Effect of Myricetin on Immune Function in Rats with Inflammatory Bowel Disease by Regulating the cAMP/PKA/CREB Signaling Pathway
OBJECTIVE To investigate the effect of myricetin(Myr)on immune function in rats with inflammatory bowel disease(IBD)by regulating the cAMP/PKA/CREB signaling pathway.METHODS IBD rat models were established and separated into control group,model group,low,medium,and high dose Myr(Myr-L,Myr-M,Myr-H,28,56,112 mg·kg-1·d-1 Myr)groups,and high dose Myr+PKA inhibitor H89(Myr-H+H89 112 mg·kg-1·d-1 Myr+7 mg·kg-1 d-1 H89)group.The disease activity index(DAI)of rats was scored;immune function indicators and colon length were measured;the levels of IL-6,IL-17A,TNF-α,and cAMP in serum were determined by the kit;the pathological changes of colon tissue were observed by HE staining;the proportion of Treg cells was determined by flow cytometry;immunohistochemistry was used to detect the expression of MPO in colon tissue;Western blotting was used to determine cAMP/PKA/CREB signaling pathway related proteins.RESULTS Compared with the control group,the colon tissue cells in the model group were disorderly arranged,with a large number of inflammatory cell infiltration,severe ulceration,a large number of cell necrosis,mucosal edema,the DAI score,IL-6,TNF-α,and IL-17A levels,spleen coefficient,thymus coefficient,and MPO optical density values were obviously increased(P＜0.05),the colon length,Treg cell ratio,cAMP concentration,p-PKA/PKA,and p-CREB/CREB levels were obviously reduced(P＜0.05).Compared with the model group,the arrangement of colon tissue cells in the Myr-L,Myr-M,and Myr-H groups was relatively neat;mucosal edema inflammatory cell infiltration,cell necrosis and ulcer phenomenon were reduced;the DAI score,IL-6,TNF-α,and IL-17A levels,spleen coefficient,thymus coefficient,and MPO optical density values were gradually reduced(P＜0.05);the colon length,Treg cell ratio,cAMP concentration,p-PKA/PKA,and p-CREB/CREB levels were gradually increased(P＜0.05).Compared with the Myr-H group,the pathological changes in the colon tissue of the Myr-H+H89 group worsened,the DAI score,IL-6,TNF-α,and IL-17A levels,spleen coefficient,thymus coefficient,and MPO optical density values were obviously increased(P＜0.05),the colon length,Treg cell ratio,cAMP concentration,p-PKA/PKA,and p-CREB/CREB levels were obviously reduced(P＜0.05).CONCLUSION Myr may inhibit inflammation levels,regulate immune function,and exert protective effects on IBD rats by activating the cAMP/PKA/CREB signaling pathway.
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