Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways

Wang, Yanyan; Tai, Yunling; Zhao, Derrick; Zhang, Yuan; Yan, Junkai; Kakiyama, Genta; Wang, Xuan; Gurley, Emily C.; Liu, Jinze; Liu, Jinpeng; Liu, Jimin; Lai, Guan–Hua; Hylemon, Phillip B.; Pandak, William M.; Chen, Weidong; Zhou, Huiping

doi:10.3390/cells10020210

Cited by 40 publications

(34 citation statements)

References 65 publications

(92 reference statements)

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“…Previous studies have indicated that the direct beneficial effects of BBR involving modulation of the expression of multiple genes involved in HSC activation, cholangiocyte proliferation and liver fibrosis are linked to the downregulation of two important ribonucleotide molecules that promote liver fibrosis progression: microRNA34a and long noncoding RNA H19. ( Wang et al, 2021 ). Another commonly reported mechanism is the induction of HSC cycle arrest in G1 phase, which inhibits HSC activation and prevents liver fibrosis.…”

Section: Anti-fibrosis Effects Of Berberine In the Livermentioning

confidence: 99%

“…BBR could also significantly reduce hepatic lipid accumulation by modulating fatty acid synthesis and metabolism to prevent the progression of non-alcoholic steatohepatitis and liver fibrosis. ( Wang et al, 2021 ). Several latent mechanisms, such as oxidative stress ( Zhang BJ.…”

Section: Berberine Alleviates Liver Fibrosis By Modifying Lipid Metab...mentioning

confidence: 99%

“…BBR also restores bile acid homeostasis by targeting multiple pathways that markedly inhibit inflammation, thereby alleviating non-alcoholic steatohepatitis and liver fibrosis. ( Wang et al, 2021 ). Bile acids serve as key regulators of lipid and glucose homeostasis, energy consumption and inflammation.…”

Section: Contributions Of Intestinal Flora To the Biological Function...mentioning

confidence: 99%

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Therapeutic Effects of Berberine on Liver Fibrosis are associated With Lipid Metabolism and Intestinal Flora

et al. 2022

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Liver cirrhosis is a form of liver fibrosis resulting from chronic hepatitis caused by various liver diseases, such as viral hepatitis, alcoholic liver damage, nonalcoholic steatohepatitis, autoimmune liver disease, and by parasitic diseases such as schistosomiasis. Liver fibrosis is the common pathological base and precursors of cirrhosis. Inflammation and disorders of lipid metabolism are key drivers in liver fibrosis. Studies have determined that parts of the arachidonic acid pathway, such as its metabolic enzymes and biologically active products, are hallmarks of inflammation, and that aberrant peroxisome proliferator-activated receptor gamma (PPARγ)-mediated regulation causes disorders of lipid metabolism. However, despite the ongoing research focus on delineating the mechanisms of liver fibrosis that underpin various chronic liver diseases, effective clinical treatments have yet to be developed. Berberine (BBR) is an isoquinoline alkaloid with multiple biological activities, such as anti-inflammatory, anti-bacterial, anti-cancer, and anti-hyperlipidemic activities. Many studies have also found that BBR acts via multiple pathways to alleviate liver fibrosis. Furthermore, the absorption of BBR is increased by nitroreductase-containing intestinal flora, and is strengthened via crosstalk with bile acid metabolism. This improves the oral bioavailability of BBR, thereby enhancing its clinical utility. The production of butyrate by intestinal anaerobic bacteria is dramatically increased by BBR, thereby amplifying butyrate-mediated alleviation of liver fibrosis. In this review, we discuss the effects of BBR on liver fibrosis and lipid metabolism, particularly the metabolism of arachidonic acid, and highlight the potential mechanisms by which BBR relieves liver fibrosis through lipid metabolism related and intestinal flora related pathways. We hope that this review will provide insights on the BBR-based treatment of liver cirrhosis and related research in this area, and we encourage further studies that increase the ability of BBR to enhance liver health.

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Section: Anti-fibrosis Effects Of Berberine In the Livermentioning

confidence: 99%

Section: Berberine Alleviates Liver Fibrosis By Modifying Lipid Metab...mentioning

confidence: 99%

Section: Contributions Of Intestinal Flora To the Biological Function...mentioning

confidence: 99%

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Therapeutic Effects of Berberine on Liver Fibrosis are associated With Lipid Metabolism and Intestinal Flora

et al. 2022

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“…Interestingly, this study also found that the plasma levels of conjugated primary BAs (TCA and GCA) efficiently discriminate NASH status independent of other confounding factors such as obesity and insulin resistance [ 81 ]. Our recent studies also showed that serum levels of TCA and TβMCA were markedly increased in high-fat diet and high-sugar water-induced NASH mouse models [ 82 ]. TCA-induced activation of S1PR2 is involved in cholangiocyte proliferation and hepatic fibrosis [ 83 ].…”

Section: Gut–liver Axis In Nafldmentioning

confidence: 99%

Bile Acid Receptors and the Gut–Liver Axis in Nonalcoholic Fatty Liver Disease

Xue

Lai

et al. 2021

Cells

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The prevalence of nonalcoholic fatty liver disease (NAFLD) has been significantly increased due to the global epidemic of obesity. The disease progression from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is closely linked to inflammation, insulin resistance, and dysbiosis. Although extensive efforts have been aimed at elucidating the pathological mechanisms of NAFLD disease progression, current understanding remains incomplete, and no effective therapy is available. Bile acids (BAs) are not only important physiological detergents for the absorption of lipid-soluble nutrients in the intestine but also metabolic regulators. During the last two decades, BAs have been identified as important signaling molecules involved in lipid, glucose, and energy metabolism. Dysregulation of BA homeostasis has been associated with NAFLD disease severity. Identification of nuclear receptors and G-protein-coupled receptors activated by different BAs not only significantly expanded the current understanding of NAFLD/NASH disease progression but also provided the opportunity to develop potential therapeutics for NAFLD/NASH. In this review, we will summarize the recent studies with a focus on BA-mediated signaling pathways in NAFLD/NASH. Furthermore, the therapeutic implications of targeting BA-mediated signaling pathways for NAFLD will also be discussed.

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“…In addition, berberine can also regulate liver TG synthesis and hepatic steatosis through the activation of AMPK-SREBP-1c-SCD1 pathway both in HFD mice and in HepG2/ AML12 cells exposed to high glucose and palmitic acid [ 125 ]. In conclusion, berberine can not only reduce hepatic lipid accumulation by modulating fatty acid synthesis and metabolism, but also restore the bile acid homeostasis [ 126 ]. Furthermore, it markedly inhibits inflammation by reducing immune cell infiltration, neutrophil activation and inflammatory gene expression.…”

Section: Effects and Mechanisms Of Commonly Used Single Herb Drugs In Tcm On Nafldmentioning

confidence: 99%

Traditional Chinese Medicine in nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives

et al. 2021

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Nonalcoholic fatty liver disease (NAFLD) has become the world's largest chronic liver disease, while there is still no specific drug to treat NAFLD. Traditional Chinese Medicine (TCM) have been widely used in hepatic diseases for centuries in Asia, and TCM’s holistic concept and differentiation treatment of NAFLD show their advantages in the treatment of this complex metabolic disease. However, the multi-compounds and multi-targets are big obstacle for the study of TCM. Here, we summarize the pharmacological actions of active ingredients from frequently used single herbs in TCM compounds. The combined mechanism of herbs in TCM compounds are further discussed to explore their comprehensive effects on NAFLD. This article aims to summarize multiple functions and find the common ground for TCM treatment on NAFLD, thus providing enrichment to the scientific connotation of TCM theories and promotes the exploration of TCM therapies on NAFLD.

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Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways

Cited by 40 publications

References 65 publications

Therapeutic Effects of Berberine on Liver Fibrosis are associated With Lipid Metabolism and Intestinal Flora

Therapeutic Effects of Berberine on Liver Fibrosis are associated With Lipid Metabolism and Intestinal Flora

Bile Acid Receptors and the Gut–Liver Axis in Nonalcoholic Fatty Liver Disease

Traditional Chinese Medicine in nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives

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