小檗碱调节肠肝轴治疗非酒精性脂肪肝病的研究进展

Research progress on berberine in treatment of nonalcoholic fatty liver disease by regulating gut-liver axis

非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)是临床常见慢性肝病,是导致肝硬化、肝细胞癌、心血管疾病的危险因素,临床缺乏有效药物。NAFLD存在多因素的发病机制,肠-肝轴在其发病过程中具有重要地位。肠道菌群的失调可引起肠道屏障的破坏,导致相关有毒代谢产物入血和细菌移位的发生,诱发肝脏炎症反应和损伤,是NAFLD发生发展的一个重要诱因。小檗碱是黄连Coptis chinensis的主要药用成分,有确切的减轻肝细胞脂质积累、抗炎、抗纤维化等作用,对NAFLD呈现典型的多靶点、多系统的药理作用,是中药成分在NAFLD治疗机制研究中的典型代表。小檗碱在多个相互关联的水平上影响肠-肝轴,包括保护肠黏膜上皮屏障,减少肝脏微生物暴露和促炎环境,调节肠道微生物群结构,改变微生物衍生代谢物如短链脂肪酸和次级胆汁酸,激活肠道法尼酯衍生物X受体信号途径调节肝脏代谢,从而发挥对NAFLD的保护作用。一些中药复方具有治疗NAFLD的临床效果,作用机制研究初步显示了中药复方对肠-肝轴的调节作用。由于中药复方的成分过于复杂,开展中药单体配伍的研究能够降低维度、减小难度,有助于揭示中药复方的作用机制。

Non-alcoholic fatty liver disease(NAFLD)is a common clinical chronic liver disease.It is a risk factor leading to liver cirrhosis,hepatocellular carcinoma and cardiovascular diseases.There is a lack of effective drugs in clinic.NAFLD has a multi-factor pathogenesis,and the gut-liver axis plays an important role in its pathogenesis.There is a multifactorial pathogenesis of NAFLD.The gut-liver axis plays an important role in the pathogenesis of NAFLD.The imbalance of intestinal flora can lead to the destruction of intestinal barrier,the entry of relevant toxic metabolites into the blood and bacterial translocation,and the induction of liver inflammation and injury occured,which is an important inducement for the development of NAFLD.Berberine is the main medicinal component of Huanglian(Coptis chinensis),which has specific effects such as reducing liver cell lipid accumulation,anti-inflammation and anti-fibrosis,etc.It has typical multi-target and multi-system pharmacological effects on NAFLD,and is a typical representative of traditional Chinese medicine components in the research on the therapeutic mechanism of NAFLD.Berberine affects the gut-liver axis in a number of interrelated levels,including protecting the intestinal mucosal epithelial barrier,reducing liver microbial exposure and proinflammatory environment,adjusting the gut microbiota structure,changing the microorganism metabolites derived from such as short chain fatty acids and secondary bile acids,activating the intestinal farnesoid X receptor signaling pathways to regulate liver metabolism,thus plays a protective role of NAFLD.Some TCM compounds have shown the clinical effect of treating NAFLD,and studies on the mechanism of action have preliminarily shown the regulatory effect of TCM compounds on the gut-liver axis.However,the components of TCM compounds are too complex,so the research on the compatibility of TCM monomers can reduce the dimension and difficulty,and help to reveal the action mechanism of TCM compounds.