Qian Yu1, Minda Zhang2, Lifen Qian1, Dan Wen1, Guanzhong Wu3. 1. Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China. 2. State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China. 3. Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China. Electronic address: wwbsabc@163.com.
Abstract
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.