Hydroxysafflor yellow A induces apoptosis in activated hepatic stellate cells through ERK1/2 pathway in vitro

• Published in: European journal of pharmaceutical sciences Vol. 46; no. 5; pp. 397 - 404
• Main Authors: Li, Cheng-Chong, Yang, Chun-Zhuang, Li, Xiao-Ming, Zhao, Xue-Mei, Zou, Yu, Fan, Li, Zhou, Li, Liu, Ji-Cheng, Niu, Ying-Cai
• Format: Journal Article
• Language: English
• Published: Kindlington Elsevier B.V 15.08.2012; Elsevier
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Biological and medical sciences; Blotting, Western; Cell Cycle - drug effects; Cells, Cultured; Chalcone - analogs & derivatives; Chalcone - pharmacology; DNA Fragmentation - drug effects; Dose-Response Relationship, Drug; Enzyme Activation; ERK1/2; Flow Cytometry; Gene Expression Regulation - drug effects; General pharmacology; Hepatic stellate cells; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - enzymology; Hepatic Stellate Cells - pathology; Hydroxysafflor yellow A; Liver Cirrhosis - enzymology; Liver Cirrhosis - pathology; Liver Cirrhosis - prevention & control; Male; MAP Kinase Signaling System - drug effects; Medical sciences; Mitochondria - drug effects; Mitochondria - metabolism; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 3 - metabolism; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phosphorylation; Protein Kinase Inhibitors - pharmacology; Quinones - pharmacology; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Time Factors; Hydroxysafflor yellow A; Hepatic stellate cells; ERK1/2; Apoptosis; Pharmaceutical technology; Enzyme; Cell death; Transferases; Mitogen-activated protein kinase; Ito cell; In vitro
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2012.03.003

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.