Nutrition 21 (2005) 389-394

www.elsevier.com/locate/nut
Basic nutritional investigation

Differential anti-inflammatory effects of phenolic compounds from

extra virgin olive oil identified in human whole blood cultures
Elizabeth A. Miles, Ph.D.*, Pinelope Zoubouli, B.Sc., Philip C. Calder, Ph.D., D.Phil.
Institute of Human Nutrition, School of Medicine, University of Southampton, Southampton, United Kingdom

Manuscript received February 24, 2004; accepted June 7, 2004.

Abstract Objective: The olive oil–rich Mediterranean diet protects against cardiovascular disease, which
involves inflammatory processes. This study investigated the effects of phenolic compounds found
in extra virgin olive oil on inflammatory mediator production by human mononuclear cells.
Methods: Diluted human blood cultures were stimulated with lipopolysaccharide in the presence
of phenolics (vanillic, p-coumaric, syringic, homovanillic and caffeic acids, kaempferol, oleuropein
glycoside, and tyrosol) at concentrations of 10⫺7 to 10⫺4 M. Concentrations of the inflammatory
cytokines tumor necrosis factor-␣, interleukin-1␤, and interleukin-6 and of the inflammatory
eicosanoid prostaglandin E2 were measured by enzyme-linked immunosorbent assay.
Results: Oleuropein glycoside and caffeic acid decreased the concentration of interleukin-1␤. At a
concentration of 10⫺4 M, oleuropein glycoside inhibited interleukin-1␤ production by 80%, whereas
caffeic acid inhibited production by 40%. Kaempferol decreased the concentration of prostaglandin
E2. At a concentration of 10⫺4 M, kaempferol inhibited prostaglandin E2 production by 95%. No
effects were seen on concentrations of interleukin-6 or tumor necrosis factor-␣ and there were no
effects of the other phenolic compounds.
Conclusions: Some, but not all, phenolic compounds derived from extra virgin olive oil decrease
inflammatory mediator production by human whole blood cultures. This may contribute to the
antiatherogenic properties ascribed to extra virgin olive oil. © 2005 Elsevier Inc. All rights
reserved.

Keywords: Olive oil; Phenolics; Cytokines; Inflammation; Prostaglandin

Introduction and/or anti-inflammatory effects of oleic acid [4,7]. How-

The Mediterranean diet protects against cardiovascular
disease [1,2]. This diet is rich in olive oil [3], leading to the
suggestion that it is the high consumption of olive oil that
confers the health benefit [4]. Olive oil consists primarily of
triacylglycerols rich in the monounsaturated fatty acid, oleic
acid. The non-glyceridic constituents of extra virgin olive
oil (EVOO), which comprise approximately 0.5% to 1.0%,
include at least 30 phenolic compounds [5]. The compo-
nents of EVOO that protect against cardiovascular disease
have not been fully elucidated. The development of cardio-
vascular disease includes a strong inflammatory component
[6]. Some researchers have demonstrated antiatherosclerotic
* Corresponding author. Tel.: ⫹44-23-8059-4689; fax: ⫹44-23-8059-
4383.
E-mail address: eam@soton.ac.uk (E.A. Miles).
ever, recent interest has been focusing on the biological
activities of the phenolic compounds found in EVOO. An
intake of phenolic compounds as large as 25 mg/d was
identified among populations that consumed large amounts
of EVOO [5]. This level of intake of phenolic compounds
has been associated with a lower incidence of cardiovascu-
lar disease [8]. Some EVOO phenolics have been shown to
inhibit eicosanoid production by animal and human cells in
vitro, suggesting that they might exert anti-inflammatory
effects [9,10]. This is supported by experiments with a
macrophage cell line in which phenolic compounds signif-
icantly decreased the production of the inflammatory cyto-
kine interleukin (IL)–1␤ at the level of protein and mRNA
[11]. Others have demonstrated that different EVOO phe-
nolics can increase or decrease the production of another
inflammatory mediator, nitric oxide, by macrophage cell
lines [12,13]. There are no reports of the effects of EVOO-

0899-9007/05/$ – see front matter © 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.nut.2004.06.031
390 E.A. Miles et al. / Nutrition 21 (2005) 389-394
Fig. 1. Chemical structures of some of the phenolic compounds studied.
derived phenolics on the production of inflammatory cyto-
kines by human cells. Therefore, in this study we investi-
gated the effects of eight EVOO-derived phenolic
compounds on the production of a range of proinflammatory
mediators (IL-1␤, IL-6, tumor necrosis factor-␣ [TNF-␣],
and prostaglandin E2 [PGE2]) by human whole blood cell
cultures stimulated with bacterial lipopolysaccharide (LPS).
The phenolics tested were vanillic acid, p-coumaric acid,
syringic acid, homovanillic acid, caffeic acid, oleuropein
glycoside, and tyrosol, which are commonly identified in
EVOO [5]. In addition, kaempferol was tested; this is
present in some preparations of EVOO as a minor constit-
uent (M. H. Gordon, personal communication, May 10,
2004). The structures of the phenolic compounds tested are
shown in Figs. 1 and 2.
Materials and methods
Materials
RPMI 1640 culture medium (without glutamine) was
purchased from Autogen Bioclear (Calne, UK). L-glu-
Fig. 2. Chemical structures of oleuropein and kaempferol.
tamine, benzyl penicillin, streptomycin sulfate, LPS,
vanillic acid, p-coumaric acid, syringic acid, homovanillic
acid, kaempferol, and caffeic acid were purchased from
Sigma Chemical Company (Poole, UK). Oleuropein glyco-
side and tyrosol were purchased from Extrasynthase
(Genay, France). Cytokine enzyme-linked immunosorbent
assay kits were purchased from Biosource Europe (Nivelles,
Belgium). PGE2 enzyme-linked immunosorbent assay kits
were manufactured by Neogen Corporation (Lexington,
KY, USA).
Whole blood culture
Blood was collected from fasted (⬎10 h) healthy male
volunteers (ages 18 to 25 y) into heparin (n ⫽ 6). Whole
blood was diluted 1:5 with RPMI 1640 medium supple-
mented with 0.75 mM L-glutamine and antibiotics (0.05
␮g/mL each of benzyl penicillin and streptomycin sulfate).
The diluted blood (1.7 mL/well) was placed in the wells of
a 24-well culture plate. Phenolic compounds were added to
provide final concentrations of 10⫺7, 10⫺6, 10⫺5, and 10⫺4
M. Phenolics were added in 80 ␮L of 2.5% ethanol to
produce a final concentration of 0.1% ethanol in culture.
Control cultures contained 0.1% ethanol but no phenolic
compound. LPS (0.2 mL; 50 ␮g/mL final concentration)
was added to stimulate cytokine production by monocytes.
The addition of 20 ␮L of RPMI 1640 medium produced a
final culture volume of 2 mL. Cultures were incubated at
37°C in a 5% CO2 atmosphere for 48 h. At the end of the
culture period, plates were centrifuged at 1000 rpm for 5
min. The supernatant medium was then carefully removed
to avoid disturbance, and aliquots were frozen at ⫺70°C
until analysis.
Measurement of cytokine and PGE2 concentrations
Cytokine (TNF-␣, IL-1␤, and IL-6) and PGE2 concen-
trations in cell culture supernatants were measured by en-
zyme-linked immunosorbent assay in accordance with the
manufacturers’ instructions. Limits of detection were 3
pg/mL (TNF-␣), 2 pg/mL (IL-1␤ and IL-6), and 0.1 ng/mL
(PGE2).
 E.A. Miles et al. / Nutrition 21 (2005) 389-394 391

* Cultures were incubated with or without the olive oil– derived phenolic compounds (vanillic acid, p-coumaric acid, syringic acid, homovanillic acid, kaempferol, tyrosol, oleuropein glycoside, and caffeic
acid). Data are shown as medians (25th, 75th quartiles) of cultures from six separate individuals. Median values down a column not sharing a superscript letter are significantly different from one another
Statistics

9021 (6659, 10 762)

9173 (7382, 11 334)
8189 (6185, 11 232)
8256 (5236, 9318)

4862 (3659, 6811)

Data are presented as medians and 25th and 75th quar-

Caffeic acid
tiles. The Kruskal-Wallis one-factor analysis of variance
(factor was phenolic concentration) was used to determine
whether each phenolic compound affected the production of
a particular mediator. Where a significant effect was ob-

7605a (5980, 11 802)

7870a (4451, 11 482)
8256a (5236, 9318)

7135a (5312, 9655)

1632b (1203, 3040)
served, Wilcoxon’s signed rank test was used to test for
significant differences between pairs. Linear relations be-
tween concentrations of phenolics and inflammatory medi-

Oleuropein
glycoside
ators were determined as Spearman’s correlations. In all
analyses, P ⱕ 0.05 was deemed statistically significant. All
statistical analyses were performed with SPSS 11.0 for

8362 (5638, 11 986)

8585 (5992, 12 071)
7943 (5923, 11 905)
7608 (5560, 11 269)
Windows (SPSS, Inc., Chicago, IL, USA).

8256 (5236, 9318)

Tyrosol
Results

Interleukin-1␤

8085 (5415, 10 079)

9082 (6217, 10 991)
9685 (7285, 12 380)
8256 (5236, 9318)

7075 (5371, 9974)

Unstimulated whole blood cultures contained 2287
pg/mL (985, 4730) of IL-1␤. Stimulation with LPS resulted

Kaempferol
in an increase in IL-1␤ concentration to 8256 pg/mL (5236,
9318). IL-1␤ concentration in LPS-stimulated cultures was
not significantly affected by vanillic acid, p-coumaric acid,
syringic acid, homovanillic acid, kaempferol, or tyrosol

8662 (7328, 10 341)

9034 (7688, 10 059)
9324 (8273, 10 038)
Homovanillic acid

8256 (5236, 9318)

8373 (6888, 9963)

(Table 1). The addition of oleuropein glycoside at 10⫺4 M
Interleukin-1␤ concentrations (pg/mL) in human whole blood cultures stimulated with lipopolysaccharide*

decreased the IL-1␤ concentration by an average of 80% to

1632 pg/mL (1203, 3040). This was significantly lower than
the IL-1␤ concentration in the stimulated control and in the
cultures with oleuropein glycoside at 10⫺7, 10⫺6, and 10⫺5
M (Table 1). The oleuropein glycoside concentration in the
8776 (7082, 10 866)
8463 (7627, 10 851)
8284 (8022, 11 344)
8022 (7311, 10 303)
8256 (5236, 9318)

cultures was significantly negatively correlated with the

IL-1␤ concentration (P ⬍ 0.001). There was also a signif-
Syringic acid

icant inverse correlation between the concentration of caf-

feic acid in the cultures and IL-1␤ concentration (P ⫽
0.017; Table 1).
8151 (5414, 10 236)
7916 (6790, 10 095)
6878 (5060, 10 210)
8256 (5236, 9318)
7920 (5629, 9798)

Interleukin-6
p-Coumaric acid

IL-6 concentration in the unstimulated cultures was

14 743 pg/mL (10 088, 20 769), which increased to 43 064
pg/mL (37 334, 47 250) in the LPS-stimulated cultures.
Phenolic compounds at concentrations up to 10⫺4 M did not
(P ⬍ 0.05, Wilcoxon’s signed rank test).
9201 (6146, 10 277)
8997 (6363, 10 243)
8728 (7260, 11 127)
9001 (5763, 10 728)

significantly alter the concentration of IL-6 in the culture

8256 (5236, 9318)

supernatants (data not shown).

Vanillic acid

Tumor necrosis factor-␣

Stimulation of whole blood cultures with LPS increased

concentration (M)

the concentration of TNF-␣ from 957 pg/mL (613, 1322) to

4967 pg/mL (343, 5935). Phenolic compounds at concen-
trations up to 10⫺4 M did not significantly alter the concen-
Phenolic
Table 1

tration of TNF-␣ in the culture supernatants (data not

10⫺7
10⫺6
10⫺5
10⫺4

shown).
0
392 E.A. Miles et al. / Nutrition 21 (2005) 389-394

* Cultures were incubated with or without the olive oil-derived phenolic compounds (vanillic acid, p-coumaric acid, syringic acid, homovanillic acid, kaempferol, tyrosol, oleuropein glycoside, and caffeic
acid). Data are shown as medians (25th, 75th quartiles) of cultures from six separate individuals. Median values down a column not sharing a superscript letter are significantly different from one another
Prostaglandin E2

287 (161, 1033)

544 (343, 986)
424 (200, 634)
449 (191, 633)
120 (47, 212)
Caffeic acid
PGE2 concentration increased from 8 ng/mL (7, 36) to
287 ng/mL (161, 1033) with the addition of LPS to the
cultures. Kaempferol caused a concentration-dependent de-
crease in the concentration of PGE2 in the cultures
(Kruskal-Wallis P ⫽ 0.001; Table 2). There was a signifi-

Oleuropein glycoside
cant negative correlation between concentrations of

287 (161, 1033)

615 (135, 1023)
469 (272, 1577)
kaempferol and PGE2 in the cultures (P ⫽ 0.027). PGE2

440 (73, 738)

116 (43, 406)
concentration in the presence of 10⫺4 M kaempferol was
significantly lower than in the cultures containing 10⫺7,
10⫺6, and 10⫺5 M kaempferol and in the control cultures (P
⬍ 0.03 in all cases; Table 2). PGE2 concentration in the
presence of 10⫺5 M kaempferol was significantly lower

287 (161, 1033)

645 (149, 1029)
than in the cultures containing 10⫺7 or 10⫺6 M kaempferol

620 (394, 940)

351 (144, 613)
145 (44, 1336)
(P ⬍ 0.03; Table 2). None of the other phenolic compounds

Tyrosol
tested significantly affected PGE2 production (Table 2).

Discussion

287a (161, 1033)

964a (206, 2201)
369a (207, 1069)
123b (39, 320)
8c (3, 19)
Kaempferol
The lower incidence of cardiovascular disease in Medi-
terranean countries has led to the suggestion that high con-
sumption of olive oil is protective against the development
of atherosclerosis [1,2]. Recently, interest has been focused
on the phenolic compounds contained in EVOO. EVOO
Homovanillic acid
Prostaglandin E2 concentrations (ng/mL) in human whole blood cultures stimulated with lipopolysaccharide*
phenolics have strong antioxidant properties and can protect

287 (161, 1033)

435 (331, 831)
387 (276, 675)
340 (229, 450)
166 (106, 311)
low-density lipoprotein from oxidative damage [14 –16].
Low-density lipoprotein oxidation is a prerequisite to ath-
erosclerotic plaque formation; thus, it has been postulated
that this is the mechanism by which EVOO-derived pheno-
lics protect against cardiovascular disease [14]. However,
the development of atherosclerotic plaques also has a strong
287 (161, 1033)

384 (197, 1028)

457 (218, 813)

279 (161, 574)

inflammatory component [6], with infiltration of the vessel

180 (90, 632)
Syringic acid

wall by leukocytes, including monocytes, which produce

inflammatory cytokines that play a prominent role [17–19].
There appears to be no information about the ability of
EVOO-derived phenolics to influence the production of
inflammatory cytokines by human cells. Therefore, in this
p-Coumaric acid

287 (161, 1033)

study we investigated the effects of eight EVOO-derived

403 (237, 632)
167 (92, 371)

302 (69, 371)

261 (56, 426)

phenolic compounds on the production of three inflamma-

tory cytokines and the inflammatory eicosanoid PGE2 by
LPS-stimulated human whole blood cultures. In such cul-
tures, inflammatory mediators are mainly produced by
monocytes.
(P ⬍ 0.05, Wilcoxon’s signed rank test).
287 (161, 1033)
718 (301, 1021)
214 (131, 1390)

The addition of oleuropein glycoside significantly de-

352 (192, 584)
287 (172, 698)
Vanillic acid

creased the concentration of IL-1␤ in the culture superna-

tants. Oleuropein glycoside is among the most abundant of
polyphenols in EVOO [5]. To our knowledge, this is the
first time that an EVOO-derived phenolic compound has
been shown to influence the production of IL-1␤ or of any
concentration (M)

inflammatory cytokine by human cells. There was also a

significant inverse correlation between concentrations of
caffeic acid and IL-1␤, indicating that this phenolic also
Phenolic
Table 2

inhibits IL-1␤ production. These observations are in agree-

10⫺7
10⫺6
10⫺5
10⫺4

ment with data from Crouvezier et al. [20] who demon-

0
 E.A. Miles et al. / Nutrition 21 (2005) 389-394
strated that phenolic compounds derived from green tea can
decrease the production of IL-1␤ by human leukocytes.
The addition of kaempferol significantly decreased and,
at a concentration of 10⫺4 M, almost abrogated, the pro-
duction of PGE2 by LPS-stimulated human cells in culture.
The concentration of kaempferol was negatively correlated
to the concentration of PGE2. Other groups have demon-
strated inhibitory effects of phenolic compounds on eico-
sanoid production by inflammatory cells in vitro [9,10,21].
De la Puerta et al. [9] studied a range of EVOO phenolics in
rat peritoneal leukocyte cultures. In these experiments oleu-
ropein glycoside, caffeic acid, and tyrosol at concentrations
of 1 to 2 ⫻ 10⫺6 M were able to inhibit leukotriene B4
production [9]. However, de la Puerta et al. did not measure
PGE2 concentrations in these cultures [9]. Another group
investigating effects of EVOO phenolics on eicosanoid gen-
eration by human platelets and leukocytes showed an inhi-
bition of thromboxane B2 and leukotriene B4 production
[10,21]. PGE2 is synthesized by cyclo-oxygenase-2. Phe-
nolic compounds from plant sources other than olives have
been shown to inhibit cyclo-oxygenase-2 activity [22] and
transcription [23] in human cell lines. Thus, it is feasible
that kaempferol decreased PGE2 production by LPS-stimu-
lated human cells by inhibition of cyclo-oxygenase-2. How-
ever, this requires further investigation.
In this study different phenolic compounds affected dif-
ferent inflammatory mediators, and many of the compounds
tested did not affect the production of IL-1␤ or PGE2 and
none of them affected the production of IL-6 or TNF-␣.
This is in agreement with the results of Crouvezier et al.
who showed that, of a range of tea-derived phenolics tested,
only some inhibited IL-1␤ production in human whole
blood cultures stimulated with LPS, and none altered IL-6
or TNF-␣ production [20]. Further, a study comparing the
effects of EVOO-derived phenolic compounds on adhesion
molecule expression by cultured human endothelial cells
demonstrated differential potencies of the compounds tested
[24]. The differing patterns of effects of the phenolic com-
pounds tested here and elsewhere [20,24] suggest that only
some of these compounds are anti-inflammatory or that
more than one mechanism may be involved in the anti-
inflammatory action of phenolics. The present study sug-
gests that phenolic compounds with a simple structure,
involving only a single phenol ring, may be unlikely to exert
anti-inflammatory effects by inhibition of production of
inflammatory cytokines or PGE2 and that a more complex
structure may be required to exert these effects. In accor-
dance with this idea, Carluccio et al. reported that oleuro-
pein aglycone was much more potent than tyrosol or hy-
droxytyrosol in decreasing adhesion molecule expression on
cultured human endothelial cells [24]. The reason for the
differential potencies of phenolic compounds is not clear,
but it may relate to the ability of cells to take up particular
phenolic compounds or to specific structural elements that
are required for interaction with cell signaling and transcrip-
tion factor systems.
393
Although the bioavailability of different phenolic com-
pounds varies [25], it appears that those from EVOO are
well absorbed in humans. For example, Vissers et al. re-
ported greater than 55% absorption of a range of EVOO-
derived phenolic compounds by human volunteers [26].
Nevertheless, it is unlikely that the plasma concentration of
these compounds will exceed 10⫺6 M, in common with
other phenolics [25,27]. Therefore, one limitation of the
results of the present study is that the phenolics that were
active had effects at concentrations that are unlikely to be
achieved in vivo. The present study used oleuropein glyco-
side, although the aglycone form of oleuropein is present in
larger amounts in EVOO [28]. Because oleuropein glyco-
side was able to inhibit IL-1␤ concentration, it will be
important to identify the effect of the more common agly-
cone. Carluccio et al. demonstrated that oleuropein agly-
cone was a more potent inhibitor of adhesion molecule
expression on cultured human endothelial cells than was the
glycoside [24]. In addition, it will be of interest to examine
the effects of hydroxytyrosol, which is found at higher
concentrations than tyrosol in EVOO [28], and which may
be more active, as demonstrated by Carluccio et al. [24].
In summary, our results show that some, but not all,
phenolic compounds from EVOO can inhibit IL-1␤ and
PGE2 production by LPS-stimulated human whole blood
cultures. This demonstrates, for the first time, a new anti-
inflammatory action of these compounds. In addition to the
reported antioxidant properties of these compounds [14 –
16], this may contribute to the antiatherosclerotic effect of
diets rich in olive oil [1,2].
References
[1] Hu FB. The Mediterranean diet and mortality— olive oil and beyond.
N Engl J Med 2003;348:2595– 6.
[2] Barzi F, Woodward M, Marfisi RM, Tavazzi L, Valagussa F, Mar-
chioli R. Mediterranean diet and all-causes mortality after myocardial
infarction: results from the GISSI-Prevenzione trial. Eur J Clin Nutr
2003;57:604 –11.
[3] Wahrburg U, Kratz M, Cullen P. Mediterranean diet, olive oil and
health. Eur J Lipid Sci Technol 2002;104:698 –705.
[4] Harwood JL, Yaqoob P. Nutritional and health aspects of olive oil.
Eur J Lipid Sci Technol 2002;104:685–97.
[5] Tuck KL, Hayball PJ. Major phenolic compounds in olive oil: me-
tabolism and health effects. J Nutr Biochem 2002;13:636 – 44.
[6] Ross R. Mechanisms of disease—atherosclerosis—an inflammatory
disease. N Engl J Med 1999;340:115–26.
[7] Massaro M, Carluccio MA, De Caterina R. Direct vascular anti-
atherogenic effects of oleic acid: a clue to the cardioprotective effects
of the Mediterranean diet. Cardiologia 1999;44:507–13.
[8] Hertog MGL, Feskens EJM, Hollman PCH, Katan MB, Kromhout D.
Dietary antioxidant flavonoids and risk of coronary heart-disease—
the Zutphen Elderly Study. Lancet 1993;342:1007–11.
[9] de la Puerta R, Gutierrez VR, Hoult JRS. Inhibition of leukocyte
5-lipoxygenase by phenolics from virgin olive oil. Biochem Pharma-
col 1999;57:445–9.
[10] Petroni A, Blasevich M, Papini N, Salami M, Sala A, Galli C.
Inhibition of leukocyte leukotriene B-4 production by an olive oil-
394 E.A. Miles et al. / Nutrition 21 (2005) 389-394
derived phenol identified by mass-spectrometry. Thromb Res
1997;87:315–22.
[11] Blonska M, Czuba ZP, Krol W. Effect of flavone derivatives on
interleukin-1 beta (IL-1 beta) mRNA expression and IL-1 beta protein
synthesis in stimulated RAW 264.7 macrophages. Scand J Immunol
2003;57:162– 6.
[12] Visioli F, Bellosta S, Galli C. Oleuropein, the bitter principle of
olives, enhances nitric oxide production by mouse macrophages. Life
Sci 1998;62:541– 6.
[13] Kim HK, Cheon BS, Kim YH, Kim SY, Kim HP. Effects of naturally
occurring flavonoids on nitric oxide production in the macrophage
cell line RAW 264.7 and their structure-activity relationships. Bio-
chem Pharmacol 1999;58:759 – 65.
[14] Visioli F, Galli C. The effect of minor constituents of olive oil on
cardiovascular disease: new findings. Nutr Rev 1998;56:142–7.
[15] Masella R, Giovannini C, Vari R, di Benedetto R, Coni E, Volpe R,
et al. Effects of dietary virgin olive oil phenols on low density
lipoprotein oxidation in hyperlipidemic patients. Lipids 2001;36:
1195–202.
[16] Gimeno E, Fito M, Lamuela-Raventos RM, Castellote AI, Covas M,
Farre M, et al. Effect of ingestion of virgin olive oil on human low-
density lipoprotein composition. Eur J Clin Nutr 2002;56:114 –20.
[17] Frostegard J, Ulfgren AK, Nyberg P, Hedin U, Swedenborg J,
Andersson U, Hansson GK. Cytokine expression in advanced human
atherosclerotic plaques: dominance of pro-inflammatory (Th1) and
macrophage-stimulating cytokines. Atherosclerosis 1999;145:33– 43.
[18] Plutzky J. Inflammatory pathways in atherosclerosis and acute coro-
nary syndromes. Am J Cardiol 2001;88:10K –5.
[19] Glass CK, Witztum JL. Atherosclerosis. The road ahead. Cell 2001;
104:503–16.
[20] Crouvezier S, Powell B, Keir D, Yaqoob P. The effects of phen-
olic components of tea on the production of pro- and anti-inflam-
matory cytokines by human leukocytes in vitro. Cytokine 2001;
13:280 – 6.
[21] Petroni A, Blasevich M, Salami M, Papini N, Montedoro GF, Galli C.
Inhibition of platelet-aggregation and eicosanoid production by phe-
nolic components of olive oil. Thromb Res 1995;78:151– 60.
[22] Banerjee T, Van der Vliet A, Ziboh VA. Downregulation of COX-2
and iNOS by amentoflavone and quercetin in A549 human lung
adenocarcinoma cell line. Prostaglandins Leukot Essent Fatty Acids
2002;66:485–92.
[23] Chen YC, Shen SC, Lee WR, Hou WC, Yang LL, Lee TJF. Inhibition
of nitric oxide synthase inhibitors and lipopolysaccharide induced
inducible NOS and cyclooxygenase-2 gene expressions by rutin,
quercetin, and quercetin pentaacetate in RAW 264.7 macrophages.
J Cell Biochem 2001;82:537– 48.
[24] Carluccio MA, Siculella L, Ancora MA, Massaro M, Scoditti E,
Storelli C, et al. Olive oil and red wine antioxidant polyphenols
inhibit endothelial activation—antiatherogenic properties of Mediter-
ranean diet phytochemicals. Arterioscler Thromb Vasc Biol 2003;23:
622–9.
[25] Scalbert A, Williamson G. Dietary intake and bioavailability of poly-
phenols. J Nutr 2000;130:2073S– 85.
[26] Vissers MN, Zock PL, Roodenburg AJC, Leenen R, Katan MB. Olive
oil phenols are absorbed in humans. J Nutr 2002;132:409 –17.
[27] Paganga G, RiceEvans CA. The identification of flavonoids as gly-
cosides in human plasma. FEBS Lett 1997;401:78 – 82.
[28] Servili M, Montedoro G. Contribution of phenolic compounds to
virgin olive oil quality. Eur J Lipid Sci Technol 2002;104:602–13.
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