Development of new dehydrocostuslactone derivatives for treatment of atopic dermatitis via inhibition of the NF-κB signaling pathway.
Xiaoyi LiCheng LuWenxia DuQiuping ZouRuirui WangChunyan HuYanping LiYi ZhangZewei MaoPublished in: RSC medicinal chemistry (2024)
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.
Keyphrases
- signaling pathway
- lps induced
- inflammatory response
- induced apoptosis
- pi k akt
- atopic dermatitis
- cell cycle arrest
- epithelial mesenchymal transition
- oxidative stress
- lipopolysaccharide induced
- toll like receptor
- structure activity relationship
- type diabetes
- cell proliferation
- cell death
- nuclear factor
- combination therapy
- skeletal muscle
- diabetic rats
- single cell
- endothelial cells
- endoplasmic reticulum stress
- wound healing
- wild type