title: Hydroxysafflor yellow A attenuates carbon tetrachloride-induced hepatic fibrosis in rats by inhibiting ERK5 signaling.
abstract: Hepatic stellate cells (HSCs) undergo activation during the development of liver fibrosis. Transcription factor myocyte enhancer factor (MEF2) 2C plays a key role in this process. In the present study, we investigated the effect of hydroxysafflor yellow A (HSYA) on hepatic fibrosis and further investigated potential mechanisms in vivo. Sprague-Dawley rats were administered with CCl(4) together with or without HYSA for 12 weeks. The effect of HYSA on hepatic fibrosis was evaluated using hematoxylin-eosin and Van Gieson staining. Messenger RNA expression was quantified by real-time polymerase chain reaction, and protein was quantified by Western blot or immunohistochemistry. Our results revealed that CCl(4) treatment induced micronodular hepatic fibrosis with a pronounced deposition of collagen fibers. Treatment with HYSA resulted in a significant decrease in fibrosis, protein expression of α-SMA, and MEF-2C gene expression. This was accompanied by a decreased expression of Tβ-RI, Tβ-RII, MEKK3, MEK5, and phosphorylation of ERk5. HYSA alone had no effect on the measured parameters. Our findings demonstrate that HSYA protected, at least in part, the rat liver from CCl(4)-caused fibrogenesis through inhibition of hepatic stellate cell (HSC) activation, attenuation of transforming growth factor beta (TGF-β) signaling. HSYA may become a novel and promising agent for the inhibition of hepatic fibrosis.
authors: Institute of Medicine, Qiqihar Medical University, China.
authors: Ying-Bo
authors: YB
authors: Zhang
authors: Han-Ying
authors: HY
authors: Dong
authors: Xue-Ming
authors: XM
authors: Zhao
authors: Li
authors: L
authors: Fan
authors: Yu
authors: Y
authors: Zou
authors: Chun
authors: C
authors: Zhang
authors: Gang
authors: G
authors: Li
authors: Ji-Cheng
authors: JC
authors: Liu
authors: Ying-Cai
authors: YC
authors: Niu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride; D031178:Carthamus / Q000737:chemistry*; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D064326:MEF2 Transcription Factors; D008297:Male; D048054:Mitogen-Activated Protein Kinase 7 / Q000037:antagonists & inhibitors*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011809:Quinones / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000199:Actins; D002251:Carbon Tetrachloride; D002599:Chalcone; D003094:Collagen; D064326:MEF2 Transcription Factors; D048054:Mitogen-Activated Protein Kinase 7; D018006:Myogenic Regulatory Factors; D010936:Plant Extracts; D011809:Quinones; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C578042:MEF2C protein, rat; C498862:Acta2 protein, rat; C085278:hydroxysafflor yellow A