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Yu Gan Long Ameliorates Hepatic Fibrosis by Inhibiting PI3K/AKT, Ras/ERK and JAK1/STAT3 Signaling Pathways in CCl4-induced Liver Fibrosis Rats.
Curr Med Sci. 2020 Jun; 40(3):539-547.CM

Abstract

Yu Gan Long (YGL) is a Chinese traditional herbal formula which has been reported to attenuate liver fibrosis for many years and we have explored its anti-fibrotic mechanism through blocking transforming growth factor (TGF-β) in the previous study. But the mechanisms associated with platelet-derived growth factor (PDGF)-BB remain obscure. In this study, we further investigated the mechanism of YGL reducing carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Our results showed that YGL suppressed CCl4-induced upregulation of collagen IV (Col IV), type HI precollagen (PCHI), hyaluronuc acid (HA) and laminin (LN), which are implicated in liver fibrosis. Also, YGL reduced the α-smooth muscle actin (α-SMA) expression, which acts as the indicator of liver fibrosis. Furthermore, YGL decreased the serum levels of hepatic stellate cell (HSC) mitogen PDGF-BB and inflammation cytokines, including TNF-α, IL-1β, IL-6. Markers involved in liver fibrosis, such as Ras, p-Raf-1, p-ERK1/2, p-JNK, p-P38, p-PI3K, p-AKT, p-JAKl, p-STAT3 were downregulated significantly after treatment with YGL. Our results indicated that YGL ameliorated CCl4-induced liver fibrosis by reducing inflammation cytokines production, and suppressing Ras/ERK, PI3K/AKT, and JAK1/STAT3 signaling pathways, which provided further evidence towards elucidation of the anti-fibrotic mechanism of YGL.

Authors+Show Affiliations

Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China. tptyou@hbtcm.edu.cn.Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.Wuhan Junan Pharmaceutical Co., Ltd., Wuhan, 430023, China. 1035158535@qq.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32681257

Citation

Li, Hou-Gang, et al. "Yu Gan Long Ameliorates Hepatic Fibrosis By Inhibiting PI3K/AKT, Ras/ERK and JAK1/STAT3 Signaling Pathways in CCl4-induced Liver Fibrosis Rats." Current Medical Science, vol. 40, no. 3, 2020, pp. 539-547.
Li HG, You PT, Xia Y, et al. Yu Gan Long Ameliorates Hepatic Fibrosis by Inhibiting PI3K/AKT, Ras/ERK and JAK1/STAT3 Signaling Pathways in CCl4-induced Liver Fibrosis Rats. Curr Med Sci. 2020;40(3):539-547.
Li, H. G., You, P. T., Xia, Y., Cai, Y., Tu, Y. J., Wang, M. H., Song, W. C., Quan, T. M., Ren, H. Y., Liu, Y. W., Dan, H. X., & Xu, S. Q. (2020). Yu Gan Long Ameliorates Hepatic Fibrosis by Inhibiting PI3K/AKT, Ras/ERK and JAK1/STAT3 Signaling Pathways in CCl4-induced Liver Fibrosis Rats. Current Medical Science, 40(3), 539-547. https://doi.org/10.1007/s11596-020-2211-3
Li HG, et al. Yu Gan Long Ameliorates Hepatic Fibrosis By Inhibiting PI3K/AKT, Ras/ERK and JAK1/STAT3 Signaling Pathways in CCl4-induced Liver Fibrosis Rats. Curr Med Sci. 2020;40(3):539-547. PubMed PMID: 32681257.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Yu Gan Long Ameliorates Hepatic Fibrosis by Inhibiting PI3K/AKT, Ras/ERK and JAK1/STAT3 Signaling Pathways in CCl4-induced Liver Fibrosis Rats. AU - Li,Hou-Gang, AU - You,Peng-Tao, AU - Xia,Yu, AU - Cai,Yu, AU - Tu,Yi-Jun, AU - Wang,Meng-Heng, AU - Song,Wan-Ci, AU - Quan,Tai-Min, AU - Ren,Hui-Ying, AU - Liu,Yan-Wen, AU - Dan,Han-Xiong, AU - Xu,Shi-Qing, Y1 - 2020/07/17/ PY - 2020/01/09/received PY - 2020/06/04/revised PY - 2020/7/19/entrez PY - 2020/7/19/pubmed PY - 2021/5/19/medline KW - JAK1/STAT3 KW - PI3K/AKT KW - Ras/ERK KW - Yu Gan Long KW - liver fibrosis KW - traditional Chinese herbal therapy SP - 539 EP - 547 JF - Current medical science JO - Curr Med Sci VL - 40 IS - 3 N2 - Yu Gan Long (YGL) is a Chinese traditional herbal formula which has been reported to attenuate liver fibrosis for many years and we have explored its anti-fibrotic mechanism through blocking transforming growth factor (TGF-β) in the previous study. But the mechanisms associated with platelet-derived growth factor (PDGF)-BB remain obscure. In this study, we further investigated the mechanism of YGL reducing carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Our results showed that YGL suppressed CCl4-induced upregulation of collagen IV (Col IV), type HI precollagen (PCHI), hyaluronuc acid (HA) and laminin (LN), which are implicated in liver fibrosis. Also, YGL reduced the α-smooth muscle actin (α-SMA) expression, which acts as the indicator of liver fibrosis. Furthermore, YGL decreased the serum levels of hepatic stellate cell (HSC) mitogen PDGF-BB and inflammation cytokines, including TNF-α, IL-1β, IL-6. Markers involved in liver fibrosis, such as Ras, p-Raf-1, p-ERK1/2, p-JNK, p-P38, p-PI3K, p-AKT, p-JAKl, p-STAT3 were downregulated significantly after treatment with YGL. Our results indicated that YGL ameliorated CCl4-induced liver fibrosis by reducing inflammation cytokines production, and suppressing Ras/ERK, PI3K/AKT, and JAK1/STAT3 signaling pathways, which provided further evidence towards elucidation of the anti-fibrotic mechanism of YGL. SN - 2523-899X UR - https://www.unboundmedicine.com/medline/citation/32681257/Yu_Gan_Long_Ameliorates_Hepatic_Fibrosis_by_Inhibiting_PI3K/AKT_Ras/ERK_and_JAK1/STAT3_Signaling_Pathways_in_CCl4_induced_Liver_Fibrosis_Rats_ L2 - https://doi.org/10.1007/s11596-020-2211-3 DB - PRIME DP - Unbound Medicine ER -