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DGT, a novel heterocyclic diterpenoid, effectively suppresses psoriasis via inhibition of STAT3 phosphorylation.

Authors :
Bian, Gang
Wang, Lidan
Xie, Qing
Wang, Yanping
Feng, Haimei
Yu, Yunhui
Chen, Zijun
Deng, Shiping
Li, Yunsen
Source :
British Journal of Pharmacology. Feb2021, Vol. 178 Issue 3, p636-653. 18p. 3 Color Photographs, 1 Black and White Photograph, 1 Diagram, 3 Graphs.
Publication Year :
2021

Abstract

Background and Purpose: Psoriasis is a chronic immune‐mediated inflammatory skin disease that easily recurs and is difficult to cure. DGT is a novel synthetic heterocyclic diterpenoid, whose structure has not been previously reported. We have investigated the action of DGT against psoriasis, specifically the hyperproliferation of epidermal keratinocytes, angiogenesis and pathogenic inflammatory responses. Experimental Approach We investigated its pharmacokinetics in skin after topical administration. We characterized its pharmacological actions in vitro and in vivo using cell proliferation assay, cell apoptosis assay, diethylstilbestrol‐induced mouse vaginal epithelial cell mitosis model, tube formation assay, cell migration assay, chick embryonic chorioallantoic membrane (CAM) assay, histological, flow cytometric analysis and imiquimod (IMQ)‐induced psoriasis‐like model. Key Results: DGT was found to be mainly distributed in the epidermis and dermis, which indicated that DGT was suitable as a topical treatment. DGT inhibited cell proliferation and induced apoptotic cell death of keratinocytes in vitro and in vivo. Moreover, DGT inhibited endothelial cell proliferation, tube formation and migration of in vitro angiogenesis, as well as in vivo CAM angiogenesis. In an IMQ‐induced psoriasis‐like skin inflammation murine model, topical application of DGT ameliorated keratinocyte proliferation and inflammatory response, especially in IL‐17‐related psoriasiform dermatitis. Furthermore, our results demonstrated that DGT prevented these pathological processes of psoriasis through suppression of STAT3 phosphorylation. Conclusion and Implications: DGT has great potential as a novel therapeutic agent for the treatment of psoriatic skin disease. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00071188
Volume :
178
Issue :
3
Database :
Academic Search Index
Journal :
British Journal of Pharmacology
Publication Type :
Academic Journal
Accession number :
148146995
Full Text :
https://doi.org/10.1111/bph.15306