Probable targets and mechanism of ginsenoside Rg1 for non-alcoholic fatty liver disease: a study integrating network pharmacology, molecular docking, and molecular dynamics simulation

AbstractGinsenoside Rg1 (GRg1), a key bioactive component of medicinal herbs, has shown beneficial effects on non-alcoholic fatty liver disease (NAFLD) and numerous other conditions. Nevertheless, the specific targets that are actively involved and the potential mechanisms underlying NAFLD treatment remain unclear. This study aimed to elucidate the therapeutic effects and mechanism of GRg1 in alleviating NAFLD using a combined approach of network pharmacology and molecular biology validation. The analysis yielded 294 targets for GRg1 and 1293 associated with NAFLD, resulting in 89 overlapping targets. Through protein-protein interactions (PPI) network topology analysis, 10 key targets were identified. Upon evaluating the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis, GRg1 may exert therapeutic effects on NAFLD by negatively regulating the apoptotic process, insulin and endocrine resistance, the AGE-RAGE signaling pathway in diabetic complications, and the Estrogen, PI3K/Akt, and MAPK pathways. The three differential gene targets for Akt1, EGFR, and IGF1 were identified through the compound-target network in conjunction with the aforementioned methods. The molecular docking and molecular dynamics (MD) simulations showed that AKT1 and EGFR had a strong binding affinity with GRg1. Overall, our findings point to a novel therapeutic strategy involving NAFLD, with further in vivo and in vitro studies promising to deepen our comprehension and validate its potential advantages.Communicated by Ramaswamy H. SarmaKeywords: Ginsenoside Rg1non-alcoholic fatty liver diseasenetwork pharmacologymolecular dockingMD simulation Ethical approval and participant consentConsidering the nature of this study, which did not involve any experimentation with animals or patients, ethical approval or participant consent was not required.Disclosure statementNo potential conflict of interest was reported by the author(s).Authors’ contributionDNW was responsible for conducting the study and drafting the manuscript. The study design was a collaborative effort of DNW, MJC, HFD, and WXH, who also contributed to manuscript revisions. DNW, JZ, JYP, and KXT were responsible for language editing. All participating authors reviewed and endorsed the final version of the manuscript.Data availability statementAll information scrutinized or generated during this study can be found in the body of the article and its corresponding supplementary materials.Additional informationFundingThis work was supported by the Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission, China, in 2022 under Grant CSTB2022NSCQ-MSX0092.