Huang Sihong, Zhou Rong, Yuan Yuyun, Shen Yiyun
Department of Pediatrics, Shanghai Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201999, China.
Aging (Albany NY). 2024 Apr 4;16(7):6478-6487. doi: 10.18632/aging.205716.
Stigmasterol is a common dietary phytosterol with high nutritional value and physiological activity. In this study, we evaluated the effects of stigmasterol on inflammatory cytokines and the TGF-β1/Smad2 and IL-17A signaling pathway in an ovalbumin (OVA)-induced asthma mouse model. Stigmasterol treatment improved airway remodeling. In addition, it significantly attenuated the symptoms of asthma attacks, reduced the number of macrophages, lymphocytes, neutrophils, and eosinophils in BALF and inflammatory cytokines, including IL-1β, IL-5, IL-6, and IL-13. It further decreased the level of IL-17A in BALF, serum and spleen. Spleen single-cell suspension analysis via flow cytometry showed that IL-17A level was consistent with the results obtained in BALF, serum and spleen. Stigmasterol decreased the protein expression levels of TGF-β, p-Smad2 and IL-17A in the spleen, by increasing the protein expression level of IL-10. After 24 h of co-culture of TGF-β, IL-6 and stigmasterol, the level of IL-17 in CD4 T cell supernatant was lower relative to levels in the group without stigmasterol. Meanwhile, stigmasterol treatment attenuated the expression level of TGF- β, p-Smad2 and IL-17A proteins in CD4 T cells and enhanced the expression levels of IL-10 protein. These data suggested that stigmasterol inhibited the TGF-β1/Smad2 and IL-17A signaling pathway to achieve anti-asthmatic effects in the OVA-induced asthma mouse model. Collectively, the results of this study are that stigmasterol has achieved preliminary efficacy in the non-clinical laboratory, further studies are needed to consider the clinical application of stigmasterol.
豆甾醇是一种常见的具有高营养价值和生理活性的膳食植物甾醇。在本研究中，我们在卵清蛋白（OVA）诱导的哮喘小鼠模型中评估了豆甾醇对炎性细胞因子以及TGF-β1/Smad2和IL-17A信号通路的影响。豆甾醇治疗改善了气道重塑。此外，它显著减轻了哮喘发作的症状，减少了支气管肺泡灌洗液（BALF）中的巨噬细胞、淋巴细胞、中性粒细胞和嗜酸性粒细胞数量以及炎性细胞因子，包括IL-1β、IL-5、IL-6和IL-13。它还进一步降低了BALF、血清和脾脏中IL-17A的水平。通过流式细胞术对脾脏单细胞悬液进行分析表明，IL-17A水平与在BALF、血清和脾脏中获得的结果一致。豆甾醇通过增加IL-10的蛋白表达水平降低了脾脏中TGF-β、p-Smad2和IL-17A的蛋白表达水平。在TGF-β、IL-6和豆甾醇共培养24小时后，CD4 T细胞上清液中IL-17的水平相对于无豆甾醇组较低。同时，豆甾醇治疗减弱了CD4 T细胞中TGF-β、p-Smad2和IL-17A蛋白的表达水平，并增强了IL-10蛋白的表达水平。这些数据表明，在OVA诱导的哮喘小鼠模型中，豆甾醇通过抑制TGF-β1/Smad2和IL-17A信号通路来实现抗哮喘作用。总体而言，本研究结果是豆甾醇在非临床实验室中已取得初步疗效，需要进一步研究以考虑豆甾醇的临床应用。
