Exploring the Molecular Mechanism of Ixora coccinea Against Parkinson’s Disease Via Network Pharmacology and Molecular Dynamics Simulation with Its Validation

Ixora coccinea , a medicinally important evergreen shrub, has been reported to exhibit numerous pharmacological activities, including neuroprotective effects. Hence, the current study aimed to investigate the molecular mechanisms and therapeutic potential of I. coccinea in managing Parkinson’s disease using integrated in silico and in vivo approaches. In a computational approach, bioactives of I. coccinea were screened and evaluated for their bioavailability. The potential targets regulated by bioactives were assessed via network, gene enrichment, and gene ontology analyses. Molecular docking was performed to predict the binding affinities, followed by molecular dynamics (MD) simulation. In experimental pharmacology, haloperidol was used to induce Parkinsonism in albino Wistar rats. Two doses of I. coccinea extract (200 and 400 mg/kg) were administered in conjunction with regular Syndopa. In the 21 days of treatment, rats were assessed for various neurobehavioral studies, biochemical, antioxidant and histological parameters. The network pharmacology revealed that stigmast-4-en-3-one showed the highest drug-likeness score of 0.91. Gene enrichment analysis predicted C-C motif chemokine 2, peroxisome proliferator-activated receptor alpha, and nuclear factor erythroid 2-related factor 2 (NFE2L2) as the top genes. Molecular docking revealed that NFE2L2, Catalase (CAT), and Peroxisome proliferator-activated receptor gamma (PPARG) showed the binding energy of −9.9, −9.5, and −9.3 kcal/mol, respectively. Molecular mechanics and MD simulation Poisson-Boltzmann study of surface area showed that the complex of CAT with 3-hydroxyflavone and PPARG with beta-sitosterol were most stable throughout the MD run. Further, I. coccinea ameliorated motor function, improved dopamine levels, reduced acetylcholinesterase (AChE) activity and oxidative stress, and displayed neuroprotection in the cerebral cortex region. The ethanolic extract of I. coccinea exhibited anti-Parkinson’s potential, possibly because PPARG and CAT are regulated by a variety of bioactives.