Extract of Averrhoacarambola L. (Oxalidaceae) roots ameliorates carbon tetrachloride-induced hepatic fibrosis in rats
Extract of Averrhoacarambola L. (Oxalidaceae) roots ameliorates carbon tetrachloride-induced hepatic fibrosis in rats
复制标题
Averroacarambola L.（酢浆草科）根提取物可改善四氯化碳诱导的大鼠肝纤维化。
DOI：
10.1016/j.biopha.2019.109516
复制
发表时间：
2020-01-01
影响因子：
7.5
通讯作者：
Huang, Renbin
中科院分区：
文献类型：
--
作者：
Huang, Xiang;Wang, Lihui;Huang, Renbin
民族药理意义：杨桃根是一种传统中药，古代主要用于治疗尿路结石、反复头痛和关节痛。目的：探讨杨桃根提取物(EACR)对四氯化碳(CCl4)诱导的大鼠肝纤维化的潜在治疗作用，并探讨其分子机制。材料与方法：雄性SD大鼠6组，分别为橄榄油对照组、CCl4组、C4+秋水仙碱组、C4+EACR 1.0g/kg组。CCl_4+EACR 0.5g/kg和CCl_4+EACR 0.25g/kg。12周末检测肝功能、肝纤维化、肝脏氧化应激和抗氧化状态等生物标志物，并进行肝组织病理组织学和免疫组织化学评价，观察肝组织损伤和纤维化程度。用定量聚合酶链式反应和/或免疫印迹法检测Col-1a1、α-SMA、转化生长因子-β1、Smad2、Smad3、Smad4和TIMP2的表达。结果：EACR治疗可明显降低CCl4诱导的血清转氨酶活性、肝纤维化指标和氧化应激程度。EACR治疗组大鼠肝脏胶原沉积及α-SMA、TGF-β1、Smad2、Smad4、Smad2、Smad2、Smad4、Smad2、Smad4、Smad2、Smad4此外，EACR还能明显逆转CCl4诱导的Col-1a1、α-SMA、TIMP2、TGF-β1、Smad2和Smad4的mRNA表达，抑制α-SMA、TIMP2、TGF-β1、Smad2、3和4、Bax和裂解的caspase-3蛋白的表达。同时，EACR还能显著上调Smad7的mRNA表达和Smad7、Bcl2蛋白的表达。结论：EACR具有抗肝纤维化作用。EACR体内的抗纤维化作用与增强抗氧化、抑制细胞凋亡、增加基质金属蛋白酶-2/TIMP-2的表达比值有关，并与调节转化生长因子-β1/Smad信号通路有关。
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.