Cherry plum powder alleviates excessive proliferation and inflammation of keratinocytes in psoriasis by reducing N6 methyladenosine-modified S100A4.

Cherry plum powder (CPP) is a pure natural plant extract with antioxidant and anti-inflammatory effects, and its role in psoriasis has not yet been elucidated. In this study, Balb/c mice were treated by imiquimod (IMQ) for a consecutive 7 days to establish psoriasis models, and then administrated with CPP by gavage for 2 weeks. CPP treatment obviously alleviated IMQ-induced psoriasis-like dermatitis, epidermal thickening and inflammatory cytokines secretion in mice. Through in vitro keratinocytes models, CPP was also found to suppress tumor necrosis factor tumor necrosis factor-alpha (TNF-α)-induced excessive proliferation and inflammatory cytokines production in HaCaT cells. Besides, CPP significantly reduced the expression of soluble protein 100 protein A4 (S100A4) and the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase (AKT) in psoriasis models in vivo and in vitro. In mechanism, methyltransferase-like protein 14 (METTL14)-mediated N6 methyladenosine (m6A) methylation stabilized and upregulated S100A4 mRNA, and then activated the downstream PI3K/AKT signaling, which was reversed by CPP treatment. Overexpression of METTL14 or S100A4 counteracted the therapeutic effects of CPP on TNF-α-induced HaCaT cells, which were then restored by a PI3K inhibitor. To conclude, CPP alleviates excessive proliferation and inflammation of keratinocyte to improve psoriasis through suppressing METTL14-mediated m6A modification of S100A4 mRNA and inactivating the downstream PI3K/AKT signaling pathway.