Transcript

Abstracts of Pharma Nutrition 2013 / PharmaNutrition 2 (2014) 75–119 97

Keywords: Cow’s milk allergy; Non digestible oligosaccharides;Cytokines; Mouse model

http://dx.doi.org/10.1016/j.phanu.2013.11.060

[P20]

Effects of saw palmetto on voiding function and bladder mus-carinic receptors in rats

Y. Ito 1,∗, N. Kojima 1, M. Kitamura 1, E. Hikiyama 1, A. Suzuki 2, M.Kurokawa 2, S. Yamada 1

1 University of Shizuoka, Japan2 Q’sai Co., Ltd., Japan

Saw palmetto extract (SPE), an extract from the ripe berried ofthe American dwarf palm, has been widely used as a therapeuticremedy for urinary dysfunction due to benign prostatic hyperplasia(BPH). SPE contained free fatty acid (more than 90%). So we exam-ined the effects of SPE and free fatty acids on the micturition andon muscarinic receptors in rats.

Binding activities of SPE and free fatty acids (lauric acid, oleicacid and myristic acid) for muscarinic receptors were measuredby inhibitory effect on specific binding of selective radioligand,[3H]Nmethylscopolamine (NMS) in rat brain. In order to test theeffect of SPE on lower urinary functions, SPE (60 mg/kg) or fattyacid (24 mg/kg) were orally administered to Goto-Kakizai rats (GKrats) for two month to test the effect of repeated administrationof SPE or fatty acids on the voiding behaviors. The time of micturi-tion and micturition volume was measured after the administrationof pure water (30 mL/kg). Micturition frequency, voiding speed,voiding volume and micturition interval were calculated from therecorded data.

SPE and oleic acid inhibited specific [3H]NMS binding in rat brainin a concentration-dependent manner with IC50 values of 131.2and 176.5 �g/mL, respectively. Lauric acid and myristic acid did notinhibit specific [3H]NMS binding. However, lauric acid and myristicacid potentiated inhibition by oleic acid of specific [3H]NMS bind-ing. Repeated (2-month) oral administration of SPE and mixtureof oleic acid and lauric acid which are main components of SPE,increased significantly the voided volume in GK rats.

The present results revealed that oleic acid could bind to mus-carinic receptor and that lauric acid and myristic acid potentiatedmuscarinic receptor binding by oleic acid. Repeated administrationof SPE and mixture of oleic acid and lauric acid increased signifi-cantly the bladder capacity.

Keywords: Lower urinary function; Muscarinic receptor; Uri-nary dysfunction; Free fatty acid

http://dx.doi.org/10.1016/j.phanu.2013.11.061

[P21]

Prostalandin E2 (PGE2) production by RAW264.7 macrophagesis suppressed by newly synthesized �7-eicosatrienoic acid(�7,11,14–20:3)

L.T. Chuang

Yuanpei University, Taiwan

�7-Eicosatrienoic acid (�7-ETrA; �7,11,14–20:3) is a rarepolyunsaturated fatty acid (PUFA) originally identified in seedsof Pinaceae plants. We showed previously that pinolenic acid(PNA; �7,11,14–20:3) and its elongation metabolite �7-ETrAcould substitute for arachidonic acid (AA) in the phospholipids ofcultured macrophages, with concomitant inhibition of lipopolysac-charide (LPS)-stimulated prostaglandin E2 (PGE2) production. Since

�7-ETrA is not commercially available, we chemically synthe-sized �7-ETrA from PNA and investigated whether �7-ETrAalone was capable of suppressing PGE2 production by RAW264.7macrophages.

We demonstrate that �7-ETrA can be synthesized successfullyby 2-carbon elongation from PNA, and isolated in pure form usingargentated column chromatography. The identity and purity (>98%)of �7-ETrA were confirmed by gas chromatography (GC)/GC–massspectroscopy. Supplementation of cultured macrophages withdifferent concentrations of �7-ETrA (10, 25, 50 or 100 �M) signifi-cantly reduced PGE2 production (by up to 84%) and down-regulatedtype-2 cyclooxygenase (COX-2) expression at both the transla-tion and transcription levels. Additional studies revealed that theseinhibitory effects on the production of pro-inflammatory mediatorscould be accounted for, in part, by blocking the translocation ofnuclear factor-kappa B (NF-�B) into nucleus, but not to the acti-vation of mitogen-activated protein kinases (MAPK). Exogenous�7-ETrA was incorporated into cellular phospholipids and substi-tuted AA in a dose-dependent manner. Based on the results of fattyacid competition experiments, the reduction in PGE2 productioncaused by supplementation of cells with �7-ETrA might also bethe result of competition between this unusual fatty acid and AAfor COX-2. In conclusion, we have shown that synthesized �7-ETrAsuppresses PGE2 production by macrophages by substituting for AAin cellular phospholipids, competing with AA for COX-2 enzymeand down-regulating NF-�B-mediated COX-2 expression.

This work was supported by National Science Council, Taipei,Taiwan (101-2628-E-264-001-).

Keywords: �7-Eicosatrienoic acid; Prostaglandin E2; Type-2cyclooxygenase

http://dx.doi.org/10.1016/j.phanu.2013.11.062

[P22]

The effects of non digestible oligosaccharides in a murine modelfor chronic allergic asthma

K.A.T. Verheijden 1, L.E.M. Willemsen 1, S.A. Overbeek 1, J.Garssen 1,2, A.D. Kraneveld 1, G. Folkerts 1,∗

1 Utrecht University, The Netherlands2 Danone Research, The Netherlands

Chronic allergic asthma is an inflammatory disorder of theairways characterized by airway hyperresponsiveness, inflamma-tion and reversible airway obstruction. In addition, structuralchanges in the airways, like sub-epithelial fibrosis, smooth musclehypertrophy/hyperplasia, intra-epithelial eosinophils and gobletcell hyperplasia are observed. In recent years, there has been anincreased interest in using prebiotics as a novel anti-allergic ther-apy.

Prebiotics are ‘selectively fermented ingredients that result inspecific changes in the composition and/or activity of the gastroin-testinal microbiota, thus conferring benefit(s) upon host health’. Inthe present study, we investigated the effect of prebiotics on thedevelopment of chronic asthma.

BALB/c mice were sensitized with phosphate buffered saline(PBS) or 10 �g ovalbumin on day 0 and 12. Mice were dailychallenged with PBS or 5% ovalbumin on day 17 till 23and 3 times/week from day 24 till 55. From day −21 till56 mice were fed with a control diet or a diet contain-ing a mixture of short-chain-galacto-oligosaccharides (scGOS),long-chain-fructo-oligosaccharides (lcFOS) and pectin derived-acidic-oligosaccharides (pAOS) in a ratio of 9:1:2. On day 56, airwayhyperresponsiveness was measured, bronchoalveolar-lavage fluidand serum were collected.

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