AUTHOR=Xiao Juanjuan , Lu Hui , Ma Tengfei , Ni Xiaofang , Chang Teding , Liu Man , Li Nijie , Lu Peijiang , Ke Changshu , Tian Qin , Zou Ling , Wang Fei , Wang Wei , Zhang Lu , Yuan Ping , Liu Lin , Zhang Jianmin , Shi Fei , Duan Qiuhong , Zhu Feng TITLE=Worenine Prevents Solar Ultraviolet–Induced Sunburn by Inhibiting JNK2 JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.881042 DOI=10.3389/fphar.2022.881042 ISSN=1663-9812 ABSTRACT=

Excessive solar ultraviolet (SUV) radiation often causes dermatitis, photoaging, and even skin cancer. In the pathological processes of SUV-induced sunburn, JNK is activated by phosphorylation, and it in turn phosphorylates its downstream transcription factors, such as ATF2 and c-jun. The transcription factors further regulate the expression of pro-inflammatory genes, such as IL-6 and TNF-α, which ultimately leads to dermatitis. Therefore, inhibiting JNK may be a strategy to prevent dermatitis. In this study, we screened for worenine as a potential drug candidate for inhibiting sunburn. We determined that worenine inhibited the JNK-ATF2/c-jun signaling pathway and the secretion of IL-6 and TNF-α in cell culture and in vivo, confirming the role of worenine in inhibiting sunburn. Furthermore, we determined that worenine bound and inhibited JNK2 activity in vitro through the MST, kinase, and in vitro kinase assays. Therefore, worenine might be a promising drug candidate for the prevention and treatment of SUV-induced sunburn.