Abstract

Due to the absence of approved treatments, liver fibrosis remains a leading cause of liver cirrhosis and liver failure. Our previous study demonstrated that lipophilic constituents of Salvia miltiorrhiza Bunge can treat hepatic fibrosis by inhibiting hepatic stellate cells activation and regulating the janus kinase 1/signal transducer and the activator of the transcription 3 signaling pathway. However, specific active compounds in Salvia miltiorrhiza Labiatae sp that exert anti-fibrotic effects through this mechanism of action are yet to be identified. In this study, we treated and analyzed transforming growth factor beta-1-induced LX-2 and HSC-T6 cells with purchasable compounds in Salvia miltiorrhiza Labiatae sp via cell viability assays, which identified cryptotanshinone as an effective representative of Salvia miltiorrhiza Labiatae sp. Subsequent flow cytometry and western blot experiments revealed that cryptotanshinone could inhibit hepatic stellate cells activation by promoting apoptosis and reducing the expression of fibrosis markers such as transforming growth factor beta-1 and alpha-smooth muscle actin, along with downregulating the levels of janus kinase 1, phosphorylated-janus kinase 1 and signal transducer and the activator of the transcription 3 (p<0.05). Molecular docking studies further confirmed its binding affinity with janus kinase 1 and signal transducer and the activator of the transcription 3. This study provides a scientific basis for the application of Salvia miltiorrhiza Labiatae sp in the treatment of hepatic fibrosis and partially explains the pharmacological mechanism of cryptotanshinone against liver fibrosis.