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3rd meeting of young researchers at UP 1 - IJUP - Universidade do ...

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Inhibition <strong>of</strong> angiogenesis and inflamm<strong>at</strong>ion by a xanthohumolenriched<br />

beer in a r<strong>at</strong> skin-wound healing model<br />

Costa R. 1 , Magalhães P.J. 2 , Duarte D. 1 , Taveira T. 1 , Mendanha M. 1 , Soares R. 1 and Negrão<br />

R. 1<br />

1 Department <strong>of</strong> Biochemistry (U38/FCT), Faculty <strong>of</strong> Medicine, University <strong>of</strong> Porto, Portugal<br />

2 REQUIMTE – Department <strong>of</strong> Chemistry, Faculty <strong>of</strong> Sciences, University <strong>of</strong> Porto, Portugal<br />

Xanthohumol (XN), the principal flavonoid <strong>of</strong> the hop plant (Humulus lupulus L.) and a<br />

constituent <strong>of</strong> beer, has been suggested to have potential cancer chemopreventive activities [1].<br />

Angiogenesis, the form<strong>at</strong>ion <strong>of</strong> new blood vessels from pre-existing ones, in adulthood is<br />

localized and self-limited in time, as happens in tissue regener<strong>at</strong>ion, and it is closed rel<strong>at</strong>ed<br />

with inflamm<strong>at</strong>ory process [2]. It is well known th<strong>at</strong> most cancer chemopreventive agents show<br />

antiangiogenic properties in vitro and in vivo, a concept we termed “angioprevention” [3].<br />

Our aim was to evalu<strong>at</strong>e the effects <strong>of</strong> a XN-enriched beer on angiogenesis and inflamm<strong>at</strong>ion,<br />

in the skin-wound healing process.<br />

For skin wound-healing assay, two full skin-thickness longitudinal incisions were cre<strong>at</strong>ed on<br />

the <strong>do</strong>rsal skin <strong>of</strong> Wistar r<strong>at</strong>s, after the consumption <strong>of</strong> a stout beer enriched with 10 mg XN /L<br />

and a control stout beer (without XN) during 30 days. Beverages consumption was maintained<br />

until day 7 after skin incisions. The number <strong>of</strong> vessels formed in the incision area (vWF<br />

staining), and the nitric oxide (NO) release , N-acetylglucosaminidase (NAG) activity and IL-<br />

1β content in serum were measured. St<strong>at</strong>istical difference between various groups was<br />

evalu<strong>at</strong>ed by ANOVA followed by the Bonferroni test. Student’s t-test was used for<br />

comparison between two groups. Differences were considered significant whenever p< 0.05.<br />

The consumption <strong>of</strong> XN-enriched beer led to decreased number <strong>of</strong> vessels formed and decrease<br />

NAG activity, NO released as well as IL-1β content. The in vivo modul<strong>at</strong>ion <strong>of</strong> angiogenic and<br />

inflamm<strong>at</strong>ory effects by XN occurred in accordance with our previous in vitro results and also<br />

occurred when XN is topically administered in the same in vivo model.<br />

The nutritional supplement<strong>at</strong>ion <strong>of</strong> beer with XN manifested anti-angiogenic and antiinflamm<strong>at</strong>ory<br />

properties. These findings emphasize the cross-talk between angiogenesis and<br />

inflamm<strong>at</strong>ion and, provide clues to the development <strong>of</strong> useful therapeutic agents against<br />

inflamm<strong>at</strong>ion- and angiogenesis-associ<strong>at</strong>ed p<strong>at</strong>hologies. These findings also suggest th<strong>at</strong> these<br />

polyphenols may affect wound healing process, in wh<strong>at</strong> concerns inflamm<strong>at</strong>ion and<br />

angiogenesis, by gastrointestinal administr<strong>at</strong>ion. These health-promoting properties <strong>of</strong> XN can<br />

be interesting to the brewing community, concerning the production <strong>of</strong> XN-enriched beers.<br />

Supported by FCT (SFRH/BD/41888/2007 and SFRH/BD/27834/2006), iBeSa (P10-08) and<br />

University <strong>of</strong> Porto/Santander Totta.<br />

References:<br />

[1] P.J. Magalhães, D.O. Carvalho, J.M. Cruz, L.F. Gui<strong>do</strong>, A.A. Barros, N<strong>at</strong>. Prod. Communic<strong>at</strong>ions, 4<br />

(2009), 591-610.<br />

[2] C. Costa, J. Incio, R. Soares, Angiogenesis 10 (2007), 149-66.<br />

[3] A. Albini, R. Dell’Eva, R. Vené, N. Ferrari, D.R. Buhler, D.M. Noonan, G. Fassina, The FASEB<br />

Journal, 20 (2006) 527-529.<br />

284 3 rd <strong>meeting</strong> <strong>of</strong> <strong>young</strong> <strong>researchers</strong> <strong>at</strong> <strong>UP</strong>

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