Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8525197 | Biomedicine & Pharmacotherapy | 2018 | 8 Pages |
Abstract
Scabiosa comosa inflorescence is a traditional Mongolian medicine in the treatment of liver diseases. In the study, we investigated the anti-fibrotic efficacy of flavonoid-rich Scabiosa comosa inflorescence extract (TF-SC) in a rat model of CCl4-induced hepatic fibrosis and explored its underlying mechanism in vitro and in vivo. Rats (Wistar, Male, weight 200-250â¯g) were injected intraperitoneally with CCl4 (1:1v/v in peanut oil, 2â¯mL/kg body weight) to induce liver fibrosis, followed by treatment with TF-SC or vehicle. In addition, transforming growth factor-β1 (TGF-β1)-activated hepatic stellate cells (HSCs) were used for measuring Smad3 phosphorylation. We found decrease in liver function and liver fibrosis markers in serums. Also, TF-SC decreased hydroxyproline content and collagen deposition in liver tissues. TF-SC also decreased the expression of α-SMA, collagen I and fibronectin in CCl4-induced hepatic fibrosis rats. Mechanistically, TF-SC attenuated liver fibrosis by selectively inhibiting Smad3 phosphorylation. In TGF-β1-stimulated HSCs, TF-SC blocked the interaction between Smad3 and TGF-β type I receptor (TβRI), suppressed subsequent phosphorylation and nuclear translocation of Smad3, and down-regulated the transcription of fibrotic genes. In conclusion, the study demonstrated that TF-SC was an effective therapeutic agent for treatment of hepatic fibrosis, and provided a molecular basis through which TF-SC exerts its anti-fibrotic effects.
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Authors
Yuehong Ma, Hongwei Yuan, Rong Jin, Xiaomei Bao, Haisheng Wang, Xiaoli Su, Meng Gen Si Li Mu, Jie Liang, Jianyu Zhang, Xingwei Wu,