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Flavonoid-rich Scabiosa comosa inflorescence extract attenuates CCl4-induced hepatic fibrosis by modulating TGF-β-induced Smad3 phosphorylation.
Biomed Pharmacother. 2018 Oct; 106:426-433.BP

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 200-250 g) were injected intraperitoneally with CCl4 (1:1v/v in peanut oil, 2 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.

Authors+Show Affiliations

Department of Pharmacology, School of Basic Medicine, Inner Mongolia medical university, Hohhot, 010110, China. Electronic address: myh19982002@sina.com.Department of Pathology, School of Basic Medicine, Inner Mongolia medical university, Hohhot, 010110, China.Department of Pharmacology, School of Basic Medicine, Inner Mongolia medical university, Hohhot, 010110, China.Department of Pharmaceutical Engineering, School of Pharmacy, Inner Mongolia medical university, Hohhot, 010110, China.Department of Biochemistry, School of Basic Medicine, Inner Mongolia medical university, Hohhot, 010110, China.Laboratory of Functional Science, School of Basic Medicine, Inner Mongolia medical university, Hohhot, 010110, China.Department of Pharmacology, School of Basic Medicine, Inner Mongolia medical university, Hohhot, 010110, China.Department of Pharmacology, School of Basic Medicine, Inner Mongolia medical university, Hohhot, 010110, China.Department of Biochemistry, School of Basic Medicine, Inner Mongolia medical university, Hohhot, 010110, China.Department of Pharmacy, Sichuan Provincial People's Hospital, Chengdu, 610072, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29990830

Citation

Ma, Yuehong, et al. "Flavonoid-rich Scabiosa Comosa Inflorescence Extract Attenuates CCl4-induced Hepatic Fibrosis By Modulating TGF-β-induced Smad3 Phosphorylation." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 106, 2018, pp. 426-433.
Ma Y, Yuan H, Jin R, et al. Flavonoid-rich Scabiosa comosa inflorescence extract attenuates CCl4-induced hepatic fibrosis by modulating TGF-β-induced Smad3 phosphorylation. Biomed Pharmacother. 2018;106:426-433.
Ma, Y., Yuan, H., Jin, R., Bao, X., Wang, H., Su, X., Mu, M. G. S. L., Liang, J., Zhang, J., & Wu, X. (2018). Flavonoid-rich Scabiosa comosa inflorescence extract attenuates CCl4-induced hepatic fibrosis by modulating TGF-β-induced Smad3 phosphorylation. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 106, 426-433. https://doi.org/10.1016/j.biopha.2018.06.118
Ma Y, et al. Flavonoid-rich Scabiosa Comosa Inflorescence Extract Attenuates CCl4-induced Hepatic Fibrosis By Modulating TGF-β-induced Smad3 Phosphorylation. Biomed Pharmacother. 2018;106:426-433. PubMed PMID: 29990830.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Flavonoid-rich Scabiosa comosa inflorescence extract attenuates CCl4-induced hepatic fibrosis by modulating TGF-β-induced Smad3 phosphorylation. AU - Ma,Yuehong, AU - Yuan,Hongwei, AU - Jin,Rong, AU - Bao,Xiaomei, AU - Wang,Haisheng, AU - Su,Xiaoli, AU - Mu,Meng Gen Si Li, AU - Liang,Jie, AU - Zhang,Jianyu, AU - Wu,Xingwei, Y1 - 2018/07/11/ PY - 2018/02/08/received PY - 2018/06/21/revised PY - 2018/06/22/accepted PY - 2018/7/11/pubmed PY - 2018/12/15/medline PY - 2018/7/11/entrez KW - Flavonoids KW - Liver fibrosis KW - Scabiosa comosa KW - Smad3 KW - TGF-β1 SP - 426 EP - 433 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 106 N2 - 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 200-250 g) were injected intraperitoneally with CCl4 (1:1v/v in peanut oil, 2 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. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/29990830/Flavonoid_rich_Scabiosa_comosa_inflorescence_extract_attenuates_CCl4_induced_hepatic_fibrosis_by_modulating_TGF_β_induced_Smad3_phosphorylation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(18)30912-0 DB - PRIME DP - Unbound Medicine ER -