Triptolide combined with salvianolic acid B alleviates CCL4-induced liver fibrosis by suppressing the Th17/IL-17A axis.

Liver fibrosis represents a significant public health challenge, with immune dysregulation being a key pathological mechanism involved in its progression. The combined use of triptolide and salvianolic acid B has been demonstrated effective in ameliorating CCL4-induced liver fibrosis, but the underlying mechanism remains to be elucidated. In this study, we integrated network pharmacology and experimental validation to uncover the therapeutic mechanisms of the combined use of triptolide and salvianolic acid B. First, animal experiments demonstrated that the combination notably alleviated CCL4-induced liver injury and fibrosis. Second, network pharmacology was employed to predict the potential mechanisms, and the results highlighted Th17 cell differentiation and the IL-17 signaling pathway as the key pathways mediating the anti-fibrotic effects of the combination. Next, with the help of flow cytometry analysis, we confirmed that the combination effectively inhibited the differentiation of Th17 cells, both in vivo and in vitro, and decreased the expression of pro-inflammatory/fibrotic cytokines. Finally, to preliminary ascertain the role of IL-17 signaling in HSC activation and if the combination could affect it, we used recombinant human IL-17A protein to trigger LX-2 cells, the results suggested that IL-17A signaling did engage in HSC activation, and the combination could significantly suppress IL-17A-induced LX-2 activation partly by inhibiting the expression of IL-17RA. Taken together, those results implied that the combined use of triptolide and salvianolic acid B could attenuate CCL4-induce liver fibrosis, and this effect was related to the suppression of inflammation and hepatic stellate cell activation via Th17/IL-17A axis.