背景:α-突触核蛋白(α-syn)聚集产物可能导致神经损伤和几种神经退行性疾病(ND),称为α-突触核蛋白病。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。特别是α-突触核蛋白病相关的ND。
目的:总结有关生物碱在α-突触核蛋白病中的抑制特性的最新科学数据,尤其是在帕金森病中。
方法:使用基于Web的数据库(包括WebofScience,PubMed,和Scopus直到2024年1月,英语语言。
结果:Harmala生物碱,咖啡因,lycorine,哌啶,乙酰山林碱,Berberin,罂粟碱,角鲨胺,已经发现trodusquemine和nicotin是对抗突触核蛋白病最活跃的天然生物碱。导致这种作用的潜在机制是抑制α-syn聚集;消除形成的聚集体;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。
结论:本研究的发现强调了生物碱对突触核蛋白病的抑制活性。然而,没有临床数据支持报道的人类活动,这需要注意进行临床试验以阐明疗效的必要性,安全,适当的剂量,生物碱在人体中的有害作用和药代动力学方面。
BACKGROUND: 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.
OBJECTIVE: To summarize the latest scientific data on the inhibitory properties of alkaloids in α- synucleinopathies, especially in Parkinson\'s disease.
METHODS: Literature search was performed using web-based databases including Web of Science, PubMed, and Scopus up to January 2024, in the English language.
RESULTS: 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.
CONCLUSIONS: 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.