Inhibitory effect of naturally occurring Ocimum sanctum extract on α-Synuclein aggregation in aqueous solution

Abstract

α-Synuclein (α-Syn) has a propensity to form amyloids and is one of the major causes of neurodegenerative disorders like Parkinson’s disease (PD). Despite a lot of research, there is no obviating therapy available for PD and related disorders. Therefore, discovering new inhibitors against α-Syn aggregation is a subject of intense research. Against this backdrop, we have investigated the attenuating effect of naturally occurring Ocimum sanctum (OS) against aggregation in aqueous solution using various biochemical and biophysical studies. In this report, Thioflavin (ThT) and Congo red binding assays have shown the hindering effect of OS extract on β-sheet formation in α-Syn, and eventually leading to inhibition of aggregation. ANS binding assay indicated its modulatory effect on hydrophobic patches of α-Syn protein. SDS-PAGE, turbidity measurement, and light scattering assays indicated the role of OS extract in increasing protein solubility. Morphological studies conducted by TEM and DLS suggested that OS extract prevents the formation of large fibrils. This work also extends to reveal the inhibitory and disaggregation effects of OS extract on A53T mutant induced aggregation and pre-existing fibrils respectively. Also, MTT assay implied the protective effect of OS extract on neuroblastoma cells against fibril induced cytotoxicity. Furthermore, docking studies of α-Syn with different molecules of OS extract navigated for putative interacting amino acid residues. Thus, due to the presence of polyphenolic compounds, OS extract binds with α-Syn and inhibits its aggregation. This study implicates that OS extract and associated molecules may become a potential therapeutic intervention against PD and other aggregation related disorders.