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Published on: May 13, 2016
Paeoniflorin alleviates liver fibrosis by inhibiting HIF-1α through mTOR-dependent pathway
Yanling Zhao1, Xiao Ma2, Jiabo Wang1
1China Military Institute of Chinese Medicine, 302 Military Hospital of China, Beijing 100039, China.
Abstract:
HIF-1α/mTOR signaling pathway is considered to play a crucial role in genesis and progress of tissue fibrosis. The elevation of HIF-1α and mTOR is relevant to CCl4 induced liver fibrotic rats. Paeoniflorin has been consistently shown to exhibit multiple pharmacological effects in liver disease. However, so far, no research demonstrates the relationship between paeoniflorin and HIF-1α/mTOR fibrogenesis pathway in liver fibrosis. In this study, the liver fibrosis was performed by CCl4 rats and HSC-T6 cell line. The data demonstrated that paeoniflorin treatment could attenuate liver fibrosis and inhibit the activation of HSC. Moreover, paeoniflorin significantly enhanced hepatic function by decreasing serum level of ALT, AST and ALP, and increasing level of ALB, TP. Meanwhile, ECM degradation was modulated by paeoniflorin treated rats with a remarkable reduce of α-SMA and collagen III mRNA expression. Moreover, the alleviation effect of liver fibrosis was relevant to inhibiting HIF-1α and phosphor-mTOR. Our data indicate that paeoniflorin alleviates liver fibrosis by inhibiting HIF-1α expression partly through mTOR pathway and paeoniflorin may be a potential therapeutic agent for liver fibrosis.
Insights
Paeoniflorin treatment alleviates liver fibrosis by inhibiting the HIF-1α/mTOR pathway. This study suggests paeoniflorin as a potential therapeutic agent for liver fibrosis.
Area of Science:
- Pharmacology
- Hepatology
- Cell Biology
Background:
- The Hypoxia-Inducible Factor 1-alpha (HIF-1α) and mechanistic Target of Rapamycin (mTOR) signaling pathway is implicated in tissue fibrosis.
- Elevated HIF-1α and mTOR levels are observed in carbon tetrachloride (CCl4)-induced liver fibrosis in rats.
- Paeoniflorin possesses known pharmacological effects beneficial for liver disease, but its role in the HIF-1α/mTOR fibrogenesis pathway remains unexplored.
Purpose of the Study:
- To investigate the therapeutic potential of paeoniflorin in liver fibrosis.
- To elucidate the relationship between paeoniflorin and the HIF-1α/mTOR signaling pathway in liver fibrosis.
Main Methods:
- Liver fibrosis was induced in rats using CCl4 and in the HSC-T6 cell line.
- Paeoniflorin treatment was administered to assess its effects on fibrotic markers and hepatic function.
- Key molecular targets, including HIF-1α, phosphor-mTOR, α-SMA, and collagen III mRNA, were analyzed.
Main Results:
- Paeoniflorin treatment attenuated liver fibrosis and inhibited hepatic stellate cell (HSC) activation.
- Hepatic function was significantly improved, evidenced by normalized serum enzyme levels (ALT, AST, ALP) and protein levels (ALB, TP).
- Paeoniflorin reduced α-SMA and collagen III mRNA expression, indicating modulation of extracellular matrix (ECM) degradation and inhibited HIF-1α and phosphor-mTOR signaling.
Conclusions:
- Paeoniflorin effectively alleviates liver fibrosis, partly by inhibiting the HIF-1α/mTOR pathway.
- Paeoniflorin demonstrates potential as a therapeutic agent for treating liver fibrosis.
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