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

Abstract

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.

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

“…Arachidonic acid metabolites have also been reported to be PPARγ ligands and transcriptional activators that repress the activation of inflammatory signals and thus regulate LF via PPARγ. These findings imply that BBR reduces TGF-β-induced extracellular matrix of HSC through arachidonic acid pathway-mediated PPARγ activation [217] . Sixth, immune cell infiltration and activation caused by hepatocyte injury further promote HSCs activation and bile duct cell proliferation.…”

Association Between Monocyte to High-Density Lipoprotein Cholesterol Ratio and Risk of Non-alcoholic Fatty Liver Disease: A Cross-Sectional Study

“…As both monocytes and HDL-C play important roles in the progression of NAFLD, several studies have reported that MHR could serve as a novel, cost-effective predictor of inflammation, especially in cardiovascular events ( 41 ) and metabolic disorders ( 42 ). Besides, the presence of fibrosis may affect lipid production in the liver and hepatic fibrosis can distort the hepatic articulture of the hepatocytes causing an altered production of lipids ( 43 ). This might partly explain the positive associations between MHR and the prevalence of significant liver fibrosis and cirrhosis found in our current study.…”

Potential Therapeutic Activity of Berberine in Thyroid-Associated Ophthalmopathy: Inhibitory Effects on Tissue Remodeling in Orbital Fibroblasts

“…As a major ingredient of a classical Chinese herb, berberine has recently attracted much more attention for its various therapeutic effects in multiple diseases, including fibrosis-related pathologies, cancer, and cardiovascular and metabolic disorders. 28 , 34 , 35 According to recent studies, BBR exerts the above pharmacologic effects by regulating inflammation, oxidative stress, apoptosis, fibrosis, and glucose and lipid metabolism, probably covering a large part of TAO pathogenesis. Additionally, increasingly more studies have demonstrated the safety of BBR at conventional doses, 26 , 36 which makes its clinical transformation easier in TAO management compared with other new drugs.…”