| 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 myricetin (Myr-L, Myr-M, Myr-H, 28, 56, 112mg/kg/d Myr) groups, and high dose myricetin+PKA inhibitor H89 (Myr-H+H89112mg/kg/d Myr+7mg/kg/d H89) group. The Disease Activity Index (DAI) of rats was scored; immune function indicators and colon length were measured; reagent kits were applied to measure the levels of IL-6, IL-17A, TNF-α, and cAMP in serum; HE staining was applied to observe pathological changes in colon tissue; flow cytometry was applied to determine the proportion of Treg cells; immunohistochemistry was applied to detect the expression of MPO in colon tissue; Western blot was applied 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, and colon wall thickening, 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 and colon wall thickening were reduced, and 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: Myricetin may inhibit inflammation levels, regulate immune function, and exert protective effects on IBD rats by activating the cAMP/PKA/CREB signaling pathway. |
