Swietenine (Swi), isolated from Swietenia macrophylla King ameliorates inflammation and oxidative stress, and diabetic nephropathy has a close connection with them. So the effects of Swi on diabetic nephropathy and its mechanism of action was explored. We divided human mesangial cells into five groups and determined the expression of NF-κB and NLRP3 inflammasomes in each group. The levels of inflammatory factors IL-1β and IL-18 were also measured. To explore the relationship between NF-κB and NLRP3, we added PDTC, a specific NF-κB inhibitor, and LPS, and divided the experimental groups into seven groups. We measured the expressions of NF-κB and NLRP3, and then added MCC950, a specific inhibitor of NLRP3 and LPS, the expression of NLRP3, Caspase-1, and IL-1β and IL-18 were measured.Animals divided into four groups and administered over 8 weeks. Protein excretion, creatinine, urea nitrogen, and uric acid were measured. Swi down regulated the expression of NF-κB, NLRP3, and Caspase-1. It reduced the levels of IL-1β and IL-18.PDTC decreased the expression of NF-κB and NLRP3. Compared with the HG + PDTC group, the expression of NF-κB and NLRP3 in the HG + Swi + PDTC group decreased significantly. After adding lipopolysaccharide, the expression of NF-κB and NLRP3 increased, but this situation was reversed after adding Swi. After adding LPS, the expression of NLRP3 and Caspase-1 increased, and the levels of IL-1β and IL-18 also increased, but this situation was reversed after the addition of Swi.Swi significantly improved the renal function of mice with diabetic nephropathy and inhibited the activation of NF-κB and the NLRP3 inflammasome and reduced inflammation by regulating the NF-κB/NLRP3/Caspase-1 signaling pathway, thereby improving diabetic nephropathy.

Oxidative stress is an important factor that causes pancreatic β‐cell dysfunction leading to the development and aggravation of diabetes. Swietenine (Stn) and swietenolide (Std) were isolated from the fruits of Swietenia macrophylla King and had the potential effects on treatment and prevention of diabetes. The aim of this study is to investigate the effects of Stn and Std on insulin secretion and apoptosis in H2O2 induced insulinoma cell line (INS‐1) cells. In the present study, INS‐1 cells were treated with 300 μM H2O2 for 4 h to establish the oxidative damage model. Cell apoptosis, insulin secretion, reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) levels, and Caspase‐3 enzyme activity were measured via corresponding methods. Finally, pancreatic duodenal home box factor‐1 (PDX‐1), B cell lymphoma‐2 (Bcl‐2), and Bax protein expression were detected by western blot. Experimental results showed that Stn and Std could significantly improve the INS‐1 cell viability, increase the secretion of insulin and reduce the ROS level in H2O2 induced INS‐1 cells. Furthermore, the SOD and GSH levels increased, and the MDA levels decreased compared with the model group after Stn and Std treatment. In addition, after treated with Stn and Std, cell apoptosis was improved, and the activity of Caspase 3 was also significantly inhibited. Meanwhile, Western blot results showed that Stn and Std could up‐regulate the expression of PDX‐1 protein, and affect the cell apoptosis pathway by up‐regulating the expression of Bcl‐2 protein and down‐regulating the expression of Bax protein. In conclusion, Stn and Std can signifcantly improve the insulin secretion function, protect oxidative stress injury, and reduce apoptosis in H2O2 induced INS‐1 cells, which provides a research basis for Stn and Std to be new drug candidates for the treatment and prevention of diabetes.