Introduction: Psoriasis is an autoimmune, chronic and debilitating disorder, mainly characterized by the presence of inflamed, dry and scaly patches of skin. This study aimed to investigate the possible anti-psoriasis effect of methanolic extract of Phoenix dactylifera seeds in mice. Methods: Thirty-five Wistar albino male mice were divided randomly into 5 groups (n = 7). Group 1 represented the normal group (received the cream base only), group 2 through 5 received a single daily application of imiquimod 5% cream; while, groups 3, 4 and 5 received once daily application of clobetasol 0.05%, P. dactylifera seeds methanol extract 2% and 5%, respectively. All animals received the test substances on the shaved back for 10 consecutive days. Scoring for skin inflammation severity (scaling, erythema and thickness) was recorded on daily basis, and the animals were sacrificed on day 11. Skin and spleen samples were taken to evaluate histopathological and spleen index changes, respectively. Results: Imiquimod successfully induced psoriasis like lesion in mice as well as significant increase in the skin neovascularization. Topical methanol extract of P. dactylifera cream significantly reduced the signs of inflammation as well as skin neovascularization in a concentration-dependent manner, where 5% methanol extract cream showed better reduction in the inflammatory parameters than 2% methanol extract cream. These findings were supported by the results of the histopathological examination. Conclusion: Results of the study suggest that methanol extract of P. dactylifera seeds possesses anti-psoriasis activity and could be used efficiently for the alleviation of psoriatic symptoms
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