title: Resveratrol Regulates Activated Hepatic Stellate Cells by Modulating NF-κB and the PI3K/Akt Signaling Pathway.
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.
authors.affiliation: Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian Univ, Yanji, 133002, Jilin Province, China.
authors.forename: De-Quan
authors.initials: DQ
authors.lastname: Zhang
authors.affiliation: Dept. of Pharmacy, Yanbian Univ. Hospital, Yanji, 133000, Jilin Province, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian Univ, Yanji, 133002, Jilin Province, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian Univ, Yanji, 133002, Jilin Province, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian Univ, Yanji, 133002, Jilin Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian Univ, Yanji, 133002, Jilin Province, China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian Univ, Yanji, 133002, Jilin Province, China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian Univ, Yanji, 133002, Jilin Province, China.
authors.forename: Ji-Xing
authors.initials: JX
authors.lastname: Nan
authors.affiliation: Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian Univ, Yanji, 133002, Jilin Province, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Lian
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000199:Actins; D003094:Collagen; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D058539:Phosphatidylinositol 3-Kinase; D019869:Phosphatidylinositol 3-Kinases; D010936:Plant Extracts; D017346:Protein Serine-Threonine Kinases; D000077185:Resveratrol; D013267:Stilbenes; D051197:Toll-Like Receptor 4; C507781:Myd88 protein, rat; C495347:Tlr4 protein, rat; C498862:Acta2 protein, rat
keywords: Akt; NF-κB; PI3K; hepatic stellate cell; resveratrol