Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Changsari, Guwahati, Assam, 781101, India.
Mol Biol Rep. 2024 May 6;51(1):620. doi: 10.1007/s11033-024-09579-2.
Recent years of evidence suggest the crucial role of renal tubular cells in developing diabetic kidney disease. Scopoletin (SCOP) is a plant-based coumarin with numerous biological activities. This study aimed to determine the effect of SCOP on renal tubular cells in developing diabetic kidney disease and to elucidate mechanisms.
In this study, SCOP was evaluated in vitro using renal proximal tubular (HK-2) cells under hyperglycemic conditions to understand its mechanism of action. In HK-2 cells, SCOP alleviated the high glucose-generated reactive oxygen species (ROS), restored the levels of reduced glutathione, and decreased lipid peroxidation. High glucose-induced alteration in the mitochondrial membrane potential was markedly restored in the SCOP-treated cells. Moreover, SCOP significantly reduced the high glucose-induced apoptotic cell population in the Annexin V-FITC flow cytometry study. Furthermore, high glucose markedly elevated the mRNA expression of fibrotic and extracellular matrix (ECM) components, namely, transforming growth factor (TGF)-β, alfa-smooth muscle actin (α-SMA), collagen I, and collagen III, in HK-2 cells compared to the untreated cells. SCOP treatment reduced these mRNA expressions compared to the high glucose-treated cells. Collagen I and TGF-β protein levels were also significantly reduced in the SCOP-treated cells. Further findings in HK-2 cells revealed that SCOP interfered with the epithelial-mesenchymal transition (EMT) in the high glucose-treated HK-2 cells by normalizing E-cadherin and downregulating the vimentin and α-SMA proteins.
In conclusion, SCOP modulates the high glucose-generated renal tubular cell oxidative damage and accumulation of ECM components and may be a promising molecule against diabetic nephropathy.
近年来的证据表明，肾小管细胞在糖尿病肾病的发生发展中起着关键作用。东莨菪内酯（SCOP）是一种具有多种生物活性的植物香豆素。本研究旨在探讨 SCOP 对糖尿病肾病发生发展中肾小管细胞的作用及机制。
本研究采用高糖条件下体外培养的人近端肾小管（HK-2）细胞来评估 SCOP，以了解其作用机制。在 HK-2 细胞中，SCOP 减轻了高糖产生的活性氧（ROS），恢复了还原型谷胱甘肽的水平，并降低了脂质过氧化。高葡萄糖诱导的线粒体膜电位改变在 SCOP 处理的细胞中明显恢复。此外，SCOP 在 Annexin V-FITC 流式细胞术研究中显著减少了高糖诱导的凋亡细胞群体。此外，与未处理的细胞相比，高葡萄糖可显著上调 HK-2 细胞中成纤维细胞和细胞外基质（ECM）成分的 mRNA 表达，即转化生长因子（TGF）-β、α-平滑肌肌动蛋白（α-SMA）、胶原 I 和胶原 III。与高糖处理的细胞相比，SCOP 处理降低了这些 mRNA 的表达。SCOP 处理的细胞中胶原 I 和 TGF-β 蛋白水平也显著降低。在 HK-2 细胞中的进一步研究表明，SCOP 通过使 E-钙粘蛋白正常化并下调波形蛋白和 α-SMA 蛋白，干扰高糖处理的 HK-2 细胞中的上皮-间充质转化（EMT）。
综上所述，SCOP 可调节高糖引起的肾小管细胞氧化损伤和 ECM 成分的积累，可能是一种有前途的抗糖尿病肾病的分子。
