J Nat Prod 1997 Aug;60(8):775-8
Flavonoids as inhibitors
or enhancers of the cytotoxicity of tumor necrosis factor-alpha
in L-929 tumor cells.
Department of Physiology and Pharmacology, University
of Strathclyde, Glasgow, U.K. email@example.com
The effects of some selected flavonoids on tumor necrosis
factor-alpha (TNF)-induced cytotoxicity in murine fibroblast
L-929 cells were studied. All of the flavanones tested
as well as a flavan, epicatechin, protected L-929 cells
from TNF-induced cell death of the flavanones tested,
hesperetin, isosakuranetin, and pinocembrin failed to
modify TNF cytotoxicity, but the 3',4'-dihydroxyflavanones,
eriodictyol and taxifolin, showed a protective effect.
Eriodictyol was the most potent protective agent of
all the flavonoids tested, while a 4'-hydroxyflavanone,
naringenin, rather showed enhancement of TNF cytotoxicity.
Of the flavones tested, chrysin and apigenin markedly
augmented the cytotoxicity of TNF, while luteolin showed
a weak protective effect. The magnitude of protection
and potentiation by these flavonoids were concentration-dependent
and these effects were not altered when the flavonoids
were added as much as 2 h after TNF treatment.
PMID: 9287415, UI: 97433502
J Pharm Pharmacol 1998 May;50(5):561-4
morphine withdrawal in-vitro.
Capasso A, Piacente S, Pizza C, Sorrentino L
Department of Pharmaceutical Sciences, University of
Salerno, Penta di Fisciano, Italy.
The effects of quercetin, flavone, catechin and chrysin
on the naloxone-precipitated withdrawal contracture
of the acute morphine-dependent guinea-pig ileum have
been investigated in-vitro. After 4 min in-vitro exposure
to morphine a strong contracture of guinea-pig isolated
ileum was observed after the addition of naloxone. All
the flavonoids, injected 10 min before morphine at concentrations
between 10(-7) and 10(-5) M, were capable of blocking
naloxone-induced contracture after exposure to morphine
in a concentration-dependent fashion. IC50 values calculated
for quercetin, flavone, catechin and chrysin were 2.7
x 10(-6), 7.3 x 10(-7), 8.5 x 10(-7) and 5.3 x 10(-6)
M, respectively. These results suggest that flavonoids
might play an important role in the control of morphine
PMID: 9643451, UI: 98305604
Science 1984 Sep 7;225(4666):1032-4
Inhibition of human estrogen
synthetase (aromatase) by flavones.
Kellis JT Jr, Vickery LE
Several naturally occurring and synthetic flavones were
found to inhibit the aromatization of androstenedione
and testosterone to estrogens catalyzed by human placental
and ovarian microsomes. These flavones include (in order
of decreasing potency) 7,8-benzoflavone, chrysin, apigenin,
flavone, flavanone, and quercetin; 5,6-benzoflavone
was not inhibitory. 7,8-Benzoflavone and chrysin were
potent competitive inhibitors and induced spectral changes
in the aromatase cytochrome P-450 indicative of substrate
displacement. Flavones may thus compete with steroids
in their interaction with certain monooxygenases and
thereby alter steroid hormone metabolism.
PMID: 6474163, UI: 84300283
Biochem Pharmacol 1990 Nov 15;40(10):2227-31
a naturally-occurring ligand for benzodiazepine receptors,
with anticonvulsant properties.
JH, Paladini AC, Wolfman C, Levi de Stein M, Calvo D,
Diaz LE, Pena C
Instituto de Biologia Celular, Facultad de Medicina,
Buenos Aires, Argentina.
Chrysin (5,7-di-OH-flavone) was identified in
Passiflora coerulea L., a plant used as a sedative in
folkloric medicine. Chrysin was found to be a ligand
for the benzodiazepine receptors, both central (Ki =
3 microM, competitive mechanism) and peripheral (Ki
= 13 microM, mixed-type mechanism). Administered to
mice by the intracerebroventricular route, chrysin was
able to prevent the expression of tonic-clonic seizures
induced by pentylenetertrazol. Ro 15-1788, a central
benzodiazepine receptor antagonist, abolished this effect.
In addition, all of the treated mice lose the normal
righting reflex which suggests a myorelaxant action
of the flavonoid. The presence in P. coerulea of benzodiazepine-like
compounds was also confirmed.
PMID: 2173925, UI: 91058598
Arch Pharm Res 1994 Apr;17(2):71-5
of plant flavonoids in the Salmonella assay system.
Choi JS, Park KY, Moon SH, Rhee SH, Young HS
Dept. of Food and Nutrition, National Fisheries University
of Pusan, Korea.
The antimutagenic effects of 27 kinds of plant flavonoids
on the mutagenicity of aflatoxin B1(AFB1) and N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)
in Salmonella typhimurium TA100 were investigated. In
the mixed applications of AFB1 (1 microgram/plate) with
the flavonoids (300 micrograms/plate) in the presence
of a mammalian metabolic activation system (S9 mix),
chrysin, apigenin, luteolin and its glucoside, kaempferol,
fisetin, morin, naringenin, hesperetin, persicogenin,
(+)-catechin and (-)-epicatechin showed the antimutagenic
effect against AFB1 with more than 70% inhibition rate.
A little or no antimutagenicities except flavone against
MNNG (0.5 microgram/plate) were observed. For the antimutagenicity
of the flavonoids on AFB1, the flavonoid structure that
contains the free 5-, 7-hydroxyl group seemed to be
essential. However, saturation of the 2,3-double bond
or elimination of the 4-keto group did not affect the
PMID: 10319134, UI: 99252692
Biochem Pharmacol 1984 May 1;33(9):1525-30
Modification of platelet
function and arachidonic acid metabolism by bioflavonoids.
Landolfi R, Mower RL, Steiner M
The mechanism of the antiaggregating activity of flavonoids
was studied in vitro. The activity of fifteen different
compounds was tested on platelet aggregation and arachidonic
acid metabolism. The effect of flavonoids on platelet
adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels
under basal conditions, as well as after stimulation
by prostacyclin (PGI2), was also measured. The glycons
of flavonoids in general and the flavanone derivatives
that we tested did not affect platelet function. On
the other hand, flavone, chrysin , apigenin and phloretin
inhibited platelet aggregation by depressing the cyclooxygenase
pathway. In addition, flavone, chrysin and apigenin
reduced the platelet cyclic AMP response to PGI2. This
effect was probably mediated by an inhibition of adenylate
cyclase. Myricetin and quercetin, however, increased
the PGI2-stimulated rise of platelet cyclic AMP. Both
of these flavonoids inhibited primarily lipoxygenase
activity. Modification of platelet cyclic AMP metabolism
through inhibition of phosphodiesterase activity was
found to be the probable mechanism of their antiaggregating
PMID: 6329230, UI: 84231526
J Steroid Biochem Mol Biol 1993 Sep;46(3):381-8
of aromatase enzyme activity in human preadipocytes.
Campbell DR, Kurzer MS
Department of Food Science and Nutrition, University
of Minnesota, St. Paul 55108, USA.
Eleven flavonoid compounds were compared with aminoglutethimide
(AG), a pharmaceutical aromatase inhibitor, for their
abilities to inhibit aromatase enzyme activity in a
human preadipocyte cell culture system. Flavonoids exerting
no effect on aromatase activity were catechin, daidzein,
equol, genistein, beta-naphthoflavone (BNF), quercetin
and rutin. The synthetic flavonoid, alpha-naphthoflavone
(ANF), was the most potent aromatase inhibitor, with
an I50 value of 0.5 microM. Three naturally-occurring
flavonoids, chrysin, flavone, and genistein 4'-methyl
ether (Biochanin A) showed I50 values of 4.6, 68, and
113 microM, respectively, while AG showed an I50 value
of 7.4 microM. Kinetic analyses showed that both AG
and the flavonoids acted as competitive inhibitors of
aromatase. The Ki values, indicating the effectiveness
of inhibition, were 0.2, 2.4, 2.4, 22, and 49 microM,
for ANF, AG, chrysin, flavone, and Biochanin A, respectively.
Chrysin, the most potent of the naturally-occurring
flavonoids, was similar in potency and effectiveness
to AG, a pharmaceutical aromatase inhibitor used clinically
in cases of estrogen-dependent carcinoma. These data
suggest that flavonoid inhibition of peripheral aromatase
activity may contribute to the observed cancer-preventive
hormonal effects of plant-based diets.
PMID: 9831487, UI: 99047382
Environ Health Perspect 1998 Feb;106(2):85-92
Molecular basis of the
inhibition of human aromatase (estrogen synthetase)
by flavone and isoflavone phytoestrogens: A site-directed
Kao YC, Zhou C, Sherman M, Laughton CA, Chen S
Division of Immunology, Beckman Research Institute of
the City of Hope, Duarte, CA 91010, USA.
Flavone and isoflavone phytoestrogens are plant chemicals
and are known to be competitive inhibitors of cytochrome
P450 aromatase with respect to the androgen substrate.
Aromatase is the enzyme that converts androgen to estrogen;
therefore, these plant chemicals are thought to be capable
of modifying the estrogen level in women. In this study,
the inhibition profiles of four flavones [chrysin (5,
7-dihydroxyflavone), 7,8-dihydroxyflavone, baicalein
(5,6,7-trihydroxyflavone), and galangin (3,5,7-trihydroxyflavone)],
two isoflavones [genistein (4,5,7-trihydroxyisoflavone)
and biochanin A (5,7-dihydroxy-4-methoxyisoflavone)],
one flavanone [naringenin (4, 5,7-trihydroxyflavanone)],
and one naphthoflavone (alpha-naphthoflavone) on the
wild-type and six human aromatase mutants (I133Y, P308F,
D309A, T310S, I395F, and I474Y) were determined. In
combination with computer modeling, the binding characteristics
and the structure requirement for flavone and isoflavone
phytoestrogens to inhibit human aromatase were obtained.
These compounds were found to bind to the active site
of aromatase in an orientation in which rings A and
C mimic rings D and C of the androgen substrate, respectively.
This study also provides a molecular basis as to why
isoflavones are significantly poorer inhibitors of aromatase
PMID: 9435150, UI: 99289389
Pharmacol Biochem Behav 1997 Dec;58(4):887-91
Anxiolytic natural and
synthetic flavonoid ligands of the central benzodiazepine
receptor have no effect on memory tasks in rats.
JB, Ardenghi P, Dias M, Ferreira MB, Izquierdo I, Medina
Centro de Memoria, Departamento de Bioquimica, I.C.B.S.,
Universidade Federal do Rio Grande do Sul, Porto Alegre,
The naturally occurring flavonoids, chrysin (5,7-dihydroxyflavone)
and apigenin (5,7,4'-trihydroxyflavone), and the synthetic
compound, 6,3'-dinitroflavone have been recently reported
to selectively bind with high affinity to the central
benzodiazepine receptor, and to exert powerful anxiolytic
and other benzodiazepine-like effects in rats. Their
chemical analog, quercetin, shares none of these effects.
In the present article we find that, in contrast to
diazepam, chrysin, apigenin, and 6,3'-dinitroflavone
have no amnestic effect on acquisition or retention
of three different learning tasks (inhibitory avoidance,
shuttle avoidance, and habituation to an open field),
even when given at doses higher than those previously
reported to be anxiolytic. Apigenin had a slight enhancing
effect on training session performance and, when given
posttraining, on test session retention, of crossing
responses in the open field and hindered retention of
inhibitory avoidance, and showed no anxiolytic action
in an elevated plus maze. Unlike diazepam, none of these
drugs had any analgesic effect in the tail-flick test.
The data suggest that chrysin, apigenin, and 6,3'-dinitroflavoine,
three flavonoids derivatives possessing anxioselective
effects acting on central benzodiazepine receptors,
may deserve clinical trials as anxiolytic agents.
PMID: 9408191, UI: 98070129
Arch Pharm Res 1999 Jun;22(3):309-12
aromatase activity by flavonoids.
Jeong HJ, Shin YG, Kim IH, Pezzuto JM
Department of Medicinal Chemistry and Pharmacognosy,
College of Pharmacy, University of Illinois at Chicago,
60612, USA. firstname.lastname@example.org
In searching for potent cancer chemopreventive agents
from synthetic or natural products, 28 randomly selected
flavonoids were screened for inhibitory effects against
partially purified aromatase prepared from human placenta.
Over 50% of the flavonoids significantly inhibited aromatase
activity, with greatest activity being demonstrated
with apigenin (IC50: 0.9 microg/mL), chrysin (IC50:
1.1 microg/mL), and hesperetin (IC50: 1.0 microg/mL).
PMID: 10403137, UI: 99329931
AIDS Res Hum Retroviruses 1996 Jan 1;12(1):39-46
Inhibition of HIV activation
in latently infected cells by flavonoid compounds.
Critchfield JW, Butera ST, Folks TM
Retrovirus Diseases Branch, National Center for Infectious
Diseases, Centers for Disease Control and Prevention,
Atlanta, Georgia 30333, USA.
Acute HIV-1 infection of H9 and C8166 cultures has been
shown to be suppressed by certain flavonoids, and evidence
for inhibition of HIV-1 protease, integrase, and reverse
transcriptase by flavonoids also exists. The present
aim was to determine whether flavonoids inhibit HIV-1
activation in models of latent infection. By screening
flavonoids from six different classes, three structurally
related compounds (chrysin, acacetin, and apigenin)
were identified that inhibited HIV expression in TNF-alpha-treated
OM-10.1 cultures. The three compounds had favorable
potencies against HIV activation in relation to their
growth inhibitory effects (therapeutic index 5-10).
Chrysin also inhibited HIV expression in response to
PMA in OM-10.1 cells, in ACH-2 cells stimulated with
either TNF-alpha or PMA, and in 8E5 cultures. Furthermore,
return to viral latency in OM-10.1 cells previously
exposed to TNF-alpha occurred over a shorter time interval
when chrysin was added. The inhibition of HIV activation
was not dependent on preincubation with flavonoids relative
to TNF, and was characterized by a lack of HIV RNA accumulation
by Northern analysis. Gel-shift experiments revealed
that NF-kappa B activation after TNF-alpha treatment
was not inhibited by these agents, suggesting that some
other critical factor(s) needed for viral transcription
was being affected. These findings indicate that flavonoids
inhibit HIV-1 activation via a novel mechanism, and
that these agents are potential candidates for therapeutic
strategies aimed at maintaining a cellular state of
PMID: 8825617, UI: 96423016
Steroids 1997 Apr;62(4):365-72
and antiestrogenic activities of phytochemicals with
the human estrogen receptor expressed in yeast.
Collins BM, McLachlan JA, Arnold SF
Tulane-Xavier Center for Bioenvironmental Research,
Tulane University Medical Center, New Orleans, LA 70112,
We have used the expression of the human estrogen receptor
(hER) and two estrogen response elements linked to the
lacZ gene in yeast (YES) to study the estrogenic and
antiestrogenic activities of various phytochemicals.
Coumestrol, alpha-zearalenol, or genistein could produce
beta-galactosidase activity comparable to estradiol,
but these required concentrations 100 to 1000-fold greater
than estradiol. These compounds did not possess antiestrogenic
activity. Narigenin, kaempferide, phloretin, biochanin
A, flavone, or chrysin only partially induced beta-galactosidase
activity in the YES at any concentration tested. When
narigenin, kaempferide, or phloretin was given concurrently
with estradiol, the estradiol-dependent beta-galactosidase
activity was not inhibited by more than 50%. However,
biochanin A, flavone, or chrysin could inhibit the activity
of estradiol in a dose-response manner with IC50 values
of 500 nM, 2 microM, and 10 microM, respectively. Combinations
of biochanin A, chrysin, and flavone decreased estradiol-dependent
beta-galactosidase activity in an additive fashion.
Similar to the antiestrogens tamoxifen or ICI 182, 780,
the antiestrogenic activity of these compounds with
the exception of chrystin involved the disruption of
hER dimerization, as demonstrated in the yeast two-hybrid
system. Biochanin A, chrysin, or flavone were less effective
in inhibiting the activity of an estrogenic polychlorinated
biphenyl than they were inhibiting the activity of estradiol.
Interestingly, this latter group of antiestrogenic phytocompounds
did not inhibit the estrogenic activity of such phytochemicals
as coumestrol or genistein. These results suggest that
the antiestrogenic activity of biochanin A and flavone
occurs by a mechanism similar to tamoxifen or ICI 182,780.
Moreover, it seems that phytochemicals functioning as
antiestrogens do not inhibit the activity of all estrogenic
chemicals to the same extent. This suggests that conformational
changes induced by different estrogens bound to the
hER may regulate the antiestrogenic activity of a compound.
PMID: 9090797, UI: 97246198
Bioorg Med Chem Lett 1999 Mar 22;9(6):869-74
Synthesis and hypoglycemic
effect of chrysin derivatives.
Shin JS, Kim KS, Kim MB, Jeong JH, Kim BK
College of Pharmacy, Seoul National University, Korea.
A series of 18 chrysin derivatives, prepared by alkylation
and condensation, were fully characterized by NMR and
other techniques and tested in vivo against the diabetes
mellitus. Several modified compounds especially those
with propyl, butyl, octyl and tolyl groups were found
to have hypoglycemic effect on diabetec mice in spite
of the fact that chrysin itself had inhibited insulin
release by 40-60%. None of the test animals died at
the maximum dose 500mg/kg and did not cause any significant
change in general feature, water and food consumption,
body weight and organ weight when we examined the acute
oral toxicity of those compounds having significant
PMID: 10206552, UI: 99221393
Microbiologica 1990 Jul;13(3):207-13
Effects of propolis
flavonoids on virus infectivity and replication.
M, Tateo F, Pagani L, Luini M, Romero E
Istituto di Microbiologia, Universita degli Studi di
The effect of five propolis flavonoids on the
infectivity and replication of some herpesvirus, adenovirus,
coronavirus and rotavirus strains has been studied.
Experiments were performed in vitro in cell cultures
using the viral plaque reduction technique. The cytotoxicity
of flavonoids, including chrysine, kaempferol, acacetin,
galangin and quercetin, was evaluated on uninfected
monolayers to determine their effect on cell growth
and viability. Chrysine and kaempferol caused a concentration-dependent
reduction of intracellular replication of herpes-virus
strains when monolayers were infected and subsequently
cultured in a drug-containing medium. However, virus
infectivity was not significantly affected. Acacetin
and galangin had no effect on either the infectivity
or replication of any of the viruses studied. Quercetin
reduced infectivity and intracellular replication, but
only at the highest concentrations tested.
PMID: 2125682, UI: 91109590
J Nat Prod 1994 Jan;57(1):42-51
Anti-AIDS agents, 10.
Acacetin-7-O-beta-D-galactopyranoside, an anti-HIV principle
from Chrysanthemum morifolium and a structure-activity
correlation with some related flavonoids.
Hu CQ, Chen K, Shi Q, Kilkuskie RE, Cheng YC, Lee
Natural Products Laboratory, School of Pharmacy, University
of North Carolina, Chapel Hill 27599.
An active anti-HIV principle, acacetin-7-O-beta-D-galactopyranoside,
has been isolated from Chrysanthemum morifolium. Seven
additional flavonoids isolated from this plant, 13 known
related flavonoids, and 14 synthetic flavonoids were
also evaluated as inhibitors of HIV replication in H9
cells. A known flavone, chrysin, was found to be the
most promising compound in this series. Flavonoids with
hydroxy groups at C-5 and C-7 and with a C-2-C-3 double
bond were more potent inhibitors of HIV growth. In general,
the presence of substituents (hydroxyl and halogen)
in the B-ring increased toxicity and/or decreased activity.
PMID: 8158164, UI: 94209934
Biosci Biotechnol Biochem 1999 Oct;63(10):1787-90
Inhibition of xanthine
oxidase by flavonoids.
Nagao A, Seki M, Kobayashi H
National Food Research Institute, Ministry of Agriculture,
Forestry and Fisheries, Tsukuba, Ibaraki, Japan. email@example.com
Various dietary flavonoids were evaluated in vitro for
their inhibitory effect on xanthine oxidase, which has
been implicated in oxidative injury to tissue by ischemia-reperfusion.
Xanthine oxidase activity was determined by directly
measuring uric acid formation by HPLC. The structure-activity
relationship revealed that the planar flavones and flavonols
with a 7-hydroxyl group such as chrysin, luteolin, kaempferol,
quercetin, myricetin, and isorhamnetin inhibited xanthine
oxidase activity at low concentrations (IC50 values
from 0.40 to 5.02 microM) in a mixed-type mode, while
the nonplanar flavonoids, isoflavones and anthocyanidins
were less inhibitory. These results suggest that certain
flavonoids might suppress in vivo the formation of active
oxygen species and urate by xanthine oxidase.
PMID: 10671036, UI: 20127172
Pharmacol Biochem Behav 1994 Jan;47(1):1-4
Possible anxiolytic effects
of chrysin, a central benzodiazepine receptor ligand
isolated from Passiflora coerulea.
C, Viola H, Paladini A, Dajas F, Medina JH
Instituto de Biologia Celular, Facultad de Medicina,
The pharmacological effects of 5,7-dihydroxyflavone
(chrysin), a naturally occurring monoflavonoid that
displaces [3H]flunitrazepam binding to the central benzodiazepine
(BDZ) receptors, were examined in mice. In the elevated
plus-maze test of anxiety, diazepam (DZ, 0.3-0.6 mg/kg)
or chrysin (1 mg/kg) induced increases in the number
of entries into the open arms and in the time spent
on the open arms, consistent with an anxiolytic action
of both compounds. The effects of chrysin on the elevated
plus-maze was abolished by pretreatment with the specific
BDZ receptor antagonist Ro 15-1788 (3 mg/kg). In the
holeboard, diazepam (1 mg/kg) and chrysin (3 mg/kg)
increased the time spent head-dipping. In contrast,
high doses of DZ (6 mg/kg) but not of chrysin produced
a decrease in the number of head dips and in the time
spent head-dipping. In the horizontal wire test, diazepam
(6 mg/kg) had a myorelaxant action. In contrast, chrysin
(0.6-30 mg/kg) produced no effects in this test. These
data suggest that chrysin possesses anxiolytic actions
without inducing sedation and muscle relaxation. We
postulate that this natural monoflavonoid is a partial
agonist of the central BDZ receptors.
PMID: 7906886, UI: 94159642
J Endocrinol 1985 Oct;107(1):1-8
Effects of flavonoids
on insulin secretion and 45Ca2+ handling in rat islets
Hii CS, Howell SL
The effects of some flavonoids, a group of naturally
occurring pigments one of which has been claimed to
possess antidiabetic activities, on insulin release
and 45Ca2+ handling have been studied in isolated rat
islets of Langerhans. Insulin release was enhanced by
approximately 44-70% when islets were exposed to either
(-)epicatechin (0.8 mmol/l) or quercetin (0.01-0.1 mmol/l);
others such as naringenin (0.1 mmol/l) and chrysin (0.08
mmol/l) inhibited hormone release by approximately 40-60%.
These effects were observed only in the presence of
20 mmol glucose/l. Quercetin (0.01 mmol/l) and (-)epicatechin
(0.8 mmol/l) both inhibited 45Ca2+ efflux in the presence
and absence of extracellular Ca2+. In the presence of
20 mmol glucose/l both the short-term (5 min) and steady-state
(30 min) uptake of 45Ca2+ were significantly increased
by either quercetin or (-)epicatechin. These results
suggest that the stimulatory compounds such as quercetin
and (-)epicatechin may, at least in part, exert their
effects on insulin release via changes in Ca2+ metabolism.
PMID: 3900267, UI: 86010058
Thyroid 1999 Apr;9(4):369-76
Growth inhibitory effects
of flavonoids in human thyroid cancer cell lines.
Yin F, Giuliano AE, Van Herle AJ
Division of Endocrinology, UCLA School of Medicine,
Los Angeles, California 90024, USA.
Previous studies have indicated that flavonoids exhibit
antiproliferative properties on some hormone-dependent
cancer cell lines, such as breast and prostate cancer.
In the present study, the effects of some selected flavonoids,
genistein, apigenin, luteolin, chrysin, kaempferol,
and biochanin A on human thyroid carcinoma cell lines,
UCLA NPA-87-1 (NPA) (papillary carcinoma), UCLA RO-82W-1
(WRO) (follicular carcinoma), and UCLA RO-81A-1 (ARO)
(anaplastic carcinoma) have been examined. Among the
flavonoids tested, apigenin and luteolin are the most
potent inhibitors of these cell lines with IC50 (concentration
at which cell proliferation was inhibited by 50%) values
ranging from 21.7 microM to 32.1 microM. The cells were
viable at these concentrations. Using NPA cells known
to be estrogen receptor positive (ER+), it was shown
that no significant [3H]-E2 displacement occurred with
these flavonoids at the IC50 concentration. In WRO cells
that are known to have an antiestrogen binding site
(AEBS), biochanin A caused a stronger inhibitory growth
effect (IC50 = 64.1 microM) than in NPA and ARO cells.
In addition, it was observed that biochanin A has an
appreciable binding affinity for the AEBS as indicated
by the displacement of [3H]-tamoxifen from the WRO cells.
In summary, flavonoids have potent antiproliferative
activity in vitro against various human thyroid cancer
cell lines. The inhibitory activity of certain flavonoid
compounds may be mediated via the AEBS and/or type II
EBS. The observation that ARO cells that lack both the
AEBS and the ER are effectively inhibited by apigenin
and luteolin suggest that other mechanisms of action
are operative as well. The present study suggests that
flavonoids may represent a new class of therapeutic
agents in the management of thyroid cancer.
PMID: 10319943, UI: 99251661
The effect of flavonoids
on ofloxacin-induced mutagenicity in Euglena gracilis.
Krizkova L, Nagy M, Polonyi J, Ebringer L
Institute of Molecular and Subcellular Biology, Faculty
of Science, Comenius University, Bratislava, Slovak
The antimutagenicity of 14 naturally occurring flavonoids
(20 mumol/l) on ofloxacin (43 mumol/l and 86 mumol/l)-induced
bleaching (mutagenicity) was studied in Euglena gracilis.
The flavonoids chrysin, techtochrysin, chrysin-5-methylether
galangin, galangin-5-methylether, pinocembrin and pinobanksin
possess considerable antimutagenic properties against
ofloxacin-induced bleaching of E. gracilis. Apigenin
and isalpinin had only weak antimutagenic potency. Pinobanksin-5-methylether
and pinobanksin-3-acetate showed very weak or no antimutagenic
effect. However, kempferol, quercetin-3-methylether
and quercetin-3,3'-dimethylether showed co-mutagenic
or no antimutagenic effect depending on the concentration
of ofloxacin. Two possible modes of action of the flavonoids
on ofloxacin-induced bleaching of E. gracilis are discussed.
PMID: 9725994, UI: 98394057
Influence of benzodiazepines
on body weight and food intake in obese and lean Zucker
Laboratoires de Recherches Metaboliques de la Faculte
de Medicine, Universite de Geneve, Suisse.
[Medline record in process]
1. The gamma-aminobutyric acid (GABA)-ergic system,
which is functionally altered in obese (fa/fa) Zucker
rats, plays an important role in controlling energy
balance within the central nervous system. 2. GABA receptors
seem to be involved in the dysfunction of the hypothalamic
energy homeostasis-controlling mechanisms in these animals
due to a genetically-induced defect of the leptin-neuropeptide
Y system. 3. To shed further light on the possible role
played by the GABA system in the pathogenesis of this
rat model, two benzodiazepine (BDZ) receptor agonists
(diazepam and clonazepam) and one BDZ antagonist (flumazenil)
were administered intraperitoneally in obese and lean
Zucker rats. 4. Body weight gain was reduced by the
BDZ agonists in both phenotypes, and one receptor-agonist
(diazepam) lowered insulin concentration in obese rats.
In GABA-antagonist-treated obese rats, the daily amount
of body weight gain and food intake acquired an oscillatory
rhythm similar to that of normal rodents. 5. By demonstrating
the role of BDZ receptors, these findings may help clarify
the pathophysiology of obesity and insulin resistance
in fatty Zucker rats.
PMID: 10958151, UI: 20412329