Systems Pharmacology and Pharmacokinetics Strategy to Decode Bioactive Ingredients and Molecular Mechanisms from Zingiber officinale as Phyto-therapeutics against Neurological Diseases

Background: The bioactive constituents from Zingiber officinale (Z. officinale) have shown a positive effect on neurodegenerative diseases like Alzheimer's disease (AD), which manifests as progressive memory loss and cognitive impairment. Objective: This study investigates the binding ability and the pharmaco-therapeutic potential of Z. officinale with AD disease targets by molecular docking and molecular dynamic (MD) simulation approaches. Methods: By coupling enormous available phytochemical data and advanced computational technologies, the possible molecular mechanism of action of these bioactive compounds was deciphered by evaluating phytochemicals, target fishing, and network biological analysis. Results: As a result, 175 bioactive compounds and 264 human target proteins were identified. The gene ontology and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis and molecular docking were used to predict the basis of vital bioactive compounds and biomolecular mechanisms involved in the treatment of AD. Amongst selected bioactive compounds, 10- Gingerdione and 1-dehydro-[8]-gingerdione exhibited significant anti-neurological properties against AD targeting amyloid precursor protein with docking energy of -6.0 and -5.6, respectively. Conclusion: This study suggests that 10-Gingerdione and 1-dehydro-[8]-gingerdione strongly modulates the anti-neurological activity and are associated with pathological features like amyloid-β plaques and hyperphosphorylated tau protein are found to be critically regulated by these two target proteins. This comprehensive analysis provides a clue for further investigation of these natural compounds' inhibitory activity in drug discovery for AD treatment.