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Src kinase is a direct target of apigenin against UVB-induced skin inflammation
Sanguine Byun1, Jiman Park, Eunjung Lee
1Department of Agricultural Biotechnology, WCU Biomodulation Major, Seoul National University, Seoul 151-921, Republic of Korea.
Abstract:
Apigenin, a flavonoid abundant in various vegetables and fruits, including parsley and onions, has been reported to possess anticarcinogenic effects. However, the direct molecular target of apigenin and its chemopreventive effect on ultraviolet (UV)-induced skin inflammation are not understood fully. Herein, we examined the anti-inflammatory effect of apigenin and its associated mechanisms in JB6 P+ cell line and SKH-1 hairless mouse model. Apigenin inhibited UVB-induced cyclooxygenase-2 (COX-2) expression, which is a well-known key mediator of inflammation and cancer, and restored the upstream stimulatory factor level in JB6 P+ cells. Immunoblot and kinase assay data demonstrate that Src activity was attenuated by apigenin, and this led to subsequent inhibition of UVB-induced phosphorylation of epidermal growth factor receptor, mitogen-activated protein kinases and Akt signaling. Inhibitory effects of apigenin on UVB-induced signaling were also confirmed in HaCaT human keratinocytes. In addition, in vitro pull-down assays revealed that apigenin binds Src in an adenosine triphosphate-competitive manner. Results using in vivo skin model indicate apigenin significantly inhibits UVB-induced ear edema development, COX-2 expression and Src kinase activity in SKH-1 hairless mice. Collectively, these findings suggest that apigenin exerts potent chemopreventive activity against UVB-induced skin inflammation primarily by targeting Src.
Insights
Apigenin, a natural flavonoid, effectively reduces skin inflammation caused by UV radiation by inhibiting Src kinase activity. This study identifies Src as a key molecular target for apigenin's chemopreventive effects against UV damage.
Area of Science:
- Biochemistry
- Dermatology
- Molecular Biology
Background:
- Flavonoids, like apigenin found in fruits and vegetables, show potential anticarcinogenic properties.
- The precise molecular targets and anti-inflammatory mechanisms of apigenin, particularly against UV-induced skin inflammation, require further elucidation.
Purpose of the Study:
- To investigate the anti-inflammatory effects and molecular mechanisms of apigenin in UV-induced skin inflammation.
- To identify the direct molecular target of apigenin in the context of UV radiation exposure.
Main Methods:
- Utilized JB6 P+ cell lines and SKH-1 hairless mouse models to study UVB-induced inflammation.
- Employed immunoblotting, kinase assays, and in vitro pull-down assays to analyze signaling pathways and molecular interactions.
- Assessed UVB-induced ear edema, cyclooxygenase-2 (COX-2) expression, and Src kinase activity in vivo.
Main Results:
- Apigenin inhibited UVB-induced cyclooxygenase-2 (COX-2) expression and restored upstream stimulatory factor levels.
- Apigenin attenuated Src kinase activity, leading to the inhibition of UVB-induced phosphorylation of EGFR, MAPKs, and Akt signaling pathways.
- In vivo studies confirmed that apigenin significantly reduced UVB-induced ear edema, COX-2 expression, and Src kinase activity.
Conclusions:
- Apigenin demonstrates significant chemopreventive activity against UVB-induced skin inflammation.
- The findings strongly suggest that apigenin targets Src kinase, thereby inhibiting key inflammatory signaling pathways and exerting its protective effects.
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