Forsythiae Fructuse water extract attenuates liver fibrosis via TLR4/MyD88/NF-κB and TGF-β/smads signaling pathways

Ethnopharmacological relevance: Forsythiae Fructuse water extract (FSE) is a water-soluble component extracted from the traditional Chinese medicine Forsythiae Fructuse (The fruit of Forsythia suspensa (Thunb.) Vahl) usually used to treat inflammatory diseases. However, little is known about the therapeutic effect of FSE on liver fibrosis.

Aim of the study: The purpose of our study was to investigate the therapeutic effect of FSE on liver fibrosis and reveal the underlying mechanism.

Materials and methods: Liver fibrosis model was established by subcutaneous injection of olive oil containing 40% CCl₄. Rat liver tissue morphologic pathology was investigated by using HE staining, Masson staining and Sirius red staining. Several biochemical markers including liver (ALT, AST, AKP, γ-GT), fibrosis (HA, LN, PC III, Col IV) and inflammation (IL-6, IL-1β, TNF-α) were determined by using Elisa kits. Immunohistochemistry was used to observe the distribution of α-SMA and COL1 in liver tissue. Effects of FSE on inflammatory pathway (TLR4/MyD88/NF-κB) and fibrotic pathway (TGF-β/smads) were detected by western blot and qPCR.

Results: The results showed that hepatic histopathological injury, abnormal liver function, fibrosis and inflammation induced by CCl₄ were improved by FSE (2.5, 5 g/kg). Immunohistochemistry and western blot results indicated that the expression of α-SMA and COL1 in liver tissue was inhibited by FSE (2.5, 5 g/kg). Western blot and qPCR results further proved that FSE (2.5, 5 g/kg) inhibited the transduction of TLR4/MyD88/NF-κB and TGF-β/smads signaling pathways.

Conclusion: FSE can inhibit the expression of inflammatory factors and fibrotic cytokines, reduce liver injury, and inhibit the development of liver fibrosis through TLR4/MyD88/NF-κB and TGF-β/smads signaling pathways.

Keywords: Forsythiae Fructuse water extract; Inflammation; Liver fibrosis; TGF-β/smads; TLR4/MyD88/NF-κB.