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Bunge(丹参)粗提物的乙酸乙酯馏分通过调节纤维化信号改善糖尿病肾病损伤。

Ethyl Acetate Fractions of Bunge (Danshen) Crude Extract Modulate Fibrotic Signals to Ameliorate Diabetic Kidney Injury.

机构信息

Departments of Nephrology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.

Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.

出版信息

Int J Mol Sci. 2024 Aug 18;25(16):8986. doi: 10.3390/ijms25168986.

Abstract

Diabetic nephropathy, a leading cause of end-stage renal disease, accounts for significant morbidity and mortality. It is characterized by microinflammation in the glomeruli and myofibroblast activation in the tubulointerstitium. Bunge, a traditional Chinese medicine, is shown to possess anti-inflammatory and anti-fibrotic properties, implying its renal-protective potential. This study investigates which type of component can reduce the damage caused by diabetic nephropathy in a single setting. The ethyl acetate (EtOAc) layer was demonstrated to provoke peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ activities in renal mesangial cells by dual luciferase reporter assay. In a high glucose (HG)-cultured mesangial cell model, the EtOAc layer substantially inhibited HG-induced elevations of interleukin-1β, transforming growth factor-β1 (TGF-β1), and fibronectin, whereas down-regulated PPAR-γ was restored. In addition, among the extracts of , the EtOAc layer effectively mitigated TGF-β1-stimulated myofibroblast activation. The EtOAc layer also showed a potent ability to attenuate renal hypertrophy, proteinuria, and fibrotic severity by repressing diabetes-induced proinflammatory factor, extracellular matrix accumulation, and PPAR-γ reduction in the STZ-induced diabetes mouse model. Our findings, both in vitro and in vivo, indicate the potential of the EtOAc layer from for future drug development targeting diabetic nephropathy.

摘要

糖尿病肾病是终末期肾病的主要病因,可导致严重的发病率和死亡率。其特征在于肾小球内的微炎症和小管间质中的肌成纤维细胞激活。Bunge 是一种中药,具有抗炎和抗纤维化特性,表明其具有肾脏保护潜力。本研究旨在探讨哪种成分可以在单一环境中减轻糖尿病肾病的损害。通过双荧光素酶报告基因检测,发现乙酸乙酯(EtOAc)层可刺激肾系膜细胞中过氧化物酶体增殖物激活受体(PPAR)-α和 PPAR-γ的活性。在高糖(HG)培养的系膜细胞模型中,EtOAc 层可显著抑制 HG 诱导的白细胞介素 1β、转化生长因子-β1(TGF-β1)和纤维连接蛋白的升高,同时下调 PPAR-γ。此外,在 的提取物中,EtOAc 层可有效抑制 TGF-β1 刺激的肌成纤维细胞激活。EtOAc 层还通过抑制糖尿病诱导的促炎因子、细胞外基质积累和 STZ 诱导的糖尿病小鼠模型中 PPAR-γ 的减少,显示出减轻肾脏肥大、蛋白尿和纤维化严重程度的强大能力。我们的体内外研究结果均表明,Bunge 的 EtOAc 层具有针对糖尿病肾病的未来药物开发潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66d3/11354680/25ee92640bfe/ijms-25-08986-g001a.jpg

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