Deciphering the Neuroprotective Potential of the Ayurvedic Ashokarishta GC–MS Derived Bioactives Through Network Pharmacology and in silico Multi-Target Analysis Against Alzheimer’s and Parkinson’s Diseases

Ashokarishta belongs to the traditional Ayurvedic polyherbal fermented medicine in managing hormonal, gynaecological and menstrual disorders. However, the potent utility against neurodegenerative disorders, including Alzheimer’s (AD) and Parkinson’s dementia (PD), has not been addressed earlier. In this study, cumulative assessments incorporating phytochemicals and network analyses to identify target proteins and drug interactions for AD and PD. Total phenolic and flavonoid content of Ashokarishta was quantified. Ashokarishta exhibited dose-dependent antioxidant effects against DPPH (63.57 ± 1.81%), ABTs (60.66 ± 1.82%), and nitric oxide (61.66 ± 2.39%). GC-MS analysis revealed 82 phytoconstituents, of which the TCMSP database selected 28 as targets for AD and PD genes. Further, the target genes were evaluated for protein–protein interaction network, Gene ontology and KEGG pathway enrichment analysis. Seven compounds strongly interacted with multiple target genes among the 28 metabolites. Estra-1,3,5(10)-triene-3,17-diol and Morphinan-6-ol, 7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-, (5alpha, 6alpha)-(9CI) showed better hydrogen-bond interactions and binding scores when docked with primary hub genes. Molecular dynamics simulations revealed that the interacting complexes of Estra-1,3,5(10)-triene-3,17-diol with TNF and AKT1 exhibited potential stability over a 200-ns timescale. Estra-1,3,5(10)-triene-3,17-diol was identified as the potential compound and it can be rationalized for further drug discovery approaches to combat AD and PD employing Ashokarishta.