Microcirculation. 1996 Sep;3(3):279-86.
Apigenin inhibits tumor necrosis factor-induced intercellular adhesion molecule-1 upregulation in vivo.

Panés J1, Gerritsen ME, Anderson DC, Miyasaka M, Granger DN.
Author information
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Apigenin is a flavonoid that effectively blocks intercellular adhesion molecule-1 (ICAM-1) upregulation and leukocyte adhesion in response to cytokines in vitro. In the present study, we characterized the effects of tumor necrosis factor (TNF) on ICAM-1 expression in different tissues of the rat. We then assessed whether apigenin alters this response.
ICAM-1 expression was measured under baseline conditions or 5 h after treatment with rTNF. We used 125I-labeled anti-rat ICAM-1 monoclonal antibody (mAb) and an isotype-matched control mAb labeled with 131I to correct for nonspecific accumulation of the binding mAb. Animals were pretreated with either placebo, apigenin, narigenin (a flavonoid without inhibitory effect in vitro), or vehicle. Additional groups of animals were treated with either allopurinol, glutathione, dimethyl-thiourea, or an anti-CD18 monoclonal antibody in order to assess possible actions of flavonoids that were mediated via free radical scavenging or through interference with neutrophil function.
Treatment with rTNF resulted in a marked increase in ICAM-1 expression in all organs studied. The magnitude of the response varied in different organs and increases ranged from onefold (lung) to threefold (muscle). Treatment with apigenin blocked ICAM-1 upregulation in organs with low to intermediate responses to rTNF and it significantly attenuated the increased ICAM-1 expression in organs that normally exhibit more marked upregulation. Treatment with narigenin or vehicle did not affect rTNF-induced ICAM-1 upregulation in all tissues studied. Pretreatment with either allopurinol, free radical scavengers, or anti-CD18 monoclonal antibody did not affect the ICAM-1 upregulatory response to rTNF.
TNF-induced ICAM-1 upregulation in vivo effectively is blocked by apigenin through a mechanism that is unrelated to free radical scavenging or leukocyte function.


233-245 6/12/06 20:13 Page 241
Apigenin and cancer chemoprevention:
Progress, potential and promise (Review)
Department of Urology, 1Case Western Reserve University, 2University Hospitals of
Cleveland, 3Case Comprehensive Cancer Center, Cleveland, OH 44106, USA
Received March 7, 2006; Accepted May 9, 2006

6. Major limitations of apigenin
Apigenin in its pure form is unstable and is not very soluble
in water or organic solvents. These properties restrict the use
of apigenin in its pure forms. In its natural form, apigenin is
present in foods mostly as glycoside conjugates and various
acylated derivatives, which are more water soluble than the
parent compound (119, 120 and references therein). The
moiety with which apigenin is conjugated is an important
determinant of its absorption and bioavailability, since these
attributes may require enzymatic cleavage by mammalian
or microbial glucosidases (120). Studies have shown that
human absorption of quercetin glycoside from onions is far
better than that of pure quercetin (121,122). Consequently
it seems likely that apigenin in natural form bound to ß-
glycosides may be provide its best bioavailability.
Upon reaching the gut, apigenin is extensively metabolized
via the dual recycling scheme involving both enteric and
enterohepatic recycling (123,124). Apigenin has been shown
to be rapidly metabolized via UDP glucuronosyltransferase
UGT1A1 as glucoroside and sulfate conjugates which are more
readily transported in the blood and excreted in bile or urine
(125). Gradolatto et al (126) have shown that oral intake after
a single dose of radio-labeled apigenin in rats resulted in 51%
recovery of radioactivity in urine, 12% in feces, 1.2% in blood,
0.4% in the kidneys, 9.4% in the intestine, 1.2% in liver and
24.8% in the rest of the body within 10 days. The radioactivity
appeared in blood 24 h after oral apigenin intake. The kinetics
of apigenin in blood exhibited a relatively high elimination
half-time of 91.8 h compared to other dietary flavonoids.
These results suggest that although the bioavailability of
apigenin is limited, the slow pharmacokinetics may lead to
possible accumulation of this flavonoid in the tissues to
effectively impart its chemopreventive effects.

Ann Nutr Metab. 2006;50(3):167-72. Epub 2006 Jan 10.
Bioavailability of apigenin from apiin-rich parsley in humans.

Meyer H1, Bolarinwa A, Wolfram G, Linseisen J.
Author information
Absorption and excretion of apigenin after the ingestion of apiin-rich food, i.e. parsley, was tested.
Eleven healthy subjects (5 women, 6 men) in the age range of 23-41 years and with an average body mass index of 23.9 +/- 4.1 kg/m2 took part in this study. After an apigenin- and luteolin-free diet, a single oral bolus of 2 g blanched parsley (corresponding to 65.8 +/- 15.5 micromol apigenin) per kilogram body weight was consumed. Blood samples were taken at 0, 4, 6, 7, 8, 9, 10, 11 and 28 h after parsley consumption and 24-hour urine samples were collected. Apigenin was analyzed in plasma, urine and red blood cells by means of HPLC-ECD.
On average, a maximum apigenin plasma concentration of 127 +/- 81 nmol/l was reached after 7.2 +/- 1.3 h with a high range of variation between subjects. For all participants, plasma apigenin concentration rose after bolus ingestion and fell within 28 h under the detection limit (2.3 nmol/l). The average apigenin content in 24-hour urine was 144 +/- 110 nmol/24 h corresponding to 0.22 +/- 0.16% of the ingested dose. The flavone could be detected in red blood cells without showing dose-response characteristics.
A small portion of apigenin provided by food reaches the human circulation and, therefore, may reveal biological effects.
Copyright 2006 S. Karger AG, Basel.

PMID: 16407641 DOI: 10.1159/000090736