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: Ying-Bo Zhang, Han-Ying Dong, Xue-Ming Zhao, Li Fan, Yu Zou, Chun Zhang, Gang Li, Ji-Cheng Liu, Ying-Cai Niu
• Journal: The American journal of Chinese medicine (Am J Chin Med) Vol. 40 Issue 3 Pg. 481-94 ( 2012) ISSN: 1793-6853 [Electronic] Singapore
• PMID: 22745065 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• MEF2 Transcription Factors
• MEF2C protein, rat
• Myogenic Regulatory Factors
• Plant Extracts
• Quinones
• RNA, Messenger
• Transforming Growth Factor beta
• smooth muscle actin, rat
• hydroxysafflor yellow A
• Chalcone
• Collagen
• Carbon Tetrachloride
• Mitogen-Activated Protein Kinase 7

Topics

• Actins (metabolism)
• Animals
• Carbon Tetrachloride
• Carthamus (chemistry)
• Chalcone (analogs & derivatives, pharmacology, therapeutic use)
• Chemical and Drug Induced Liver Injury (drug therapy, metabolism)
• Collagen (metabolism)
• Gene Expression (drug effects)
• Hepatic Stellate Cells (drug effects, metabolism)
• Liver (cytology, drug effects, pathology)
• Liver Cirrhosis, Experimental (chemically induced, drug therapy, metabolism)
• MEF2 Transcription Factors
• Male
• Mitogen-Activated Protein Kinase 7 (antagonists & inhibitors)
• Myogenic Regulatory Factors (genetics, metabolism)
• Phosphorylation
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Quinones (pharmacology, therapeutic use)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Transforming Growth Factor beta (metabolism)