Introduction

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder, characterized by progressive deterioration of memory and cognition. (1) Its pathological hallmarks include β-amyloid (Aβ) plaques, neurofibrillary tangles of hyperphosphorylated tau, and degeneration of cholinergic neurons in the forebrain, resulting in reduced acetylcholine (ACh). (2–4) Additional contributing factors include oxidative stress, neuroinflammation, hormonal alterations, and amyloid deposition. (5) Despite extensive research, curative interventions remain limited. This study evaluates the neuroprotective potential of spice oleoresins as a natural strategy against AD.

Oleoresins are concentrated extracts that combine volatile and non-volatile fractions responsible for flavor and pungency. They are obtained through solvent extraction (methanol, ethanol, acetone, ethyl acetate, etc.) followed by complete solvent removal. (6,7)

Black pepper (Piper nigrum L.): Its main alkaloid, piperine, has demonstrated anti-inflammatory, analgesic, antioxidant, cytoprotective, antidepressant, antiulcer, and pro-cognitive effects, with evidence of neuroprotective properties. (8–16)

Turmeric (Curcuma longa): Rich in curcuminoids and turmerone oil, it possesses antioxidant and anti-inflammatory activities. Curcumin can inhibit Aβ fibril formation, destabilize preformed fibrils, and attenuate lipid peroxidation in animal models. (17–26)

Chili pepper (Capsicum annuum L.): Provides capsaicin, vitamins, carotenoids, and polyphenols with antioxidant activity; it has been associated with increased ACh availability and potential benefits in neurodegenerative disorders. (27–30)

Although approved drugs exist (AChE inhibitors, anti-inflammatories, receptor antagonists, MAO inhibitors), their tolerability is limited by adverse effects. (31) Hence the interest in natural compounds. This study investigates pepper, turmeric, and chili oleoresins in a scopolamine-induced cognitive impairment model in rats.

Results and Discussion (Summary)

Behavior (MWM and Locomotor Activity)

Scopolamine increased locomotor activity. Treatment with chili oleoresin and donepezil reduced it, while pepper and turmeric caused little change. In the Morris Water Maze, pepper and chili significantly improved escape latency time (ELT) and time spent in the target quadrant (TSTQ), indicating better learning and memory. Turmeric showed a more modest effect.

Biochemical Biomarkers

Scopolamine increased AChE activity and lipid peroxidation (MDA), and decreased GSH, GPx, SOD, and catalase levels. The oleoresins, particularly chili, reduced AChE activity and oxidative stress while partially restoring antioxidant defenses. Pepper and turmeric also contributed, though to a lesser extent.

Histopathology

Scopolamine treatment caused neuronal degeneration and hippocampal atrophy. Oleoresrin treatments attenuated the damage, with pepper and chili showing greater neuroprotection against disorganization of the pyramidal layer.

Conclusions

Chili and pepper oleoresins demonstrated neuroprotective and pro-cognitive effects in rats with scopolamine-induced Alzheimer-like impairment: inhibition of AChE, reduction of oxidative stress, and improved memory performance. These results support the potential of spices as natural candidates for managing cognitive decline, justifying further studies on Aβ, tau, and inflammatory cytokines, as well as translational validation.