TY - JOUR
T1 - Yu Gan Long reduces rat liver fibrosis by blocking TGF-β1/Smad pathway and modulating the immunity
AU - Xia, Yu
AU - Yu, Bo
AU - Ma, Chaozhi
AU - Tu, Yijun
AU - Zhai, Ling
AU - Yang, Yanfang
AU - Liu, Dan
AU - Liu, Yanwen
AU - Wu, Hezhen
AU - Dan, Hanxiong
AU - You, Pengtao
N1 - Funding Information:
This study was supported by China Postdoctoral Science Foundation (No. 2016M592320 , 2016M600670 ), Hubei Provincial Natural Science Foundation of China (No. 2018CFB657 ) and the National Natural Science Foundation of China (No. 81601605 ).
Publisher Copyright:
© 2018 Elsevier Masson SAS
PY - 2018/10
Y1 - 2018/10
N2 - Yu Gan Long (YGL) is a Chinese traditional herbal medicine that has been used in the treatment of liver fibrosis for many years in clinical practice. However, its anti-hepatofibrotic mechanism has not been studied yet. In this study, the effect and mechanism of YGL in reducing liver fibrosis was demonstrated in vivo. Our results showed that liver fibrosis biomarkers collagen IV (Col IV), type III precollagen (PCIII), hyaluronuc acid (HA) and laminin (LN), were increased after CCl4 treatment and decreased by YGL. Among the liver fibrosis indicators, α-smooth muscle actin (α-SMA) was decreased by YGL in the CCl4-treated rats, while MMP2 and MMP9 was upregulated followed by TIMP1 downregulation. Proteins involved in liver fibrosis such as p-Smad2, p-Smad3 and Smad4 were down-regulated, while Smad7 protein was up-regulated by YGL after CCl4-induced liver damage. YGL also suppressed the increase of TGF-β1, TNF-α, IL-1β, IL-6, IL-4 and IL-17 A induced by CCl4 treatment, while promoted IFN-γ expression. Finally, the transcription factors ROR-γt and GATA3 were decreased, while T-bet was increased after YGL treatment. These results suggested that YGL attenuated CCl4-induced hepatic fibrosis by accelerating the extracellular matrix degradation, blocking the TGF-β1/Smad signaling pathway and modulating the balance among IL-4, IL-17 A and IFN-γ, demonstrating YGL protective effect and its potential mechanisms in treating liver fibrosis.
AB - Yu Gan Long (YGL) is a Chinese traditional herbal medicine that has been used in the treatment of liver fibrosis for many years in clinical practice. However, its anti-hepatofibrotic mechanism has not been studied yet. In this study, the effect and mechanism of YGL in reducing liver fibrosis was demonstrated in vivo. Our results showed that liver fibrosis biomarkers collagen IV (Col IV), type III precollagen (PCIII), hyaluronuc acid (HA) and laminin (LN), were increased after CCl4 treatment and decreased by YGL. Among the liver fibrosis indicators, α-smooth muscle actin (α-SMA) was decreased by YGL in the CCl4-treated rats, while MMP2 and MMP9 was upregulated followed by TIMP1 downregulation. Proteins involved in liver fibrosis such as p-Smad2, p-Smad3 and Smad4 were down-regulated, while Smad7 protein was up-regulated by YGL after CCl4-induced liver damage. YGL also suppressed the increase of TGF-β1, TNF-α, IL-1β, IL-6, IL-4 and IL-17 A induced by CCl4 treatment, while promoted IFN-γ expression. Finally, the transcription factors ROR-γt and GATA3 were decreased, while T-bet was increased after YGL treatment. These results suggested that YGL attenuated CCl4-induced hepatic fibrosis by accelerating the extracellular matrix degradation, blocking the TGF-β1/Smad signaling pathway and modulating the balance among IL-4, IL-17 A and IFN-γ, demonstrating YGL protective effect and its potential mechanisms in treating liver fibrosis.
KW - Liver fibrosis
KW - Mechanisms
KW - Pathway
KW - TGF-β1
KW - YGL
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U2 - 10.1016/j.biopha.2018.07.081
DO - 10.1016/j.biopha.2018.07.081
M3 - Article
C2 - 30119204
AN - SCOPUS:85050095925
SN - 0753-3322
VL - 106
SP - 1332
EP - 1338
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
ER -