Objective  To explore the mechanism of jatrorrhizine hydrochloride (JH) in the treatment of alcoholic hepatitis (AH) based on network pharmacology and in vitro cellular experiments.

Methods  Drug ingredients of JH were queried based on PubMed, drug action targets were predicted based on SWISS database, and AH target points were found in GeneCards and OMIM databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed based on DAVID database. The protein-protein interaction network (PPI) was established by using STRING database and Cytoscape software, and verified by in vitro cell experiments. An inflammation model was developed in vitro using RAW264.7 cells stimulated with lipopolysaccharide (LPS), and these cells were then categorized into five groups. The effect of different concentrations of JH on cell activity was determined by MTT assay. Enzyme-linked immunosorbent assay (ELISA) was used to determine the activity of JH on the production and release of inflammatory factors, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).

Results The network pharmacology yielded a total of 25 key targets of JH and AH. Combined with the results of GO and KEGG enrichment analysis and PPI construction, ESRI, NT5E, and PGR and other genes were identified as the targets for subsequent experiments. The results of ELISA further confirmed that the secretion of inflammation-related factors TNF-α and IL-6 in M1 macrophages of RAW264.7 in LPS group was significantly increased compared with that in the control group. Compared with LPS group, the secretion of inflammatory factors TNF-α and IL-6 in the cell supernatant of the groups containing JH had a tendency to decrease, especially with the increase of JH concentration, the decrease effect was more significant.

Conclusion  In inflammatory model cells, JH can regulate M1 polarization, suggesting that JH is a potential molecule for the treatment of AH.

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