Xiayuxue Decoction (symbols; see text) attenuates hepatic stellate cell activation and sinusoidal endothelium defenestration in CCl4-induced fibrotic liver of mice.
- Author:
Li-jun ZHANG
1
;
Ming-yu SUN
;
Bing-bing NING
;
Wen-meng ZHANG
;
Gao-feng CHEN
;
Yong-ping MU
;
Hua ZHANG
;
Jia LIU
;
Yan-qin BIAN
;
Ping LIU
Author Information
- Publication Type:Journal Article
- MeSH: Actins; metabolism; Animals; Carbon Tetrachloride Poisoning; drug therapy; Collagen Type I; metabolism; Disease Models, Animal; Drugs, Chinese Herbal; pharmacology; Endothelium; drug effects; pathology; Hepatic Stellate Cells; drug effects; pathology; ultrastructure; Liver Cirrhosis; chemically induced; drug therapy; pathology; Male; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Myofibroblasts; drug effects; pathology; ultrastructure; Platelet Endothelial Cell Adhesion Molecule-1; metabolism; Primary Cell Culture; Rats, Sprague-Dawley
- From: Chinese journal of integrative medicine 2014;20(7):516-523
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo investigate the effects of ancient Chinese medical formula Xiayuxue Decoction ([symbols; see text], XYXD) on activation of hepatic stellate cells (HSCs) and defenestration of sinusoidal endothelial cells (SECs) in CCl4-induced fibrotic liver of mice.
METHODSHigh performance liquid chromatography was used to identify the main components of XYXD and control the quality of extraction. C57BL/6 mice were induced liver fibrosis by CCl4 exposure and administered with XYXD for 6 weeks simultaneously. Liver tissue was investigated by hematoxylin-eosin and Sirius-red staining. Sinusoidal fenestrations were observed by scanning electronic microscopy and fluorescent immunohistochemistry of PECAM-1 (CD31). Whole liver lysates were detected of α-smooth muscle actin (α-SMA) and type-I collagen by Western blot. Primary rat HSCs-T6 cells were analyzed by detecting α-SMA, F-actin, DNA fragmentation through confocal microscopy, Western blot, terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and cellomics arrayscan, respectively.
RESULTSAmygdalin and emodin in XYXD were identified. XYXD (993 mg/kg) inhibited Sirius red positive area up to 70.1% (P<0.01), as well as protein levels of α-SMA and type-I collagen by 42.0% and 18.5% (P<0.05) respectively. In vitro, XYXD (12.5 μg/mL, 50 μg/mL) suppressed the activation of HSCs and reversed the myofibroblastic HSCs into quiescent, demonstrated as inhibition of fluorescent F-actin by 32.3% and 46.6% (P<0.05). Besides, XYXD induced the apoptosis of HSC-T6 cells by 20.0% (P<0.05) and 49.5% (P<0.01), evidenced by enhanced TUNEL positivity. Moreover, ultrastructural observation suggested XYXD inhibited defenestration of SECs, which was confirmed by 31.1% reduction of protein level of CD31 (P<0.05).
CONCLUSIONSXYXD inhibited both HSCs activation and SECs defenestration which accompany chronic liver injuries. These data may help to understand the underlying mechanisms of XYXD for prevetion of chronic liver diseases.