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.
Highlights
Liver cirrhosis is a major global disease burden and leads to increased morbidity.(de Marco et al, 1999)
Germ-free mice show more severe ECM deposition and liver fibrosis than normal mice. (Mazagova et al, 2015; Henderson et al, 2020). These results suggest that some intestinal flora are hepatoprotective and others are harmful, and that the dysbiosis of intestinal flora is a key driver of hepatic stellate cells (HSCs) activation and liver fibrosis
We found that BBR alleviates liver fibrosis by inducing ferrous-ion redox reactions to activate reactive oxygen species (ROS)-mediated ferroptosis in hepatic stellate cells, which suggests a possible strategy for the treatment of liver fibrosis. (Yi et al, 2021)
Summary
Liver cirrhosis is a major global disease burden and leads to increased morbidity.(de Marco et al, 1999). The major causes of liver cirrhosis are viral hepatitis, alcoholic liver diseases and nonalcoholic fatty liver diseases, and some parasitic diseases. Liver fibrosis is the pathological hallmark and precursor of cirrhosis, and it is dependent. It has been determined that the balance between liver tissue regeneration and fibrosis, and their relationship with disorders of the liver microenvironment, play an important role in the pathology of liver fibrosis. Aberrant inflammatory processes in the liver and primary metabolic pathways in hepatocytes, together with intestinal flora, shape the liver microenvironment, with lipid metabolism playing a crucial role in this regard. Liver cirrhosis is a complicated, multi-phase, multi-pathway disease, whose pathogenesis remains to be fully characterized
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