Neuroprotective effects of naringin on cerebral ischemia-reperfusion injury in rats and its mechanisms
Objective To investigate the neuroprotective effect of naringin on cerebral ischemia-reperfusion(CIR)injury in rats and its mechanism.Methods A total of 54 SD rats were divided into six groups:the model group,the nifedipine group,the high-dose naringin group(100 mg/kg),medium-dose naringin group(50 mg/kg),low-dose naringin group(25 mg/kg),and the sham operation group.The CIR model was established using the thread occlusion method in the first five groups,while the sham operation was performed in the sham group.Nifedipine(15 mg/kg),naringin(100 mg/kg,50 mg/kg,and 25 mg/kg)were orally administrated in nifedipine group,and high,medium,and low-dose naringin groups for 7 d before modelling,respectively;while the model group and the sham operation group received oral administration of 0.9％sodium chloride solution.After 24 h of reperfusion,the neurological function of the rats was evaluated using the Zea Longa score and the Garcia score.Brain tissue samples were collected after euthanasia for the measurement of brain water content using the wet-dry method and for histological staining to determine the percentage of brain infarction.Blood samples were collected from the orbital venous plexus for detection of pro-inflammatory cytokines(TNF-α,IL-8)and anti-inflammatory cytokine(IL-10)levels using ELISA.The levels of superoxide dismutase(SOD),malondialdehyde(MDA),reduced glutathione(GSH),reduced/oxidized nicotinamide adenine dinucleotide phosphate(NADPH/NADP+),ferrous ions,and total iron.Western blot was used to detect the expression of ferroptosis related proteins in brain tissue.Including transferrin receptor 1(TFR1),NADPH oxidase 4(NOX4),fatty acid binding enzyme 3(ACSL3),solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4).Results The Zea Longa scores,brain water content,percentage of brain infarction,TNF-α,IL-8,MDA,ferrous ions,and total iron levels,as well as ACSL3,TFR1,and NOX4 expression levels were all lower those in the nifedipine group,and high-dose,medium-dose and low-dose naringin groups,and sham operation group compared to the model group(all P＜0.05).On the other hand,the Garcia scores,IL-10,SOD,GSH,NADPH/NADP+,SLC7A11,and GPX4 levels were all higher in the nifedipine group,three naringin treatment groups,and sham operation group compared to the model group(all P＜0.05).Conclusion Naringin can exert neuroprotective effects and alleviate CIR injury through various mechanisms in a concentration-dependent manner,including anti-inflammatory,antioxidant,and inhibition of ferroptosis pathways.
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