Zhu Xiaopeng, Bian Hua, Gao Xin
Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Institute of Metabolic Disease, Fudan University, Shanghai 200032, China.
Molecules. 2016 Oct 14;21(10):1336. doi: 10.3390/molecules21101336.
Nonalcoholic fatty liver disease (NAFLD) is a globally observed metabolic disease with high prevalence both in adults and children. However, there is no efficient medication available yet. Increased evidence indicates that berberine (BBR), a natural plant product, has beneficial effects on NAFLD, though the mechanisms are not completely known. In this review, we briefly summarize the pathogenesis of NAFLD and factors that influence the progression of NAFLD, and focus on the potential mechanisms of BBR in the treatment of NAFLD. Increase of insulin sensitivity, regulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, improvement of mitochondrial function, alleviation of oxidative stress, LDLR mRNA stabilization, and regulation of gut microenvironment are the major targets of BBR in the treatment of NAFLD. Additionally, reduction of proprotein convertase subtilisin/kexin 9 (PCSK9) expression and DNA methylation are also involved in pharmacological mechanisms of berberine in the treatment of NAFLD. The immunologic mechanism of BBR in the treatment of NAFLD, development of berberine derivative, drug combinations, delivery routes, and drug dose can be considered in the future research.
非酒精性脂肪性肝病（NAFLD）是一种在全球范围内都有发现的代谢性疾病，在成人和儿童中都有很高的患病率。然而，目前尚无有效的药物。越来越多的证据表明，小檗碱（BBR）作为一种天然植物产物，对NAFLD有有益作用，但其机制尚不完全清楚。在本综述中，我们简要总结了NAFLD的发病机制以及影响NAFLD进展的因素，并重点关注BBR治疗NAFLD的潜在机制。提高胰岛素敏感性、调节腺苷单磷酸激活蛋白激酶（AMPK）途径、改善线粒体功能、减轻氧化应激、稳定低密度脂蛋白受体（LDLR）mRNA以及调节肠道微环境是BBR治疗NAFLD的主要靶点。此外，前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）表达的降低和DNA甲基化也参与了小檗碱治疗NAFLD的药理机制。未来的研究可以考虑BBR治疗NAFLD的免疫机制、小檗碱衍生物的开发、药物联合使用、给药途径和药物剂量。
