College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.
Food Funct. 2020 Sep 23;11(9):7456-7467. doi: 10.1039/d0fo00401d.
Aristolochic acid I (AA-I) remains a leading cause of aristolochic acid nephropathy (AAN), however few prevention and treatment strategies exist. In this work, the nephroprotective effect of diosgenin, a steroidal saponin distributed abundantly in several plants, on AA-I-induced renal injury and its underlying mechanism were investigated. Sprague-Dawley rats were intragastrically administered with 30 mg kg-1 d-1 diosgenin two hours before exposure to 10 mg kg-1 d-1 AA-I for consecutive four weeks, and the histological change, the renal and liver function, apoptosis, autophagy and the involved pathways were investigated. The results showed that diosgenin relieved AA-I-induced renal histological damage, including mild edematous disorder of renal tubular arrangement and widening of renal tubular lumen. No obvious changes in the hepatic tissue structure were observed in all treatment groups. Moreover, diosgenin up-regulated the expression of Bcl-2 and down-regulated Bax, and subsequently inhibited AIF expression and the cleaved form of Caspase-3, thereby alleviating apoptosis triggered by AA-I. Diosgenin also mitigated AA-I-induced renal mitochondrial dynamics disorder by increasing the expression of mitochondrial dynamics-related proteins including DRP1 and MFN2. Diosgenin inhibited AA-I-evoked autophagy via ULK1-mediated inhibition of the mTOR pathway. Overall, these results suggest that diosgenin has a protective effect against AA-I-induced renal damage and it may be a potential agent for preventing AA-I-induced AAN.
马兜铃酸 I（AA-I）仍然是导致马兜铃酸肾病（AAN）的主要原因，然而，目前几乎没有有效的预防和治疗策略。在这项工作中，研究了薯蓣皂苷元（一种在多种植物中广泛分布的甾体皂苷）对 AA-I 诱导的肾损伤的肾保护作用及其潜在机制。SD 大鼠在连续四周每天接受 10 mg/kg AA-I 暴露前两小时，每天给予 30mg/kg 薯蓣皂苷元灌胃，检测其组织学变化、肾功能和肝功能、细胞凋亡、自噬及相关通路。结果表明，薯蓣皂苷元缓解了 AA-I 诱导的肾组织学损伤，包括肾小管排列轻度水肿紊乱和肾小管腔变宽。所有治疗组的肝组织结构均无明显变化。此外，薯蓣皂苷元上调 Bcl-2 的表达，下调 Bax 的表达，从而抑制 AIF 的表达和 Caspase-3 的裂解形式，从而减轻 AA-I 诱导的细胞凋亡。薯蓣皂苷元还通过增加包括 DRP1 和 MFN2 在内的线粒体动力学相关蛋白的表达，减轻 AA-I 诱导的肾线粒体动力学紊乱。总之，这些结果表明，薯蓣皂苷元对 AA-I 诱导的肾损伤具有保护作用，可能是预防 AA-I 诱导的 AAN 的潜在药物。
