Worenine Prevents Solar Ultraviolet–Induced Sunburn by Inhibiting JNK2

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.

TOPK promotes the development of psoriasis and worenine alleviates psoriasiform dermatitis by inhibiting TOPK activity

“…Worenine is one of the main bioactive components extracted from the dried rhizome of Coptis chinensis 11 . Our previous paper found that worenine prevented Solar UltraViolet‐induced sunburn by inhibiting JNK2 signalling 12 . In this work, the anti‐psoriasis effect of worenine by inhibiting TOPK was determined in cell model and animal model.…”

“…ELISA was performed as previously described 12 . ELISAs were performed using ELISA kits according to the manufacturer's instructions.…”

“…ELISA was performed as previously described. 12 ELISAs were performed using ELISA kits according to the manufacturer's instructions. Human IL-8/CXCL8 ELISA kits, human IL-6 ELISA kits and human IL-23 ELISA kits were purchased from T A B L E 1 A list of selected TOPK-downregulated phosphoproteins.…”

“…The expression and purification of pGEX-GST-H2AX were described in our previous paper. 12 For the in vitro kinase assay, different doses of worenine were preincubated with active TOPK kinase (0.15 μg for each group) and subsequently incubated with the inactive substrate GST-Histone-H2AX (3 μg) in the presence of ATP. The samples were then subjected to western blot analysis.…”

“…11 Our previous paper found that worenine prevented Solar UltraViolet-induced sunburn by inhibiting JNK2 signalling. 12 In this work, the anti-psoriasis effect of worenine by inhibiting TOPK was determined in cell model and animal model. Taken together, TOPK might be a promising drug target for the prevention and treatment of psoriasis, and worenine might inhibit TOPK to alleviate psoriasis, providing new strategies for clinical intervention.…”