College of Food Science and Engineering, Northwest A&F University (NWAFU), Yangling, Shaanxi, 712100, China.
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing, 100048, China.
Mol Nutr Food Res. 2021 Aug;65(15):e2001202. doi: 10.1002/mnfr.202001202. Epub 2021 Jun 21.
Diosgenin (DIO) is a natural steroid sapogenin presented in various plants. It exerts anti-oxidant, anti-inflammatory and anti-diabetic nephropathy properties. The present study evaluates the intervention effect of DIO on nephrotoxicity induced by food contaminant 3-chloro-1, 2-propanediol (3-MCPD) in vivo and in vitro.
Treatment with DIO (15 mg kg d ) in Sprague-Dawley rats for 4-week relieves kidney injury induced by 3-MCPD (30 mg kg d ). In vitro, DIO (2, 6, and 8 µM) alleviates cell injury and apoptosis effectively in human embryonic kidney (HEK293) cells. DIO realizes its protective function via the regulation of endoplasmic reticulum (ER) stress and mitochondrial apoptosis pathway. Blockage of ER stress by 4-phenylbutyric acid (4-PBA), a specific ER stress antagonist, inhibits mitochondrial apoptosis, suggesting a connection between mitochondrial apoptosis and ER stress. Furthermore, the study demonstrates that the maintenance of Ca homeostasis and Bcl2 expression, two main targets of ER stress, contributes to the protection role of DIO on mitochondrial-dependent apoptosis. In addition, DIO relieves the impairment of oxidative phosphorylation.
This study demonstrates that DIO exerts protective effect against kidney injury, mitochondrial dysfunction, and apoptosis through the inhibition of ER stress and the further maintenance of Ca homeostasis and Bcl2 expression.
薯蓣皂苷元（DIO）是一种天然甾体皂素，存在于多种植物中。它具有抗氧化、抗炎和抗糖尿病肾病的特性。本研究评估了薯蓣皂苷元对体内和体外食品污染物 3-氯-1,2-丙二醇（3-MCPD）引起的肾毒性的干预作用。
在 Sprague-Dawley 大鼠中用 DIO（15mg/kg/d）治疗 4 周可缓解 3-MCPD（30mg/kg/d）引起的肾损伤。在体外，薯蓣皂苷元（2、6 和 8µM）可有效减轻人胚肾（HEK293）细胞的细胞损伤和凋亡。DIO 通过调节内质网（ER）应激和线粒体凋亡途径实现其保护功能。用 4-苯丁酸（4-PBA）阻断 ER 应激，一种特定的 ER 应激拮抗剂，抑制线粒体凋亡，表明线粒体凋亡和 ER 应激之间存在联系。此外，该研究表明，内质网应激的两个主要靶点 Ca 离子稳态和 Bcl2 表达的维持有助于 DIO 对线粒体依赖性凋亡的保护作用。此外，DIO 可减轻氧化磷酸化的损伤。
本研究表明，DIO 通过抑制 ER 应激和进一步维持 Ca 离子稳态和 Bcl2 表达，对肾损伤、线粒体功能障碍和细胞凋亡发挥保护作用。
