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基于网络药理学的红景天治疗糖尿病肾病的作用机制研究

Mechanistic insights of Rhodiola crenulata in treating diabetic kidney disease via network pharmacology.

作者信息

Li Junhan, Cui Yuying, Yao Jinming, Guo Congcong, Jiao Mingwen

出版信息

J Mol Endocrinol. 2025 Jun 30;75(1). doi: 10.1530/JME-25-0006. Print 2025 Jul 1.

DOI:10.1530/JME-25-0006
PMID:40504978
Abstract

Rhodiola crenulata (RC) has been traditionally used for its therapeutic benefits, including alleviating high-altitude sickness, fatigue, and diabetes. Diabetic kidney disease (DKD), a severe complication of diabetes, often leads to progressive renal fibrosis. This study explored the protective effects of RC against kidney fibrosis in DKD rat models, identifying active compounds and their therapeutic targets, with a focus on salidroside (SAL), a key component of RC. After administering RC to DKD rats, network pharmacology analysis identified 22 core components and 141 DKD-related therapeutic targets, with TGFB1 emerging as a primary target in kidney fibrosis. In vivo experiments demonstrated that RC reduced fibrosis markers by decreasing glomerular mesangial expansion, collagen deposition, and myofibroblast proliferation, alongside lowering TGF-β1 levels. In vitro analyses revealed that SAL inhibited high glucose-induced fibroblast activation and suppressed TGF-β1 expression in proximal renal tubular epithelial cells (PTECs), suggesting its direct role in slowing fibrosis progression. These findings indicate that the antifibrotic effects of RC in DKD may be attributed to SAL's ability to regulate fibroblast activity and suppress TGF-β1, highlighting its potential as a therapeutic component for DKD management.

摘要

传统上,红景天(Rhodiola crenulata,RC)因其治疗功效而被使用,包括缓解高原病、疲劳和糖尿病。糖尿病肾病(DKD)是糖尿病的一种严重并发症,常导致进行性肾纤维化。本研究探讨了红景天对DKD大鼠模型肾纤维化的保护作用,确定了活性成分及其治疗靶点,重点关注红景天的关键成分红景天苷(SAL)。给DKD大鼠施用红景天后,网络药理学分析确定了22个核心成分和141个与DKD相关的治疗靶点,其中转化生长因子β1(TGFB1)成为肾纤维化的主要靶点。体内实验表明,红景天通过减少肾小球系膜扩张、胶原沉积和成肌纤维细胞增殖来降低纤维化标志物,同时降低TGF-β1水平。体外分析显示,红景天苷抑制高糖诱导的成纤维细胞活化,并抑制近端肾小管上皮细胞(PTECs)中TGF-β1的表达,表明其在减缓纤维化进展中具有直接作用。这些发现表明,红景天在DKD中的抗纤维化作用可能归因于红景天苷调节成纤维细胞活性和抑制TGF-β1的能力,突出了其作为DKD治疗成分的潜力。

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