title: 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.
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.
authors.affiliation: Department of Oriental Medicinal Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea.
authors.forename: Sungeun
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Ginseng Bank, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea.
authors.forename: Muhammad Hanif
authors.initials: MH
authors.lastname: Siddiqi
authors.affiliation: Department of Oriental Medicinal Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea.
authors.forename: Veronica Castro
authors.initials: VC
authors.lastname: Aceituno
authors.affiliation: Ginseng Bank, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea.
authors.forename: Shakina Yesmin
authors.initials: SY
authors.lastname: Simu
authors.affiliation: Ginseng Bank, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea.
authors.forename: Jinglou
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Ginseng Bank, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea.
authors.forename: Zuly Elizabeth
authors.initials: ZE
authors.lastname: Jimenez Perez
authors.affiliation: Department of Oriental Medicinal Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Oriental Medicinal Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea. yangdeokchun@gmail.com.|Ginseng Bank, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea. yangdeokchun@gmail.com.|Department of Oriental Medicinal Materials and Processing, Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin, 449-701, South Korea. yangdeokchun@gmail.com.
authors.forename: Deok-Chun
authors.initials: DC
authors.lastname: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D054414:Chemokine CCL17 / Q000378:metabolism*; D054422:Chemokine CCL22 / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C515482:CCL22 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D036145:Ginsenosides; D008070:Lipopolysaccharides; C498143:RELA protein, human; D017382:Reactive Oxygen Species; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C572381:ginsenoside Rg5; D009569:Nitric Oxide; D007371:Interferon-gamma; D051550:I-kappa B Kinase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Atopic dermatitis; Inflammation; Keratinocytes/macrophages TARC/CCL17; NF-κB; STAT1; p38 MAPK