Servicio de Información Comunitario sobre Investigación y Desarrollo - CORDIS

FP5

PROFOOD Informe resumido

Project ID: QLK1-CT-2001-01080
Financiado con arreglo a: FP5-LIFE QUALITY
País: Germany

In vivo data on possible health benefits of high-flavonoid tomato fruits generated by mouse and C. elegans feeding studies

In cooperation with BASF Plant Science (BPS) it was evaluated which animal system might be suitable for evaluating characterized tomato fruit material with elevated flavonoid content for disease preventing effects. Different systems were compared and the human CRP (C.reactive protein) transgenic mouse model was
chosen. CRP appears to be a good risk marker (and risk factor) for cardiovascular diseases.

Interleukin 1beta induces levels of CRP in human beings as well as in transgenic mice carrying the human CRP gene. Statins as well as fenofibrate decrease expression of transgenic CRP (positive control). A scientific plan was designed to elucidate whether flavonoid containing tomato material would reduce CRP expression as well. TNO Pharma (Leiden, The Netherlands) was identified as a partner running the mouse experiments. A contract for collaboration between partner 1 and TNO Pharma was signed.

Two different extracts derived from transgenic tomato skin were compared with non-transgenic material and a fenofibrate diet. The tomato material was prepared by partner 5 and delivered to TNO pharma.

As the feeding trials started only in November/December a neutral prolongation of the PROFOOD project was granted.

Four groups of hCRPtg mice received chow diet either not supplemented (control) or supplemented with wildtype tomato peel (0.4% w/w, Tom-Con), or flavonoid-enriched tomato peel (0.4% w/w, Flavo), or fenofibrate (0.1% w/w, positive control) for a total of 7 weeks. After 6 weeks mice were intraperitoneally challenged with IL-1beta to raise hCRP expression.

After recovery in week 7, mice
were subjected to a 2 weeks-rebound period and fed a standard chow diet to test whether the tomato peel-induced effects on basal hCRP expression disappeared. RESULTS: Basal hCRP-levels rapidly decreased in both tomato peel-fed groups and remained significantly lower than starting values until the end of the intervention period (except for the Flavo group in week 4). Two animals of the Flavo group looked unhealthy from week 3 onwards and also displayed a high plasma fibrinogen level, which is an inflammation marker independent of hCRP. When these unhealthy animals were excluded, the maximal hCRP-lowering effect in the Flavo group was 55%(P<0.05; week 4) as compared to the chow-fed control group, whereas the hCRP-lowering effect in the Tom-Con group was less pronounced and only 44% (P<0.05; week 4). The additional effect of flavonoid-enriched tomato peel compared to wildtype tomato peel on basal hCRP levels became significant in week 6 and 7. Both types of tomato peel did not suppress an IL-1beta-induced expression of hCRP, whereas the positive control, fenofibrate, strongly suppressed this acute inflammatory effect of IL-1beta. After a 2-weeks rebound period in which all groups received standard chow diet, plasma hCRP levels recovered in all treatment groups and returned to the initial levels at t=0, except in the Tom-Con group, in which hCRP levels remained decreased. CONCLUSION: The relatively strong reduction of basal plasma hCRP levels achieved with tomato peel indicates that tomato peel-feeding strongly dampens low-grade chronic inflammation associated with cardiovascular disease. The anti-inflammatory potency of tomato peel is lower than that of fenofibrate and does not allow to suppress an acute, IL-1beta-based inflammatory stimulus. Compared to control tomato peel, flavonoid-enriched tomato peel is more advantageous because its inflammation-dampening effect is a) stronger and b) very specific (cf. reversibility of the hCRP-lowering effect). These beneficial properties of flavonoid-enriched tomato peel may have relevance for the prevention of atherosclerotic lesion development.

A second study on possible health promoting effects of high-flavonoid toamtoes was carried out using the model system C. elegans. The tomato extracts displayed a remarkable wide spectrum of activities with some that depending on the flavonoid content and their particular composition reduce effectively ageing processes in the nematode C. elegans in vivo. It is highly suggestive that similar phenomena take place also in humans.

Contacto

Karin HERBERS, (Head of unit)
Tel.: +49-621-6028106
Fax: +49-621-6027789
Correo electrónico
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