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

Abstract

Excessive exposure to solar UV (SUV) is related with numerous human skin disorders, such as skin inflammation, photoaging and carcinogenesis. T-LAK cell- originated protein kinase (TOPK), an upstream of p38 mitogen-activated protein kinase (p38) and c-Jun N-terminal kinases (JNKs), plays an important role in SUV -induced skin inflammation, and targeting TOPK has already been a strategy to prevent skin inflammation. In this study, we found that the expression of TOPK, phosphorylation of p38 or JNKs was increased in human solar dermatitis tissues. The level of phosphorylation of p38 or JNKs increased in a dose and time dependent manner in HaCat cells or JB6 Cl41 cells after SUV treatment. Paeonol is an active component isolated from traditional Chinese herbal medicines, and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2H-tetrazdium) assay showed that it has no toxicity to cells. Microscale thermophoresis (MST) assay showed that paeonol can bind TOPK ex vivo. In vitro kinase assay showed paeonol can inhibit TOPK activity. Ex vivo studies further showed paeonol suppressed SUV-induced phosphorylation level of p38, JNKs, MSK1 and histone H2AX by inhibiting TOPK activity in a time and dose dependent manner. Paeonol inhibited the secretion of IL-6 and TNF-α in HaCat and JB6 cells ex vivo. In vivo studies demonstrated that paeonol inhibited SUV-induced increase of TOPK, the phosphorylation of p38, JNKs and H2AX, and the secretion of IL-6 and TNF-α in Babl/c mouse. In summary, our data indicated a protective role of paeonol against SUV-induced inflammation by targeting TOPK, and paeonol could be a promising agent for the treatment of SUV-induced skin inflammation.

3-Deoxysappanchalcone Inhibits Skin Cancer Proliferation by Regulating T-Lymphokine-Activated Killer Cell-Originated Protein Kinase in vitro and in vivo

“…Furthermore, targeting TOPK has been a strategy to prevent solar-related inflammation ( Xue et al, 2017 ), and 3-DSC showed anti-inflammatory effects in previous research ( Kim et al, 2014 ). In our study, we also found that 3-DSC prevented skin thickening, which was induced by acute SSL ( Figure 2 ).…”

“…Excess solar ultraviolet (SUV) radiation is the dominant risk factor for skin cancer ( Ratushny et al, 2012 ; Gao et al, 2017 ). It has been suggested that acute solar-simulated light (SSL) irradiation enhances T-lymphokine-activated killer cell-originated protein kinase (TOPK) expression and induces inflammation in SKH1 mice dorsal skin ( Xue et al, 2017 ; Roh et al, 2018 ). Therefore, targeting TOPK may be a promising strategy for skin cancer prevention and treatment ( Gao et al, 2017 ; Roh et al, 2018 ).…”

Cynanchum paniculatum and Its Major Active Constituents for Inflammatory‐Related Diseases: A Review of Traditional Use, Multiple Pathway Modulations, and Clinical Applications

“…Various clinical observations have reported the treatment effect of Cynanchum paniculatum in dermatological diseases. In vivo and in vitro studies suggested a protective role of paeonol against solar ultraviolet- (SUV-) induced skin inflammation via targeting T-LAK cell-originated protein kinase (TOPK), an upstream of p38 kinases and JNKs [ 92 ]. Furthermore, paeonol inhibits IL-6 and TNF- α secretion in a skin inflammation mouse model [ 93 ].…”

The effectiveness and safety of Chinese herbal formulas on skin photoaging

“…[ 17 ] Recent works have shown that paeonol can regulate inflammatory factors (interleukin [IL]-6, TNF-α) and inhibit inflammatory reaction; improve the protein content of JNKs, H2AX, TOPK, and p38 through p38MAPK and JNKs signaling pathway. [ 18 ] Gypenosides can inhibit the secretion of inflammatory factors (IL-6, TNF-α, IL-1β) from HaCaT cells damaged by light. Salvianolic acid B can reduce hydroxyproline content, superoxide dismutase activity, and the formation of free radical metabolites.…”