Exploration of chemical components and Rac1-dependent anti-hepatic fibrosis mechanism by total flavonoids derived from .

[OBJECTIVE] This study is mainly to elucidate the characteristic components, hepatoprotective effect, and the underlying anti-hepatic fibrosis molecular mechanism of the total flavonoids of Diels & Gilg (SYQTF).

[METHODS] The components of SYQTF were confirmed based on global natural products social molecular networking (GNPS) as well as the hepatoprotective effect on CCl-induced acute liver injury. Cell toxicity and viability, cell cycle, and apoptosis analyses were then performed to determine the effects of SYQTF in transforming growth factor-1 (TGF-1) (10 ng/mL)-induced HSC-T6 hepatic fibrosis cell model. Finally, the lentiviral particles to package recombinant Ras-related C3 botulinum toxin substrate 1 (Rac1) over-expression and Rac1 knockdown plasmids were transfected into TGF-β1-induced HSC-T6 cells to elucidate the mechanism of anti-hepatic fibrosis of SYQTF targeting Rac1, respectively.

[RESULTS] Our findings demonstrated that 86 components in SYQTF were identified in MS and FastDDA mode with the aid of GNPS. Moreover, S-ZJ, the genuine functional food and medicinal materials of , was significantly different from other regions by multivariate statistical methods based on progenesis QI. Remarkably, kaempferol-3--furananose7--rhamnosyl-glucoside, the highest response intensity in S-ZJ, may act as the potential Q-marker of genuine functional food and medicinal materials of in Zhejiang Province distinguished from other areas. In addition, the experiments revealed that SYQTF greatly alleviated CCl-induced acute liver injury. Furthermore, SYQTF can reversible the activation and proliferation of HSC-T6 cells, block the cell cycle in the G/G phase, and promote cell apoptosis. Remarkably, the study is the first to reveal that SYQTF exhibited the anti-hepatic fibrosis effect through targeting Rac1 in the hedgehog signaling pathway.

[CONCLUSION] Rac1 is an important signaling molecule for the activation of the hedgehog pathway in HSC-T6. Importantly, SYQTF exerted its anti-hepatic fibrosis effect by inhibiting the Rac1-hedgehog signaling pathway. Furthermore, kaempferol-3--furananose7--rhamnosyl-glucoside could be a potential Q-marker of in Zhejiang Province distinguished from other areas.