Extract of Averrhoacarambola L. (Oxalidaceae) roots ameliorates carbon tetrachloride-induced hepatic fibrosis in rats

被引:12
作者
Huang, Xiang [1 ]
Wang, Lihui [1 ,2 ]
Meng, Mingyu [1 ]
Zhang, Shijun [1 ]
Thi Thai Hoa Pham [1 ]
Jiang, Luhui [1 ]
Chen, Lixiu [1 ]
Li, Yuchun [1 ]
Zhou, Xing [1 ]
Qin, Luhui [1 ]
Wu, Xingchun [1 ]
Zou, Chunlin [2 ]
Huang, Renbin [1 ]
机构
[1] Guangxi Med Univ, Dept Pharmacol, 22 Shuangyong Rd, Nanning, Guangxi, Peoples R China
[2] Guangxi Med Univ, Ctr Translat Med, Sch Preclin Med, Key Lab Longev & Aging Related Dis,Minist Educ, Nanning, Guangxi, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
Averrhoa carambola L. root; Carbon tetrachloride; Liver fibrosis; TGF-beta; 1; Oxidative stress; Apoptosis; LIVER FIBROSIS; STELLATE CELLS; IN-VIVO; KAPPA-B; MECHANISMS; EXPRESSION; REGRESSION; 2-DODECYL-6-METHOXYCYCLOHEXA-2,5-DIENE-1,4-DIONE; FIBROGENESIS; RESISTANCE;
D O I
10.1016/j.biopha.2019.109516
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Ethnopharmacological relevance: The root of Averrhoa carambola L. (Oxalidaceae), a traditional Chinese medicine, was mainly used in ancient times in the treatment of urinary calculi, recurrent headache and joint pain. Aim of the study: Our aims were to explore the potential therapeutic effect of the extract of Averrhoa carambola L. (Oxalidaceae) roots (EACR) against hepatic fibrosis in CCl4-treated rats and to understand the underlying molecular mechanism. Materials and methods: Six groups of male Sprague Dawley rats were treated as follows: vehicle (olive oil), CCl4 alone, CCl4+colchicine, CCl4+EACR 1.0 g/kg, CCl4+EACR 0.5 g/kg and CCl4+EACR 0.25 g/kg. At the end of the 12th week, biomarkers of liver function, liver fibrosis, hepatic oxidative stress and antioxidant status were assayed, and histopathological and immunohistochemical evaluation of liver tissue were conducted to investigate the liver damage and fibrosis degree. Furthermore, expressions of COL-1a1, alpha-SMA, TGF-beta 1, Smad2, smad3, Smad4 and TIMP2 were examined by qPCR and/or western blot. The expressions of apoptosis-related proteins were also detected using western blot analysis. Results: EACR treatment markedly reduced the CCl4-induced elevation of serum aminotransferase activities, liver fibrosis indexes, and the extent of oxidative stress. EACR treatment also significantly reduced the accumulation of collagen and the immunostaining of alpha-SMA, TGF-beta 1 and Smad2, 4 and 7 in the liver of CCl4 treated rats. In addition, EACR treatment markedly reversed the CCl4-induced increase in mRNA expression of COL-1a1, alpha-SMA, TIMP2, TGF-beta 1, Smad2 and Smad4 and suppressed the expressions of alpha-SMA, TIMP2, TGF-beta 1, smad2, 3 and 4, BAX and cleaved caspase-3 proteins. Meanwhile, EACR treatment also significantly elevated the mRNA expression of Smad7 and the protein expression of Smad7 and Bcl-2. Conclusion: These results suggest that EACR has protective activity against liver fibrosis. The anti-fibrotic activity of EACR in vivo is associated with enhanced antioxidant, apoptosis-inhibition and increased MMP-2/TIMP-2 expression ratio, and with modulation of TGF-beta 1/Smad signaling pathway.
引用
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页数:10
相关论文
共 48 条
[1]  
Abedin Mohammed Forhad, 2014, Euroasian J Hepatogastroenterol, V4, P14, DOI 10.5005/jp-journals-10018-1090
[2]  
[Anonymous], [No title captured]
[3]  
[Anonymous], [No title captured]
[4]  
[Anonymous], [No title captured]
[5]  
[Anonymous], [No title captured]
[6]  
[Anonymous], [No title captured]
[7]   Hepatoprotective activity of aqueous extract of Portulaca oleracea in combination with lycopene in rats [J].
Anusha, M. ;
Venkateswarlu, M. ;
Prabhakaran, V. ;
Taj, S. Shareen ;
Kumari, B. Pushpa ;
Ranganayakulu, D. .
INDIAN JOURNAL OF PHARMACOLOGY, 2011, 43 (05) :563-567
[8]  
Chopra S., 2018, Curr. Pharmacol. Rep, V4, P182, DOI [10.1007/s40495-018-0136-3, DOI 10.1007/S40495-018-0136-3]
[9]   Regression of liver fibrosis by taurine in rats fed alcohol: Effects on collagen accumulation, selected cytokines and stellate cell activation [J].
Devi, Shanmugam Lakshmi ;
Viswanathan, Periyaswamy ;
Anuradha, Carani V. .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2010, 647 (1-3) :161-170
[10]   Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats [J].
Dooley, S ;
Hamzavi, J ;
Breitkopf, K ;
Wiercinska, E ;
Said, HM ;
Lorenzen, J ;
Ten Dijke, P ;
Gressner, AM .
GASTROENTEROLOGY, 2003, 125 (01) :178-191