A characterized ethanol extract of Rosa rugosa inhibits hepatic stellate cell activation through elevating Hint1 and subsequent upregulation of Smad7

Abstract

Our study aimed to explore effects of a characterized ethanol extract of Rosa rugosa (ERS) on hepatic stellate cells (HSCs) activation and mouse liver fibrosis and their molecular mechanisms. ERS suppressed TGF-β1-induced activation of LX-2 HSCs. Moreover, ERS boosted Smad7 and inhibited TGF-β1-induced phosphorylation of Smad2/3. Knockdown of Smad7 eliminated protective effects of ERS. Furthermore, ERS elevated Hint1 whose expression was positively related with that of Smad7. Knockdown of Hint1 abolished ERS-mediated upregulation of Smad7 and subsequent suppression of LX-2 HSC activation. Suppressive effects of ERS on Smad2/3 signaling were also eliminated. In primary mouse HSCs, ERS potentiated Hint1/Smad7 axis and suppressed their spontaneous activation. Finally, it was unveiled that gavage of ERS dramatically mitigated mouse liver fibrosis provoked by CCl4. Our findings collectively indicated that ERS inhibits HSC activation and alleviates liver fibrosis. Mechanically, ERS elevates expression of Hint1 which suppresses TGF-β1 pathway via upregulating Smad7 in HSCs.

Keywords

• Rosa rugosa
• Hepatic stellate cell activation
• TGF-β1
• Smad7
• Hint1