Paeonol alleviates CCl4-induced liver fibrosis through suppression of hepatic stellate cells activation via inhibiting the TGF-β/Smad3 signaling

Objective: Paeonol is a natural phenolic component isolated from the root bark of peony with multiple pharmacological activities. We investigated the anti-fibrotic effect and underlying mechanism of paeonol. Methods: Twenty-four male C57BL/6J mice were divided into 4 groups (n = 6 in each group), injected with CCl₄ to induce liver fibrosis and administrated with paeonol according to the regimen. The serum activity of ALT and AST, and H&E staining were to assess liver injury. Sirius and Masson staining, and hydroxyproline content were to evaluate the degree of liver fibrosis. TNF-α, IL-6, TGF-β, MDA, GSH-PX, SOD, and CAT were detected to reflect inflammation and oxidative stress. RT-qPCR and Western blot analysis to assess the activation of HSCs and TGF-β/Smad3 signaling. Results: Paeonol ameliorated liver injury and liver fibrosis, reflected by the decrease of ALT, AST, less lesion in H&E staining, mitigated fibrosis in Sirius and Masson staining, lessened content of hydroxyproline. Paeonol attenuated the level of IL-6 and TNF-α, and elevated the activity of GSH-PX, SOD, and CAT with reducing the level of MDA. The expression of col 1a, α-SMA, vimentin, and desmin were down-regulated and TGF-β/Smad3 signaling pathway was inhibited. Conclusion: These data demonstrated that paeonol could alleviate CCl₄-induced liver fibrosis through suppression of hepatic stellate cells activation via inhibiting the TGF-β/Smad3 signaling.