AMPK通路介导中医药改善非酒精性脂肪肝的分子机制及研究进展OA

This article reviews the molecular mechanism and progress in the last 5 years of the AMP-activated protein kinase(AMPK)pathway-mediated improvement of non-alcoholic fatty liver disease(NAFLD)by traditional Chinese medicine(TCM).The pathogenesis of NAFLD involves disorders of glucose and lipid metabolism,inflammation and mitochondrial dysfunction.AMPK,as a core hub of energy metabolism,plays a key role in NAFLD by regulating fatty acid synthesis,oxidation,autophagy and inflammation.Studies have shown that a variety of herbal monomers(e.g.,the terpene catalpol,the flavonoid geraniol,the al-kaloid berberine,the glycosides astragaloside,phenols and thujaplicins,and the polysaccharides honeysuckle polysaccharides)in-hibit the key factors of lipid synthesis(SREBP-1c,FAS,ACC),promote fatty acid oxidation(PPARα,CPT-1),improves insu-lin resistance,enhances autophagy(ULK1,LC3),and inhibits inflammation(NF-κB)and oxidative stress(Nrf2)to improve NAFLD in a multidimensional manner by targeting the activation of AMPK or its upstream kinases(LKB1,CaMKKβ,Adi-poR1,etc.).By virtue of the synergistic effect of multiple components,the TCM compound formula(e.g.the classic formula Zex-ie Decoction,Wuling Powder,and Danggui Shaoyao Powder;the empirical formula Qishu Formula,and Liuwei Jiangzhi Decoc-tion;and the proprietary Chinese medicines Elimination of Lipids Fang,and Cerebro-Cardio-Clear,etc.)can regulate the down-stream network of AMPK(e.g.LKB1/AMPK/PGC-1α,AMPK/mTOR/ULK1,and AMPK/SIRT1)in a systematic way,and comprehensively promote the catabolism of lipids,inhibit synthesis,enhance autophagy and anti-inflammation,reflecting the sci-entific connotation of Chinese medicine's treatment methods such as"dredging the liver and strengthening the spleen"and"activat-ing the blood and resolving turbidities".In conclusion,Chinese medicine provides important molecular evidence and the basis for the integration of Chinese and Western medicine for the prevention and treatment of NAFLD by targeting AMPK to remodel the homeostasis of liver energy metabolism.In the future,we need to overcome the heterogeneity of the model,deeply analyze the synergistic mechanism of the compound and the interaction of the pathways,and promote the clinical translation.