Abstract: Objective　To explore the protective effect of marine natural product Xyloketal B (Xyl-B) on brain damage after seizure in developing rats and its regulation on oxidative stress pathway. Methods　Forty SD rats on the 20th day were randomly divided into 4 groups, control group, KA group, KA+Xyl-B (25 mg/kg) group and KA+Xyl-B (50 mg/kg) group. The rat seizure model was constructed through intraperitoneal injection of kainic acid. The control group was injected with saline only. In KA+Xyl-B group, Xyl-B was administered intraperitoneally 2 hours before KA induced seizure. Rats were sacrificed 24 hours after seizure, hippocampal tissue was separated. The number of mature neurons and activated astrocytes were detected by immunofluorescence. The mRNA and protein expression levels of Keap1, Nrf2, HO-1, NQO1, caspase3, Bcl-2 and IL6 were detected by qPCR and Western blot assay, respectively. Results　The immunofluorescence results showed that the number of neurons decreased significantly and the activated astrocytes increased significantly in the KA group compared with those of the control group. Xyloketal B treatment can increase the number of mature neurons and  the activated astrocytes. Compared with the control group, the mRNA and protein expression levels of Keap1 increased significantly, while the expression levels of Nrf2, HO-1 and NQO1 were significantly reduced. Xyloketal B treatment could reverse the mRNA and protein levels after KA-induced seizure. The mRNA and protein expression levels of caspase3 and IL-6 increased significantly, Bcl-2 decreased significantly in the KA group (P＜0.05). Xyloketal B treatment (50 mg/kg) can inhibit the expression levels of caspase3 and IL-6 and increase the expression of Bcl-2, which showed a better therapeutic effect than those of Xyl-B (25 mg/kg). Conclusion　Xyloketal B can activate the Nrf2 anti-oxidative stress pathway, inhibit the activation of astrocytes, inflammatory response and the expression of apoptosis protein, increase anti-apoptosis protein and surviving neurons, and thus play a protective role against brain damage after seizure.

Key words: seizures, brain injuries, NF-E2-related factor 2, hippocampus, neurons, astrocytes, Xyloketal B