Protocatechuic aldehyde ameliorates psoriasis-like skin inflammation and represses keratinocyte-derived IL-1α and CXCL9 via inhibiting STAT3 activation.

Psoriasis is a chronic inflammatory skin disease. Consistent activation of Signal Transducer and Activator of Transcription 3 (STAT3) in epidermal keratinocyte transactivates various keratinocyte-derived pro-inflammatory cytokines and elicits spontaneous psoriasis-like skin inflammation. In the current study, we first report that topical application of protocatechuic aldehyde (PA), the bioactive compound from Salvia miltiorrhiza (Danshen), significantly improved psoriasis-like skin symptoms and reduced immune cell infiltration in psoriatic lesions. Further molecular mechanism studies demonstrated that PA inactivated STAT3 and inhibited STAT3-mediated transactivation of interleukin-1α (IL-1α) and C-X-C motif chemokine ligand 9 (CXCL9) in epidermal keratinocyte both in vivo and in vitro. Knockdown of STAT3 attenuated the repression effect on IL-1α and CXCL9 by PA. Our results suggested that PA repressed the transactivation of IL-1α and CXCL9 through inhibiting STAT3 in keratinocyte. PA could be potentially used for psoriasis topical treatment or be as a lead compound for drug development.