Resveratrol Regulates Activated Hepatic Stellate Cells by Modulating NF‐κB and the PI3K/Akt Signaling Pathway |
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Authors: | De‐Quan Zhang Peng Sun Quan Jin Xia Li Yu Zhang Yu‐Jing Zhang Yan‐Ling Wu Ji‐Xing Nan Li‐Hua Lian |
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Affiliation: | 1. Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian Univ, Yanji, Jilin Province, China;2. Dept. of Pharmacy, Yanbian Univ. Hospital, Yanji, Jilin Province, China |
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Abstract: | In the present study, we investigated whether resveratrol could suppress the hepatic fibrogenesis in activated hepatic stellate cells. The immortalized rat hepatic stellate cells, t‐HSC/Cl‐6, were treated with resveratrol 1 h prior to lipopolysaccharide (LPS, 1 μg/mL). Resveratrol decreased t‐HSC/Cl‐6 cell viability at much lower concentrations within 24 h. Resveratrol pretreatment also decreased the LPS‐induced protein expression of α‐SMA and collagen I. In addition, resveratrol significantly reduced the protein expression of Toll‐like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88), and the expression of phosphorylated phosphatidylinositol 3‐kinase (PI3K) and phosphorylated serine/threonine kinase B (Akt). Moreover, resveratrol markedly blocked the translocation of nuclear factor (NF)‐κB in LPS‐activated HSCs. Furthermore, resveratrol inhibited HSCs activation through stimulating LXRβ, but did not influence LXRα. Overall, we conclude that the antifibrotic effect of resveratrol is the result of blocking NF‐κB activation and PI3K/Akt phosphorylation, which inhibits HSC activation to obstruct liver fibrosis. Thus, resveratrol may be a natural agent for preventing hepatic fibrosis. |
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Keywords: | Akt hepatic stellate cell NF‐κ B PI3K resveratrol |
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