Xu Jingwen, Tang Youying, Shen Chenjun, Li Kewei, Zhao Mengjia, Zhou Fangmei, Tian Shasha, Yu Jie, Ding Zhishan, Chen Yuchi
School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Yuyao Municipal Center for Disease Prevention and Control, Yuyao, 315400, China.
Int Immunopharmacol. 2025 Aug 28;161:115054. doi: 10.1016/j.intimp.2025.115054. Epub 2025 Jun 8.
Allergic rhinitis (AR) is a prevalent nasal disorder characterized by chronic inflammation and hypersensitivity, with limited effective treatments. Melastoma dodecandrum polysaccharide (MDP), derived from a medicinal herb, exhibits anti-inflammatory and immunomodulatory properties, making it a potential therapeutic candidate for AR. This study evaluated the therapeutic efficacy of MDP in AR mice and explored its underlying mechanisms. An ovalbumin (OVA)-induced AR mouse model was established, with MDP administered via gavage or inhalation. MDP reduced sneezing and nasal scratching in AR mice. Treatment alleviated nasal mucosa thickness, goblet cell hyperplasia, and cellular disarray, as assessed by H&E and Alcian blue staining. MDP decreased serum IgE, IL-17, and IL-1β levels, as measured by ELISA, and reduced the proportion of Th17 cells, analyzed by flow cytometry. In nasal mucosa, MDP downregulated the expression of NLRP3, GSDMD, and IL-17A proteins, and reduced the mRNA levels of NLRP3, IL-17, IL-1β, and IL-18, as determined by immunohistochemistry and qRT-PCR. MDP also mitigated tissue cell death, as shown by TUNEL staining. In vitro, MDP suppressed NLRP3 inflammasome activation and pyroptosis in bone marrow-derived macrophages (BMDMs) treated with LPS and nigericin. These effects were confirmed by western blot, qRT-PCR, and immunofluorescence, along with pyroptosis assessment and scanning electron microscopy, which revealed reduced pyroptosis and membrane damage. In conclusion, MDP effectively alleviates AR symptoms in mice, with its therapeutic effects involving the modulation of the NLRP3 inflammasome and the IL-17 signaling pathway, highlighting its clinical potential for AR management.
变应性鼻炎（AR）是一种常见的鼻腔疾病，其特征为慢性炎症和超敏反应，有效治疗方法有限。从一种草药中提取的地稔多糖（MDP）具有抗炎和免疫调节特性，使其成为AR的潜在治疗候选物。本研究评估了MDP对AR小鼠的治疗效果，并探讨其潜在机制。建立了卵清蛋白（OVA）诱导的AR小鼠模型，通过灌胃或吸入方式给予MDP。MDP减少了AR小鼠的喷嚏和鼻搔抓行为。通过苏木精-伊红（H&E）和阿尔辛蓝染色评估，治疗减轻了鼻黏膜厚度、杯状细胞增生和细胞紊乱。通过酶联免疫吸附测定（ELISA）测量，MDP降低了血清免疫球蛋白E（IgE）、白细胞介素-17（IL-17）和白细胞介素-1β（IL-1β）水平，并通过流式细胞术分析减少了辅助性T细胞17（Th17）细胞的比例。通过免疫组织化学和定量逆转录聚合酶链反应（qRT-PCR）测定，在鼻黏膜中，MDP下调了NOD样受体蛋白3（NLRP3）、Gasdermin D（GSDMD）和IL-17A蛋白的表达，并降低了NLRP3、IL-17、IL-1β和白细胞介素-18（IL-18）的信使核糖核酸（mRNA）水平。TUNEL染色显示，MDP还减轻了组织细胞死亡。在体外，MDP抑制了用脂多糖（LPS）和尼日利亚菌素处理的骨髓来源巨噬细胞（BMDM）中NLRP3炎性小体的激活和细胞焦亡。蛋白质免疫印迹法、qRT-PCR、免疫荧光以及细胞焦亡评估和扫描电子显微镜证实了这些作用，结果显示细胞焦亡和膜损伤减少。总之，MDP有效减轻了小鼠的AR症状，其治疗效果涉及对NLRP3炎性小体和IL-17信号通路的调节，突出了其在AR治疗中的临床潜力。
