Indole 3 carbinol attenuated memory impairment, oxidative stress, inflammation, and apoptosis in bilateral common carotid artery occlusion induced brain damage in rats.

Abstract

Global cerebral ischemia (GCI) is associated with a multifaceted etiology, including increased oxidative stress, inflammation, and elevated acetylcholinesterase (AChE) activity, ultimately leading to cognitive and memory impairments. This study aimed to evaluate the neuroprotective, cognitive, and memory-enhancing effects of indole 3-carbinol (I3C), a phytochemical found in cruciferous vegetables. Additionally, network pharmacology analyses were conducted to identify potential molecular targets of I3C in GCI. Bilateral common carotid artery occlusion (BCCAO) surgery was performed to induce GCI. I3C was administered orally for 14 days, and cognitive and memory functions were assessed using the Y-maze and Morris water maze paradigms. Biomarkers of oxidative stress (MDA, Nrf2, SOD, and CAT), inflammatory markers (NF-κB, TNF-α, and IL-10), and AChE enzyme activity were evaluated. The results demonstrated that I3C treatment significantly inhibited AChE activity, improved spontaneous alternation (%) in the Y-maze test, increased the number of entries and time spent in the platform zone, and reduced escape latency in the Morris water maze test, indicating enhanced cognitive and memory functions. I3C treatment also increased brain levels of Nrf2, SOD, and CAT while reducing MDA levels. Furthermore, it decreased pro-inflammatory markers such as NF-κB and TNF-α and elevated the anti-inflammatory marker IL-10, suggesting neuroprotection through the mitigation of oxidative stress and inflammation. Histopathological analysis revealed improved integrity of CA1 neurons in BCCAO rats treated with I3C. Network pharmacology studies identified TP53, AKT1, TNF, STAT3, BCL2, SRC, ESR1, CCND1, CASP8, and CASP3 as the top ten molecular targets for I3C in the context of GCI. Our in vivo data, supported by network pharmacology studies, suggest that I3C's neuroprotective and cognitive-enhancing effects are driven by its ability to alleviate oxidative stress, inflammation, and apoptosis. Overall, this study suggests that I3C is a promising neuroprotective and memory-enhancing agent for global cerebral ischemia.