The Anti-inflammatory And Anti-oxidant Lung Damage Effects And Mechanism Of Rosmarinic Acid On Mouse Asthma Model

Asthma is a chronic airway inflammatory disease which seriously does harm to human and animal health,which is regulated by a variety of inflammatory cells and cytokines.Rosmarinic acid,a kind ofbioactive natural products,shows a broad spectrum of biological effects,such as antioxidant,anti-inflammatory,antibacterial and antiviral actions.In the present study,a mouse model of allergic asthma induced by ovalbumin(Ova)and a asthmatic model of oxidative lung damage in mice induced by Ova and H2O2 were conducted in order to investigate the anti-inflammatory and anti-oxidant effects as well as related mechanism of rosmarinic acid(RA)on mouse asthma models.This study will provide a theoretical basis for the veterinary application of RA in the future.Methods:(1)Female BALB/c mice weighing approximately 18-20 g were randomly divided into the blank control group,Ova asthma model group,RA pre-treatment groups(5,10,20 mg/kg)and 2 mg/kg dexamethasone(Dex)pre-treatment group.RA or Dex were administered intraperitoneally one day before Ova challenge.The serum,BALF,lung tissues of mice harvested 24 h after the final Ova challenge were measured related experimental indicators to assessed the preventive effects of RA on airway inflammation of asthmatic mice.(2)The mice were randomly divided into the blank control group,20 mg/kg RA control group,Ova asthma model group,20 mg/kg RA treatment group and Dex treatment group.RA or Dex were administered intraperitoneally after three-day Ova challenge.The samples harvested 24 h after the final Ova challenge were measured the related experimental indicators to assess the therapeutic effects of RA on airway inflammation of asthmatic mice.(3)The mice were randomly divided into the blank control group,40 mg/kg RA control group,Ova control group,the asthmatic model of oxidative lung damage group,RA intervention groups(10,20,40 mg/kg)and Dex intervention group.RA or Dex were administered intraperitoneally 1h after Ova and H2O2 challenge.The samples harvested 24 h after the final Ova challenge were measured related experimental indicators to evaluate the protective effects of RA on the oxidative lung damage of asthmatic mice.Results:(1)RAinhibited the development of airway inflammation of allergic asthmatic mice induced by Ova:significantly reduced the number of inflammatory cells;obviously decreased the concentrations of IL-4,IL-5,IL-13 and total protein;significantly reduced levels of total IgE,Ova-IgE and eotaxin;markedly attenuated the pathological changes of lung tissues and AHR;regulated MAPK and NF-?B signaling pathway;inhibited the relative expression of AMCase,CCL11,CCR3,Ym2,E-selectin.(2)RA reduced oxidative lung damage in a murine model of allergic asthma induced by Ova and H2O2:significantly increased the activities of total SOD,CAT,total GPx,decreased the level of ROS;significantly up-regulated the protein and mRNA expression of Cu/Zn SOD,down-regulated the protein and mRNA expression of NOX-2 and NOX-4;substantially reduced the pathological changes of lung tissues;significantly decreased levels of IL-4,IL-5,IL-13 and total protein,elevated the level of IFN-y in BALF.Conclusion:RA effectively ameliorated airway inflammation in a murine model of allergic asthma,and the suppression of MAPK(ERK,JNK and p38)and NF-?B(I?B? and p65)activation may be principal therapeutic mechanism of RA;RA siginificantly alleviated oxidative lung injury in asthmatic mice,and the mechanism may be related to the regulation of NOX-2,NOX-4 and Cu/Zn SOD.The results mentioned above suggested that RA could effectively inhibit airway inflammation and alleviate oxidative lung damage.