Ruiyu Xiang, Linghan Hu, Siyuan Li, Ziyu Wei, Zhongya Song, Zhiming Chen, Yihe Liu, Juan Liu, Xiaoguang Lei, Yong Yang*
J. Dermatol. Sci. 2022, 107, 32-40
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.
Ruiyu Xiang, Linghan Hu, Siyuan Li, Ziyu Wei, Zhongya Song, Zhiming Chen, Yihe Liu, Juan Liu, Xiaoguang Lei, Yong Yang*
J. Dermatol. Sci. 2022, 107, 32-40
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.
Novel TNF-α inhibitor was identified via high-throughput screening (HTS) and its anti-inflammatory activity was evaluated.
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.
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.
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.