Blocking Effect of an Immuno-Suppressive Agent, Cynarin, on CD28 of T-Cell Receptor

Dong, Guo-Chung; Chuang, Ping-Hsien; Chang, Kai‐Chun; Jan, Pey-Shynan; Hwang, Pei-Ing; Wu, Huan-Bin; Yi, Myunggi; Zhou, Huan‐Xiang; Chen, Hueih Min

doi:10.1007/s11095-008-9754-5

Cited by 31 publications

(24 citation statements)

References 13 publications

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“…Concentrations of their extract at 50 or 100 μg/mL were cytotoxic to Jurkat cells in contrast to EchNWA used here which had no effects on T cell viability at these doses [34]. Dong et al reported that cynarin down-regulated CD28-dependent IL-2 production in T-cells and later showed that this was likely to occur in the “G-pocket” of CD28 and therefore to act by interrupting the site of interaction between CD28 and CD80 [32,45]. …”

Section: Discussionmentioning

confidence: 97%

Echinacea purpurea (L.) Moench modulates human T-cell cytokine response

Fonseca

Papanicolaou

Lin

et al. 2014

International Immunopharmacology

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The study objective was to evaluate the composition of a neutral and weakly acidic water-soluble extract from Echinacea purpurea (L.) Moench (EchNWA) previously shown to modify murine influenza infection, and to assess immunomodulatory effects on human T-cells. EchNWA extract from fresh aerial parts was extracted with water, ethanolic precipitation, and size-exclusion chromatography. The chemical profile of EchNWA was characterized by chromatography (size-exclusion, HPLC, GC–MS), and small molecule finger-print analysis performed by HPLC–PDA. Jurkat T-cells at high and low cell density were pretreated or not with doses of EchNWA, followed by activation with phorbol 12-myristate 13-acetate plus ionomycin (PMA+I). Interleukin-2 (IL-2) and interferon gamma (IFNg) cytokine secretions were measured by multi-cytokine luminex technology. Results showed that EchNWA contains 80% polysaccharides, predominantly a 10 kDa entity; phenolic compounds, cynarin, cichoric and caftaric acids, but no detectable alkylamides. Cytokine production required stimulation and was lower after PMA+I activation in high-density compared to low-density conditions. EchNWA mediated a strong dose-dependent enhancement of high-density T-cell production of IL-2 and IFNg response to PMA+I. EchNWA alone did not stimulate T-cells. EchNWA enhanced mean fluorescence intensity of IL-2 in Jurkat T-cells activated by PMA+1 or ionomycin alone. Conversely EchNWA mediated modest but significant suppression of IFNg response and reduced the percentage of CD25+ T-cells under low-density conditions. Conclusions are that EchNWA polysaccharides, but not phenolic compounds have dose-related adjuvant effects on human T-cell cytokine responses characterized by enhancing and suppressive effects that are regulated by T-cell density.

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Section: Discussionmentioning

confidence: 97%

Echinacea purpurea (L.) Moench modulates human T-cell cytokine response

Fonseca

Papanicolaou

Lin

et al. 2014

International Immunopharmacology

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“…Slanina et al (2001) indicated that CYN did not have cytotoxic effects on HeLa cells until 400 µM, while 250 µM inhibited the growth of MT-2 (human T-cell leukemia) cells. Dong et al (2009) reported that CYN did not have cytotoxic effects on Jurkat T cells until 1000 µM.…”

Section: Discussionmentioning

confidence: 99%

Artichoke compound cynarin differentially affects the survival, growth, and stress response of normal, immortalized, and cancerous human cells

Gezer¹,

Yücecan²,

Rattan³

2015

Turk J Biol

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Cynarin (CYN) is the main derivative of caffeoylquinic acid, found in leaves and heads of artichoke. It may have hepatoprotective, antiatherosclerotic, antioxidative, choleretic, and cholesterol-lowering effects. We tested the effects of various doses of CYN on the proliferative potential, survival, morphology, and stress response (SR) markers heme oxygenase-1 (HO-1) and heat shock protein-70 (HSP70) in normal human skin fibroblasts (FSF-1), telomerase-immortalized mesenchymal stem cells (hTERT-MSC), and cervical cancer cells (HeLa). The effects of CYN on cell proliferation and morphology were dose-and cell type-dependent, with 500 µM CYN as the upper limit for all cell types. While the growth and proliferation of cells decreased after exposure to 75 µM CYN for 3 days, overall survival of FSF-1 and hTERT-MSC was higher than that of HeLa cells. Furthermore, CYN induced the oxidative SR marker HO-1 in both fibroblasts and stem cells in a biphasic manner. A slight induction of HSP70 was observed only in the stem cells. Thus, CYN may be useful for protection against the growth and survival of potentially cancerous cells and may promote longevity of normal cells by inducing SR proteins. Further advanced research related to CYN and artichoke is recommended.

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“…1,3-Dicaffeoylquinic acid is a major component found in artichoke and Echinacea purpurea [31, 32]. Pharmacological studies demonstrated that it exhibits antimicrobial and antioxidant activity [31, 33].…”

Section: Discussionmentioning

confidence: 99%

“…1,3-Dicaffeoylquinic acid blocked HIV-1 integrase activity, leading to interference of insertion of viral DNA into the genome of the victim cell [10]. Another study demonstrated that it inhibited the interaction between CD28 of T-cell receptor and CD80 of antigen presenting cells, blocking “signal 2” of T-cell activation [32]. Due to its potential development as a therapeutic agent, systemic exposure in clinical applications may reach high levels.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Natural Dietary and Herbal Anionic Compounds and Flavonoids with Human Organic Anion Transporters 1 (SLC22A6), 3 (SLC22A8), and 4 (SLC22A11)

Wang

Sweet

2013

Evidence-Based Complementary and Alternative Medicine

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Active components of complementary/alternative medicines and natural supplements are often anionic compounds and flavonoids. As such, organic anion transporters (OATs) may play a key role in their pharmacokinetic and pharmacological profiles, and represent sites for adverse drug-drug interactions. Therefore, we assessed the inhibitory effects of nine natural products, including flavonoids (catechin and epicatechin), chlorogenic acids (1,3- and 1,5-dicaffeoylquinic acid), phenolic acids (ginkgolic acids (13 : 0), (15 : 1), and (17 : 1)), and the organic acids ursolic acid and 18β-glycyrrhetinic acid, on the transport activity of the human OATs, hOAT1 (SLC22A6), hOAT3 (SLC22A8), and hOAT4 (SLC22A11). Four compounds, 1,3- and 1,5-dicaffeoylquinic acid, ginkgolic acid (17 : 1), and 18β-glycyrrhetinic acid, significantly inhibited hOAT1-mediated transport (50 μM inhibitor versus 1 μM substrate). Five compounds, 1,3- and 1,5-dicaffeoylquinic acid, ginkgolic acids (15 : 1) and (17 : 1), and epicatechin, significantly inhibited hOAT3 transport under similar conditions. Only catechin inhibited hOAT4. Dose-dependency studies were conducted for 1,3-dicaffeoylquinic acid and 18β-glycyrrhetinic acid on hOAT1, and IC50 values were estimated as 1.2 ± 0.4 μM and 2.7 ± 0.2 μM, respectively. These data suggest that 1,3-dicaffeoylquinic acid and 18β-glycyrrhetinic acid may cause significant hOAT1-mediated DDIs in vivo; potential should be considered for safety issues during use and in future drug development.

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Blocking Effect of an Immuno-Suppressive Agent, Cynarin, on CD28 of T-Cell Receptor

Cited by 31 publications

References 13 publications

Echinacea purpurea (L.) Moench modulates human T-cell cytokine response

Echinacea purpurea (L.) Moench modulates human T-cell cytokine response

Artichoke compound cynarin differentially affects the survival, growth, and stress response of normal, immortalized, and cancerous human cells

Interaction of Natural Dietary and Herbal Anionic Compounds and Flavonoids with Human Organic Anion Transporters 1 (SLC22A6), 3 (SLC22A8), and 4 (SLC22A11)

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