Augmentation of NAD+ by Dunnione Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice

Abstract

Background Dunnione has anti-inflammatory properties arising from its ability to alter the ratio of NAD + /NADH through NAD(P)H quinone oxidoreductase 1 (NQO1) enzymatic action, followed by subsequent inhibition of NF-κB and inflammatory cytokines. Psoriasis is a chronic, inflammatory skin disorder in which the IL-23/Th17 axis plays an important role in inflammation. However, it is unclear whether modulation of NAD + levels affects psoriasis, such as skin inflammation. Therefore, in this study, we investigated the effect of NAD + /NADH ratio modulation on imiquimod (IMQ)-induced, psoriasis-like skin inflammation in mice. Methods Psoriasis-like skin inflammation was generated by daily topical application of IMQ cream. The severity of dermatitis was assessed using the Psoriasis Area Severity Index (PASI) and histochemistry. Expression of inflammatory cytokines was detected by enzyme-linked immunosorbent assay and quantitative PCR. Acetylation of NF-κB p65 and STAT3 was determined by Western blotting. Results Dunnione improved IMQ-induced epidermal hyperplasia and inflammation, consistent with decreased levels of inflammatory cytokines (IL-17, IL-22, and IL-23) in skin lesions. Moreover, we found that an increase in the NAD + /NADH ratio by dunnione restored SIRT1 activity, thereby reduced imiquimod-induced STAT3 acetylation, which modulates the expression of psoriasis-promoting inflammatory cytokines, such as IL-17, IL-22, and IL-23. Conclusion Pharmacological modulation of cellular NAD + levels could be a promising therapeutic approach for psoriasis-like skin disease.

Assessment of NADH/NAD+ Redox Imbalance in Psoriatic Lesions Using the FMSF Technique: Therapeutic Aspects

“…We have already shown that the topical composition of NAD + can effectively be used for the treatment of psoriasis, with effects comparable to conventional therapy with anthralin [13]. More recent research has confirmed that the augmentation of NAD + can result in the amelioration of psoriasis-like dermatitis [14]. This effect is linked to elevated Sirt1 activity, which is an NAD + -dependent process.…”