Tussilagonone Ameliorates Psoriatic Features in Keratinocytes and Imiquimod-Induced Psoriasis-Like Lesions in Mice via NRF2 Activation

Lee, Joohee; Song, Kwangho; Hiebert, Paul; Werner, Sabine; Kim, Tae Gyun; Kim, Yeong Shik

Abstract

Psoriasis is a common inflammatory skin disorder that is characterized by keratinocyte hyperproliferation and abnormal differentiation, resulting in the thickening of the epidermis and stratum corneum. In this study, we investigated in vitro and in vivo pharmacological effects of tussilagonone (TGN), a sesquiterpenoid isolated from Tussilago farfara, on transcription factors relevant for the pathogenesis of psoriasis. TGN inhibited activation of NF-κB and STAT3, leading to the attenuated expression of psoriasis-related inflammatory genes and suppression of keratinocyte hyperproliferation. Mechanistically, we show that the inhibition of NF-κB and STAT3 by TGN is mediated through activation of the cytoprotective transcription factor NRF2. Evaluation of in vivo antipsoriatic effects of topical TGN in the imiquimod-induced psoriasis-like dermatitis mouse model demonstrated amelioration of imiquimod-induced phenotypical changes, lesion severity score, epidermal thickening, and reduction in dermal cellularity. The spleen index also diminished in TGN-treated mice, suggesting anti-inflammatory properties of TGN. Moreover, TGN significantly attenuated the imiquimod-induced mRNA levels of psoriasis-associated inflammatory cytokines and antimicrobial peptides and reduced epidermal hyperproliferation. Taken together, TGN, as a potent NRF2 activator, is a promising therapeutic candidate for the development of antipsoriatic agents derived from medicinal plants.

Citation

Lee, J., Song, K., Hiebert, P., Werner, S., Kim, T. G., & Kim, Y. S. (2020). Tussilagonone Ameliorates Psoriatic Features in Keratinocytes and Imiquimod-Induced Psoriasis-Like Lesions in Mice via NRF2 Activation. Journal of Investigative Dermatology, 140(6), 1223-1232.e4. https://doi.org/10.1016/j.jid.2019.12.008

• Journal Article Type: Article
• Acceptance Date: Dec 3, 2019
• Online Publication Date: Dec 23, 2019
• Publication Date: Jun 1, 2020
• Deposit Date: Feb 20, 2024
• Journal: Journal of Investigative Dermatology
• Print ISSN: 0022-202x
• Electronic ISSN: 1523-1747
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 140
• Issue: 6
• Pages: 1223-1232.e4
• DOI: https://doi.org/10.1016/j.jid.2019.12.008
• Public URL: https://hull-repository.worktribe.com/output/4554052