In-silico and In-vitro Exploration of Neuroprotective Phytoconstituents from Barleria terminalis and Calacanthus grandiflorus Acting on Cholinergic and Dopaminergic Pathways in Alzheimer’s and Parkinson’s Diseases

Abstract

Neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are driven by oxidative stress, neurotransmitter imbalance, and protein aggregation, leading to progressive neuronal loss. Both plant extracts represent promising phytopharmacological sources with multitarget neuroprotective potential, warranting further isolation, in-vivo validation, and mechanistic studies. This study aims to investigate the neuroprotective potential of Barleria terminalis and Calacanthus grandiflorus through integrated in-silico and in-vitro studies targeting key AD and PD enzymes and pathways. Methanolic extracts were characterized using LC–MS and FTIR, followed by molecular docking against AChE, MAO-B, and aggregation-related proteins. In-vitro assays including AChE/MAO-B inhibition, DPPH/ABTS antioxidant tests, cytoprotective MTT assay on SH-SY5Y cells, and Thioflavin T aggregation assays were performed. The identified compounds, catechin, antirrhinoside, monotropein, and swertiamarin, showed favorable relative docking scores (−8.3 to −9.5 kcal·mol⁻¹). Extracts demonstrated potent AChE (IC50 38.2 μg/mL) and MAO-B (IC50 33.7 μg/mL) inhibition, significant antioxidant activity (IC50 42–47 μg/mL), and enhanced neuronal viability (~88%). Anti-aggregatory assays showed 58– 65% inhibition of Aβ and α-synuclein fibrils. Both plants exhibit multitarget neuroprotective action through combined antioxidant, enzyme inhibitory, and anti-aggregatory mechanisms. B. terminalis and C. grandiflorus are promising phytopharmacological resources for developing safe, multitarget therapeutics against AD and PD.