1.Data Mining and Experimental Validation of Total Ginsenosides Ameliorating Alcoholic Hepatitis
Shuling CHEN ; Yitao LIU ; Xiao WU ; Duo ZHANG ; Jinhui AI ; Taohua YUAN ; Jianfei SUN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):95-103
ObjectiveTo explore new targets and herbal medicines of total ginsenosides in ameliorating alcoholic hepatitis (AH) by data mining and experimental validation and to provide new directions for the clinical treatment of AH. MethodGSE28619 was selected as the test set from the GEO database and GSE83148 and GSE103580 were selected as the validation sets. The limma package and weighted gene co-expression network analysis (WGCNA) were employed to identify the AH-related differentially expressed genes and modular genes, and Venny was used to extract the common genes. The protein-protein interaction (PPI) network was constructed and the enrichment analysis was carried out. The hub genes were further screened and evaluated for their diagnostic value. After validation with the datasets, new potential targets of AH and traditional Chinese medicine were predicted. Molecular docking between the targets and active ingredients of traditional Chinese medicine was performed, and the results were validated by experiments. Eight out of 48 SD rats were randomly selected into a blank group and received an equal amount of normal saline. The rest rats were subjected to modeling with ethanol by gavage and then randomized into low- (10 mg·kg-1), medium- (20 mg·kg-1), and high-dose (40 mg·kg-1) total ginsenosides, model, and positive control (metadoxine, 117 mg·kg-1) groups. After 3 weeks of gavage, serum samples were collected for the measurement of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and liver samples were collected for hematoxylin-eosin (HE) staining. Western blot and Real-time PCR were employed to determine the protein and mRNA levels, respectively, of potential targets in the liver tissue. ResultData mining predicted the potential genes: Proto-oncogene FOS and collagen type Ⅰ alpha 2 (COL1A2). Experimental validation showed that the liver injury was alleviated after drug administration compared with that after modeling. The serum AST and ALT levels were reduced after drug administration. The protein and mRNA levels of FOS were significantly up-regulated, while those of COL1A2 were down-regulated after drug administration. ConclusionTotal ginsenosides ameliorate HA via FOS and COL1A2.