Neuroprotective effects of Indole 3-carbinol against Scopolamine-Induced cognitive and memory impairment in rats: modulation of oxidative stress, inflammatory and cholinergic pathways

Indole 3-carbinol (I3C), a natural compound found in cruciferous vegetables, has demonstrated neuroprotective effects by modulating oxidative stress, inflammation, and cholinergic pathways. This study aimed to evaluate the efficacy of I3C in preventing cognitive impairment induced by scopolamine in rats. Male Wistar rats were assigned to six groups: Control, Scopolamine (1 mg/kg), I3C (25 mg/kg), I3C (50 mg/kg), I3C (100 mg/kg), and Donepezil (5 mg/kg). Memory function was evaluated through behavioral assessments using the Y-maze and Novel Object Recognition (NOR) tests. Biochemical analyses were conducted to assess acetylcholinesterase (AChE) activity and oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). ELISA were utilized to quantify oxidative stress regulators (NRF2 and HO-1), inflammatory cytokines (NF-kB, TNF-alpha, IL-6, and IL-10), and apoptosis-related markers (Cytochrome C, caspase 9, and caspase 3). Additionally, H&E and Nissl staining were performed to evaluate histopathological abnormalities. The findings revealed that I3C administration markedly enhanced cognitive performance in the Y-maze and NOR tests, which were attributed to decreased AChE activity and increased acetylcholine (ACh) levels. Furthermore, I3C significantly alleviated oxidative stress by upregulating antioxidant enzymes, including NRF2 and HO-1. Moreover, I3C mitigated inflammatory responses, as evidenced by elevated levels of IL-10 and reduced levels of NF-kB, TNF-alpha, and IL-6. These findings indicate that I3C exhibits neuroprotective effects by reducing oxidative stress, suppressing inflammation, and addressing abnormalities in the cholinergic pathway, highlighting its potential as a therapeutic approach for alleviating cognitive deficits.