Abstract: Objective To evaluate the therapeutic effect of evodiamine (Evo) on atopic dermatitis (AD) in rat models by regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element binding protein (CREB) signaling pathway. Methods A rat model of AD was established by administration of multiple doses of 2,4-dinitrochlorobenzene (DNCB).The animals were randomly divided into AD group, Evo-low-dose (Evo-L, 5 mg/kg) group, Evo-high-dose (Evo-H, 10 mg/kg) group, Evo-H+H-89 (5 mg/kg) group and dexamethasone (0.1 mg/kg) group. Normal rats were used as the control group and then the degree of skin damage of rats in each group was scored. Abdominal blood was taken to detect the levels of interleukin-4 (IL-4), cAMP, and tumor necrosis factor-α(TNF-α) in serum; Skin lesion tissue was collected to detect pathological change, counting of mast cells, PKA/CREB related protein expression and expression of IL-4 and TNF-α mRNA in the tissue. Results Compared with control group, the level of cAMP in serum, the expression of p-PKA/PKA, and p-CREB/CREB in skin lesions of AD group were reduced, the severity score of skin lesions, level of IL-4 and TNF-α, epidermal thickness, number of mast cells and mRNA expression of IL-4 and TNF-α in skin lesion tissues were all significantly increased (P＜0.05). Compared with AD group, the level of cAMP in serum, the expression of p-PKA/PKA, and p-CREB/CREB in skin lesions in Evo-L group, Evo-H group, and dexamethasone group were increased, the severity score of skin lesions, level of IL-4 and TNF-α, epidermal thickness, number of mast cells, and mRNA expression of IL-4 and TNF-α in skin lesion tissues all reduced (P＜0.05). Compared with the Evo-H group, the level of cAMP in serum, the expression of p-PKA/PKA, and p-CREB/CREB in skin lesions in Evo-H+H-89 group was reduced and the severity score of skin lesion, level of IL-4 and TNF-α, epidermal thickness, number of mast cells, and mRNA expression of IL-4 and TNF-α in skin lesion tissues significantly increased(P＜0.05). Conclusions Evo inhibits inflammatory response and pathological damage through regulation of cAMP/PKA/CREB signaling pathway in AD rat models.

Key words: evodiamine, cAMP/PKA/CREB signaling pathway, atopic dermatitis, inflammation