Chrysin
Flavonoids as inhibitors
or enhancers of the cytotoxicity of tumor necrosis
factor-alpha in L-929 tumor cells.
Habtemariam S
Department of Physiology and Pharmacology, University
of Strathclyde, Glasgow, U.K. s.habtemariam@strath.ac.uk
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
Flavonoids reduce
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 withdrawal.
PMID: 9643451, UI: 98305604
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
Chrysin (5,7-di-OH-flavone),
a naturally-occurring ligand for benzodiazepine receptors,
with anticonvulsant properties.
Medina
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
Antimutagenic effect
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 activity.
PMID: 10319134, UI: 99252692
Modification of
platelet function and arachidonic acid metabolism
by bioflavonoids. Structure-activity relations.
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 effect.
PMID: 6329230, UI: 84231526
Flavonoid inhibition
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
Molecular basis
of the inhibition of human aromatase (estrogen synthetase)
by flavone and isoflavone phytoestrogens: A site-directed
mutagenesis study.
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 than
flavones.
PMID: 9435150, UI: 99289389
Anxiolytic natural
and synthetic flavonoid ligands of the central benzodiazepine
receptor have no effect on memory tasks in rats.
Salgueiro
JB, Ardenghi P, Dias M, Ferreira MB, Izquierdo I,
Medina JH
Centro de Memoria, Departamento de Bioquimica, I.C.B.S.,
Universidade Federal do Rio Grande do Sul, Porto Alegre,
Brazil.
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
Inhibition of 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. hyehjean@nmdhst.cc.nih.gov
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
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
HIV-1 latency.
PMID: 8825617, UI: 96423016
The estrogenic 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, USA.
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
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 hypoglycemic effect.
PMID: 10206552, UI: 99221393
Effects of propolis
flavonoids on virus infectivity and replication.
Debiaggi
M, Tateo F, Pagani L, Luini M, Romero E
Istituto di Microbiologia, Universita degli Studi
di Pavia, Italy.
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
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
KH
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
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. nagao@nfri.affrc.go.jp
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
Possible anxiolytic
effects of chrysin, a central benzodiazepine receptor
ligand isolated from Passiflora coerulea.
Wolfman
C, Viola H, Paladini A, Dajas F, Medina JH
Instituto de Biologia Celular, Facultad de Medicina,
UBA, Argentina.
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
Effects of flavonoids
on insulin secretion and 45Ca2+ handling in rat islets
of Langerhans.
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
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
Republic.
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
rats.
Blasi
C
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
