Abstract: To evaluate the protective effect and mechanism of negletein against hypobaric hypoxia-induced brain damage in mice.First,50 mice were used in normobaric hypoxia test to determine the optimal dosage of negletein.Then 88 BALB/C mice were randomly divided into normal control group,hypoxia model group,rutin group and negletein group.The drugs were administered intragastrically to the mice for 5 consecutive days.After 60 min of the last administration,mice were exposed to hypobaric hypoxia (8000 m) for 12 h.The water content,H₂O₂,NO MDA level,LDH,antioxidant enzymes activity and the expression levels of Nrf2 and HO-1 in brain were monitored.The results indicated that the content of water,H₂O₂,NO,and MDA as well as LDH activity in hypoxia model group significantly increased while antioxidant enzymes activity markedly decreased compared with these of normal control group.Hypobaric hypoxia exposure signi?cantly upregulated the expression levels of Nrf2 and HO-1.Prior administration of negletein decreased the brain water content,H₂O₂,NO,MDA levels and LDH activity while increased antioxidant enzymes activity.Negletein also further unregulated Nrf2 and HO-1 expression.These results suggested that negletein can ameliorate hypobaric hypoxia induced oxidative stress injury in mice brain,which can be explained in part by its free radical scavenging activity,improvement of antioxidant enzyme activity by activating the Nrf2/ARE/HO-1 pathway.

Key words: negletein, hypobaric hypoxia, brain tissue, antioxidant enzyme, Nrf2/ARE/HO-1 pathway