| As a common disease,food allergy has a variety of clinical symptoms,is difficult to cure and has a high incidence of disease,which seriously affects patients’ health and life.Many natural active substances have been reported to have some anti-food allergy activity.Studies have found that many natural active substances have the potential to relieve food allergies.Marine resources are rich and unique,and they are an important source of natural active substances.Due to their special growth environment,deep-sea microorganisms often produce metabolites with novel structures and high biological activity.However,the research on the anti-allergic activity mechanism of deep-sea microbial compounds is still relatively scarce.In this study,compounds with high antiallergic activity were screened from 247 compounds from deep sea by rat basophilic leukemia degranulation model,and their antiallergic activity and mechanism were studied.Viridicatol(Vir),a secondary metabolite of Penicillium Yiseofulvum(half-inhibition rate6.67 ± 0.6 μg/m L),was selected as the research object to establish ovalbumin-induced mouse model to investigate the anti-food allergy activity of Vir in vivo.The results showed that Vir could relieve diarrhea,hypothermia and other allergic symptoms of allergic mice,repair intestinal barrier and inhibit the proliferation and degranulation of mast cell(MC)in jejunum.The effect was most significant at 20 mg/kg,the levels of histamine,tumor necrosis factor and mast cell protease in serum were significantly decreased to 471.07 ng/m L,515.19 pg/m L and555.60 pg/m L,respectively.It can reduce the serum ovalbumin specific immunoglobulin E antibody level and up-regulate the interleukin-10 level to a certain extent.By regulating the immune cell population,Vir exhibited anti-allergy activity,down-regulated the proportion of B lymphocytes and MC in the spleen of mice,and up-regulated the proportion of regulatory T cells.In order to further clarify the mechanism of Vir against food allergy,cell model and transcriptome sequencing technology were used to conduct in-depth investigation.The results showed that Vir inhibited calcium influx and degranulation in MC,and down-regulated the expression of many key genes in MC that were up-regulated due to activation.Vir also regulates important signaling pathways such as MAPK and JAK-STAT by inhibiting the phosphorylation levels of JNK,ERK,p38 and STAT 6 proteins,thus exerts anti-food allergy activity.Furthermore,by analyzing and comparing the inhibitory effects of Vir and its homologues on the degranulation of MC,it was found that the antiallergic activity of Vir was closely related to the position and quantity of hydroxyl groups in the structure.In summary,Vir with strong anti-allergy activity was selected from 247 deep-sea derived compounds in this study.Vir can repair intestinal barrier,relieve allergic symptoms in mice,and regulate immune cell population.The main target cell of Vir with anti-food allergy activity in vivo is MC.Vir inhibits the activation and degranulation of MC by inhibiting calcium influx,regulating the phosphorylation levels of MAPK,JAK-STAT and other signaling pathways as well as related proteins,so as to exert its anti-food allergy activity.The results of this study may provide a theoretical basis for the development of food or drugs against food allergy. |
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