Abstract
Formula Le-Cao-Shi (LCS), a traditional Chinese medicine (TCM), has been used as folk remedy for treating hepatitis B for a long time. In our previous study, the anti-hepatitis B effects of LCS have been verified. In the present study, the anti-hepatitis B activities of LCS and its three single herbs were investigated in vitro by HepG2.2.15 cellular model, and the mechanisms against hepatitis B were deciphered via network pharmacology and gut microbiota analysis. By network pharmacology method, twelve key compounds that played a vital role in LCS were filtered from 213 ingredients. The targets RORA, CDK2, RELA, AKT1, IKBKG, PRKCβ and CASP3 were directly related to hepatitis B pathway, which indicated that LCS could exert anti-hepatitis B effect by co-regulating cell cycle and inflammatory pathways. The interactions between candidate compounds and target proteins that were directly involved in hepatitis B pathway were validated by molecular docking simulation and RT-PCR. By gut microbiota analysis, it was revealed that LCS could alter the disordered microbial composition in the infected ducks towards normal, especially the restoration of three key strains, namely Streptococcus alacto-lyticus, Enterococcus cecorum and Bacteroidesfragilis. The above findings could provide a scientific basis for further development and utilization of LCS against hepatitis B.