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Ampelopsin attenuates carbon tetrachloride-induced mouse liver fibrosis and hepatic stellate cell activation associated with the SIRT1/TGF-β1/Smad3 and autophagy pathway.
Int Immunopharmacol. 2019 Dec; 77:105984.II

Abstract

Ampelopsin (Amp), a natural flavonoid found in the vine tea of Ampelopsis grossedentata, exhibited anti-cancer, anti-oxidant, anti-inflammatory, anti-apoptosis and hepatoprotective properties. The current study instigates the protective effect of Amp on carbon tetrachloride (CCl4)-induced hepatic fibrosis and explores its underlying mechanisms. The results indicated Amp decreased the levels of liver injury markers. Amp inhibited liver fibrosis, as indicated by decreases in hepatic collagen deposition, extracellular matrix (ECM) deposition and α-smooth muscle actin (α-SMA). Amp blocked the activation of hepaticstellate cells (HSCs) by decreasing the expression of collage I, α-SMA, tissue inhibitor of matrix metalloproteinases (TIMPs) 1, transforming growth factor (TGF)-β1, phosphorylated Smad3 (p-Smad3) and increasing the expression of matrix metalloproteinases (MMPs) 9 and SIRT1 in the model of liver fibrosis and cultured HSCs. The sirtuin 1 (SIRT1) specific inhibitor Sirtinol activated the TGF-β1/Smad3 pathway and enhanced ECM accumulation. Attractively, Amp up-regulates the expression of autophagy-related proteins microtubule-associated protein light chain three II (LC3-II) and Beclin-1 in vivo and in vitro. However, depletion of autophagy by specific inhibitor 3-MA obviously abolished the inhibiting effect of Amp on HSC activation and hepatic fibrosis. Conclusively, these results suggest that Amp could decrease CCl4-induced hepatic fibrosis through regulating the SIRT1/TGF-β1/Smad3 and autophagy pathway.

Authors+Show Affiliations

School of Chemistry Engineering, Sichuan University of Science and Engineering, No. 180, Huixing Road, Zigong City, 643000 Sichuan Province, PR China. Electronic address: a1032042419@126.com.College of Integrated Chinese and Western Medicine, Shandong Liming Polytechnic Vocational College, No. 389, Jiwei Road, Shizhong District, Jinan City, 250116 Shandong Province, PR China.School of Life Science, Jiangsu Normal University, No.101, Shanghai Road, Tongshan New Area, Xuzhou City 221116, Jiangsu Province, PR China.School of Life Science, Jiangsu Normal University, No.101, Shanghai Road, Tongshan New Area, Xuzhou City 221116, Jiangsu Province, PR China.School of Life Science, Jiangsu Normal University, No.101, Shanghai Road, Tongshan New Area, Xuzhou City 221116, Jiangsu Province, PR China.School of Life Science, Jiangsu Normal University, No.101, Shanghai Road, Tongshan New Area, Xuzhou City 221116, Jiangsu Province, PR China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31677501

Citation

Ma, Jie-Qiong, et al. "Ampelopsin Attenuates Carbon Tetrachloride-induced Mouse Liver Fibrosis and Hepatic Stellate Cell Activation Associated With the SIRT1/TGF-β1/Smad3 and Autophagy Pathway." International Immunopharmacology, vol. 77, 2019, p. 105984.
Ma JQ, Sun YZ, Ming QL, et al. Ampelopsin attenuates carbon tetrachloride-induced mouse liver fibrosis and hepatic stellate cell activation associated with the SIRT1/TGF-β1/Smad3 and autophagy pathway. Int Immunopharmacol. 2019;77:105984.
Ma, J. Q., Sun, Y. Z., Ming, Q. L., Tian, Z. K., Yang, H. X., & Liu, C. M. (2019). Ampelopsin attenuates carbon tetrachloride-induced mouse liver fibrosis and hepatic stellate cell activation associated with the SIRT1/TGF-β1/Smad3 and autophagy pathway. International Immunopharmacology, 77, 105984. https://doi.org/10.1016/j.intimp.2019.105984
Ma JQ, et al. Ampelopsin Attenuates Carbon Tetrachloride-induced Mouse Liver Fibrosis and Hepatic Stellate Cell Activation Associated With the SIRT1/TGF-β1/Smad3 and Autophagy Pathway. Int Immunopharmacol. 2019;77:105984. PubMed PMID: 31677501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ampelopsin attenuates carbon tetrachloride-induced mouse liver fibrosis and hepatic stellate cell activation associated with the SIRT1/TGF-β1/Smad3 and autophagy pathway. AU - Ma,Jie-Qiong, AU - Sun,Yun-Zhi, AU - Ming,Qing-Lei, AU - Tian,Zhi-Kai, AU - Yang,Hui-Xin, AU - Liu,Chen-Min, Y1 - 2019/10/31/ PY - 2019/07/22/received PY - 2019/10/13/revised PY - 2019/10/16/accepted PY - 2019/11/5/pubmed PY - 2020/4/18/medline PY - 2019/11/3/entrez KW - Ampelopsin KW - Autophagy KW - CCl(4) KW - Hepatic fibrosis KW - SIRT1 KW - TGF-β1 SP - 105984 EP - 105984 JF - International immunopharmacology JO - Int Immunopharmacol VL - 77 N2 - Ampelopsin (Amp), a natural flavonoid found in the vine tea of Ampelopsis grossedentata, exhibited anti-cancer, anti-oxidant, anti-inflammatory, anti-apoptosis and hepatoprotective properties. The current study instigates the protective effect of Amp on carbon tetrachloride (CCl4)-induced hepatic fibrosis and explores its underlying mechanisms. The results indicated Amp decreased the levels of liver injury markers. Amp inhibited liver fibrosis, as indicated by decreases in hepatic collagen deposition, extracellular matrix (ECM) deposition and α-smooth muscle actin (α-SMA). Amp blocked the activation of hepaticstellate cells (HSCs) by decreasing the expression of collage I, α-SMA, tissue inhibitor of matrix metalloproteinases (TIMPs) 1, transforming growth factor (TGF)-β1, phosphorylated Smad3 (p-Smad3) and increasing the expression of matrix metalloproteinases (MMPs) 9 and SIRT1 in the model of liver fibrosis and cultured HSCs. The sirtuin 1 (SIRT1) specific inhibitor Sirtinol activated the TGF-β1/Smad3 pathway and enhanced ECM accumulation. Attractively, Amp up-regulates the expression of autophagy-related proteins microtubule-associated protein light chain three II (LC3-II) and Beclin-1 in vivo and in vitro. However, depletion of autophagy by specific inhibitor 3-MA obviously abolished the inhibiting effect of Amp on HSC activation and hepatic fibrosis. Conclusively, these results suggest that Amp could decrease CCl4-induced hepatic fibrosis through regulating the SIRT1/TGF-β1/Smad3 and autophagy pathway. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/31677501/Ampelopsin_attenuates_carbon_tetrachloride_induced_mouse_liver_fibrosis_and_hepatic_stellate_cell_activation_associated_with_the_SIRT1/TGF_β1/Smad3_and_autophagy_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(19)31614-5 DB - PRIME DP - Unbound Medicine ER -