The Protective Effect Of Apigenin On Airway Inflammation And Oxidative Stress In Allergic Asthma By Regulating AMPK/Nrf2/HO-1 Signaling Pathway

Objective:The purpose of this study is to investigate the protective effect of apigenin on allergic asthma mouse model by inhibiting airway inflammation and oxidative stress though the AMPK/Nrf2/HO-1 signaling pathway.Methods : Allergic asthma was induced in forty 6-8 weeks old BALB/C mice by sensitization and challenge with OVA.The mice were divided into four groups,namely control group,asthma group,high-dose apigenin group(30mg/kg)and low-dose apigenin group(15mg/kg).Asthma mouse model was prepared by OVA.Airway resistance was detected by pulmonary function 24 hour after the last challenge.And the level of Th2 cytokine including IL-4,IL-5,IL-13 and IFN-γ in bronchoalveolar lavage fluid(BALF),MDA,SOD and ROS in lung tissues and serum total Ig E were determined by enzyme-linked immunosorbent assay(ELISA).Lung tissues were stained with Hematoxylin eosin(H&E)for inflammatory cells infiltration and periodate and Schiff(PAS)staining for mucus secretion and goblet cell hyperplasia.The level of AMPK,Nrf2 and HO-1 in lung tissues were determined by Western blot.Results:1.The detection of mouse pulmonary function instrument showed that the airway resistance of mice in the asthma model group increased significantly,while apigenin could effectively alleviate the increase of airway resistance in asthma model mice(P<0.05).2.ELISA results showed that the secretion of inflammatory cytokines IL-4,IL-5 and IL-13 in BALF in mice in the asthma model group increased,and the secretion of IFN-γdecreased,while apigenin could reduce the secretion of inflammatory cytokines IL-4,IL-5 and IL-13 in BALF(P<0.05)and increase the secretion of IFN-γ(P<0.05).3.ELISA results showed that the expression of oxidative stress proteins MDA and ROS and serum total Ig E increased(P<0.05)and decreased the expression of negative regulatory protein SOD in the asthma model group,while apigenin could reduce the expression of MDA and ROS and serum total Ig E(P<0.05)and increase the expression of SOD(P<0.05).4.The pathological results of lung histologies showed that the airway inflammatory cells infiltrate,mucosal edema and high mucus secretion in the asthma model group were high,while apigenin could reduce airway inflammatory cell infiltration,mucosal edema and mucus secretion.5.Western blot method and immunohistochemistry showed that the expression levels of AMPK,Nrf2 and HO-1 in the lung tissues of mice in the asthma model group decreased,while the intervention of apigenin promoted the expression levels of AMPK,Nrf2 and HO-1 in lung tissues(P<0.05)Conclusion: This study suggests that apigenin has a significant anti-allergic effect in OVA-induced asthma mouse model by inhibiting airway inflammation and oxidative stress through the AMPK/Nrf2/HO-1 signaling pathway.