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反式-2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷通过下调 p-ERK1/2 和 p-Smad1/2 对 CCl4 诱导的肝纤维化和肾损伤的保护作用。

Protective effects of trans-2,3,5,4'-tetrahydroxystilbene 2-O-β-d-glucopyranoside on liver fibrosis and renal injury induced by CClvia down-regulating p-ERK1/2 and p-Smad1/2.

机构信息

Hubei Key Laboratory for Processing and Application of Catalytic Materials, Huanggang Normal University, Huanggang, 438000, China.

出版信息

Food Funct. 2019 Aug 1;10(8):5115-5123. doi: 10.1039/c9fo01010f. Epub 2019 Jul 31.

Abstract

Both as a food and an herbal plant, Polygonum multiflorum (PM) has long been used in food and prescriptions for several centuries in Southeast Asia. trans-2,3,5,4'-tetrahydroxystilbene 2-O-β-d-glucopyranoside (trans-THSG) is one of the major compounds derived from PM and has been reported to exhibit multiple biological activities such as antioxidation and anti-obesity activities among others. The current study was aimed at investigating the effects of trans-THSG on liver fibrosis and renal injury in a carbon tetrachloride (CCl) induced rodent model via oral feeding. Research results have demonstrated that administration of trans-THSG (100 and 300 mg kg) significantly ameliorated liver fibrosis, manifested by reduced expression of desmin and α-smooth muscle actin (α-SMA) plus collagen deposition. Specifically, treatment with trans-THSG effectively decreased the levels of transforming growth factor-β (TGF-β) and reduced the phosphorylation of Smad1/2 (p-Smad1/2) and extracellular signal-regulated kinases 1/2 (p-ERK1/2). Furthermore, we found that trans-THSG significantly down-regulated CCl-induced excessive collagen secretion and increased the levels of desmin, MMP2 and MMP9 in rat liver tissues, suggesting that trans-THSG prevents liver fibrosis by attenuating the activation of hepatic stellate cells (HSCs) through the inhibition of Smad and ERK signaling pathways. Hence, the present findings demonstrate that trans-THSG is an effective antifibrotic agent in protecting liver from CCl-induced toxicity.

摘要

何首乌(PM)既是食物又是草药,在东南亚几个世纪以来一直被用于食品和处方中。反式-2,3,5,4'-四羟基二苯乙烯-2-O-β-D-吡喃葡萄糖苷(trans-THSG)是从 PM 中提取的主要化合物之一,据报道具有多种生物活性,如抗氧化和抗肥胖活性等。本研究旨在通过口服给予 trans-THSG 来研究其对四氯化碳(CCl)诱导的啮齿动物模型中肝纤维化和肾损伤的影响。研究结果表明,trans-THSG(100 和 300mg/kg)给药显著改善了肝纤维化,表现为结蛋白和α-平滑肌肌动蛋白(α-SMA)的表达减少以及胶原沉积减少。具体而言,trans-THSG 治疗有效降低了转化生长因子-β(TGF-β)的水平,并降低了 Smad1/2(p-Smad1/2)和细胞外信号调节激酶 1/2(p-ERK1/2)的磷酸化。此外,我们发现 trans-THSG 显著下调了 CCl 诱导的胶原过度分泌,并增加了大鼠肝组织中结蛋白、MMP2 和 MMP9 的水平,表明 trans-THSG 通过抑制 Smad 和 ERK 信号通路来减轻肝星状细胞(HSCs)的激活,从而预防肝纤维化。因此,本研究结果表明,trans-THSG 是一种有效的抗纤维化药物,可保护肝脏免受 CCl 诱导的毒性。

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