HBOA ameliorates CCl4-incuded liver fibrosis through inhibiting TGF-?1/Smads, NF-?B and ERK signaling pathways - 09/06/19
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Highlights |
• | HBOA alleviates CCl4-induced hepatic fibrosis. |
• | HBOA inhibits the TGF-β1/Smads pathway. |
• | HBOA inhibits the NF-κB pathway. |
• | HBOA blocks the ERK pathway. |
• | HBOA suppresses HSC activation. |
Abstract |
An ingredient was isolated from Acanthus ilicifolius and identified as 4-hydroxy-2(3H)-benzoxazolone (HBOA). Its protective effects and underlying mechanism on liver fibrosis were investigated. Briefly, rats were intragastrically administrated with 50% CCl4 twice a week for 12 weeks to induce liver fibrosis. Meanwhile, the animals were treated with various medicines from weeks 8 to 12. Then the histological change, serum biochemical index, inflammatory factors and hepatocyte apoptosis were detected. Moreover, the TGF-β1/Smads, NF-κB and ERK signaling pathways were also detected to illustrate the underlying mechanism. The results showed that HBOA significantly ameliorated CCl4-induced liver injury and collagen accumulation in rats, as evidenced by the histopathologic improvement. Moreover, HBOA markedly decreased hepatocyte apoptosis by regulating the expression levels of caspase-3, -9 and -12, as well as the Bcl-2 family. The mechanism study showed that HBOA significantly decreased the expressions of α-smooth muscle actin (α-SMA) and collagen and inhibited the generation of excessive extracellular matrix (ECM) components by restoring the balance between matrix metalloproteinases (MMPs) and its inhibitor (TIMPs). HBOA markedly alleviated oxidative stress and inflammatory cytokines through inhibiting the NF-κB pathway. In addition, HBOA significantly down-regulated the levels of TGF-β1, Smad2/3, Smad4 and up-regulated the level of Smad7, inhibiting the TGF-β1/Smads signaling pathway. Moreover, HBOA significantly blocked the ERK signaling pathway, leading to the inactivation of hepatic stellate cells. This study suggests that HBOA exerts a protective effect against liver fibrosis via modulating the TGF-β1/Smads, NF-κB and ERK signaling pathways, which will be developed as a potential agent for the treatment of liver fibrosis.
Le texte complet de cet article est disponible en PDF.Keywords : Hepatic fibrosis, 4-Hydroxy-2(3H)-benzoxazolone (HBOA), TGF-β1/Smads pathway, NF-κB pathway, ERK pathway, Apoptosis
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Vol 115
Article 108901- juillet 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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