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Triclosan targeting of gut microbiome ameliorates hepatic steatosis in high fat diet-fed mice. J Antibiot (Tokyo) 2022; 75:341-353. [PMID: 35440769 DOI: 10.1038/s41429-022-00522-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 03/17/2022] [Accepted: 03/28/2022] [Indexed: 12/02/2022]
Abstract
Antibiotic use provides a promising strategy for the treatment of non-alcoholic fatty liver disease (NAFLD) by regulating the gut microbiota composition. Triclosan, a widely used antibiotic, may improve gut microbiome dysbiosis associated with NAFLD through the suppression of pathogenic gram-negative bacteria. However, the effects of triclosan on gut microbiota and hepatic steatosis and have not been explored in NAFLD mouse model. In this study, C57BL/6J mice were fed with high fat diet (HFD) for continuous 20 weeks and treated with triclosan at 400 mg/kg/d for 8 weeks from week 13. We explored the effects of triclosan on hepatic lipid accumulation and gut microbiome in HFD-fed mice by histological examination and 16 S ribosomal RNA sequencing, respectively. Analysis on the composition of gut microbiota indicated that triclosan suppressed pathogenic gram-negative bacteria, including Helicobacter, Erysipelatoclostridium and Citrobacter, and increased the ratio of Bacteroidetes/Firmicutes in HFD-fed mice. Meanwhile, triclosan increased the relative abundance of beneficial gut microbiomes including Lactobacillus, Bifidobacterium and Lachnospiraceae, which protected against metabolic abnormality. The results of alpha-diversity and beta-diversity also showed the improvement of triclosan on bacterial diversity and richness in HFD-fed mice. Pathway analysis further confirmed that triclosan can regulate nutrient and energy metabolism through the elimination of deleterious bacteria. As a result, triclosan intervention significantly reduced lipid accumulation and alleviated hepatic steatosis in HFD-fed mice. In conclusion, our results suggest that triclosan can alleviate liver steatosis in HFD-fed mice by targeting the gut microbiome.
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Wang RR, Zhang LF, Chen LP, Wang JY, Zhang L, Xu YS, Yang PL, Ji G, Liu BC. Structural and Functional Modulation of Gut Microbiota by Jiangzhi Granules during the Amelioration of Nonalcoholic Fatty Liver Disease. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:2234695. [PMID: 34966475 PMCID: PMC8712166 DOI: 10.1155/2021/2234695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 11/26/2021] [Indexed: 11/17/2022]
Abstract
Recently, accumulating evidence revealed that nonalcoholic fatty liver disease (NAFLD) is highly associated with the dysbiosis of gut microbiota. Jiang Zhi Granule (JZG), which is composed of five widely used Chinese herbs, has shown hypolipidemic effect, while whether such effect is mediated by gut microbiota is still unclear. Here, we found that both low and high doses of JZG (LJZ and HJZ) could improve hepatic steatosis and function, as well as insulin resistance in NAFLD mice. 16S rRNA gene sequencing revealed that JZG treatment could reverse the dysbiosis of intestinal flora in NAFLD mice, exhibiting a dose-dependent effect. Notably, HJZ could significantly reduce the relative abundance of Desulfovibrionaceae, while increasing the relative abundance of such as S24_7 and Lachnospiraceae. PICRUSt analysis showed that HJZ could significantly alter the functional profile of gut microbiota, including the reduction of the lipopolysaccharide biosynthesis and sulfur metabolism pathway, which is verified by the decreased levels of fecal hydrogen sulfide (H2S) and serum lipopolysaccharide binding protein (LBP). In addition, hepatic mRNA sequencing further indicated that the HJZ group can regulate the peroxisome proliferator-activated receptor (PPAR) pathway and inflammatory signaling pathway, as validated by RT-PCR and Western blot. We also found that different doses of JZG may regulate lipid metabolism through differentiated pathways, as LJZ mainly through the promotion of hepatic lipid hydrolysis, while HJZ mainly through the improvement of hepatic lipid oxidation. Taken together, JZG could modulate gut dysbiosis with dose-effect, alleviate inflammation level, and regulate hepatic lipid metabolism, which may subsequently contribute to the improvement of NAFLD. Our study revealed the underlying mechanisms in the improvement of NAFLD by a Chinese herbal compound, providing future guidance for clinical usage.
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Affiliation(s)
- Rui-rui Wang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai 201203, China
| | - Lin-fang Zhang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai 201203, China
- Oxford Suzhou Centre for Advanced Research, Building A, 388 Ruo Shui Road, Suzhou Industrial Park, Jiangsu 215123, China
| | - Lu-ping Chen
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai 201203, China
| | - Jian-ying Wang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai 201203, China
| | - Lei Zhang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai 201203, China
| | - Yue-song Xu
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai 201203, China
| | - Pei-lin Yang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai 201203, China
| | - Guang Ji
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai 201203, China
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, No. 725 South Wanping Road, Shanghai 200032, China
| | - Bao-cheng Liu
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai 201203, China
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Gao Y, Yang R, Guo L, Wang Y, Liu WJ, Ai S, Woon TH, Wang Z, Zhai Y, Wang Z, Peng L. Qing-Re-Xiao-Zheng Formula Modulates Gut Microbiota and Inhibits Inflammation in Mice With Diabetic Kidney Disease. Front Med (Lausanne) 2021; 8:719950. [PMID: 34604258 PMCID: PMC8481597 DOI: 10.3389/fmed.2021.719950] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 08/17/2021] [Indexed: 01/02/2023] Open
Abstract
Evidence indicates that the metabolic inflammation induced by gut microbiota dysbiosis contributes to diabetic kidney disease. Prebiotic supplementations to prevent gut microbiota dysbiosis, inhibit inflammatory responses, and protect the renal function in DKD. Qing-Re-Xiao-Zheng formula (QRXZF) is a Traditional Chinese Medicine (TCM) formula that has been used for DKD treatment in China. Recently, there are growing studies show that regulation of gut microbiota is a potential therapeutic strategy for DKD as it is able to reduce metabolic inflammation associated with DKD. However, it is unknown whether QRXZF is effective for DKD by regulating of gut microbiota. In this study, we investigated the reno-protective effect of QRXZF by exploring its potential mechanism between gut microbiota and downstream inflammatory pathways mediated by gut-derived lipopolysaccharide (LPS) in the kidney. High-fat diet (HFD) and streptozotocin injection-induced DKD mice model was established to assess the QRXZF effect in vivo. Mice treated with QRXZF for 8 weeks had significantly lower levels of urinary albumin, serum cholesterol and triglycerides. The renal injuries observed through histological analysis were attenuated as well. Also, mice in the QRXZF group had higher levels of Zonula occludens protein-1 (ZO-1) expression, lower levels of serum fluorescein-isothiocyanate (FITC)-dextran and less-damaged colonic mucosa as compared to the DKD group, implying the benefit role for the gut barrier integrity. QRXZF treatment also reversed gut dysbiosis and reduced levels of gut-derived LPS. Notably, the expression of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB), which are important inflammation pathways in DKD, were suppressed in the QRXZF groups. In conclusion, our results indicated that the reno-protective effects of QRXZF was probably associated with modulating gut microbiota and inhibiting inflammatory responses in the kidney.
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Affiliation(s)
- Yabin Gao
- Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Ruibing Yang
- Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Lan Guo
- Jitang College of North China University of Science and Technology, Hebei, China
| | - Yaoxian Wang
- Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Wei Jing Liu
- Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Sinan Ai
- Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | | | - Zheng Wang
- The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Yuanyuan Zhai
- College of Life Sciences, Hebei University, Hebei, China
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China
| | - Zhen Wang
- Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Liang Peng
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, Department of Pharmacology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China
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Ren S, Ma X, Wang R, Liu H, Wei Y, Wei S, Jing M, Zhao Y. Preclinical Evidence of Berberine on Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Animal Studies. Front Pharmacol 2021; 12:742465. [PMID: 34566663 PMCID: PMC8458904 DOI: 10.3389/fphar.2021.742465] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 08/16/2021] [Indexed: 12/20/2022] Open
Abstract
As lifestyle and diet structure impact our health, non-alcoholic fatty liver disease (NAFLD) is prevalent all over the world. Some phytomedicines containing berberine (BBR) have been extensively used for centuries in Ayurvedic and traditional Chinese medicine. The goal of this systematic review is to investigate the preclinical evidence of BBR on NAFLD models. The following relevant databases, including Web of Science, PubMed, the Cochrane Library, and Embase, were retrieved from inception to May 2021. The content involved BBR on different animal models for the treatment of NAFLD. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) Animal Experiment Bias Risk Assessment Tool was used to assess the methodological quality and RevMan 5.4 software was used to conduct the meta-analysis based on the Cochrane tool. A total of 31 studies involving 566 animals were included, of which five models and five animal breeds were reported. The results showed that TC, TG, ALT, AST, HDL-C, LDL-C, FBG, FINS, and FFA in the group treated with BBR were significantly restored compared with those in the model group. HOMA-IR had a significant downward trend, but the result was not significantly different (P = 0.08). The subgroup analysis of the different models and different animal breeds indicated that BBR could ameliorate the aforementioned indicator levels, although some results showed no significant difference. Finally, we summarized the molecular mechanisms by which berberine regulated NAFLD/NASH, mainly focusing on activating the AMPK pathway, improving insulin sensitivity and glucose metabolism, regulating mitochondrial function, reducing inflammation and oxidative stress, regulating cell death and ER stress, reducing DNA methylation, and regulating intestinal microenvironment and neurotoxicity. The preclinical evidence suggested that BBR might be an effective and promising drug for treating NAFLD/NASH. In addition, further studies with more well-designed researches are needed to confirm this conclusion.
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Affiliation(s)
- Sichen Ren
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiao Ma
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ruilin Wang
- Integrative Medical Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Honghong Liu
- Integrative Medical Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ying Wei
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shizhang Wei
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Manyi Jing
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yanling Zhao
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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5
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Pharmacokinetics and Pharmacological Activities of Berberine in Diabetes Mellitus Treatment. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:9987097. [PMID: 34471420 PMCID: PMC8405293 DOI: 10.1155/2021/9987097] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 08/09/2021] [Accepted: 08/16/2021] [Indexed: 02/07/2023]
Abstract
Traditional Chinese medicine (TCM) has good clinical application prospects in diabetes treatment. In addition, TCM is less toxic and/or has fewer side effects and provides various therapeutic effects. Berberine (BBR) is isolated as the main component in many TCM kinds (e.g., Rhizoma Coptidis and Berberidis Cortex). Furthermore, BBR can reduce blood sugar and blood fat, alleviate inflammation, and improve the state of patients. Based on the recent study results of BBR in diabetes treatment, the BBR pharmacokinetics and mechanism on diabetes are mainly studied, and the specific molecular mechanism of related experimental BBR is systematically summarized and analyzed. Clinical studies have proved that BBR has a good therapeutic effect on diabetes, suggesting that BBR may be a promising drug candidate for diabetes. More detailed BBR mechanisms and pathways of BBR need to be studied further in depth, which will help understand the BBR pharmacology in diabetes treatment.
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6
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Zhang L, Wu X, Yang R, Chen F, Liao Y, Zhu Z, Wu Z, Sun X, Wang L. Effects of Berberine on the Gastrointestinal Microbiota. Front Cell Infect Microbiol 2021; 10:588517. [PMID: 33680978 PMCID: PMC7933196 DOI: 10.3389/fcimb.2020.588517] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 12/31/2020] [Indexed: 01/14/2023] Open
Abstract
The gastrointestinal microbiota is a multi-faceted system that is unraveling novel contributors to the development and progression of several diseases. Berberine has been used to treat obesity, diabetes mellitus, atherosclerosis, and metabolic diseases in China. There are also clinical trials regarding berberine use in cardiovascular, gastrointestinal, and endocrine diseases. Berberine elicits clinical benefits at standard doses and has low toxicity. The mechanism underlying the role of berberine in lipid‐lowering and insulin resistance is incompletely understood, but one of the possible mechanisms is related to its effect on the gastrointestinal microbiota. An extensive search in electronic databases (PubMed, Scopus, Embase, Web of Sciences, Science Direct) was used to identify the role of the gastrointestinal microbiota in the berberine treatment. The aim of this review was to summarize the pharmacologic effects of berberine on animals and humans by regulation of the gastrointestinal microbiota.
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Affiliation(s)
- Lichao Zhang
- Department of Parasitology of Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China.,Provincial Engineering Technology Research Center for Biological Vector Control, Guangzhou, China
| | - Xiaoying Wu
- Department of Parasitology of Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China.,Department of Gastroenterology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ruibing Yang
- Medical Department, Xizang Minzu University, Xianyang, China
| | - Fang Chen
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Yao Liao
- Department of Parasitology of Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China.,Provincial Engineering Technology Research Center for Biological Vector Control, Guangzhou, China
| | - Zifeng Zhu
- Department of Parasitology of Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China.,Provincial Engineering Technology Research Center for Biological Vector Control, Guangzhou, China
| | - Zhongdao Wu
- Department of Parasitology of Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China.,Provincial Engineering Technology Research Center for Biological Vector Control, Guangzhou, China
| | - Xi Sun
- Department of Parasitology of Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China.,Provincial Engineering Technology Research Center for Biological Vector Control, Guangzhou, China
| | - Lifu Wang
- Department of Parasitology of Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.,Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China.,Provincial Engineering Technology Research Center for Biological Vector Control, Guangzhou, China
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7
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Moszak M, Szulińska M, Walczak-Gałęzewska M, Bogdański P. Nutritional Approach Targeting Gut Microbiota in NAFLD-To Date. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:1616. [PMID: 33567710 PMCID: PMC7916007 DOI: 10.3390/ijerph18041616] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 01/05/2021] [Accepted: 01/25/2021] [Indexed: 12/18/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a significant clinical and epidemiological problem that affects around 25% of the adult global population. A large body of clinical evidence highlights that NAFLD is associated with increased liver-related morbidity and mortality and an increased risk of cardiovascular disease, extrahepatic cancers, type 2 diabetes, and chronic kidney disease. Recently, a series of studies revealed the pivotal role of gut microbiota (GM) dysbiosis in NAFLD's pathogenesis. The GM plays an essential role in different metabolic pathways, including the fermentation of diet polysaccharides, energy harvest, choline regulation, and bile acid metabolism. One of the most critical factors in GM stabilization is the diet; therefore, nutritional therapyappearsto be a promising tool in NAFLD therapy. This paper aims to review the current knowledge regardingthe nutritional approach and its implications with GM and NAFLD treatment. We discuss the positive impact of probiotics, prebiotics, and symbiotics in a reverse dysbiosis state in NAFLD and show the potential beneficial effects of bioactive substances from the diet. The full description of the mechanism of action and comprehensive examination of the impact of nutritional interventions on GM modulation may, in the future, be a simple but essential tool supporting NAFLD therapy.
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Affiliation(s)
- Małgorzata Moszak
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.S.); (P.B.)
| | - Monika Szulińska
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.S.); (P.B.)
| | - Marta Walczak-Gałęzewska
- Department of Internal Medicine, Metabolic Disorders, and Hypertension, Poznań University of Medical Sciences, 61-701 Poznań, Poland;
| | - Paweł Bogdański
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.S.); (P.B.)
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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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9
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Li S, Wang N, Tan HY, Chueng F, Zhang ZJ, Yuen MF, Feng Y. Modulation of gut microbiota mediates berberine-induced expansion of immuno-suppressive cells to against alcoholic liver disease. Clin Transl Med 2020; 10:e112. [PMID: 32790968 PMCID: PMC7438809 DOI: 10.1002/ctm2.112] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 06/08/2020] [Accepted: 06/09/2020] [Indexed: 12/12/2022] Open
Abstract
Background Berberine is an isoquinoline alkaloid compound derived from many herbs, which has been used extensively to improve liver function. But action mechanism of its hepatoprotection in alcoholic liver disease (ALD) is far from being clear. Aim To investigate the underlying mechanism of berberine's therapeutic effect on ALD associated with gut microbiota‐immune system axis. Method An animal model fed with ethanol that mimics drinking pattern ideally in ALD patients was established. Liver function was evaluated by biochemical test and histological examination. Immune cells were detected by flow cytometry and feces samples were collected for 16S rRNA gene amplicon sequencing. Results We first reported the promising beneficial effect of berberine on ameliorating acute‐on‐chronic alcoholic hepatic damage and explored the underlying mechanism involving gut microbiota‐immune system axis. Notably, berberine activated a population with immune suppressive function, defined as granulocytic‐ myeloid‐derived suppressor cell (G‐MDSC)‐like population, in the liver of mice with alleviating alcohol‐induced hepatic injury. Berberine remarkably enhanced the increase of G‐MDSC‐like cells in blood and liver and decreased cytotoxic T cells correspondingly. Suppression of G‐MDSC‐like population significantly attenuated the protective effect of berberine against alcohol. Berberine activated IL6/STAT3 signaling in in vitro culture of G‐MSDCs‐like population, while inhibition of STAT3 activity attenuated the activation of this population by berberine. Moreover, berberine changed the overall gut microbial community, primarily increased the abundance of Akkermansia muciniphila. Of note, depletion of gut microbiota abolished the inducing effect of berberine on G‐MDSC‐like population, and attenuated its hepatoprotective effect against alcohol in mice, suggesting intestinal flora might be involved in mediating the expansion of this protective population. Conclusion Collectively, this study delivered insight into the role of immunosuppressive response in ALD, and facilitated the understanding of the pharmacological effects and action mechanisms of berberine.
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Affiliation(s)
- Sha Li
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R, P. R. China
| | - Ning Wang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R, P. R. China
| | - Hor-Yue Tan
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R, P. R. China
| | - Fan Chueng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R, P. R. China
| | - Zhang-Jin Zhang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R, P. R. China
| | - Man-Fung Yuen
- Division of Gastroenterology and Hepatology, Queen Mary Hospital, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R, P. R. China
| | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R, P. R. China
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10
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Yan T, Yan N, Wang P, Xia Y, Hao H, Wang G, Gonzalez FJ. Herbal drug discovery for the treatment of nonalcoholic fatty liver disease. Acta Pharm Sin B 2020; 10:3-18. [PMID: 31993304 PMCID: PMC6977016 DOI: 10.1016/j.apsb.2019.11.017] [Citation(s) in RCA: 155] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 09/23/2019] [Accepted: 10/31/2019] [Indexed: 12/11/2022] Open
Abstract
Few medications are available for meeting the increasing disease burden of nonalcoholic fatty liver disease (NAFLD) and its progressive stage, nonalcoholic steatohepatitis (NASH). Traditional herbal medicines (THM) have been used for centuries to treat indigenous people with various symptoms but without clarified modern-defined disease types and mechanisms. In modern times, NAFLD was defined as a common chronic disease leading to more studies to understand NAFLD/NASH pathology and progression. THM have garnered increased attention for providing therapeutic candidates for treating NAFLD. In this review, a new model called “multiple organs-multiple hits” is proposed to explain mechanisms of NASH progression. Against this proposed model, the effects and mechanisms of the frequently-studied THM-yielded single anti-NAFLD drug candidates and multiple herb medicines are reviewed, among which silymarin and berberine are already under U.S. FDA-sanctioned phase 4 clinical studies. Furthermore, experimental designs for anti-NAFLD drug discovery from THM in treating NAFLD are discussed. The opportunities and challenges of reverse pharmacology and reverse pharmacokinetic concepts-guided strategies for THM modernization and its global recognition to treat NAFLD are highlighted. Increasing mechanistic evidence is being generated to support the beneficial role of THM in treating NAFLD and anti-NAFLD drug discovery.
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Affiliation(s)
- Tingting Yan
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Corresponding authors.
| | - Nana Yan
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
| | - Ping Wang
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yangliu Xia
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, China
| | - Haiping Hao
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
| | - Guangji Wang
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
| | - Frank J. Gonzalez
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Corresponding authors.
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11
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Osteoarthritis Is a Low-Grade Inflammatory Disease: Obesity's Involvement and Herbal Treatment. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:2037484. [PMID: 31781260 PMCID: PMC6874989 DOI: 10.1155/2019/2037484] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 09/30/2019] [Accepted: 10/03/2019] [Indexed: 12/26/2022]
Abstract
Osteoarthritis (OA) is considered a major cause of disability around the globe. This handicapping disease causes important cartilage and bone alteration that is associated with serious pains and loss of joint function. Despite its frequent association with obesity, the aetiology of OA is not fully understood. In this review, the different aspects of OA and its correlation with obesity were analysed. Through examining different mechanisms by which obesity may trigger and/or exacerbate OA, we point out some relevant signalling pathways that may evolve as candidates for pharmacological drug development. As such, we also suggest a review of different herbal medicines (HMs) and their main compounds, which specifically interfere with the identified pathways. We have shown that obesity's involvement in OA is not only limited to the mechanical weight exerted on the joints (mechanical hypothesis), but also induces an inflammatory state by different mechanisms, including increased leptin expression, compromised gut mucosa, and/or gut microbiota disruption. The main signalling pathways involved in OA inflammation, which are associated with obesity, are protein tyrosine phosphatase 1B (PTP1B) and TLR4 or DAP12. Moreover, we also underline the contamination of plant extracts with LPS as an important factor to consider when studying HM's effects on articular cells. By summarizing recent publications, this review aims at highlighting newly established aspects of obesity involvement in OA other than the mechanical one.
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12
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Zhu F, Li YM, Feng TT, Wu Y, Zhang HX, Jin GY, Liu JP. Freeze-dried Si-Ni-San powder can ameliorate high fat diet-induced non-alcoholic fatty liver disease. World J Gastroenterol 2019; 25:3056-3068. [PMID: 31293341 PMCID: PMC6603807 DOI: 10.3748/wjg.v25.i24.3056] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 05/28/2019] [Accepted: 06/01/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. However, to date, there is no ideal therapy for this disease.
AIM To study the effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice.
METHODS Twenty-four male C57BL/6 mice were randomized into three groups of eight. The control group (CON) was allowed ad libitum access to a normal chow diet. The high fat diet group (FAT) and Si-Ni-San group (SNS) were allowed ad libitum access to a high fat diet. The SNS group was intragastrically administered Si-Ni-San freeze-dried powder (5.0 g/kg) once daily, and the CON and FAT groups were intragastrically administered distilled water. After 12 wk, body weight, liver index, visceral fat index, serum alanine aminotransferase (ALT), portal lipopoly-saccharide (LPS), liver tumor necrosis factor (TNF)-α and liver triglycerides were measured. Intestinal microbiota were analyzed using a 16S r DNA sequencing technique.
RESULTS Compared with the FAT group, the SNS group exhibited decreased body weight, liver index, visceral fat index, serum ALT, portal LPS, liver TNF-α and liver triglycerides (P < 0.05). Intestinal microbiota analysis showed that the SNS group had different bacterial composition and function compared with the FAT group. In particular, Oscillospira genus was a bacterial biomarker of SNS group samples.
CONCLUSION The beneficial effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice may be associated with its anti-inflammatory and changing intestinal microbiota effects.
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Affiliation(s)
- Feng Zhu
- Department of Traditional Chinese Medicine, Hebei North University, Zhangjiakou 075000, Hebei Province, China
| | - Yong-Min Li
- Department of Traditional Chinese Medicine, Hebei North University, Zhangjiakou 075000, Hebei Province, China
| | - Ting-Ting Feng
- Department of Traditional Chinese Medicine, Hebei North University, Zhangjiakou 075000, Hebei Province, China
| | - Yue Wu
- Department of Traditional Chinese Medicine, Hebei North University, Zhangjiakou 075000, Hebei Province, China
| | - Hai-Xia Zhang
- Department of Traditional Chinese Medicine, Hebei North University, Zhangjiakou 075000, Hebei Province, China
| | - Guo-Yin Jin
- Department of Traditional Chinese Medicine, Hebei North University, Zhangjiakou 075000, Hebei Province, China
| | - Jian-Ping Liu
- Department of Gastroenterology, People’s Hospital of Changshou District, Chongqing 401220, China
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13
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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: 255] [Impact Index Per Article: 42.5] [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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14
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The Effects of Berberine on the Gut Microbiota in Apc min/+ Mice Fed with a High Fat Diet. Molecules 2018; 23:molecules23092298. [PMID: 30205580 PMCID: PMC6225274 DOI: 10.3390/molecules23092298] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Revised: 08/19/2018] [Accepted: 09/06/2018] [Indexed: 02/07/2023] Open
Abstract
Background: Berberine (BBR) has been extensively reported to inhibit colorectal cancer (CRC) development, though its bioavailability is poor. Nowadays, an increasing number of studies have shown that BBR significantly accumulates in the intestines and could regulate gut microbiota in obesity. The purpose of this study was to further explore the effects of BBR on gut microbiota in Apc min/+ mice receiving a high fat diet (HFD). Methods: Apc min/+ mice received either HFD alone or HFD and BBR for 12 weeks. The intestinal tissues were collected to evaluate the efficiency of BBR on neoplasm development by hematoxylin and eosin staining. Meanwhile, immunohistochemistry was conducted to investigate the effects of BBR on cyclin D1 and β-catenin in colon tissues. Fecal samples were subjected to 16S rRNA sequencing. Results: BBR significantly reduced intestinal tumor development and altered the structure of gut microbiota in Apc min/+ mice fed with an HFD. At the phylum level, it was able to significantly inhibit the increase in Verrucomicrobia. At the genus level, it was able to suppress Akkermansia and elevate some short chain fat acid (SCFA)-producing bacteria. Conclusions: BBR significantly alleviated the development of CRC in Apc min/+ mice fed with HFD and restored the enteric microbiome community.
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15
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Lyu M, Wang YF, Fan GW, Wang XY, Xu SY, Zhu Y. Balancing Herbal Medicine and Functional Food for Prevention and Treatment of Cardiometabolic Diseases through Modulating Gut Microbiota. Front Microbiol 2017; 8:2146. [PMID: 29167659 PMCID: PMC5682319 DOI: 10.3389/fmicb.2017.02146] [Citation(s) in RCA: 146] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 10/19/2017] [Indexed: 12/22/2022] Open
Abstract
It has become apparent that gut microbiota is closely associated with cardiometabolic diseases (CMDs), and alteration in microbiome compositions is also linked to the host environment. Next generation sequencing (NGS) has facilitated in-depth studies on the effects of herbal medicine and functional food on gut microbiota. Both herbal medicine and functional food contain fiber, polyphenols and polysaccharides, exerting prebiotics-like activities in the prevention and treatment of CMDs. The administrations of herbal medicine and functional food lead to increased the abundance of phylum Bacteroidetes, and genus Akkermansia, Bifidobacteria, Lactobacillus, Bacteroides and Prevotella, while reducing phylum Firmicutes and Firmicutes/Bacteroidetes ratio in gut. Both herbal medicine and functional food interact with gut microbiome and alter the microbial metabolites including short-chain fatty acids (SCFAs), bile acids (BAs) and lipopolysaccharides (LPS), which are now correlated with metabolic diseases such as type 2 diabetes (T2D), obesity and non-alcoholic fatty liver disease (NAFLD). In addition, trimethylamine (TMA)-N-oxide (TMAO) is recently linked to atherosclerosis (AS) and cardiovascular disease (CVD) risks. Moreover, gut-organs axes may serve as the potential strategy for treating CMDs with the intervention of herbal medicine and functional food. In summary, a balance between herbal medicine and functional food rich in fiber, polyphenols and polysaccharides plays a vital role in modulating gut microbiota (phylum Bacteroidetes, Firmicutes and Firmicutes/Bacteroidetes ratio, and genus Akkermansia, Bifidobacteria, Lactobacillus, Bacteroides and Prevotella) through SCFAs, BAs, LPS and TMAO signaling regarding CMDs. Targeting gut-organs axes may serve as a new therapeutic strategy for CMDs by herbal medicine and functional food in the future. This review aims to summarize the balance between herbal medicine and functional food utilized for the prevention and treatment of CMDs through modulating gut microbiota.
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Affiliation(s)
- Ming Lyu
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, Tianjin, China
| | - Yue-Fei Wang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, Tianjin, China
| | - Guan-Wei Fan
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, Tianjin, China.,Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiao-Ying Wang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Neuroscience Program, Neuroprotection Research Laboratory, Department of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | | | - Yan Zhu
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, Tianjin, China
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Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanisms and Therapy. Nutrients 2017; 9:nu9101124. [PMID: 29035308 PMCID: PMC5691740 DOI: 10.3390/nu9101124] [Citation(s) in RCA: 140] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 10/06/2017] [Accepted: 10/10/2017] [Indexed: 12/13/2022] Open
Abstract
The gut microbiota plays critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes(T2D), and insulin resistance(IR), highlighting the potential of gut microbiota-targeted therapies in these diseases. There are various ways that gut microbiota can be manipulated, including through use of probiotics, prebiotics, synbiotics, antibiotics, and some active components from herbal medicines. In this review, we review the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies for NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.
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The Therapeutic Effect of Berberine in the Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 2016:3593951. [PMID: 27446224 PMCID: PMC4947506 DOI: 10.1155/2016/3593951] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Accepted: 05/19/2016] [Indexed: 01/01/2023]
Abstract
Aim. To assess the efficacy of berberine in the treatment of nonalcoholic fatty liver disease through meta-analysis. Method. We searched Embase, Pubmed, Cochrane Library, and so forth, until March 2016 for randomized controlled trials using berberine to treat NAFLD. Result. Six randomized controlled trials involving 501 patients were included in this study. The results showed that the efficacy of reducing TC, LDL, ALT, 2hPG, and HbA1c in NAFLD patients of the berberine group were significantly higher than that of control group. The subgroup analyses on TG, AST, and FBG indicated that treatment combined with berberine decreased TG level in NAFLD patients significantly. Compared with other drugs, berberine alone decreased TG level in NAFLD patients significantly. We also conducted a descriptive analysis on insulin resistance and radiography results that berberine can improve NAFLD patients' insulin resistance and fatty liver. Conclusion. According to analysis result, berberine has positive efficacy on blood lipids, blood glucose, liver function, insulin resistance, and fatty liver condition of NAFLD patients. However, due to the limitation of number and quality of trials included, more clinical randomized controlled trials with high quality are needed for further verification of the efficacy of berberine on NAFLD patients.
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