2′-Hydroxycinnamaldehyde ameliorates imiquimod-induced psoriasiform inflammation by targeting PKM2-STAT3 signaling in mice

2′-Hydroxycinnamaldehyde (HCA), the active component isolated from the stem bark of Cinnamomum cassia, exerts anticancer effects through multiple mechanisms. We recently determined that HCA inhibits signal transducer and activator of transcription 3 (STAT3) signaling in prostate cancer cells. Because STAT3 overactivation has been closely associated with the development of psoriasis, a chronic autoimmune skin disease, we examined whether HCA ameliorates skin lesions in an imiquimod-induced psoriasis-like mouse model. The results showed that intraperitoneal administration of HCA alleviated imiquimod-induced psoriasis-like dermatitis, epidermal thickening, dermal infiltration of inflammatory cells, and proinflammatory cytokine production. Mechanistically, HCA inhibited pyruvate kinase isozyme M2 and STAT3 signaling, leading to the suppression of T cell activation, Th17 cell differentiation, and keratinocyte hyperproliferation. These results suggest that HCA may be a new treatment for psoriasis and other STAT3-mediated skin disorders, such as infection, inflammation and carcinogenesis.