Computational Neuroinformatics Study of Monomeric Flavans from Superfoods as Potential ACOX1 Modulators in Cerebral Ischemia–Reperfusion Injury

Cerebral ischemia–reperfusion injury (CIRI) triggers oxidative stress and neuronal damage, wherein modulation of peroxisomal lipid metabolism may confer neuroprotection. This study explores the potential of monomeric flavans from selected superfoods to target human Acyl-CoA oxidase 1 (ACOX1), a key enzyme in fatty acid β-oxidation associated with oxidative neuronal injury. Bioactive small molecules retrieved from the IMPPAT and OSADHI databases were screened using network pharmacology to identify CIRI-related gene targets. Molecular docking, MMGBSA binding energy evaluation, and 100 ns molecular dynamics simulations were conducted employing Schrödinger Glide and Desmond modules. Gene Ontology (GO) and KEGG enrichment analyses revealed involvement of lipid metabolism and oxidative stress pathways. Among the screened phytochemicals, Rutin and Chlorogenic acid demonstrated the highest binding affinities toward ACOX1 with docking scores of -12.18 ± 0.23 and -8.91 ± 0.12, and MMGBSA free energies of −44.73 and −38.76 kcal/mol, respectively. Molecular dynamics analysis indicated high structural stability of the Rutin–ACOX1 complex (RMSD ≈ 2.4 Å), while Chlorogenic acid exhibited moderate flexibility (RMSD ≈ 5.4 Å). Interactions with ACOX1 residues GLN569, ASN570, and SER568 suggested a stabilizing role in peroxisomal redox regulation. These findings highlight Rutin and Chlorogenic acid as promising natural modulators of ACOX1, supporting further mechanistic and experimental validation for their neuroprotective efficacy against ischemic brain injury.