The Anti-Food Allergic Activity And Mechanism Analysis Of Flavonoids From Lysionotus Pauciflorus Maxim

Food allergy refers to the body's allergic immune response to the food allergens.The incidence rate of food allergy is increasing year by year.The clinical symptoms are diverse,which seriously affects the quality of life of allergic people.In recent years,studies have found that natural active substances have the potential to alleviate food allergic reactions,and have the advantages of safety,wide source and wide variety,therefore they have gradually become a hot spot in the field of food allergy research.In this study,the anti-allergic activity of 118 plant-derived monomer compounds were tested by detecting rat basophilic leukemia(RBL)-2H3 degranulation and cell viability,and nevadensin(NEV)and dihydromyricetin(DMY)were investigated for their anti-food allergy activities.NEV and DMY are two flavonoids,which were extracted from Lysionotus pauciflorus Maxim,and their purity is greater than 98%.They could significantly suppress RBL-2H3 cells degranulation,and their half maximal inhibitory concentrations are 14.59 ± 3.34 ?M and 15.89 ± 4.28 ?M,respectively.Balb/c mice food allergy model was conducted,and mice were sensitized by intraperitoneal injection of ovalbumin(ovalbumin,OVA)/Alum mixed solution and stimulated by oral gavage with OVA.It was demonstrated that both NEV and DMY could relieve the symptoms of diarrhea and hypothermia in allergic mice,and reduce the levels of OVA-specific immunoglobulin E antibody,mast cell proteases,and histamine in mice serum.It was different from NEV that DMY could not only also significantly promote the secretion of interleukin-10,but also inhibit the proliferation of B lymphocytes and mast cells and promote the differentiation of regulation T cells using flow cytometry to detect the effect of DMY opon the population of spleen lymphocytes in mice.A passive cutaneous anaphylaxis model was established in mice,and it was found that both NEV and DMY significantly reduced the content of Evans blue in mice ears,which further verified the inhibitory effect of both on mast cells.RBL-2H3 and bone marrow-derived mast cells(BMMCs)models were constructed to explore the anti-allergic mechanism of NEV and DMY.It was clarified that NEV and DMY inhibited the degranulation and the release of histamine in RBL-2H3 cells,as well as decreased the degranulation in BMMCs cells.In addition,NEV also decreased the expression of c-Kit receptor on the surface of BMMCs,inhibited the proliferation of BMMCs,induced the early apoptosis of BMMCs.DMY couldn't significantly induce apoptosis in BMMCs cells,but it blocked the interaction of IgE and high affinity IgE receptor(Fc?RI)on the surface of RBL-2H3 and BMMCs cells.By comparing and analyzing the relationship between the effect of five flavonoids on the degranulation of RBL-2H3 cells and their structure,it was found that their effects were related to the number and position of the methoxy and hydroxyl groups,and the double bond in the B ring.In summary,NEV and DMY are flavonoids which extracted from L.pauciflorus.Both of them had the effect of alleviating food allergic reactions in mice,of which NEV had a stronger effect.But the mechanism of action of the two is different.NEV could reduce the expression of c-Kit receptor in mast cells,while DMY could block the interaction between IgE and Fc?RI receptor in mast cells.These research results can provide a theoretical basis for the development of anti-food allergy active pharmaceutical ingredient or special foods.