Clove (Syzygium aromaticum) and its bioactive constituent eugenol alleviate psoriatic inflammation by modulating the IL-36/IL-17A axis: a proteomic and mechanistic study

Introduction Clove ( Syzygium aromaticum ) is traditionally used for inflammatory skin disorders; however, its specific molecular mechanisms in psoriasis remain poorly defined. This study aimed to evaluate the efficacy of clove extract and its major component, eugenol, and to identify their molecular targets. Methods We used an imiquimod (IMQ)-induced mouse model to assess the effects of oral clove extract and eugenol. Proteomic alterations were identified via isobaric tags for relative and absolute quantitation-based liquid chromatography-tandem mass spectrometry and bioinformatics. The specific interaction with the interleukin-17A (IL-17A)/IL-17 receptor A (IL-17RA) interface was validated through competitive binding assays and molecular docking, with further confirmation via immunohistochemistry. Results Eugenol was identified as the major constituent of clove extract (65.8%). Clove extract and eugenol significantly alleviated psoriasiform lesions, reducing scaling scores and epidermal thickness. Proteomic analysis revealed that both treatments reversed IMQ-induced inflammatory signatures by modulating the interleukin-36 (IL-36) and IL-17 signaling pathways, specifically increasing IL-36 receptor antagonist expression while suppressing IL-36 levels. In vitro assays demonstrated that both treatments inhibited IL-17A–IL-17RA binding in a dose-dependent manner, supported by molecular docking indicating potential interactions between eugenol and IL-17A residues. Immunohistochemical analysis further confirmed reduced nuclear factor-κB (NF-κB) activation, decreased IL-17A expression, and diminished CD11b + granulocyte infiltration in psoriatic skin. Conclusion Clove extract and its major bioactive constituent eugenol exert significant anti-psoriatic effects through coordinated modulation of the IL-36/IL-17A inflammatory axis and suppression of NF-κB signaling. These findings provide mechanistic insight into the traditional use of clove in inflammatory skin disorders and highlight eugenol as a key bioactive mediator with potential as a complementary therapeutic strategy for psoriasis.