Tetrahydrocurcumin attenuates carbon tetrachloride-induced hepatic fibrogenesis by inhibiting the activation and autophagy of hepatic stellate cells

- THC was more potent than curcumin on against CCl4-indcued liver fibrosis.
- THC attenuated hepatic fibrosis via down-regulation of TGF-β1/Smad and MAPK signaling.
- THC reduced activation of HSCs via autophagy suppression.

Tetrahydrocurcumin (THC) is known to be the major metabolite of curcumin. The present study aimed to investigate the efficacy of THC and curcumin against hepatic fibrogenesis and the underlying responsible molecular mechanisms. Hepatic fibrogenesis was induced by intraperitoneal injection of CCl4 twice per week for 8 weeks. Daily oral administration of THC at 10 mg/kg and 50 mg/kg attenuated liver fibrogenesis more effectively than curcumin, as indicated by histopathological changes and a reduction in serum biochemical markers, collagen deposition, and fibrogenic molecules such as α-SMA and TGF-β1. THC exerted anti-fibrotic effects through the down-regulation of the TGF-β1/Smad and MAPKs signaling pathways. Moreover, IHC double-staining showed that THC diminished the autophagic process in activated HSCs in the liver. These findings suggest that THC alleviated hepatic fibrogenesis via inhibition of multiple signaling and autophagy suppression. THC could be used as a potent dietary supplement for the management of fibrotic liver diseases.