Capsaicin and nicotine alleviate MPTP induced olfactory dysfunction by suppressing cGAS/TBK1/STING and MAPK mediated neuroinflammation.

IF 8.2 1区医学 Q1 NEUROSCIENCES

NPJ Parkinson's Disease Pub Date : 2025-10-03 DOI:10.1038/s41531-025-01135-4

Jingjing Wei,Linhai Wang,Dingzhong Wang,Weiwei Chen,Lulu Guo,Mengqian Ren,Fangxin Guo,Sisi Ruan,Hangcui Hu,Yao Zheng,Siqi Nan,Zhiwen Xu,Yan Li,Hang Yuan,Jian Mao,Yan Xu,Jianping Xie

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引用次数: 0

Abstract

Olfactory dysfunction serves as a potential early diagnostic biomarker for Parkinson's disease (PD), providing essential evidence for investigating PD pathogenesis and developing neuroprotective strategies. Capsaicin (CAP) and nicotine (Nic), pungent flavor compounds derived from Solanaceae plants, exhibit anti-inflammatory properties. Epidemiological studies indicate that higher levels of chili pepper consumption and smoking are inversely associated with PD risk. However, the mechanisms of CAP and Nic against PD-related olfactory dysfunction remain unclear. In this study, we observed that CAP and Nic ameliorated olfactory dysfunction in MPTP intranasal-treated PD mice and alleviated dopaminergic damage in key brain regions including the olfactory bulb, anterior olfactory nucleus, striatum and substantia nigra. Both compounds suppressed microglial activation in these regions, downregulated IL-6 expression, and upregulated TGF-β protein levels. Furthermore, our findings demonstrated that CAP and Nic could effectively mitigate MPTP-induced olfactory deficits by attenuating neuroinflammation mediated through the cGAS/TBK1/STING and MAPK signaling.

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辣椒素和尼古丁通过抑制cGAS/TBK1/STING和MAPK介导的神经炎症来缓解MPTP诱导的嗅觉功能障碍。

嗅觉功能障碍是帕金森病（PD）潜在的早期诊断生物标志物，为研究PD发病机制和制定神经保护策略提供重要证据。辣椒素（CAP）和尼古丁（Nic）是从茄科植物中提取的刺激性风味化合物，具有抗炎作用。流行病学研究表明，高水平的辣椒消费和吸烟与PD风险呈负相关。然而，CAP和Nic对抗pd相关嗅觉功能障碍的机制尚不清楚。在本研究中，我们观察到CAP和Nic改善了MPTP鼻内处理PD小鼠的嗅觉功能障碍，减轻了嗅球、前嗅核、纹状体和黑质等关键脑区多巴胺能损伤。两种化合物均抑制这些区域的小胶质细胞活化，下调IL-6表达，上调TGF-β蛋白水平。此外，我们的研究结果表明，CAP和Nic可以通过减轻cGAS/TBK1/STING和MAPK信号通路介导的神经炎症，有效减轻mptp诱导的嗅觉缺陷。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

NPJ Parkinson's Disease Medicine-Neurology (clinical)

CiteScore

9.80

自引率

5.70%

发文量

156

审稿时长

11 weeks

期刊介绍： npj Parkinson's Disease is a comprehensive open access journal that covers a wide range of research areas related to Parkinson's disease. It publishes original studies in basic science, translational research, and clinical investigations. The journal is dedicated to advancing our understanding of Parkinson's disease by exploring various aspects such as anatomy, etiology, genetics, cellular and molecular physiology, neurophysiology, epidemiology, and therapeutic development. By providing free and immediate access to the scientific and Parkinson's disease community, npj Parkinson's Disease promotes collaboration and knowledge sharing among researchers and healthcare professionals.