Aim: This study evaluated the potential synergetic efficacy of sesame oil (SSO) and the acetylcholine esterase inhibitor donepezil in attenuating scopolamine (SCO)- induced neuropathological dysfunction in rats.

Methods: Thirty-five male Sprague-Dawely rats were assigned into five groups at random. Group 1, the negative control, was given saline. Group 2, the positive control, was given SCO (one mg/kg/day, intraperitoneally). Groups three to five received donepezil, sesame oil, or their combination concomitant with SCO for five weeks. SSO's antiradical and anti-inflammatory activities, levels of tocopherols, phytosterols, lignin, and fatty acid composition were also investigated using DPPH radical, membrane stabilization, and high-performance liquid and gas chromatography methods.

Results: Oral administration of donepezil, sesame oil, or their combination with SCO-treated rats decreased acetylcholinesterase activity with a concomitant increase in the acetylcholine content, mitigated the SCO-induced amyloid beta (Aβ) accumulation and restored the reduced brain-derived neurotrophic factor (BDNF) levels in the brains of SCO-treated rats. Furthermore, the tested therapies increased the levels of GSH and Bcl-2 and reduced MDA levels, along with the notable reverting of the elevated pro-inflammatory cytokines. The group that received combined SSO and donepezil therapy showed more pronounced neuroprotective effects than those treated with SSO or donepezil alone, indicating the prominent synergistic impact of the combination.

Conclusion: Sesame oil synergized with donepezil in modulating scopolamine-induced cholinergic dysfunction, amyloidopathy, oxidative stress, and neuroinflammation. It can offer a safe and efficient option for a therapeutic combination that may be very beneficial in clinical practice for the practical management of neurological disorders.