Elucidation of the anti-fibrotic diseases mechanism of chelerythrine by integrative approach of network pharmacology and experimental verification

In the present study, we conducted an integrative approach of network pharmacology and experimental validation study to elucidate the underlying mechanisms of Chelerythrine (CLT), in treating fibrotic diseases (FD), which are disorders characterised by excessive accumulation of extracellular matrix. 27 common targets of CLT against FD were analysed, and these common targets were used to construct the PPI network. The results of GO and KEGG enrichment analyses suggested that CLT exerted pharmacological effects on FD by regulating mTOR signalling pathway, AKT-PI3K pathway and apoptosis signalling pathway. Finally, molecular docking confirmed a strong binding affinity between CLT and the core target proteins. CLT has inhibitory effects on the proliferation and migration of L929 cells, CLT could promote cell apoptosis. CLT decreased levels of the Bcl-2, p-AKT/AKT, p-mTOR/mTOR and p-PI3K/PI3K, meanwhile increased levels of the Bax. Taken together, these results indicate that CLT may be a potential drug for anti-fibrotic diseases therapy.