Departments of Nephrology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.
Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.
Int J Mol Sci. 2024 Aug 18;25(16):8986. doi: 10.3390/ijms25168986.
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.
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。