Other
13 Authors
- Hofseth LJ,
- Tian X,
- Li B,
- Windust A,
- Wang XL,
- Nagarkatti P,
- Janicki JS,
- Nagarkatti M,
- Qu C,
- Tang D,
- Li H,
- Cui T,
- Lai Y
| First Author | Qu C | Year | 2015 |
| Journal | J Ethnopharmacol | Volume | 168 |
| Pages | 326-36 | PubMed ID | 25882312 |
| Mgi Jnum | J:260567 | Mgi Id | MGI:6147955 |
| Doi | 10.1016/j.jep.2015.04.004 | Citation | Qu C, et al. (2015) Identifying panaxynol, a natural activator of nuclear factor erythroid-2 related factor 2 (Nrf2) from American ginseng as a suppressor of inflamed macrophage-induced cardiomyocyte hypertrophy. J Ethnopharmacol 168:326-36 |
| abstractText | 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-kappaB)-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. |
