9, 19-Cycloartenol glycoside G3 from Cimicifuga simplex regulates immune responses by modulating Th17/Treg ratio. Issue 17 (1st September 2017)

• Record Type: Journal Article
• Authors: Su, Yang; Wu, Lun; Mu, Guangrui; Wang, Qiuhong; Yang, Bingyou; Cheng, Genhong; Kuang, Haixue
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 17(2017)
• Page Start: 4917
• Page End: 4923
• Publication Date: 2017-09-01
• Subjects: C. simplex L Cimicifuga simplex -- G3 9, 19-cycloartenol glycosides G3 -- CD4 cluster of differentiation 4 -- JAK/STAT Janus kinase/signal transducer and activator of transcription -- DCs dendritic cells -- Treg regulatory T cells -- Th17 T helper 17 -- RORγt retinoic-acid-receptor-related orphan receptor gamma t -- FoxP3 forkhead box P3 -- TNF-α tumor necrosis factor-α -- CD25 cluster of differentiation 25 -- T-bet T-box transcription factor TBX21 -- GATA-3 GATA binding protein 3 -- HPLC high-performance liquid chromatography -- ESI-MS electrospray ionization mass spectrometry -- PBMCs peripheral blood mononuclear cells -- MTT 3-(4, 5-dimethylthiazol-2-yl)-25-diphenyl tetrazolium bromide -- ELISA enzyme-linked immunosorbent assay -- ECL electrochemiluminescence -- ANOVA analysis of variance -- CC50 50% cytotoxic concentration -- IFN-γ gamma interferon -- H&E hematoxylin-eosin staining -- PCR polymerase chain reaction -- CXCL1 chemokine (C-X-C motif) ligand 1 -- CCL activation-regulated chemokine ligand -- CCR CC chemokine receptor -- COX cyclooxygenase; Cimicifuga simplex -- 9, 19-Cycloartenol glycosides -- IL-17+RORγt+/IL-10+FoxP3+ ratio -- JAK/STAT pathways; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.07.042
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Cimicifuga simplex is a medicinal herb which has a wide range of biological activities. We isolated seven 9, 19-cycloartenol glycosides from the roots of C. simplex, and among the glycosides, G3 exhibited the strongest inhibitory effect on immune responses, including suppressing the differentiation of CD 4+ T cells and directly suppressing the cytokine-induced JAK/STAT signaling pathways. In the IL-23-induced mouse ear model of skin disease, G3 repressed disease development by inhibiting the expression of pro-inflammatory mediators in murine ear skin. Moreover, G3 affected the maturation of DCs in vitro, thereby inducing T cell differentiation, resulting in an increased Treg phenotype and decreased Th17 phenotype. This study provides new evidence that G3 might ameliorate chronic inflammatory skin diseases by suppressing pathogenic CD 4+ T cell differentiation and the IL-17 + RORγt + /IL-10 + FoxP3 + ratio. These findings suggest that G3 might mediate the therapeutic effects observed in psoriasis patients following treatment with C. simplex .