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甜菊糖苷可抑制小鼠单侧输尿管梗阻诱导的肾纤维化,并上调肾脏中过氧化物酶体增殖物激活受体γ(PPARγ)的表达。

Stevioside inhibits unilateral ureteral obstruction-induced kidney fibrosis and upregulates renal PPARγ expression in mice.

作者信息

Shen Wei, Fan Ke, Zhao Ying, Zhang Junyan, Xie Meilin

机构信息

Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.

出版信息

J Food Biochem. 2020 Dec;44(12):e13520. doi: 10.1111/jfbc.13520. Epub 2020 Oct 12.

Abstract

This study aimed to examine the inhibitory effect of stevioside on unilateral ureteral obstruction (UUO)-induced kidney fibrosis. The UUO mice were daily given 50-100 mg/kg stevioside by gavage for 14 days after the operation. The results showed that stevioside decreased the levels of blood urea nitrogen and renal hydroxyproline, severity of kidney fibrosis, and expressions of renal collagen I/III and α-smooth muscle actin proteins. Importantly, stevioside increased the expressions of renal peroxisome proliferator-activated receptor γ (PPARγ) and Smad7 proteins and level of renal glutathione peroxidase, decreased the expressions of renal nuclear factor kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), p-STAT3, transforming growth factor-β1 (TGF-β1), Smad2/3, and p-Smad2/3 proteins, suggesting that the antifibrotic mechanisms are related to the activation of PPARγ and subsequent downregulations of NF-κB-mediated STAT3 and TGF-β1 expressions and inhibition of Smad-mediated signaling pathway. These findings provide an applied perspective of stevioside for kidney fibrosis. PRACTICAL APPLICATIONS: Stevioside is widely used in food products as a sweetener, and it has many beneficial biological effects, including antidiabetes, antihypertension, and renal protective action. Here, we provide a novel potential application of stevioside in the prevention and treatment of kidney fibrosis.

摘要

本研究旨在探讨甜菊糖苷对单侧输尿管梗阻(UUO)诱导的肾纤维化的抑制作用。UUO小鼠在手术后每天经口灌胃给予50 - 100 mg/kg甜菊糖苷,持续14天。结果显示,甜菊糖苷降低了血尿素氮和肾羟脯氨酸水平、肾纤维化严重程度以及肾胶原蛋白I/III和α平滑肌肌动蛋白蛋白的表达。重要的是,甜菊糖苷增加了肾过氧化物酶体增殖物激活受体γ(PPARγ)和Smad7蛋白的表达以及肾谷胱甘肽过氧化物酶水平,降低了肾核因子κB(NF-κB)、信号转导子和转录激活子3(STAT3)、p-STAT3、转化生长因子-β1(TGF-β1)、Smad2/3和p-Smad2/3蛋白的表达,提示其抗纤维化机制与PPARγ的激活以及随后NF-κB介导的STAT3和TGF-β1表达的下调和Smad介导的信号通路的抑制有关。这些发现为甜菊糖苷在肾纤维化方面提供了应用前景。实际应用:甜菊糖苷作为甜味剂广泛应用于食品中,并且具有许多有益的生物学作用,包括抗糖尿病、抗高血压和肾保护作用。在此,我们提供了甜菊糖苷在预防和治疗肾纤维化方面的一种新的潜在应用。

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