Development of new dehydrocostuslactone derivatives for treatment of atopic dermatitis via inhibition of the NF-κB signaling pathway

RSC Med Chem. 2024 Jun 27;15(8):2773-2784. doi: 10.1039/d4md00301b. eCollection 2024 Aug 14.

Abstract

Atopic dermatitis (AD), a recurrent inflammatory systemic skin disease, is difficult to cure. In the present study, several ethylenediamine-derived dehydrocostuslactone (DHCL) derivatives were prepared to assess their in vitro and in vivo anti-inflammatory activities. The results indicated that DHCL derivatives inhibited NO generation with low cytotoxicity. In particular, compound 5d exhibited the best anti-inflammatory activity. Subsequent experiments revealed that 5d not only inhibited the LPS-induced inflammatory response in RAW264.7 cells via the MAPK-NF-κB signaling pathway inhibition but also significantly decreased Th2-type cytokine levels and inhibited the NF-κB signaling pathway activation in mice with MC903-induced AD. Therefore, DHCL derivatives may be considered as new agents for the treatment of AD.