Tiamulin inhibits TNF-α and alleviates psoriasis-like dermatitis
- J Dermatol Sci. 2022 Jul;107(1):32-40. doi: 10.1016/j.jdermsci.2022.05.006.
- 1. Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Genetic Skin Disease Center; Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
- 2. Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
- 3. College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
- 4. Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Genetic Skin Disease Center; Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China. Electronic address: [email protected].
Background: TNF-α elicits a cascade amplification effect in psoriasis. Macromolecule drugs targeting TNF-α are widely used for the clinical treatment of psoriasis. However, there are currently no effective small-molecule inhibitors that can be used in the clinic.
Objective: Novel TNF-α inhibitor was identified via high-throughput screening (HTS) and its anti-inflammatory activity was evaluated.
Methods: Two cell death models were established to identify inhibitors of TNF-α through HTS from a library of 3256 compounds. The effect of the inhibitor of TNF-α was tested by HaCaT cells in vitro and IMQ-induced psoriasis-like mouse model in vivo.
Results: Tiamulin fumarate (TF) was identified as an effective inhibitor of TNF-α. TF significantly blocked the NF-κB and MAPK signaling pathways in TNF-α-stimulated HaCaT cells. Additionally, systemic and topical administration of TF improved IMQ-induced psoriasis-like dermatitis in the mouse model.
Conclusion: Our study established a HTS method to identify TF as an inhibitor of TNF-α. The protective roles of TF in psoriasis-related inflammation reveal the potential therapeutic value of TF for psoriasis.
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