Frontiers in Pharmacology (Jul 2022)

Worenine Prevents Solar Ultraviolet–Induced Sunburn by Inhibiting JNK2

  • Juanjuan Xiao,
  • Juanjuan Xiao,
  • Hui Lu,
  • Hui Lu,
  • Tengfei Ma,
  • Xiaofang Ni,
  • Teding Chang,
  • Man Liu,
  • Nijie Li,
  • Peijiang Lu,
  • Changshu Ke,
  • Qin Tian,
  • Ling Zou,
  • Fei Wang,
  • Wei Wang,
  • Lu Zhang,
  • Ping Yuan,
  • Lin Liu,
  • Jianmin Zhang,
  • Fei Shi,
  • Qiuhong Duan,
  • Feng Zhu,
  • Feng Zhu,
  • Feng Zhu,
  • Feng Zhu

DOI
https://doi.org/10.3389/fphar.2022.881042
Journal volume & issue
Vol. 13

Abstract

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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.

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