| DOI | Resolve DOI: https://doi.org/10.1016/j.jep.2015.04.004 |
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| Author | Search for: Qu, Chen; Search for: Li, Bin; Search for: Lai, Yimu; Search for: Li, Hechu; Search for: Windust, Anthony1; Search for: Hofseth, Lorne J.; Search for: Nagarkatti, Mitzi; Search for: Nagarkatti, Prakash; Search for: Wang, Xing Li; Search for: Tang, Dongqi; Search for: Janicki, Joseph S.; Search for: Tian, Xingsong; Search for: Cui, Taixing |
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| Affiliation | - National Research Council of Canada. Measurement Science and Standards
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| Format | Text, Article |
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| Subject | American ginseng; panaxynol; Nrf2; inflammation; macrophages; cardiomyocytes |
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| Abstract | 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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| Publication date | 2015-06 |
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| Publisher | Elsevier |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NPARC number | 23001501 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 5131d449-a11a-4a2b-9475-621a7c6480f4 |
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| Record created | 2017-02-20 |
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| Record modified | 2020-04-22 |
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