Hannan_2022_Evid.Based.Complement.Alternat.Med_2022_1015310

Convolvulus pluricaulis (CP), a Medhya Rasayana (nootropic) herb, is a major ingredient in Ayurvedic and Traditional Chinese formulae indicated for neurological conditions, namely, dementia, anxiety, depression, insanity, and epilepsy. Experimental evidence suggests various neuroactive potentials of CP such as memory-enhancing, neuroprotective, and antiepileptic. However, precise mechanisms underlying the neuropharmacological effects of CP remain unclear. The study, therefore, aimed at deciphering the molecular basis of neuroprotective effects of CP phytochemicals against the pathology of dementia disorders such as Alzheimer's (AD) and Parkinson's (PD) disease. The study exploited bioinformatics tools and resources, such as Cytoscape, DAVID (Database for annotation, visualization, and integrated discovery), NetworkAnalyst, and KEGG (Kyoto Encyclopedia of Genes and Genomes) database to investigate the interaction between CP compounds and molecular targets. An in silico analysis was also employed to screen druglike compounds and validate some selective interactions. ADME (absorption, distribution, metabolism, and excretion) analysis predicted a total of five druglike phytochemicals from CP constituents, namely, scopoletin, 4-hydroxycinnamic acid, kaempferol, quercetin, and ayapanin. In network analysis, these compounds were found to interact with some molecular targets such as prostaglandin G/H synthase 1 and 2 (PTGS1 and PTGS2), endothelial nitric oxide synthase (NOS3), insulin receptor (INSR), heme oxygenase 1 (HMOX1), acetylcholinesterase (ACHE), peroxisome proliferator-activated receptor-gamma (PPARG), and monoamine oxidase A and B (MAOA and MAOB) that are associated with neuronal growth, survival, and activity. Docking simulation further confirmed interaction patterns and binding affinity of selected CP compounds with those molecular targets. Notably, scopoletin showed the highest binding affinity with PTGS1, NOS3, PPARG, ACHE, MAOA, MAOB, and TRKB, quercetin with PTGS2, 4-hydroxycinnamic acid with INSR, and ayapanin with HMOX1. The findings indicate that scopoletin, kaempferol, quercetin, 4-hydroxycinnamic acid, and ayapanin are the main active constituents of CP which might account for its memory enhancement and neuroprotective effects and that target proteins such as PTGS1, PTGS2, NOS3, PPARG, ACHE, MAOA, MAOB, INSR, HMOX1, and TRKB could be druggable targets against dementia.