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

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.

Effect of Jiangan Xiaozhi decoction on endoplasmic reticulum stress signaling pathway in methionine and choline deficiency diet-induced mice

Objective:To investigate the therapeutic effects of Jiangan Xiaozhi decoction on nonalcoholic steatohepatitis(NASH)mice model and its effects on the endoplasmic reticulum stress(ERS)signaling pathway.Methods:NASH mice model was established by methionine-choline deficient(MCD)diet induction and intragastric administration of Jiangan Xiaozhi decoction.The therapeutic effects of the decoction on NASH mice model were evaluated by measuring the body weight,hepatic index,and blood lipids and analyzing liver function-related biochemical markers,liver hematoxylin and eosin staining,and liver oil red O staining after the administration of the decoction in the mice model.Next,the levels of glucose-regulated protein 78(GRP78),inositol-requiring enzyme 1(IRE1),and X-box binding protein 1(XBP1)in the liver tissue of the mice were measured using Western blotting to investigate the mechanism underlying the treatment of NASH mice model by Jiangan Xiaozhi decoction.Results:Jiangan Xiaozhi decoction improved the body weight and hepatic index;reduced the levels of total cholesterol,transglutaminase,alanine transaminase,and aspartate aminotransferase;and improved pathological changes caused by hepatocyte necrosis,inflammatory cell infiltration,ballooning,and fat accumulation in the liver tissue of NASH mice model.The Western blot results showed that Jiangan Xiaozhi decoction reduced the levels of GRP78,IRE1,and XBP1 proteins in the liver tissues of NASH mice model.Conclusion:Jiangan Xiaozhi decoction has therapeutic effects on NASH mice model.The mechanism of its action may be related to the regulation of level of GRP78,IRE1,and XBP1 proteins in liver tissue and improvement of ERS.

Regulatory effects of evodiamine on glucose metabolism-related factors in CT26 colorectal carcinoma-bearing mice

Objective:To investigate the therapeutic effect of evodiamine(EVO)on the expression of hexokinase(HK),lactate dehydrogenase A(LDHA),and pyruvate kinase M(PKM),key enzymes of glycolysis,in the tumor-bearing mice after modeling mouse colon cancer cells(CT26).Methods:A tumor-bearing mouse model was generated by administering axillary injection of CT26 and intraperitoneally injecting different doses of EVO.The therapeutic effects of EVO on CT26 tumor-bearing mice were evaluated by measuring the thymus and spleen indices,tumor volume,tumor suppression rate,and other related indicators in the tumor tissues of mice in each group after the administration of EVO,in addition,histopathological changes in the tumor tissues of the mice in the groups were studied by hematoxylin and eosin staining.The expression levels of HK,LDHA,and PKM in the tumor tissues of each group of mice were measured by performing Western blot to investigate the mechanism of EVO treatment in CT26 tumor-bearing mice.Results:EVO inhibited the growth of tumors in CT26-bearing mice and enhanced their splenic and thymic indices.Western blot results showed that EVO reduced the expression levels of HK,LDHA,and PKM proteins in the tumor tissues of CT26 tumor-bearing mice.Conclusion:EVO has a therapeutic effect on CT26 tumor-bearing mice,and its mechanism of action may be related to the low expression of key enzymes HK,LDHA and PKM of glycolysis in tumor tissues.

The transition and current pattern of drug therapy for advanced gastric cancer

Gastric cancer is one of the most common malignant tumors in the world.Its incidence ranks fifth among all malignant tumors worldwide and is the third leading cause of death among cancer patients.Surgery is currently considered to be the only radical treatment.However,the low rate of early diagnosis means that most patients have an advanced-stage disease at diagnosis which lost the chance of surgery.Therefore,the main treatment for advanced gastric cancer includes chemotherapy,targeted therapy,immunotherapy.The purpose of this study is to review the transition and current patterns of drug therapy for advanced gastric cancer and to provide assistance for subsequent clinical studies in advanced gastric cancer.