Exploring the Role of Phytoconstituent From <i>Euphorbia neriifolia</i> Targeting IL‐17A in Psoriasis: In Silico and In Vitro Study

Psoriasis is a chronic autoimmune skin disorder characterized by persistent inflammation and excessive keratinocyte proliferation. Although conventional immunosuppressive therapies are clinically effective, their long-term use is often associated with adverse side effects, highlighting the need for safer alternative treatments. <i>Euphorbia neriifolia</i>, a traditional medicinal plant known for its anti-inflammatory properties, has been investigated for its potential anti-psoriatic activity. In the present study, molecular docking was performed to evaluate the binding affinities of key phytoconstituents from <i>E. neriifolia</i> against interleukin-17A (IL-17A; PDB ID: 5HI4), a major cytokine implicated in psoriasis pathogenesis. Docking analysis revealed that compounds such as Taraxerol, Glutinol acetate, and Epifriedelanol showed the highest binding affinities, with scores of -10.3, -10.0, and -10.0 kcal/mol, respectively, surpassing the reference drug methotrexate (-9.2 kcal/mol). Density functional theory (DFT) calculations further supported the electronic stability and reactivity of the top-ranked compounds, indicating their potential suitability as bioactive leads. The integration of docking and DFT results highlights the novelty of this study, as <i>E. neriifolia</i> phytochemicals have not been extensively explored against IL-17A compared to other medicinal plants studied for psoriasis. The in vitro biological activity of the plant extract was also evaluated by using the L929 fibroblast bioassay, and the IC₅₀ value was found to be 168.18 μg/mL. Overall, the findings suggest that selected phytochemicals from <i>E. neriifolia</i> exhibit promising interactions with IL-17A, supporting their possible therapeutic role in psoriasis. These findings support further mechanistic and in vivo studies to validate IL-17A inhibition.