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- Title
Augmentation of NAD<sup>+</sup> by Dunnione Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice.
- Authors
Lee, Seung Hoon; Kim, Hyung-Jin; Oh, Gi-Su; Lee, Su-Bin; Khadka, Dipendra; Cao, Wal; Choe, Seong-Kyu; Shim, Hyeok; Kim, Chang-Deok; Kwak, Tae Hwan; So, Hong-Seob
- 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.
- Subjects
SKIN inflammation; TOPICAL drug administration; ENZYME-linked immunosorbent assay; THERAPEUTICS; SKIN diseases
- Publication
Journal of Inflammation Research, 2022, Vol 15, p4623
- ISSN
1178-7031
- Publication type
Article
- DOI
10.2147/JIR.S372543