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1.
Proc Natl Acad Sci U S A ; 108(42): 17533-7, 2011 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-21972415

RESUMEN

A lipid extract of Perna canaliculus (New Zealand green-lipped mussel) has reportedly displayed anti-inflammatory effects in animal models and in human controlled studies. However, the anti-inflammatory lipid components have not been investigated in detail due to the instability of the lipid extract, which has made the identification of the distinct active components a formidable task. Considering the instability of the active component, we carefully fractionated a lipid extract of Perna canaliculus (Lyprinol) and detected furan fatty acids (F-acids). These naturally but rarely detected fatty acids show potent radical-scavenging ability and are essential constituents of plants and algae. Based on these data, it has been proposed that F-acids could be potential antioxidants, which may contribute to the protective properties of fish and fish oil diets against chronic inflammatory diseases. However, to date, in vivo data to support the hypothesis have not been obtained, presumably due to the limited availability of F-acids. To confirm the in vivo anti-inflammatory effect of F-acids in comparison with that of eicosapentaenoic acid (EPA), we developed a semisynthetic preparation and examined its anti-inflammatory activity in a rat model of adjuvant-induced arthritis. Indeed, the F-acid ethyl ester exhibited more potent anti-inflammatory activity than that of the EPA ethyl ester. We report on the in vivo activity of F-acids, confirming that the lipid extract of the green-lipped mussel includes an unstable fatty acid that is more effective than EPA.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Ácidos Grasos/farmacología , Perna/química , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Artritis Experimental/tratamiento farmacológico , Ácidos Grasos/química , Ácidos Grasos/aislamiento & purificación , Femenino , Furanos/química , Furanos/aislamiento & purificación , Furanos/farmacología , Humanos , Lípidos/química , Masculino , Estructura Molecular , Oncorhynchus keta/metabolismo , Ratas , Ratas Endogámicas Lew , Ratas Wistar , Testículo/química
2.
Toxicol In Vitro ; 24(6): 1720-6, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20510349

RESUMEN

Many effects of sesamol, an antioxidative constituent of sesame oil, have been reported for human health benefits due to its antioxidative action. However, we recently isolated two cytotoxic products, trimer and tetramer of sesamol, from oxidation of sesamol by an assay-guided purification. In this study, we have revealed some cytotoxic characteristics of these products in rat thymocytes and human leukemia K562 cells. Incubation of cells with trimer or tetramer at 10-30 microM for 24h significantly increased cell lethality and population of rat thymocytes containing hypodiploid DNA, suggesting cell death with DNA fragmentation, while it was not the case for 30 microM sesamol. The cytotoxic action of tetramer was more potent than that of trimer in rat thymocytes when their concentrations were 10-30 microM. The incubation of cells with 10 microM tetramer for 24h increased the population of cells with exposed phosphatidylserine, the activity of caspases, and the nick of DNA. These results indicate tetramer-induced apoptosis. In K562 cells, the incubation with tetramer at 10 microM for 72 h significantly inhibited the growth without affecting the lethality. However, tetramer at 30 microM significantly increased cell lethality. It is likely that tetramer exerts more cytotoxic action on normal non-proliferative cells (rat thymocytes) rather than proliferative cancer cells (human leukemia K562 cells). It may be necessary to consider the condition for preservation of sesamol and the safety of products from in vivo oxidation of sesamol for human health.


Asunto(s)
Antioxidantes/toxicidad , Apoptosis/efectos de los fármacos , Benzodioxoles/toxicidad , Linfocitos/efectos de los fármacos , Fenoles/toxicidad , Aceite de Sésamo/química , Animales , Antioxidantes/química , Benzodioxoles/química , Supervivencia Celular/efectos de los fármacos , Fraccionamiento Químico , Humanos , Células K562 , Linfocitos/patología , Oxidación-Reducción , Fenoles/química , Ratas , Ratas Wistar , Timo/citología
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