberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics. Theranostics 2019; 9:1923-1951. [PMID: 31037148 PMCID: PMC6485276 DOI: 10.7150/thno.30787] [Citation(s) in RCA: 244] [Impact Index Per Article: 40.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 02/05/2019] [Indexed: 12/11/2022] Open
Abstract
Cardiovascular and metabolic diseases (CVMD) are the leading causes of death worldwide, underscoring the urgent necessity to develop new pharmacotherapies. Berberine (BBR) is an eminent component of traditional Chinese and Ayurvedic medicine for more than 2000 years. Recently, BBR has attracted much interest for its pharmacological actions in treating and/or managing CVMD. Recent discoveries of basic, translational and clinical studies have identified many novel molecular targets of BBR (such as AMPK, SIRT1, LDLR, PCSK9, and PTP1B) and provided novel evidences supporting the promising therapeutic potential of BBR to combat CVMD. Thus, this review provides a timely overview of the pharmacological properties and therapeutic application of BBR in CVMD, and underlines recent pharmacological advances which validate BBR as a promising lead drug against CVMD.
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48
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Tian Y, Cai J, Gui W, Nichols RG, Koo I, Zhang J, Anitha M, Patterson AD. Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation. Drug Metab Dispos 2019; 47:86-93. [PMID: 30409838 PMCID: PMC6323626 DOI: 10.1124/dmd.118.083691] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 11/07/2018] [Indexed: 12/17/2022] Open
Abstract
Intestinal bacteria play an important role in bile acid metabolism and in the regulation of multiple host metabolic pathways (e.g., lipid and glucose homeostasis) through modulation of intestinal farnesoid X receptor (FXR) activity. Here, we examined the effect of berberine (BBR), a natural plant alkaloid, on intestinal bacteria using in vitro and in vivo models. In vivo, the metabolomic response and changes in mouse intestinal bacterial communities treated with BBR (100 mg/kg) for 5 days were assessed using NMR- and mass spectrometry-based metabolomics coupled with multivariate data analysis. Short-term BBR exposure altered intestinal bacteria by reducing Clostridium cluster XIVa and IV and their bile salt hydrolase (BSH) activity, which resulted in the accumulation of taurocholic acid (TCA). The accumulation of TCA was associated with activation of intestinal FXR, which can mediate bile acid, lipid, and glucose metabolism. In vitro, isolated mouse cecal bacteria were incubated with three doses of BBR (0.1, 1, and 10 mg/ml) for 4 hours in an anaerobic chamber. NMR-based metabolomics combined with flow cytometry was used to evaluate the direct physiologic and metabolic effect of BBR on the bacteria. In vitro, BBR exposure not only altered bacterial physiology but also changed bacterial community composition and function, especially reducing BSH-expressing bacteria like Clostridium spp. These data suggest that BBR directly affects bacteria to alter bile acid metabolism and activate FXR signaling. These data provide new insights into the link between intestinal bacteria, nuclear receptor signaling, and xenobiotics.
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Affiliation(s)
- Yuan Tian
- Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People's Republic of China (Y.T.)
| | - Jingwei Cai
- Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People's Republic of China (Y.T.)
| | - Wei Gui
- Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People's Republic of China (Y.T.)
| | - Robert G Nichols
- Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People's Republic of China (Y.T.)
| | - Imhoi Koo
- Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People's Republic of China (Y.T.)
| | - Jingtao Zhang
- Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People's Republic of China (Y.T.)
| | - Mallappa Anitha
- Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People's Republic of China (Y.T.)
| | - Andrew D Patterson
- Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania (Y.T., J.C., W.G., R.G.N., I.K., J.Z., M.A., A.D.P.); and Chinese Academy of Sciences Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, University of Chinese Academy of Sciences, Wuhan, People's Republic of China (Y.T.)
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Dai W, Mu L, Cui Y, Li Y, Chen P, Xie H, Wang X. Berberine Promotes Apoptosis of Colorectal Cancer via Regulation of the Long Non-Coding RNA (lncRNA) Cancer Susceptibility Candidate 2 (CASC2)/AU-Binding Factor 1 (AUF1)/B-Cell CLL/Lymphoma 2 (Bcl-2) Axis. Med Sci Monit 2019; 25:730-738. [PMID: 30681073 PMCID: PMC6357823 DOI: 10.12659/msm.912082] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Background Berberine, a natural isoquinoline alkaloid derived from Berberis genus plants, has been reported to have anti-cancer effects. While cell behavior can be modulated by long non-coding RNAs (lncRNAs), the contributions of lncRNAs in progression and berberine effects on colorectal cancer are largely unknown. Therefore, the present study investigated the involvement and regulatory function of lncRNA cancer susceptibility candidate 2 (CASC2) during the treatment of human colorectal cancer using berberine. Material/Methods Reverse transcription-quantitative PCR (RT-qPCR) was performed to detect the expression levels of lncRNA CASC2 and Bcl-2 mRNA in colorectal cancer cells. MTT assay was performed to evaluate cell viability. Flow cytometry and TUNEL assay were used to analyze the apoptosis of cancer cells. RNA immunoprecipitation (RIP) assay was done to verify the interaction between lncRNA CASC2 and (AU-binding factor 1) AUF1, or AUF1 and B-cell CLL/lymphoma 2 (Bcl-2). Results Treatment with berberine suppressed cell viability of colorectal cancer by promoting apoptosis level. LncRNA CASC2 was upregulated in cells treated with berberine, and knockdown of lncRNA CASC2 reversed the berberine-induced apoptosis. In addition, anti-apoptotic gene Bcl-2 was suppressed by berberine treatment and lncRNA CASC2, inducing the pro-apoptotic effects. Moreover, lncRNA CASC2 binds to AUF1, which sequestered AUF1 from binding to Bcl-2 mRNA, thus inducing the inactivation of Bcl-2 translation. Conclusions Our study reveals that lncRNA CASC2 mediates the berberine-induced pro-apoptotic effect via inhibition of Bcl-2 expression at the post-transcriptional level.
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Affiliation(s)
- Wei Dai
- Medical Laboratory, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China (mainland).,Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, Chengdu, Sichuan, China (mainland)
| | - Liyuan Mu
- Medical Laboratory, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China (mainland).,Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, Chengdu, Sichuan, China (mainland)
| | - Yali Cui
- Medical Laboratory, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China (mainland).,Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, Chengdu, Sichuan, China (mainland)
| | - Yingying Li
- Medical Laboratory, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China (mainland).,Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, Chengdu, Sichuan, China (mainland)
| | - Ping Chen
- Medical Laboratory, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China (mainland).,Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, Chengdu, Sichuan, China (mainland)
| | - Hongjian Xie
- Medical Laboratory, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China (mainland).,Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, Chengdu, Sichuan, China (mainland)
| | - Xia Wang
- Medical Laboratory, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China (mainland).,Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, Chengdu, Sichuan, China (mainland)
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Hu X, Zhang Y, Xue Y, Zhang Z, Wang J. Berberine is a potential therapeutic agent for metabolic syndrome via brown adipose tissue activation and metabolism regulation. Am J Transl Res 2018; 10:3322-3329. [PMID: 30662589 PMCID: PMC6291723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Accepted: 10/18/2018] [Indexed: 06/09/2023]
Abstract
Berberine (BBR), an isoquinoline alkaloid that derived from the Chinese medicinal plant Coptis chinensis, has been identified with multiple pharmacological activities, including regulating glucose and cholesterol levels, anti-obesity effects and anti-diabetic effects. Due to its multiple activities, BBR and its metabolites have drawn great attention in biomedical research and clinical practices. After the recent re-discovery of brown adipose tissue (BAT) in adult humans, stimulating energy-dissipating via BAT activation and white-to-brown adipose tissue conversion have been regarded as potential therapeutic strategies for obesity and diabetes. Recent studies have demonstrated the activities of BBR in the activation of BAT and white-to-brown adipose tissue conversion, showing significant effectiveness in the treatment of diabetes. This review has summarized current studies that focused on the effect of BBR in the treatment of metabolic syndrome, especially in regulating BAT activities. Besides, the potential and molecular mechanisms of BBR in treating other risk factors of metabolic syndrome, including insulin resistance and dyslipidemia, are also reviewed, showing the great potential of BBR in treating the metabolic syndrome systematically.
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Affiliation(s)
- Xiaofei Hu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University)Chongqing, PR China
| | - Yaqi Zhang
- Department of Radiology, Northwestern UniversityChicago, Illinois, USA
| | - Yuan Xue
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University)Chongqing, PR China
| | - Zhuoli Zhang
- Department of Radiology, Northwestern UniversityChicago, Illinois, USA
| | - Jian Wang
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University)Chongqing, PR China
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