Protective effects of Perilla frutescens seed oil on cognitive function, oxidative stress and acetylcholinesterase activity in a D‑galactose‑induced accelerated aging model in rats

Aging‑related cognitive decline is closely associated with oxidative stress, cholinergic dysfunction and hippocampal vulnerability. Perilla seed oil (PSO), a functional food rich in α‑linolenic acid and antioxidant phytochemicals, may have cognitive benefits; however, its efficacy and underlying mechanisms in experimental models of accelerated aging remain insufficiently understood. The present study aimed to investigate the effects of PSO supplementation on cognitive performance and neurobiological alterations in a D‑galactose (D‑Gal)‑induced accelerated aging model in rats. Wistar rats were injected subcutaneously with D‑Gal (300 mg/kg) daily for 8 weeks and simultaneously treated orally with PSO (100 or 500 mg/kg), fish oil (500 mg/kg) or vehicle. Cognitive function was evaluated using the Morris water maze and novel object recognition tests. Oxidative stress markers, including malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD), as well as acetylcholinesterase (AChE) activity, were assessed in the hippocampus. Neuronal cell density in the CA1 and CA3 regions was examined using Nissl staining. PSO supplementation significantly improved spatial memory performance and recognition memory, increased hippocampal SOD activity and reduced AChE activity compared with the D‑Gal group. Although MDA and GSH levels did not differ significantly, both exhibited a tendency toward normalization. In addition, neuronal density in the CA3 region was significantly reduced in the D‑Gal group compared with the control group, whereas no significant differences were observed in the CA1 region. These findings suggest that PSO attenuates D‑Gal‑induced cognitive impairment, which may be partially associated with enhanced antioxidant enzyme activity and modulation of cholinergic function, rather than with restoration of neuronal density. PSO may therefore represent a potential nutritional intervention for supporting cognitive function during aging‑related neurobiological changes.