An ensemble of Gleditsia sinensis Lam. and gut microbiota against alcoholic liver disease

Gleditsia sinensis Lam. (GSL) is a medicinal herb and a noticeable resource of possessing hepatic protective agents such as alcoholic liver disease (ALD). At present, it has been documented that gut microbiota (GM) is related directly to etiology of ALD. Nevertheless, the bioactive molecules in GSL, favorable GM, targets, and key mechanism(s) against ALD are yet to be revealed. Hence, we integrated the significant four components to clarify the nuanced pathogenesis with help of network pharmacology (NP) concept. We retrieved significant metabolites via gutMGene and constructed GSL or GM-Signaling pathways-Targets-Metabolites (GGSTM) networks. Finally, molecular docking test (MDT) was performed to verify the key findings. The gutMGene suggested that 16 GM and 6 metabolites were related to the two signaling pathways through GGSTM networks. Both MDT and frontier molecular orbitals (FMO) theory revealed the most stable conformers: equol from Lactobacillus paracasei JS1 on IL6, Bauer-7-en-3-one, and Urs-12-en-3-one from GSL on PPARA, PPARD, and PPARG, respectively. In conclusion, this study sheds light on the combinatorial effects of GM, and GSL in treating ALD via systems biology concept. * AFL : Alcoholic Fatty Liver AFLD : Alcoholic Fatty Liver Disease ALD : Alcoholic Liver Disease DFT : Density Functional Theory DV : Degree Value ECM : ExtraCellular Matrix EGAP : Energy gap FLD : Fatty Liver Disease FMO : Frontier Molecular Orbital GC-MS : Gas Chromatography-Mass Spectrometry GGSTM : GSL or GM-Signaling pathways-Targets-Metabolites GM : Gut Microbiota GSL : Gleditsia sinensis Lam. HC : Hepatic Cirrhosis HCC : HepatoCellular Carcinoma HOMO : Highest Occupied Molecular Orbital HS : Hepatic Steatosis HSCs : Hepatic Stellate Cells LUMO : Lowest Unoccupied Molecular Orbital LYP : Lee-Yang-Parr MDT : Molecular Docking Test MS : Mass Spectra MT : Molecular Theory NP : Network Pharmacology PPI : Protein Protein Interaction SEA : Similarity Ensemble Approach SMILES : Simplified Molecular Input Line Entry System STP : SwissTargetPrediction TPSA : Topological Polar Surface Area