Daidzein Ameliorates Cerebral Ischemic-reperfusion Induced Neuroinflammation in Wistar Rats via Inhibiting NF-κB Signaling Pathway

Abstract

Background Cerebral ischemia is a condition of acute brain damage due to the depletion of oxygenated blood supply to cerebral tissues. Daidzein is an isoflavonoid predominantly present in soya, Pueraria species, and red cloves. Traditional Chinese medicine utilizes daidzein to alleviate diseases such as inflammation, hyperglycemia, gastric diseases, allergies and aches. The neuroprotective effect of daidzein on cerebral ischemic conditions and its mechanism of action was not yet elucidated. Materials and Methods 24 healthy male adult Wistar rats were grouped into four and the control rats were sham-operated, cerebral ischemic-reperfusion induced rats subjected to middle cerebral artery occlusion (MCAO). Low- and high-dose daidzein rats were treated with 25 and 50 mg/kg daidzein respectively for 7 consecutive days before the induction of cerebral ischemic reperfusion. On completion of treatment, the rats were assessed for neurological deficit scoring and then euthanized for further analysis. The percentage of brain water content and cerebral infarct was evaluated. The ability of daidzein on preventing oxidative stress-induced damage was assessed by quantifying lipid peroxidation and antioxidant levels. The neuroprotective Daidzein was evaluated by measuring the acetylcholinesterase activity and brain ATP levels. The anti-inflammatory role of Daidzein was measured by quantifying the nitric oxide (NO) and inflammatory cytokines. Further, the anti-ischemic role of Daidzein was confirmed by estimating nuclear factor-kappa B (NF-κB) p65 and Caspase 3 levels. Results Daidzein treatment significantly prevented brain edema and cerebral infarction and neurological deficit in cerebral I/R injured rats. It also scavenged the free radicals and prevented the decline in antioxidant levels of ischemic rats. Daidzein decreased the acetylcholinesterase activity, NO, and inflammatory and significantly increased the brain ATP levels signifying its neuroprotective role in ischemic-induced rats. The reduction in the levels of NF-κB p65 and Caspase 3 confirms daidzein prevents neuroinflammation and neuronal apoptosis in ischemic rats. Conclusion Overall our analysis confirms daidzein is a potent neuroprotective drug which can effectively inhibit postischemic complications.