揭示rutaecarpine的前景:通过PPAR调节缓解帕金森病的途径

IF 4.8 2区 医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-02-06 Epub Date: 2025-01-13 DOI:10.1016/j.intimp.2025.114076
Yeying Wang, Bin Liao, Xuesong Shan, Haonan Ye, Yuqi Wen, Hua Guo, Feng Xiao, Hong Zhu
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引用次数: 0

摘要

帕金森病(PD)的病理机制是复杂的,目前还没有明确的治疗方法。本研究确定了从天然植物中提取的生物碱车尾松果碱(Rutaecarpine,车尾松果碱)是一种潜在的帕金森病治疗剂。采用网络药理学、分子对接、实验验证等方法阐明其在帕金森病中的作用机制和特异性作用。我们的研究结果证明了Rut在改善PD症状方面的功效。网络药理学分析表明,Rut通过PPAR信号通路和脂质途径发挥其治疗作用。分子对接结果表明,Rut与PPARα和PPARγ形成稳定的蛋白配体复合物。动物实验表明,车辙能改善PD小鼠的运动功能,保护多巴胺能神经元,改善脂质代谢紊乱,减轻神经炎症。本研究明确了Rut治疗PD的关键分子机制和治疗靶点,为进一步研究Rut作为潜在抗PD药物的药效学研究提供理论基础。
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Revealing rutaecarpine's promise: A pathway to parkinson's disease relief through PPAR modulation.

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.

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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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