Usman_2025_In.Silico.Pharmacol_13_171

BACKGROUND: Neurodegenerative diseases, marked by progressive brain cell damage, pose a major health challenge due to complex causes like oxidative stress and inflammation. Tamarindus indica, a plant rich in bioactive flavonoids and terpenoids, is underexplored for its neuroprotective potential against chemical-induced neuronal injury. METHODS: We used computational tools (network pharmacology, molecular docking, and molecular dynamics simulations) to investigate how Tamarindus indica fruit pulp ethanol extract's bioactive compounds might protect against neurodegeneration. Additionally, we tested the extract in a rat model of acrylonitrile-induced neuronal damage. Seventy male albino rats were divided into seven groups, receiving either acrylonitrile alone, Tamarindus indica extract (200 or 400 mg/kg) before or after acrylonitrile, or a standard drug (donepezil). Over the course of 28 days, we measured oxidative stress, inflammation, and brain enzyme activity. RESULTS: Network pharmacology, molecular docking, and molecular dynamics simulations mapped and validated interactions between T. indica bioactives and neurodegenerative pathway targets, revealing strong binding affinities and stability of T. indica bioactives, particularly apigenin, to key neuroprotective targets. In vivo, the extract significantly enhanced antioxidant enzyme activity, reduced lipid peroxidation, downregulated pro-inflammatory cytokines, and inhibited acetylcholinesterase, a key enzyme in neurodegeneration. CONCLUSIONS: These findings position T. indica extract as a promising multi-targeted therapy for neurodegenerative disorders, leveraging antioxidant and anti-inflammatory mechanisms. Further preclinical and clinical studies are needed to translate these insights into novel treatments, bridging traditional phytotherapy with modern pharmacology.