Mechanisms Of Ginsenoside Rg1 On Alcoholic Liver Injury Via Network Pharmacology

Alcoholic liver disease(ALD)is a liver disease associated with alcohol abuse,and its incidence is increasing gradually.The prevention and treatment of ALD is the current research hotspot,and traditional Chinese medicine and its components have a preventive effect on ALD.Ginsenoside Rg1(GRg1),a bioactive ingredient extracted from ginseng,has liver protection,anti-inflammatory,antioxidant and other pharmacological effects.In this study,the potential target and pathway for GRg1 preventing ALD were analyzed through network pharmacology,and the protective effect and mechanism of GRg1 on alcoholic liver injury were explored in vivo.First,the network pharmacology was used to analyze the targets of both active components in ginseng and ALD.The results showed that 31 active components were associated with 37 targets,and GRg1 was ranked the second in the degree between ingredients and ALD.The results of PPI and KEGG pathway analysis suggest that GRg1 may prevent ALD by regulating 11 potential targets,TLR and NF-κB signaling pathways.Subsequently,GRg1 was used as the research object to verify the mechanism in mice model of alcoholic liver injury.It was found that GRg1 could reduce liver tissue lesions and the release of liver enzymes(ALT,AST,LDH,AKP)through H&E staining and kit.The results of ELISA showed that GRg1 reduced the content of ROS,MDA,4-HNE,8-OHd G and increased the levels of SOD,CAT,GSH-Px,GSH in the liver,and the effect of 40 mg/kg was the most significant.Western blot and ELISA results demonstrated that GRg1 significantly down-regulate the LPS/TLR4/NF-κB pathway in the liver,thereby inhibited the levels of inflammatory cytokines including TNF-α,IL-1β,IL-6 and TGF-β1.GRg1 also inhibit intestinal inflammation by reducing the levels of LPS TNF-α,IL-1β and IL-6 in the intestine and increasing the content of IL-10.In addition,the integrity of intestinal barrier was further detected by AB staining,RT-q PCR,Western blot and ELISA.The results revealed that 40 mg/kg GRg1 could not only alleviate the intestinal pathological changes caused by alcohol,but also improve the m RNA levels of tight junction protein(ZO-1,occluding,claudin-1)and increase the levels of antimicrobial peptide(Reg3b、Reg3g)and Ig A in colon.Finally,16 S r DNA sequencing was used to analyze the gut microbiota,the results showed that GRg1 improved alcohol-induced intestinal microbiota disorders.Verrucomicrobia,Bacteroidetes,Akkermansia,Bacteroides,Lachnospiraceae＿NK4A136＿group and Alloprevotella played positive association with intestinal barrier indicators,and negative correlation with hepatic inflammation biomarkers.Our findings proved that GRg1 can alleviate alcohol-induced liver injury,and prevent alcohol-induced liver injury by inhibiting the LPS/TLR4/NF-κB inflammatory pathway and regulating intestinal homeostasis.This research provides the basis for the theoretical research on the prevention of alcoholic liver injury by GRg1,and provides a reference for the development of natural liver-protecting health care products.