The Protective Effects And Mechanisms Of Pristimerin On Airway Inflammation In A Mouse Model Of Allergic Asthma

Allergic asthma is a chronic inflammation of the airways that caused by manycells (such as eosinophils, mast cells, T lymphocytes, neutrophils, airway epithelialcells, etc.) and cellular components, mainly characterized by airwayhyperresponsiveness, airway inflammation and airway remodeling. Among them, theairway inflammation is the basic pathology of allergic asthma and recurrent majormechanisms. Different functions of T cells play a leading role in initiating andadjusting of the airway inflammation, to maintain a balance of different subsets ofantigen-specific T cell is a key to inhibit the occurrence and development of asthma.Pristimerin is a quinonemethidetriterpenes natural monomeric compound, whichis mainly present in the plant of Celastraceae and Hippocrateaceae. Celastrusorbiculatus is widely distributed and rich in resources in china, often as the mainsource of Pristimerin research. Traditional Chinese medicine has used Celastrus totreat rheumatoid arthritis and asthma, but recent studies have found that pristimerinhas variety pharmacological effects, such as prime-inflammatory, anti-tumor,anti-malarial, anti-oxidant. Further study suggests that Pristimerin is a multipleinhibitors of proteasome, NF-κB and cell cyCle, thus we speculate Pristimerin mayhas a protective effect on asthmatic airway inflammation.Our study established a OVA-induced allergic asthma mice model, to studied theprotective effect and mechanisms of Pristimerin on allergic airway inflammation. Thisstudy may help to exploit the Pristimerin as a drug treatments of allergic asthma.Methods: The BALB/c mice were divided into normal control group, asthma modelgroup, Pristimerin low-dose group (0.5mg/kg), Pristimerin high-dose group (1mg/kg)and DEX group (20mg/kg). Asthma model group, Pristimerin（0.5,1mg/kg）andDEX group were given an injection with OVA on0,7and14days. At the same time, control group were received the same amount of PBS instead of OVA. On25,26,27days, the four groups were injected with Pristimerin and1hour later, instilledintranasally with OVA. Mice were killed24h after the last OVA challenge.blood,BALF and lung tissues were collected for correlation detection.Results: Protective effects of Pristimerin on allergic airway inflammation: the lowand high dose group of Pristimerin can significantly reduce serum levels of OVA-IgEin OVA-induced allergic asthma mice, can cause a significant reduction of IL-4, IL-5,IL-13and other pro-inflammatory cytokine by Th2cells in BALF and cansignificantly improve IFN-γ secreted by Th1cells and immunomodulatory cytokinelevels of IL-10, increase Th1/Th2cell ratio. HE staining showed that Pristimerin cansignificantly inhibit inflammatory cells infiltration in lung of allergic asthma mice,significantly reduce the pathological changes in lung tissue and pulmonary edema, theresults showed a dose-dependent manner.Regulation of Pristimerin on MAPK and NF-κB inflammatory pathways: thePristimerin can significantly inhibit the phosphorylation levels of ERK, p38and JNKwhich belong to MAPK family, reduce IκB phosphorylation and NF-κB p65levels.The results showed a dose-dependent manner.In summary, we found that Pristimerin has a protective effect on OVA-inducedallergic airway inflammation in asthmatic mice, and the mechanism of the protectionmay be by regulating MAPK and NF-κBinflammatory pathways.