Morus alba extract suppresses IL-17-induced abnormal proliferation in 3D-reconstructed epidermis

•We screened anti-psoriatic plant extract and discovered Morus alba extract (MAE).•MAE suppressed IL-17-induced expression of chemokine (CCL20) on keratinocytes.•MAE suppressed the migration of keratinocytes in the 2D-culture system.•MAE suppressed the abnormal proliferation of keratinocytes in a 3D model.•MAE should become a new basis for anti-psoriasis medicine. Psoriasis is a chronic disease that is characterized by the abnormal proliferation of keratinocytes. The pathogenesis of psoriasis is initiated by the infiltration of Th17 cells, which secrete proinflammatory cytokines, including interleukin (IL)-17. IL-17 subsequently affects keratinocytes, causing abnormal proliferation and the release of cytokines and chemokines, which results in a vicious cycle of increased IL-17 production by immune cells. In this study, we aimed to search for a new remedy for treating psoriasis from natural sources. We screened plant extracts that suppress IL-17-induced chemokine, chemokine (C-C motif) ligand 20 (CCL20) by qRT–PCR from the in-house library. The hit extract was evaluated by a 2D-wound healing assay and a 3D-reconstruction epidermal model. Morus alba extract (MAE) was discovered as a candidate for a suppressor of IL-17-induced expression of CCL20. MAE also suppressed the migration of keratinocytes on wound-healing assay on a 2D culture plate. Additionally, MAE normalized the abnormal proliferation of the 3D-reconstruction model of keratinocytes induced by IL-17. MAE may offer promise as a natural treatment for psoriasis.