Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China.
State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China.
Life Sci. 2019 May 15;225:1-7. doi: 10.1016/j.lfs.2019.03.073. Epub 2019 Mar 30.
Diabetic nephropathy is a growing health concern, which is reported to be associated with inflammation. Luteolin has been explored for the treatment of some diabetic complications. Although several studies have verified the effect of luteolin on diabetic nephropathy, the mechanism by which the therapeutic effects of luteolin on diabetic nephropathy has not been established. Therefore, we aimed to investigate the effect of luteolin on diabetic nephropathy and its underlying mechanism.
We used western blot, Real-time PCR, immunofluorescence and flow cytometry to analyze the effects of luteolin on podocyte injury and NOD-like receptor family and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in high glucose (HG) condition. Reactive oxygen species (ROS) generation was measured by flow cytometry and malondialdehyde (MDA) level. To investigate the potential mechanism, we examined cell apoptosis upon transfection of siNLRP3.
We showed that luteolin treatment could protect podocyte against HG-induced cell apoptotic and mitochondrial membrane potential collapse. In addition, luteolin significantly reduced NLRP3 inflammasome formation and subsequent interleukin-1β (IL-1β) secretion in HG-induced MPC-5 cells. Interestingly, siNLRP3 abolished the effect of luteolin on cell apoptosis, suggesting that the anti-apoptotic effect was found to be mostly related to NLRP3 inflammasome.
In summary, our data demonstrated the abilities of luteolin to inhibit podocyte injury and NLRP3 inflammasome activation, which could be used in the treatment of diabetic nephropathy.
糖尿病肾病是一个日益严重的健康问题，据报道与炎症有关。木犀草素已被探索用于治疗一些糖尿病并发症。尽管有几项研究已经证实了木犀草素对糖尿病肾病的治疗作用，但木犀草素治疗糖尿病肾病的机制尚未确定。因此，我们旨在研究木犀草素对糖尿病肾病的作用及其潜在机制。
我们使用 Western blot、Real-time PCR、免疫荧光和流式细胞术来分析木犀草素对高糖（HG）条件下足细胞损伤和 NOD 样受体家族和 pyrin 结构域包含蛋白 3（NLRP3）炎性小体激活的影响。通过流式细胞术测量活性氧（ROS）的产生和丙二醛（MDA）水平。为了研究潜在的机制，我们检查了转染 siNLRP3 后细胞凋亡的情况。
我们表明，木犀草素处理可以保护足细胞免受 HG 诱导的细胞凋亡和线粒体膜电位崩溃。此外，木犀草素显著降低了 HG 诱导的 MPC-5 细胞中 NLRP3 炎性小体的形成和随后的白细胞介素-1β（IL-1β）分泌。有趣的是，siNLRP3 消除了木犀草素对细胞凋亡的影响，表明抗凋亡作用主要与 NLRP3 炎性小体有关。
总之，我们的数据表明木犀草素能够抑制足细胞损伤和 NLRP3 炎性小体激活，可用于治疗糖尿病肾病。
