Gender-Specific Neuroprotective Effects of Carum copticum and Thymol: Restoring Cholinergic Function and Cognition in an Aluminum-Induced Rat Model of Alzheimer's Disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder causing memory loss. While treatments like donepezil and memantine offer limited symptom relief, natural compounds like Carum copticum Benth (Ajwain) and its active ingredient thymol show promising neuroprotective effects. This study examines the effects of C. copticum Benth and thymol, alone/combination, or with standard drugs, in an AD-like rat model induced by aluminum chloride and d-galactose. A total of 72 rats were divided into two groups of 36 each based on sex (male and female) and were then randomly assigned to six subgroups (n = 6 per group); healthy control, AD model, donepezil, memantine, C. copticum Benth, and C. copticum Benth + thymol. Behavioral tests assessed anxiety and memory. Biochemical analyses of the prefrontal cortex and hippocampus evaluated acetylcholine (ACh), acetylcholinesterase (AChE), and M1 receptor expression. Thymol's interaction with targets was studied via molecular docking. AD rats showed cognitive impairment, increased anxiety, reduced ACh, and elevated AchE. Treatment with C. copticum Benth and thymol significantly improved behavior and cholinergic function, comparable to standard drugs, and modulated M1 receptor expression. C. copticum Benth and thymol demonstrate therapeutic potential in AD, warranting further investigation as adjunct or alternative treatments.