School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Int Immunopharmacol. 2024 May 30;133:112131. doi: 10.1016/j.intimp.2024.112131. Epub 2024 Apr 25.
Osthole is a natural active ingredient extracted from the traditional Chinese medicine Cnidium monnieri. It has been demonstrated to have anti-inflammatory, anti-fibrotic, and anti-hyperglycemic properties. However, its effect on diabetic kidney disease (DKD) remains uncertain. This study aims to assess the preventive and therapeutic effects of osthole on DKD and investigate its underlying mechanisms.
A streptozotocin/high-fat and high-sucrose diet induced Type 2 diabetic rat model was established. Metformin served as the positive drug control. Diabetic rats were treated with metformin or three different doses of osthole for 8 weeks. Throughout the treatment period, the progression of DKD was assessed by monitoring increases in urinary protein, serum creatinine, urea nitrogen, and uric acid, along with scrutinizing kidney pathology. Enzyme-linked immunosorbent assay (ELISA) was employed to detect inflammatory factors and oxidative stress levels. At the same time, immunohistochemical staining was utilized to evaluate changes in alpha-smooth muscle actin, fibronectin, E-cadherin, and apoptosis. The alterations in TGF-β1/Smads signaling pathway were ascertained through western blot and immunofluorescence. Furthermore, we constructed a high glucose-stimulated HBZY-1 cells model to uncover its molecular protective mechanism.
Osthole significantly reduced fasting blood glucose, insulin resistance, serum creatinine, uric acid, blood urea nitrogen, urinary protein excretion, and glomerular mesangial matrix deposition in diabetic rats. Additionally, significant improvements were observed in inflammation, oxidative stress, apoptosis, and fibrosis levels. The increase of ROS, apoptosis and hypertrophy in HBZY-1 cells induced by high glucose was reduced by osthole. Immunofluorescence and western blot results demonstrated that osthole down-regulated the TGF-β1/Smads signaling pathway and related protein expression.
Our findings indicate that osthole exhibits potential preventive and therapeutic effects on DKD. It deserves further investigation as a promising drug for preventing and treating DKD.
蛇床子素是一种从传统中药蛇床子中提取的天然活性成分，具有抗炎、抗纤维化和抗高血糖作用。然而，其对糖尿病肾病（DKD）的影响尚不确定。本研究旨在评估蛇床子素对 DKD 的预防和治疗作用，并探讨其潜在机制。
建立链脲佐菌素/高脂高糖饮食诱导的 2 型糖尿病大鼠模型。二甲双胍作为阳性药物对照。糖尿病大鼠用二甲双胍或三种不同剂量的蛇床子素治疗 8 周。在整个治疗期间，通过监测尿蛋白、血清肌酐、尿素氮和尿酸的增加以及观察肾脏病理变化来评估 DKD 的进展。酶联免疫吸附试验（ELISA）用于检测炎症因子和氧化应激水平。同时，免疫组织化学染色用于评估α-平滑肌肌动蛋白、纤维连接蛋白、E-钙黏蛋白和细胞凋亡的变化。通过 Western blot 和免疫荧光检测 TGF-β1/Smads 信号通路的变化。此外，我们构建了高糖刺激的 HBZY-1 细胞模型，以揭示其分子保护机制。
蛇床子素显著降低了糖尿病大鼠的空腹血糖、胰岛素抵抗、血清肌酐、尿酸、血尿素氮、尿蛋白排泄和肾小球系膜基质沉积。此外，炎症、氧化应激、细胞凋亡和纤维化水平也显著改善。蛇床子素降低了高糖诱导的 HBZY-1 细胞中 ROS、细胞凋亡和肥大的增加。免疫荧光和 Western blot 结果表明，蛇床子素下调了 TGF-β1/Smads 信号通路及其相关蛋白的表达。
我们的研究结果表明，蛇床子素对 DKD 具有潜在的预防和治疗作用。它值得进一步研究，作为预防和治疗 DKD 的一种有前途的药物。
