| DOI | Trouver le DOI : https://doi.org/10.1016/j.jep.2015.04.004 |
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| Auteur | Rechercher : Qu, Chen; Rechercher : Li, Bin; Rechercher : Lai, Yimu; Rechercher : Li, Hechu; Rechercher : Windust, Anthony1; Rechercher : Hofseth, Lorne J.; Rechercher : Nagarkatti, Mitzi; Rechercher : Nagarkatti, Prakash; Rechercher : Wang, Xing Li; Rechercher : Tang, Dongqi; Rechercher : Janicki, Joseph S.; Rechercher : Tian, Xingsong; Rechercher : Cui, Taixing |
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| Affiliation | - Conseil national de recherches du Canada. Science des mesures et étalons
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| Format | Texte, Article |
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| Sujet | American ginseng; panaxynol; Nrf2; inflammation; macrophages; cardiomyocytes |
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| Résumé | Ethnopharmacological relevance: American ginseng is capable of ameliorating cardiac dysfunction and activating Nrf2, a master regulator of antioxidant defense, in the heart. This study was designed to isolate compounds from American ginseng and to determine those responsible for the Nrf2-mediated resolution of inflamed macrophage-induced cardiomyocyte hypertrophy. Materials and methods: A standardized crude extract of American ginseng was supplied by the National Research Council of Canada, Institute for National Measurement Standards. A bioassay-based fractionization of American ginseng was performed to identify the putative substances which could activate Nrf2-mediated suppression of pro-inflammatory cytokine expression in macrophages and macrophage-mediated pro-hypertrophic growth in cardiomyocytes. Results: A hexane fraction of an anti-inflammatory crude extract of American ginseng was found to be most effective in suppressing the inflammatory responses in macrophages. Preparative, reverse-phase HPLC and a comparative analysis by analytical scale LC–UV/MS revealed the hexane fraction contains predominantly C17 polyacetylenes and linolenic acid. Panaxynol, one of the major polyacetylenes, was found to be a potent Nrf2 activator. Panaxynol posttranscriptionally activated Nrf2 by inhibiting Kelch-like ECH-associated protein (Keap) 1-mediated degradation without affecting the binding of Keap1 and Nrf2. Moreover, panaxynol suppressed a selected set of cytokine expression via the activation of Nrf2 while minimally regulating nuclear factor-kappa B (NF-κB)-mediated cytokine expression in macrophages. It also dramatically inhibited the inflamed macrophage-mediated cardiomyocyte death and hypertrophy by activating Nrf2 in macrophages. Conclusions: These results demonstrate that American ginseng-derived panaxynol is a specific Nrf2 activator and panaxynol-activated Nrf2 signaling is at least partly responsible for American ginseng-induced health benefit in the heart. |
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| Date de publication | 2015-06 |
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| Maison d’édition | Elsevier |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Numéro NPARC | 23001501 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | 5131d449-a11a-4a2b-9475-621a7c6480f4 |
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| Enregistrement créé | 2017-02-20 |
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| Enregistrement modifié | 2020-04-22 |
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