School of Pharmacy, Xuzhou Medical University, Xuzhou, China.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
Environ Toxicol. 2022 Dec;37(12):2977-2989. doi: 10.1002/tox.23653. Epub 2022 Sep 6.
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.
从苏铁中分离得到的苏铁素（Swi）可改善炎症和氧化应激，而糖尿病肾病与之密切相关。因此，本研究旨在探索 Swi 对糖尿病肾病的作用及其作用机制。我们将人肾小球系膜细胞分为五组，检测每组 NF-κB 和 NLRP3 炎性小体的表达，同时测量炎性因子 IL-1β 和 IL-18 的水平。为了探究 NF-κB 与 NLRP3 之间的关系，我们加入了 NF-κB 的特异性抑制剂 PDTC 和 LPS，并将实验组分为七组。我们检测 NF-κB 和 NLRP3 的表达，然后加入 NLRP3 的特异性抑制剂 MCC950 和 LPS，检测 NLRP3、Caspase-1、IL-1β 和 IL-18 的表达。动物实验分为四组，给药 8 周。测量蛋白质排泄、肌酐、尿素氮和尿酸。Swi 下调 NF-κB、NLRP3 和 Caspase-1 的表达，降低 IL-1β 和 IL-18 的水平。PDTC 降低 NF-κB 和 NLRP3 的表达，与 HG+PDTC 组相比，HG+Swi+PDTC 组 NF-κB 和 NLRP3 的表达明显降低。加入脂多糖后，NF-κB 和 NLRP3 的表达增加，但加入 Swi 后这种情况得到逆转。加入 LPS 后，NLRP3 和 Caspase-1 的表达增加，IL-1β 和 IL-18 的水平也增加，但加入 Swi 后这种情况得到逆转。Swi 可显著改善糖尿病肾病小鼠的肾功能，通过调节 NF-κB/NLRP3/Caspase-1 信号通路抑制 NF-κB 的激活和 NLRP3 炎性小体，从而减轻炎症反应，改善糖尿病肾病。
