Timing-dependent neuroprotective effects of Virgin coconut oil against chronic restraint stress-induced neurobehavioral and hippocampal dysfunction: GC-MS profiling and in vivo evaluation.

BACKGROUND

Chronic stress, often exacerbated by improper lifestyle, long-term physical confinement, and emotional distress, these are the major contributor to neuropsychiatric disorders, mostly through hippocampal dysfunction. Though synthetic drugs offer symptomatic relief, their side effects prompt a growing interest in natural plant-derived nutraceuticals. Virgin coconut oil (VCO), rich in medium-chain fatty acids, polyphenols, and antioxidants, has demonstrated preliminary neuroprotective activity; however, its pharmacological basis in hippocampal dysfunction induced by chronic restraint stress (CRS) remains inadequately characterized. Herein, we investigated the neuroprotective activity of VCO by administering it in a time-staggered manner (Pre-Treatment, Co-treatment, and Post-Treatment) and assessed its effects through physiological, behavioral, antioxidant, and histopathological analyses. Our secondary objective was to profile the phytoconstituents of VCO using Gas Chromatography-Mass Spectrometry (GC-MS).

METHODS

Adult male Wistar rats were randomized into six groups (n = 6): Control, CRS, VCO-alone, Pre-VCO, Co-VCO, and Post-VCO. VCO was administered in a time-staggered manner to delineate its prophylactic, adjuvant, and therapeutic potential. Animals underwent physiological, behavioral (Sucrose Preference Test, Elevated Plus Maze, radial arm maze), biochemical (corticosterone, lipid peroxidation, glutathione, superoxide dismutase, catalase), and histopathological assessments (Nissl staining). Lastly, we performed phytochemical characterization using Gas Chromatography-Mass Spectrometry (GC-MS).

RESULTS

VCO significantly enhanced spatial learning and memory while attenuating anhedonia and anxiety-like behavior. Biochemically, VCO reduced corticosterone and lipid peroxidation levels, restored antioxidant markers, and reinstated hippocampal neuronal morphology, collectively indicating modulation of neurobehavioral activity and restoration of redox homeostasis. Pre-VCO demonstrated superior neuroprotection, suggesting stronger prophylactic and adjunctive pharmacological activity. GC-MS identified caprylic acid possessing the most abundant chromatographic peak alongside polyphenolic compounds, supporting a plausible mechanistic basis for the neuroprotective effects of VCO.

CONCLUSION

VCO demonstrates significantly higher neuroprotective efficacy when administered as Pre-treatment in CRS rats. Overall, these findings establish VCO as a dietary functional food with measurable prophylactic and adjunctive neuroprotective efficacy. These may plausibly be due to the major content of the MCFA-like caprylic acid in VCO mitigating oxidative stress and hippocampal neuronal dysfunction. This study provides GC-MS-based compositional evidence and in vivo functional validation supporting VCO's translational potential as a dietary strategy to mitigate the chronic stress-associated neuropsychiatric burden in human populations.