酸枣仁皂苷A通过激活Nrf2/HO-1通路改善睡眠障碍的抗氧化机制研究OA

To investigate whether jujuboside A(JuA)improves sleep disorders and exerts antioxidant effects by activating the Nrf2/HO-1 signaling pathway.In this study,insomnia was induced in C57BL/6 mice via intraperitoneal injection of p-chlorophenylalanine(PCPA,300 mg/kg).The model mice were randomly divided into a model group,a positive drug group(eszopiclone,3 mg/kg),JuA low dose(5 mg/kg),medium dose(10 mg/kg),and high dose(20 mg/kg)groups,an inhibitor group(ML385,30 mg/kg),with a normal control group.Anxiety-like behavior and cognitive function were assessed using the open field test,the elevated plus maze,and the Morris water maze.The beha-vioral observation method was used to monitor the sleep latency and sleep duration.The levels of malondialdehyde(MDA),reactive oxygen species(ROS),glutathione(GSH),and the activities of superoxide dismutase(SOD)and catalase(CAT)in the hypothalamus were measured.ELISA was employed to determine the levels of TNF-α,IL-1 β,IL-6,GABA,5-HT and Glu in the hypothalamus.The protein expressions of Nrf2,HO-1 and NQO1 in the hypothalamus were determined by Western blot.The results indicate that,compared with the model group,JuA treatment dose-dependently improved anxiety-like behavior and spatial memory,significantly increased GSH content and SOD/CAT activities,and decreased MDA and ROS levels in the hypothalamus(P＜0.05 or P＜0.01).Furthermore,JuA dose-dependently promoted Nrf2 nuclear translocation and upregulated the expression of downstream target proteins HO-1 and NQO1(P＜0.01),suppressed the release of pro-inflammatory cytokines,and reversed the imbalance of neurotransmitters(GABA,5-HT and Glu).However,these beneficial effects of JuA were significantly abolished by co-administration of the Nrf2 inhibitor ML385(P＜0.001).Jujuboside A ameliorates PCPA-induced sleep disorders by activating the Nrf2/HO-1 signaling pathway,thereby enhancing endogenous antioxidant defenses,mitigating neuroin-flammation,and regulating neurotransmitter balance.This study provides a modern pharmacological basis for the traditional efficacy of Ziziphi Spinosae Semen in"tranquilizing the mind and calming the spirit".