ANTI-PSORIASIS ACTIVITY OF SHIKONIN, A PLANT CELL NATURAL COLORANT NAPHTHOQUINONE, VIA THE JAGGED1/NOTCH1 PATHWAY

Abstract

Shikonin, a naphthoquinone compound isolated from Lithospermum erythrorhizon Siebold & Zucc.(Pinyin: zPiny), has been reported to exert protective roles against psoriasis. However, the molecular mechanism remains largely unknown. The current study aimed to explore the mechanism of Shikonin in keratinocyte differentiation and apoptosis. It was found that overexpression of Jagged-1, Notch-1, Hes-5, but not Hes-1, on psoriatic lesions is involved in the pathogenesis of psoriasis. In vitro, the application of exogenous recombinant human Jagged-1 (rh-Jag1, ligand of Notch-1) promotes proliferation and suppresses apoptosis of keratinocytes from psoriasis, which could be blocked by DAPT (γ-secretase inhibitor). Additionally, in recombinant human Epidermal Growth Factor (rh-EGF)-stimulated HaCaT cells (to mimic hyperproliferation condition of psoriasis), Shikonin was effective on anti-proliferation and pro-apoptosis of keratinocytes with down-regulation of Jagged-1, Notch-1, Hes-5, Bcl-2, and up-regulation of caspase-9, inhibitor of caspase-activated deoxyribonucleases (ICAD). Taken together, we propose that Jagged1/Notch1/Hes5 signaling involved in the pathogenesis of psoriasis could be suppressed by Shikonin.