Centre for Neuroscience, Institute for Scientific Research and Technology Services (INDICASAT-AIP), City of Knowledge, Panama City, Republic of Panama Department of Biotechnology, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur, India.
Centre for Neuroscience, Institute for Scientific Research and Technology Services (INDICASAT-AIP), City of Knowledge, Panama City, Republic of Panama.
J Alzheimers Dis. 2014;39(2):457-65. doi: 10.3233/JAD-131187.
α-Synuclein aggregation is one of the major etiological factors implicated in Parkinson's disease (PD). The prevention of aggregation of α-synuclein is a potential therapeutic intervention for preventing PD. The discovery of natural products as alternative drugs to treat PD and related disorders is a current trend. The aqueous extract of Centella asiatica (CA) is traditionally used as a brain tonic and CA is known to improve cognition and memory. There are limited data on the role of CA in modulating amyloid-β (Aβ) levels in the brain and in Aβ aggregation. Our study focuses on CA as a modulator of the α-synuclein aggregation pattern in vitro. Our investigation is focused on: (i) whether the CA leaf aqueous extract prevents the formation of aggregates from monomers (Phase I: α-synuclein + extract co-incubation); (ii) whether the CA aqueous extract prevents the formation of fibrils from oligomers (Phase II: extract added after oligomers formation); and (iii) whether the CA aqueous extract disintegrates the pre-formed fibrils (Phase III: extract added to mature fibrils and incubated for 9 days). The aggregation kinetics are studied using a thioflavin-T assay, circular dichroism, and transmission electron microscopy. The results showed that the CA aqueous extract completely inhibited the α-synuclein aggregation from monomers. Further, CA extract significantly inhibited the formation of oligomer to aggregates and favored the disintegration of the preformed fibrils. The study provides an insight in finding new natural products for future PD therapeutics.
α-突触核蛋白聚集是帕金森病（PD）的主要病因之一。预防α-突触核蛋白聚集是预防 PD 的一种潜在治疗干预措施。发现天然产物作为治疗 PD 和相关疾病的替代药物是当前的趋势。积雪草（CA）的水提取物传统上被用作补脑剂，并且已知 CA 可以改善认知和记忆力。关于 CA 在调节大脑中淀粉样蛋白-β（Aβ）水平和 Aβ聚集中的作用的数据有限。我们的研究侧重于 CA 作为体外 α-突触核蛋白聚集模式的调节剂。我们的研究重点是：（i）CA 叶水提取物是否可以防止单体形成聚集体（第 I 阶段：α-突触核蛋白+提取物共孵育）；（ii）CA 水提取物是否可以防止寡聚物形成纤维（第 II 阶段：寡聚物形成后加入提取物）；（iii）CA 水提取物是否可以分解预先形成的纤维（第 III 阶段：将提取物加入成熟纤维中并孵育 9 天）。使用硫黄素 T 测定法、圆二色性和透射电子显微镜研究了聚合动力学。结果表明，CA 水提取物完全抑制了单体的 α-突触核蛋白聚集。此外，CA 提取物显著抑制了寡聚物到聚集体的形成，并有利于预先形成的纤维的解体。该研究为寻找用于未来 PD 治疗的新型天然产物提供了深入了解。
