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Ginsenoside Rg5:Rk1 attenuates TNF-α/IFN-γ-induced production of thymus- and activation-regulated chemokine (TARC/CCL17) and LPS-induced NO production via downregulation of NF-κB/p38 MAPK/STAT1 signaling in human keratinocytes and macrophages

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Abstract

Atopic dermatitis (AD) is a chronic skin disease that affects millions of people worldwide. Keratinocytes and macrophages are two cells types that play a pivotal role in the development of AD. These cells produced different chemokines and cytokines, especially thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), as well as nitric oxide (NO) through inducible nitric oxide synthase (iNOS) and COX2 in response to stimulation by TNF-α/IFN-γ and lipopolysaccharide (LPS) respectively. These mediators are thought to be crucial regulators of the pathogenesis of AD. Although several natural compounds to treat AD have been studied, the effect of Rg5:Rk1 from Panax ginseng (P. ginseng) on AD has not yet been investigated. In this study, we evaluated the inhibitory effect of Rg5:Rk1 on TNF-α/IFN-γ stimulated keratinocytes (HaCaT cells) and LPS-stimulated macrophages (RAW 264.7 cells). Enzyme-linked immunosorbent assay (ELISA) data showed that pretreatment of HaCaT cells with Rg5:Rk1 significantly reduced the TNF-α/IFN-γ-induced increase in TARC/CCL17 expression in a dose-dependent manner. In addition, Rg5:Rk1 decreased LPS-mediated nitric oxide (NO) and reactive oxygen species (ROS) production in RAW 264.7 cells. A considerable reduction in messenger RNA (mRNA) expression of the aforementioned AD mediators was also observed. Pretreatment with Rg5:Rk1 attenuated the TNF-α/IFN-γ-induced phosphorylation of p38 MAPK, STAT1, and NF-κB/IKKβ in HaCaT cells. Together, these findings suggest that ginsenoside Rg5:Rk1 may have a potential anti-AD effect by suppressing NF-κB/p38 MAPK/STAT1 signaling.

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Acknowledgments

This research was supported by grants 312064-03-1-HD040 and 313038-03-1-SB010 from the Korea Institute of Planning and Evaluation for Technology (iPET) of the Ministry of Food, Agriculture, Forestry and Fisheries, Republic of Korea. The ginseng sample used in this study was provided by the Ginseng Bank of Kyung Hee University.

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Authors and Affiliations

  1. Department of Oriental Medicinal Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea

    Sungeun Ahn, Veronica Castro Aceituno, Yu-Jin Kim & Deok-Chun Yang

  2. Ginseng Bank, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea

    Muhammad Hanif Siddiqi, Shakina Yesmin Simu, Jinglou Zhang, Zuly Elizabeth Jimenez Perez & Deok-Chun Yang

  3. Department of Oriental Medicinal Materials and Processing, Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin, 449-701, South Korea

    Deok-Chun Yang

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  1. Sungeun Ahn
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Correspondence to Deok-Chun Yang.

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Ahn, S., Siddiqi, M.H., Aceituno, V.C. et al. Ginsenoside Rg5:Rk1 attenuates TNF-α/IFN-γ-induced production of thymus- and activation-regulated chemokine (TARC/CCL17) and LPS-induced NO production via downregulation of NF-κB/p38 MAPK/STAT1 signaling in human keratinocytes and macrophages. In Vitro Cell.Dev.Biol.-Animal 52, 287–295 (2016). https://doi.org/10.1007/s11626-015-9983-y

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