title: Hydroxysafflor yellow A induces apoptosis in activated hepatic stellate cells through ERK1/2 pathway in vitro.
abstract: A key feature in the molecular pathogenesis of liver fibrosis requires maintenance of the activated hepatic stellate cells (HSCs) phenotype by inhibition of apoptosis. The induction of apoptosis in activated HSCs has been proposed as an antifibrotic treatment strategy. This study aims at evaluating the effect of hydroxysafflor yellow A (HSYA) on apoptosis of culture-activated HSCs and further elucidating the underlying mechanisms. Primary HSCs were isolated from rats. The analysis of the cell cycle be performed by flow cytometry, detection of apoptosis by Annexin V-FITC/ PI staining, and the results were confirmed by DNA fragmentation, and cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP). Real-time polymerase chain reaction and Western blotting were used to analyze the expression of genes. Our results revealed that HSYA significantly induced apoptosis in a dose- and time-dependent manner. HSYA suppresses the activation of ERK1/2 and ERK1/2-regulated gene expression, including Bcl-2, Cytochrome c, caspase-9, and caspase-3, leading to the enhancement of apoptosis. Pharmacological blockade of ERK1/2 kinase abrogation this action of HSYA. Our data provide a molecular basis for the anti-hepatic fibrosis activity of HSYA.
authors.affiliation: The Institute of Medicine, Qiqihar Medical University, Qiqihar 161006, China.
authors.forename: Cheng-Chong
authors.initials: CC
authors.lastname: Li
authors.forename: Chun-Zhuang
authors.initials: CZ
authors.lastname: Yang
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Li
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zou
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Liu
authors.forename: Ying-Cai
authors.initials: YC
authors.lastname: Niu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D047428:Protein Kinase Inhibitors; D011809:Quinones; C085278:hydroxysafflor yellow A; D002599:Chalcone; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3