Synthetic Curcuminoids Combined with Blue-Light-Mediated Photodynamic Therapy for Anti-Inflammatory Effect and Potential Mechanism on Imiquimod-Induced Psoriasis-like Proliferation of Keratinocytes

Psoriasis is characterized by the rapid proliferation of keratinocytes, leading to erythematous plaques with silvery scales, skin pain, and impaired quality of life. Photodynamic therapy (PDT) has emerged as a promising treatment modality for various skin disorders, including psoriasis. Curcumin, a natural photosensitizer, possesses potent anti-inflammatory and antioxidant properties. In this study, we investigated the anti-inflammatory potential of synthetic curcuminoids combined with blue-light-mediated PDT for psoriasis treatment using human keratinocyte (HaCaT) cells. MTT assays demonstrated that the synthetic curcuminoids (1E,6E)-1,7-bis(5-methylthiophen-2-yl)hepta-1,6-diene-3,5-dione (No. 11) and (1E,6E)-1,7-di(thiophen-2-yl)hepta-1,6-diene-3,5-dione (No. 12) exhibited minimal cytotoxicity toward HaCaT cells. Upon ultraviolet-visible light irradiation, curcuminoid-treated cells generated intracellular reactive oxygen species, confirming the photodynamic activity induced by blue light exposure. Treatment with synthetic curcuminoids significantly suppressed the secretion of pro-inflammatory cytokines IL-17A/F and IL-8 in imiquimod-stimulated HaCaT cells, a commonly used psoriasis-like inflammatory model, indicating notable anti-inflammatory effects. Western blot analysis further revealed an increased Bax/Bcl-2 ratio in cells treated with synthetic curcuminoids No. 11 or No. 12 under photodynamic irradiation, suggesting the induction of apoptosis. Synthetic curcuminoids combined with blue-light PDT may represent a promising and cost-effective strategy for psoriasis.