Objective: The study provides an understanding of the nature of the bioactive compounds of Tamarindus indica fruit pulp and their therapeutic potential using in vitro, in silico, and in vivo approaches.

Background: Progressive neuronal death, characterized by progressive neuronal loss, oxidative stress, and neuroinflammation, are hallmarks of neurodegenerative diseases, which pose a serious threat to global health.

Method: For the in silico study, a comprehensive drug-target-pathway network was created by identifying disease targets using bioinformatics methods, including STRING, Cytoscape, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terminology. Molecular docking and simulation verified the compounds’ interactions with their anticipated targets. Neurodegeneration was induced in albino rats after 14 days of continuous oral administration of acrylonitrile (1 mg/kg), and this was established with characteristic increased oxidative stress, neuroinflammation, and cholinergic dysfunction, including elevated acetylcholinesterase (AChE) activity. For the in vivo study, seventy (70) male albino rats randomly assigned to seven groups of 10 rats each labeled A-G were treated for 28 days as follows; normal control (A), preventive groups (B and C), treatment groups (D and E), positive control (F), and negative control (G). The rats were thereafter sacrificed, the brain was excised, and the homogenate was used for analysis using enzyme-linked immunosorbent assays (ELISA) and biochemical analysis.

Results: Phytochemical screening and GC-MS analysis identified phenolics, flavonoids, tannins, and steroids in the fruit pulp. In vitro assays revealed strong antioxidant activity in DPPH, ABTS, and FRAP values.  In vivo results demonstrated a significant increase in antioxidant enzyme activity, reduction in pro-inflammatory cytokines, and attenuation of acetylcholinesterase activity with validations through network pharmacology, molecular docking, and simulation showing interactions with key neurodegenerative targets. Toxicity evaluations indicated no significant adverse effects within the tested dose range.

Conclusion: The study highlights Tamarindus indica’s potential as a promising treatment option for neurodegenerative illnesses as these findings indicate that Tamarindus indica fruit pulp extract confers neuroprotection primarily through antioxidant, anti-inflammatory, and cholinergic modulation mechanisms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/mechanistic-insights-of-tamarindus-indica-in-acrylonitrile-induced-neurodegeneration/