In vitro evidence that an aqueous extract of Centella asiatica modulates α-synuclein aggregation dynamics.

Abstract

α-Synuclein aggregation is one of the major etiological factors implicated in Parkinson's disease (PD). The prevention of ggregation 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 aggregates and favored the disintegration of the preformed fibrils. The study provides an insight in finding new natural product for future PD therapeutics.