Khodadadi Mahdi, Javadi Behjat
Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Mini Rev Med Chem. 2025;25(2):112-127. doi: 10.2174/0113895575306884240604065754.
Alpha-synuclein (α-syn) aggregation products may cause neural injury and several neurodegenerative disorders (NDs) known as α-synucleinopathies. Alkaloids are secondary metabolites present in a variety of plant species and may positively affect human health, particularly α-synucleinopathy-associated NDs.
To summarize the latest scientific data on the inhibitory properties of alkaloids in α- synucleinopathies, especially in Parkinson's disease.
Literature search was performed using web-based databases including Web of Science, PubMed, and Scopus up to January 2024, in the English language.
Harmala alkaloids, caffein, lycorine, piperin, acetylcorynoline, berberin, papaverine, squalamine, trodusquemine and nicotin have been found to be the most active natural alkaloids against synucleinopathy. The underlying mechanisms that contribute to this effect would be the inhibition of α-syn aggregation; elimination of formed aggregates; improvement in autophagy activation; promotion of the activity and expression of antioxidative enzymes; and prevention of oxidative injury and apoptosis in dopaminergic neurons.
The findings of the present study highlight the inhibitory activities of alkaloids against synucleinopathy. However, no clinical data supports the reported activities in humans, which calls attention to the need for conducting clinical trials to elucidate the efficacy, safety, proper dosage, unwanted effects and pharmacokinetics aspects of alkaloids in humans.
α-突触核蛋白（α-syn）聚集产物可能导致神经损伤以及几种被称为α-突触核蛋白病的神经退行性疾病（NDs）。生物碱是存在于多种植物物种中的次生代谢产物，可能对人类健康产生积极影响，尤其是与α-突触核蛋白病相关的神经退行性疾病。
总结生物碱对α-突触核蛋白病，特别是帕金森病的抑制特性的最新科学数据。
截至2024年1月，使用包括Web of Science、PubMed和Scopus在内的基于网络的数据库进行英文文献检索。
已发现哈尔满生物碱、咖啡因、石蒜碱、胡椒碱、乙酰紫堇灵、小檗碱、罂粟碱、鲨胺、曲格列酮和烟碱是对抗突触核蛋白病最具活性的天然生物碱。促成这种作用的潜在机制包括抑制α-syn聚集；消除已形成的聚集体；改善自噬激活；促进抗氧化酶的活性和表达；以及预防多巴胺能神经元的氧化损伤和凋亡。
本研究结果突出了生物碱对突触核蛋白病的抑制活性。然而，尚无临床数据支持在人体中报道的这些活性，这就需要进行临床试验来阐明生物碱在人体中的疗效、安全性、适当剂量、不良反应和药代动力学方面的情况。
