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Paeonol suppresses solar ultraviolet-induced skin inflammation by targeting T-LAK cell-originated protein kinase

Peipei Xue1, Yong Wang1, Fanfan Zeng1

  • 1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.

Oncotarget
|April 14, 2017
PubMed

Insights

Paeonol, a natural compound, effectively reduces skin inflammation caused by excessive solar UV (SUV) exposure by inhibiting T-LAK cell-originated protein kinase (TOPK). This study highlights paeonol

Area of Science:

  • Dermatology
  • Molecular Biology
  • Pharmacology

Background:

  • Excessive solar UV (SUV) exposure causes skin disorders, including inflammation, photoaging, and carcinogenesis.
  • T-LAK cell-originated protein kinase (TOPK) is crucial in SUV-induced skin inflammation, making it a therapeutic target.
  • TOPK acts upstream of p38 mitogen-activated protein kinase (p38) and c-Jun N-terminal kinases (JNKs).

Purpose of the Study:

  • To investigate the protective effect of paeonol against SUV-induced skin inflammation.
  • To elucidate the mechanism of paeonol's action, focusing on TOPK inhibition.
  • To evaluate paeonol's therapeutic potential for SUV-induced skin conditions.

Main Methods:

  • Assessed TOPK, p38, and JNKs phosphorylation in human solar dermatitis tissues and cell models (HaCat, JB6 Cl41) after SUV treatment.
  • Utilized MTS assay to determine paeonol's cellular toxicity and Microscale Thermophoresis (MST) to assess its binding to TOPK.
  • Conducted in vitro kinase assays, ex vivo studies on cells, and in vivo studies on Balb/c mice to evaluate paeonol's anti-inflammatory effects and TOPK inhibition.

Main Results:

  • SUV exposure increased TOPK expression and p38/JNKs phosphorylation in skin tissues and cells.
  • Paeonol demonstrated no cellular toxicity and directly bound and inhibited TOPK activity.
  • Paeonol suppressed SUV-induced phosphorylation of p38, JNKs, MSK1, and H2AX, and reduced IL-6 and TNF-α secretion in vitro and in vivo.

Conclusions:

  • Paeonol exhibits a protective role against SUV-induced skin inflammation by targeting and inhibiting TOPK.
  • Paeonol effectively reduces key inflammatory markers and signaling pathways activated by solar UV radiation.
  • Paeonol is identified as a promising therapeutic agent for managing SUV-induced skin inflammation.
Keywords:
MAPKTOPKpaeonolskin inflammationsolar UV

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