天然产物通过抑制PI3K信号通路抗肝纤维化的研究进展  

Advances in natural products against liver fibrosis by inhibiting PI3K signaling pathway

作　　者：朱武嫦 莫孝成 苏宏梅 韦锦斌 ZHU Wu-chang;MO Xiao-cheng;SU Hong-mei;WEI Jin-bin(Dept of Pharmacology,School of Pharmacy,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学药学院药理学教研室,广西南宁530021

出　　处：《中国药理学通报》2024年第4期619-624,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81960767);广西老年病防治药物基础研究重点实验室(桂卫科教发[2020]17号)。

摘　　要：肝纤维化是慢性肝损伤的一种内在反应,其特征是细胞外基质(extracellular matrix,ECM)的合成、降解和沉积失衡,会导致肝细胞受损和肝脏正常结构被破坏。而肝星状细胞(hepatic stellate cells,HSCs)的异常激活被认为是驱动肝纤维化的关键因素。在肝损伤的过程中,HSCs能够活化并向肌成纤维细胞转化进而产生过量的ECM。炎症和氧化应激在HSCs的激活中发挥重要作用,而HSCs凋亡则有利于肝纤维化的消退。抑制磷脂酰肌醇-3-激酶(phosphatidylinositol-3-kinase,PI3K)信号通路可降低炎症反应、氧化应激,诱导HSCs凋亡,从而改善肝纤维化。来源于植物的天然产物,包括黄酮类和萜类可以抑制PI3K信号通路,对肝纤维化的发生发展起到抑制作用。该文旨在综述PI3K信号通路在肝纤维化中的作用,总结近年来黄酮类化合物和萜类化合物通过抑制PI3K信号通路抗肝纤维化作用的证据,为进一步开发能有效防治肝纤维化的药物提供参考。Liver fibrosis is an intrinsic reaction of chronic liver injury,characterized by imbalance in synthesis,degradation and deposition of extracellular matrix(ECM),which may lead to damage of hepatocytes and destruction of normal liver structure.The abnormal activation of hepatic stellate cells(HSCs)is considered to be the key factor driving liver fibrosis.In the process of liver injury,HSCs can be activated and transformed into myofibroblasts to produce excess ECM.Inflammation and oxidative stress play an important role in the activation of HSCs,while HSCs apoptosis is conducive to the regression of liver fibrosis.Inhibition of phosphatidylinositol-3-kinase(PI3K)signaling pathway can reduce inflammation and oxidative stress,induce apoptosis of HSCs,and thus ameliorate liver fibrosis.Natural products derived from plants,including flavonoids and terpenoids,can inhibit the occurrence and development of liver fibrosis by suppressing PI3K signaling pathway.Aiming to review the role of PI3K signaling pathway in liver fibrosis,this article summarizes the evidence of anti-liver fibrosis effect of flavonoids and terpenoids by inhibiting PI3K signaling pathway in recent years,in order to provide reference for further development of drugs that can effectively prevent and treat liver fibrosis.

关 键 词：肝纤维化 肝星状细胞 PI3K信号通路 天然产物 黄酮类化合物 萜类化合物 

分 类 号：R-05[医药卫生] R28R322.47R345.57R575.2