Reference - Detail
|Author||Qu C, Li B, Lai Y, Li H, Windust A, Hofseth LJ, Nagarkatti M, Nagarkatti P, Wang XL, Tang D, Janicki JS, Tian X, Cui T.|
|Title||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.|
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.
|MeSH||Animals Anti-Inflammatory Agents / isolation & purification Anti-Inflammatory Agents / pharmacology Cell Line Cytokines / metabolism Diynes / isolation & purification Diynes / pharmacology* Fatty Alcohols / isolation & purification Fatty Alcohols / pharmacology* Female Hypertrophy / drug therapy Hypertrophy / metabolism Macrophages / drug effects* Macrophages / metabolism Male Mice, Knockout Myocytes, Cardiac / drug effects* Myocytes, Cardiac / pathology NF-E2-Related Factor 2 / metabolism* Nitric Oxide Synthase Type II / metabolism Panax* Plant Extracts / chemistry Plant Extracts / pharmacology Rats|
|WOS Category||INTEGRATIVE & COMPLEMENTARY MEDICINE PLANT SCIENCES PHARMACOLOGY & PHARMACY CHEMISTRY, MEDICINAL|
|Mice||Nrf2 knockout mouse/C57BL6J(RBRC01390)|