Protocatechuic aldehyde inactivates STAT3 through disrupting the STAT3-JAK1 interaction in epidermal keratinocyte and improves atopic dermatitis-like skin inflammation.

Protocatechuic aldehyde (PA) is an active compound of Salvia miltiorrhiza (Danshen), a traditional Chinese herb wildly used for inflammatory skin diseases therapy. STAT3 activation plays a pivotal role in multiple inflammatory cutaneous diseases. We previously reported that topical treatment with PA ameliorated psoriasis-like skin inflammation, a typical Th1-mediated inflammatory skin disease, by inactivating STAT3.However, the mechanisms of STAT3 inactivation by PA remain unknown. This study evaluated the therapeutic effect on atopic dermatitis, a Th2-mediated inflammatory skin disease, which is highly associated with STAT3 overactivation. And further addressed the molecular mechanisms that PA inhibited JAK1 activation and subsequently led to disruption of the interaction between STAT3 and JAK1, thus resulting in STAT3 inactivation in keratinocyte. The transcription repression of IL-8 and TNF-α by PA in the AD-like epidermal keratinocyte is STAT3-depedent. Our results suggested that PA could be potentially used for treating STAT3-activation-associated inflammatory skin diseases.