Huajie Tian1, Lin Liu2, Zhixiong Li3, Wei Liu4, Zhaolin Sun5, Yongbin Xu6, Shunchun Wang7, Chungeng Liang8, Yamei Hai9, Qin Feng10, Yu Zhao11, Yiyang Hu12, Jinghua Peng13. 1. Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: thj199099@163.com. 2. Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: llliver@yeah.net. 3. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: zxli0715@126.com. 4. Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. 5. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: iamszl0924@163.com. 6. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: XYBpharmacy@163.com. 7. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: shunchunwang@126.com. 8. Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: ericplayboy@126.com. 9. Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: hyameismile@163.com. 10. Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: fengqin1227@163.com. 11. Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: cathy15077@163.com. 12. Institute of Clinical Pharmacology, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China. Electronic address: yyhuliver@163.com. 13. Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China. Electronic address: pengjinghua2004@163.com.
Abstract
ETHNOPHARMACOLOGICAL REVELVANCE: CGA consisting of Cordyceps sinensis mycelia polysaccharide, gypenosides and amygdalin, was demonstrated to be the effective components formula in Fuzheng Huayu (FZHY) capsule, a traditional Chinese medicine approved by China food and drug administration for treatment of liver fibrosis and to inhibit transforming growth factor-β1 (TGF-β1) signaling, previously. AIM OF THE STUDY: To evaluate the effects of CGA on hepatic apoptosis in liver fibrosis induced by carbon tetrachloride (CCl4). MATERIALS AND METHODS: The hepatic injury and histology was detected by serum biomarker assay and hematoxylin-eosin staining. The hepatic collagen was illustrated by Sirius red staining and hydroxyproline (Hyp) concentration. The hepatic stellate cells (HSCs) activation and hepatic apoptosis was visualized by immunohistochemical analysis of α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase-mediated dUPT nick-end labeling (TUNEL) assay respectively. The protein expression of collagen type I (Col-I), α-SMA, TGF-β1, Fas, tumor necrosis factor receptor 1 (TNF-R1), cleaved-caspase-8, cleaved-caspase-10, cleaved-caspase-9, cleaved-caspase-3, mitochondrial Bcl-2, Bcl-2 associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak), cytochrome C and cytoplasmic cytochrome C was detected by western-blot. RESULTS: CGA or FZHY ameliorated liver histological changes, decreasing serum alanine aminotransferase, aspartate aminotransferase, hepatic Hyp, TUNEL positive-stained area, and down-regulated the protein expression of α-SMA, TGF-β1, Col-I, Fas, TNF-R1, cleaved-caspase-8, cleaved-caspase-10, cleaved-caspase-9, and cleaved-caspase-3, mitochondrial Bax, Bak, and cytoplasmic cytochrome C, while restored the expression of mitochondrial Bcl-2 and cytochrome C. CONCLUSION: CGA formula ameliorates liver fibrosis induced by CCl4, which is correlated to its inhibition on hepatic apoptosis.
ETHNOPHARMACOLOGICAL REVELVANCE: CGA consisting of Cordyceps sinensis mycelia polysaccharide, gypenosides and amygdalin, was demonstrated to be the effective components formula in Fuzheng Huayu (FZHY) capsule, a traditional Chinese medicine approved by China food and drug administration for treatment of liver fibrosis and to inhibit transforming growth factor-β1 (TGF-β1) signaling, previously. AIM OF THE STUDY: To evaluate the effects of CGA on hepatic apoptosis in liver fibrosis induced by carbon tetrachloride (CCl4). MATERIALS AND METHODS: The hepatic injury and histology was detected by serum biomarker assay and hematoxylin-eosin staining. The hepatic collagen was illustrated by Sirius red staining and hydroxyproline (Hyp) concentration. The hepatic stellate cells (HSCs) activation and hepatic apoptosis was visualized by immunohistochemical analysis of α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase-mediated dUPT nick-end labeling (TUNEL) assay respectively. The protein expression of collagen type I (Col-I), α-SMA, TGF-β1, Fas, tumor necrosis factor receptor 1 (TNF-R1), cleaved-caspase-8, cleaved-caspase-10, cleaved-caspase-9, cleaved-caspase-3, mitochondrial Bcl-2, Bcl-2 associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak), cytochrome C and cytoplasmic cytochrome C was detected by western-blot. RESULTS: CGA or FZHY ameliorated liver histological changes, decreasing serum alanine aminotransferase, aspartate aminotransferase, hepatic Hyp, TUNEL positive-stained area, and down-regulated the protein expression of α-SMA, TGF-β1, Col-I, Fas, TNF-R1, cleaved-caspase-8, cleaved-caspase-10, cleaved-caspase-9, and cleaved-caspase-3, mitochondrial Bax, Bak, and cytoplasmic cytochrome C, while restored the expression of mitochondrial Bcl-2 and cytochrome C. CONCLUSION: CGA formula ameliorates liver fibrosis induced by CCl4, which is correlated to its inhibition on hepatic apoptosis.