Wang Yeying, Liao Bin, Shan Xuesong, Ye Haonan, Wen Yuqi, Guo Hua, Xiao Feng, Zhu Hong
Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006 Jiangxi, China; The Second Clinical Medical College of Nanchang University, Nanchang 330006 Jiangxi, China.
Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006 Jiangxi, China; Jiangxi Key Laboratory of Neurological Tumors and Cerebrovascular Diseases, Nanchang 330006 Jiangxi, China; Jiangxi Health Commission Key Laboratory of Neurological Medicine, Nanchang 330006 Jiangxi, China; Institute of Neuroscience, Nanchang University, Nanchang 330006 Jiangxi, China.
Int Immunopharmacol. 2025 Feb 6;147:114076. doi: 10.1016/j.intimp.2025.114076. Epub 2025 Jan 13.
The pathological mechanisms of Parkinson's disease (PD) is complex, and no definitive cure currently exists. This study identified Rutaecarpine (Rut), an alkaloid extracted from natural plants, as a potential therapeutic agent for PD. To elucidate its mechanisms of action and specific effects in PD, network pharmacology, molecular docking, and experimental validation methods were employed. Our findings demonstrated the efficacy of Rut in ameliorating PD symptoms. Network pharmacology analysis indicated that Rut exerts its therapeutic effects through the PPAR signaling pathway and the lipid pathway. Molecular docking results revealed that Rut forms stable protein-ligand complexes with PPARα and PPARγ. Animal experiments showed that Rut improved motor function in PD mice, protected dopaminergic neurons, ameliorated lipid metabolism disorders, and reduced neuroinflammation. This study identified the critical molecular mechanisms and therapeutic targets of Rut in the treatment of PD, providing a theoretical foundation for future investigations into the pharmacodynamics of Rut as a potential anti-PD agent.
帕金森病（PD）的病理机制复杂，目前尚无确切的治愈方法。本研究确定了从天然植物中提取的生物碱吴茱萸次碱（Rut）作为PD的一种潜在治疗药物。为阐明其在PD中的作用机制和具体效果，采用了网络药理学、分子对接和实验验证方法。我们的研究结果证明了吴茱萸次碱在改善PD症状方面的疗效。网络药理学分析表明，吴茱萸次碱通过PPAR信号通路和脂质途径发挥其治疗作用。分子对接结果显示，吴茱萸次碱与PPARα和PPARγ形成稳定的蛋白质-配体复合物。动物实验表明，吴茱萸次碱改善了PD小鼠的运动功能，保护了多巴胺能神经元，改善了脂质代谢紊乱，并减轻了神经炎症。本研究确定了吴茱萸次碱治疗PD的关键分子机制和治疗靶点，为未来研究吴茱萸次碱作为潜在抗PD药物的药效学提供了理论基础。
