Modulatory effect of Flavone on brain inflammation induced by radiation or nicotine in rats Flavone in toxicant-induced brain injury

Purpose Flavones have various beneficial health impacts, including neuroprotective activity, anti-inflammatory, antioxidant, and antimicrobial effects. Exposure to environmental toxicants like nicotine and radiation induces multi-organ toxicity and increases the risk of neurological problems. Therefore, this experimental study aimed to evaluate the anti-inflammatory and antioxidant qualities of flavone (F) against brain injury caused by IR or NIC in rats. Methods The potential targets of flavone were identified from the SwissTargetPrediction databases. The functional enrichment analyses were conducted using the KOBAS server. Sixty male Wistar rats were divided at random into 6 equal groups: normal rats; rats received flavone treatment (25 mg/kg b.wt./day) for 2 weeks; rats exposed to nicotine (1 mg/kg b.wt./day) for 3 weeks or radiation (3.5 Gy once/week for 2 weeks) with or without flavone treatment. Oxidative stress markers and calcium levels in the brain were evaluated besides histopathological examinations and grading. Additionally, the levels of caspase1, TLR4, phospho-Tau, cytochrome P450 (CYP2B1, CYP2E1) enzymes were evaluated using ELISA. Furthermore, the gene expression of brain NF-κB, NLRP3, BDNF and CDK5 were estimated. Results The results showed that flavone was associated with lower biochemical and histologic injury markers by decreasing CYP2B1 and CYP2E1 levels, oxidative stress, and calcium levels. Moreover, it mitigated neuroinflammation by suppressing the expression of TLR-4, NF-κB, NLRP3, and caspase-1, besides suppressing the CDK5 and Tau protein expression while increasing BDNF expression. Conclusion Collectively, flavone alleviated radiation- or nicotine-induced neuroinflammation and neurotoxicity, supporting further preclinical evaluation. However, short-term exposure limits definitive conclusions regarding flavone exact mode of action.