title: 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 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.
authors.affiliation: 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.
authors.forename: Ruben
authors.initials: R
authors.lastname: Berrocal
authors.affiliation: Centre for Neuroscience, Institute for Scientific Research and Technology Services (INDICASAT-AIP), City of Knowledge, Panama City, Republic of Panama.
authors.forename: Padmaraju
authors.initials: P
authors.lastname: Vasudevaraju
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
authors.forename: Shantinath Satappa
authors.initials: SS
authors.lastname: Indi
authors.affiliation: 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.
authors.forename: Krothapalli Raja Surya
authors.initials: KR
authors.lastname: Sambasiva Rao
authors.affiliation: Centre for Neuroscience, Institute for Scientific Research and Technology Services (INDICASAT-AIP), City of Knowledge, Panama City, Republic of Panama.
authors.forename: K S
authors.initials: KS
authors.lastname: Rao
mesh_terms: D000978:Antiparkinson Agents / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles; D028041:Centella; D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D005453:Fluorescence; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols / Q000737:chemistry; D055503:Protein Multimerization / Q000187:drug effects*; D013844:Thiazoles; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D014867:Water / Q000737:chemistry; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; C526146:Centella asiatica extract; D010936:Plant Extracts; D059808:Polyphenols; D013844:Thiazoles; D014315:Triterpenes; D051844:alpha-Synuclein; D014867:Water; C009462:thioflavin T
keywords: Centella asiatica; Parkinson's disease; anti-aggregation; circular dichroism; natural products; transmission electron microscopy; α-Synuclein