Zhang Xiu-Meng, Min Xin-Ran, Xie Hong-Xiao, Jiang Yan-Ning, Rui Yi-Xin, Li Bo, Zeng Nan, Liu Rong
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy/School of Modern Chinese Medicine industry, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Pharmacol. 2024 Aug 1;15:1394369. doi: 10.3389/fphar.2024.1394369. eCollection 2024.
Diabetic nephropathy (DN) is a serious complication that may occur during the later stages of diabetes, and can be further exacerbated by podocyte damage. Piperazine ferulate (PF) has well-defined nephroprotective effects and is used clinically in the treatment of chronic nephritis and other kidney diseases. However, the renoprotective effects and mechanisms of PF on DN are not clear. This study aims to investigate the protective effect of PF on DN and its mechanism of action, to inform the clinical application of PF in DN treatment. Network pharmacology was performed to predict the mechanism of action of PF in DN. Male Sprague Dawley rats were intraperitoneally injected with STZ (60 mg/kg) to establish a DN model, and then assessed for renal injury after 12 weeks of administration. , rat podocytes were treated with 25 mmol/L glucose and cultured for 24 h, followed by an assessment of cell injury. Our results showed that PF significantly improved renal function, reduced renal pathological changes, decreased inflammatory response, and alleviated podocyte damage in DN rats. PF also attenuated glucose-induced podocyte injury . Regarding molecular mechanisms, our study demonstrated that PF downregulated the expression of genes and proteins related to AGE-RAGE-mediated inflammatory signaling. In summary, PF exerts its renoprotective effects by decreasing inflammation and protecting against podocyte injury through the inhibition of the AGE/RAGE/NF-κB/NLRP3 pathway. Overall, these data support the clinical potential of PF as a renoprotective agent in DN.
糖尿病肾病（DN）是糖尿病后期可能出现的一种严重并发症，足细胞损伤会使其进一步加重。阿魏酸哌嗪（PF）具有明确的肾保护作用，临床上用于治疗慢性肾炎等肾脏疾病。然而，PF对DN的肾脏保护作用及其机制尚不清楚。本研究旨在探讨PF对DN的保护作用及其作用机制，为PF在DN治疗中的临床应用提供依据。采用网络药理学预测PF在DN中的作用机制。雄性Sprague Dawley大鼠腹腔注射链脲佐菌素（STZ，60mg/kg）建立DN模型，给药12周后评估肾损伤情况。用25mmol/L葡萄糖处理大鼠足细胞并培养24小时，然后评估细胞损伤情况。我们的结果表明，PF显著改善了DN大鼠的肾功能，减轻了肾脏病理变化，降低了炎症反应，减轻了足细胞损伤。PF还减轻了葡萄糖诱导的足细胞损伤。关于分子机制，我们的研究表明，PF下调了与AGE-RAGE介导的炎症信号相关的基因和蛋白质表达。总之，PF通过抑制AGE/RAGE/NF-κB/NLRP3途径减轻炎症并保护足细胞免受损伤，从而发挥其肾脏保护作用。总体而言，这些数据支持PF作为DN肾保护剂的临床潜力。
