Department of Nephrology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu 215101, China; Li Shicai School Inheritance Studio, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu 215101, China.
Department of Pharmacy, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu 215101, China.
Int Immunopharmacol. 2021 Jan;90:107132. doi: 10.1016/j.intimp.2020.107132. Epub 2020 Nov 19.
Shionone is a triterpenoid component derived from the herbal medicine Aster tataricus, and it has been reported to possess marked anti-inflammatory properties. The activation of NLRP3 inflammasome plays an important role in cystitis, and the effect of Shionone on NLRP3 inflammasome-dependent pyroptosis remains unclear. In this study, we established an interstitial cystitis (IC) rat model and SV-HUC-1 cell model with CYP or LPS + ATP treatment to mimic inflammation response and induce NLRP3 inflammasome activation. Shionone treatment significantly attenuated the bladder wet weight, score of edema and hemorrhage, enhanced the viability of SV-HUC-1 cell, decreased the rate of pyroptosis. Moreover, Shionone reduced the expression of NF-κB, NLRP3, ASC, Pro-caspase-1, Caspase-1, GSDMD, GSDMD-N at the mRNA and protein levels both in rat and SV-HUC-1 cell model, demonstrating NLRP3 inflammasome pathway was blocked and pyroptosis degree was reduced. These results indicated that Shionone could alleviate interstitial cystitis in Rat model and enhancing the viability of SV-HUC-1 cells via NF-κB/NLRP3/GSDMD-N pathway, which illustrated that Shionone could be used as a drug candidate for the treatment of interstitial cystitis.
莪术酮是一种从草药紫菀中提取的三萜类成分，已被报道具有显著的抗炎特性。NLRP3 炎性体的激活在膀胱炎中起着重要作用，而莪术酮对 NLRP3 炎性体依赖性细胞焦亡的影响尚不清楚。在这项研究中，我们建立了间质性膀胱炎（IC）大鼠模型和用 CYP 或 LPS+ATP 处理的 SV-HUC-1 细胞模型，以模拟炎症反应并诱导 NLRP3 炎性体激活。莪术酮处理显著减轻了膀胱湿重、水肿和出血评分，增强了 SV-HUC-1 细胞的活力，降低了细胞焦亡的比率。此外，莪术酮在大鼠和 SV-HUC-1 细胞模型中均降低了 NF-κB、NLRP3、ASC、Pro-caspase-1、Caspase-1、GSDMD、GSDMD-N 在 mRNA 和蛋白水平的表达，表明 NLRP3 炎性体通路被阻断，细胞焦亡程度降低。这些结果表明，莪术酮可以通过 NF-κB/NLRP3/GSDMD-N 通路减轻大鼠模型中的间质性膀胱炎，并增强 SV-HUC-1 细胞的活力，这表明莪术酮可作为治疗间质性膀胱炎的候选药物。
