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.