Mechanism of action of Linggui Zhugan Decoction in treating non-alcoholic fatty liver disease using untargeted metabolomics approach  

作　　者：Huan Pei Ren-Lin Li Xin-Ran Song Qian-Qian Wan Yu-Ming Wang Han-Zhou Li Wei-Quan Xu Jia-Bao Liao Wei-Bo Wen Jing Miao Huan-Tian Cui 

机构地区：[1]School of Basic Medicine,Yunnan University of Chinese Medicine,Kunming 650599,China [2]School Clinical Medical College,Yunnan University of Chinese Medicine,Kunming 650599,China [3]First School of Clinical Medicine,Yunnan University of Chinese Medicine,Kunming 650599,China [4]School of Integrative Chinese and Western Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China [5]Department of Pharmacy,Tianjin Second People's Hospital,Tianjin 300192,China

出　　处：《Traditional Medicine Research》2025年第2期65-76,共12页TMR传统医学研究

基　　金：supported by the National Natural Science Foundation of China(82274424).

摘　　要：Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver cancer.Numerous studies showed that metabolic dysfunction can promote NAFLD development.Linggui Zhugan Decoction(LGZGD)has therapeutic effects on NAFLD.The mechanism of LGZGD still remains unclear.This study was to examine the impact of LGZGD on the metabolic processes involved in the development of NAFLD.Methods:A mice model of NAFLD was treated with LGZGD.The therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of NAFLD.Additionally,this study also evaluated the influence of LGZGD on liver inflammation and oxidative stress.Results:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD mice.LGZGD improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the liver.Untargeted metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate cycle.Further RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.

关 键 词：NAFLD LGZGD untargeted metabolomics glycerophospholipid metabolism citrate cycle 

分 类 号：R575.5[医药卫生—消化系统]