RRC ID 33195
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.
Journal J Ethnopharmacol
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.
Volume 168
Pages 326-36
Published 2015-6-20
DOI 10.1016/j.jep.2015.04.004
PII S0378-8741(15)00245-7
PMID 25882312
PMC PMC4810680
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
IF 3.414
Times Cited 3
Mice Nrf2 knockout mouse/C57BL6J(RBRC01390)