Chinese medicine CGA formula ameliorates DMN-induced liver fibrosis in rats via inhibiting MMP2/9, TIMP1/2 and the TGF-beta/Smad signaling pathways

doi:10.1038/aps.2016.35

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	Chinese medicine CGA formula ameliorates DMN-induced liver fibrosis in rats via inhibiting MMP2/9, TIMP1/2 and the TGF-beta/Smad signaling pathways
	Li, Xue-mei 1,2; Peng, Jing-hua 1,3,4; Sun, Zhao-lin 5; Tian, Hua-jie 1; Duan, Xiao-hua 1; Liu, Lin 1; Ma, Xin 1; Feng, Qin 1,3,4; Liu, Ping 1,4,6; Hu, Yi-yang 1,4,6
刊名	ACTA PHARMACOLOGICA SINICA
	2016-06
卷号	37 期号:6 页码:783-793
关键词	Chinese medicine CGA formula Fuzheng Huayu capsule liver fibrosis dimethylnitrosamine TGF-beta 1 Smad MMP2/9 TIMP1/2
ISSN号	1671-4083
DOI	10.1038/aps.2016.35
文献子类	Article
英文摘要	Aim: Chinese medicine CGA formula consists of polysaccharide from Cordyceps sinensis mycelia (CS-PS), gypenosides and amygdalin, which is derived from Fuzheng Huayu (FZHY) capsule for treating liver fibrosis. In this study we attempted to confirm the therapeutic effects of CGA formula in dimethylnitrosamine (DMN)-induced liver fibrosis in rats, and to identify the mechanisms of anti-fibrotic actions. Methods: Rats were injected with DMN (10 mg.kg(-1).d(-1), ip) for 3 consecutive days per week over a 4-week period. The rats then were orally administered with CGA formula (CS-PS 60 mg.kg(-1).d(-1), gypenosides 50 mg.kg(-1).d(-1) and amygdalin 80 mg.kg(-1).d(-1)) daily in the next 2 weeks. CS-PS, gypenosides or amygdalin alone were administered as individual component controls, whereas colchicine and FZHY were used as positive controls. Serum biomarkers were measured. Hepatic injury, collagen deposition and stellate cell activation were examined. The MMP activities, expression of TIMP protein and proteins involved in the TGF-beta 1/Smad signaling pathways in liver tissues were assayed. Results: In DMN-treated rats, administration of CGA formula significantly decreased serum ALT, AST and total bilirub n and hepatic hydroxyproline levels, increased serum albumin level, and attenuated liver fibrosis as shown by histological examination. Furthermore, these effects were comparable to those caused by administration of FZHY, and superior to those caused by administration of colchicine or the individual components of CGA formula. Moreover, administration of CGA formula significantly decreased the protein levels of cc-SMA, TGF-beta 1, TGF-beta 1 receptor (T beta R-I), p-T beta R-I, p-T beta R-II, p-Smad2, p-Smad3, TIMP1 and TIMP2, as well as MMP2 and MMP9 activities in liver tissues of DMN-treated rats. Conclusion: Chinese medicine CGA formula ameliorates DMN-induced liver fibrosis in rats, and this effect was likely associated with the down-regulation of MMP2/9 activities, TIMP1/2 protein expression and the TGF-beta 1/Smad signaling pathways in the liver.
资助项目	National Science and Technology Major Project of China[2012ZX09103-201-048] ; National Natural Science Foundation of China[81303071] ; Shanghai Municipal Commission of Health and Family Planning[ZY3-RCPY-2-2010]
WOS关键词	HEPATIC STELLATE CELLS ; GROWTH-FACTOR-BETA ; FAT-STORING CELLS ; FIBROGENESIS ; MECHANISMS ; CIRRHOSIS ; ACTIVATION ; DISEASE ; DIMETHYLNITROSAMINE ; MULTICENTER
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:5722053
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000377281000007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276022]
专题	上海中药现代化研究中心
通讯作者	Hu, Yi-yang
作者单位	1.Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Inst Liver Dis, Shanghai 201203, Peoples R China; 2.Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Tianjin 300193, Peoples R China 3.Shanghai Key Lab Tradit Chinese Clin Med, Shanghai 201203, Peoples R China; 4.Shanghai Univ Tradit Chinese Med, Key Lab Liver & Kidney Dis, Minist Educ, Shanghai 201203, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 6.Shanghai Municipal Educ Commiss, E Inst TCM Internal Med, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Li, Xue-mei,Peng, Jing-hua,Sun, Zhao-lin,et al. Chinese medicine CGA formula ameliorates DMN-induced liver fibrosis in rats via inhibiting MMP2/9, TIMP1/2 and the TGF-beta/Smad signaling pathways[J]. ACTA PHARMACOLOGICA SINICA,2016,37(6):783-793.
APA	Li, Xue-mei.,Peng, Jing-hua.,Sun, Zhao-lin.,Tian, Hua-jie.,Duan, Xiao-hua.,...&Hu, Yi-yang.(2016).Chinese medicine CGA formula ameliorates DMN-induced liver fibrosis in rats via inhibiting MMP2/9, TIMP1/2 and the TGF-beta/Smad signaling pathways.ACTA PHARMACOLOGICA SINICA,37(6),783-793.
MLA	Li, Xue-mei,et al."Chinese medicine CGA formula ameliorates DMN-induced liver fibrosis in rats via inhibiting MMP2/9, TIMP1/2 and the TGF-beta/Smad signaling pathways".ACTA PHARMACOLOGICA SINICA 37.6(2016):783-793.