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Ginsenoside Rg3 attenuates skin disorders via down-regulation of MDM2/HIF1α signaling pathway

  • Han, Na-Ra (College of Korean Medicine, Kyung Hee University) ;
  • Ko, Seong-Gyu (Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University) ;
  • Moon, Phil-Dong (Center for Converging Humanities, Kyung Hee University) ;
  • Park, Hi-Joon (Department of Anatomy & Information Sciences, College of Korean Medicine, Kyung Hee University)
  • Received : 2021.02.09
  • Accepted : 2021.06.18
  • Published : 2021.09.30

Abstract

Background: Thymic stromal lymphopoietin (TSLP) acts as a master switch for inflammatory responses. Ginsenoside Rg3 (Rg3) which is an active ingredient of Panax ginseng Meyer (Araliaceae) is known to possess various therapeutic effects. However, a modulatory effect of Rg3 on TSLP expression in the inflammatory responses remains poorly understood. Methods: We investigated antiinflammatory effects of Rg3 on an in vitro model using HMC-1 cells stimulated by PMA plus calcium ionophore (PMACI), as well as an in vivo model using PMA-induced mouse ear edema. TSLP and vascular endothelial growth factor (VEGF) levels were detected using enzyme-linked immunosorbent assay or real-time PCR analysis. Murine double minute 2 (MDM2) and hypoxia-inducible factor 1α (HIF1α) expression levels were detected using Western blot analysis. Results: Rg3 treatment restrained the production and mRNA expression levels of TSLP and VEGF in activated HMC-1 cells. Rg3 down-regulated the MDM2 expression level increased by PMACI stimulation. The HIF1α expression level was also reduced by Rg3 in activated HMC-1 cells. In addition, Rg3-administered mice showed the decreased redness and ear thickness in PMA-irritated ear edema. Rg3 inhibited the TSLP and VEGF levels in the serum and ear tissue homogenate. Moreover, the MDM2 and HIF1α expression levels in the ear tissue homogenate were suppressed by Rg3. Conclusion: Taken together, the current study identifies new mechanistic evidence about MDM2/HIF1α pathway in the antiinflammatory effect of Rg3, providing a new effective therapeutic strategy for the treatment of skin inflammatory diseases.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1A5A2019413).

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