Anti-diabetes effect
Biosci Biotechnol Biochem 1997 Apr;61(4):651-654
Inhibition of aldose reductase and sorbitol accumulation by astilbin and
taxifolin dihydroflavonols in Engelhardtia chrysolepis. Haraguchi H, Ohmi I,
Fukuda A, Tamura Y, Mizutani K, Tanaka O, Chou WH Dihydroflavonol taxifolin
and its glycoside, astilbin, from Engelhardtia chrysolepis inhibited rat
lens and recombinant human aldose reductase. Taxifolin also inhibited
sorbitol accumulation in human red blood cells. Furthermore, this
dihydroflavonol aglycone maintained the clarity of rat lens incubated with a
high concentration of glucose. These dihydroflavonols may be effective for
preventing osmotic stress in hyperglycemia. J Med Chem 1988
Jun;31(6):1250-1253 An intensely sweet dihydroflavonol derivative based on a
natural product lead compound. Nanayakkara NP, Hussain RA, Pezzuto JM,
Soejarto DD, Kinghorn AD The dihydroflavonol dihydroquercetin 3-acetate (1)
was isolated as a sweet constituent of the young shoots of Tessaria
dodoneifolia (Hook. & Arn.) Cabrera (Compositae). Compound 1 and
dihydroquercetin 3-acetate 4'-(methyl ether) (2), a novel synthetic analogue
of this natural product lead compound, were rated by a taste panel as being
80 and 400 times sweeter than a 2% w/v sucrose solution, respectively.
Synthetic dihydroquercetin 4'-(methyl ether) (3) showed a reduced sweetness
intensity when compared to 2, while (+)-dihydroquercetin (4) was devoid of
sweetness. Dihydroflavonol derivatives 1-3 represent a new class of
potentially noncaloric and noncariogenic intense sweeteners.
Free radical scavenging and protection from lipid peroxidation
Chem.-Farm. Jornal, 1995. Sept. P.61 Diquertin - new antioxidant and
vasoprotector. Kolhir V.K., Tyukavkina N.A.,Bykov V.A. and others.
A
laboratory experiment revealed antioxidative and vasoprotective properties
of dihydroquercetin (in some cases more effective than quercetin), combined
by anti-inflammatory, gastric- and hepatoprotective, hypolipidemic and
diuretic effects.
Basing on the results of the experiment of DHQ antioxidant
properties it was found that DHQ demonstrates a direct antiradical effect
primarily due to the interaction with lipid radicals. However, DHQ (and
quercetin ) interaction with super oxide anions is to be considered. The
experiments prove that DHQ decreases the tetracycline- and tetrachlorin
methane-induced lipid peroxidation of liver microsoms that causes an
intensive transaminases removal from the demaged liver cells.
Biophysics, 1996, V.41-3, P.620 Dihydroquercetin antioxidant properties.
Y.O. Teselkin, B.A. Zhambalova, I.V. Babenkova, G.I. Klebanov, N.A.
Tukavkinaà The dihydroquercetin influence on the process of liposomal
membranes from egg phospholipids peroxidation induced by Fe sulphate and/or
system Fe+2- ascorbat was studied. It was shown that dihydroquercetin
antioxidative activity is compared with antioxidant activity of alpha-tokoferol.
It is suggested, that dihydroquercetin antioxidative effect occurs in
scavenging of lipid radicals.
Voprosy Pitaniya, 1996, Feb. P.33 Natural flavonoids - food antioxidants
and biologically active additives. N.A. Tukavkina, I.A. Rulenko, Y.A.
Kolesnik. The review summarizes literary data about the distribution of
flavonoid compounds (FC) in nourishment plants and their antioxidative
activity (AOA) when interacting with the structure and pharmacological
activity. A problem of the implementation of FS as food antioxidants is
discussed. FCs are not xenogenic substances for people and show a low
toxicity or the absence of it. FCs normally exceed the known synthetic
antioxidants. The regular addition of FC as a perspective direction to
provide food of vital importance with medicinal and prophylactic properties
is discussed. The advantage of individual flavonoids (quercetin and
dihydroquercetin) additives was shown in comparison with FC vegetable
compounds. Medicinal and prophylactic food with FC additives are intended
for the regions with the unfavorable environmental situation (higher
radiation, industrial pollution) and regions influenced by stress factors or
with hostile climate conditions.
Biochem Pharmacol, 1988 Mar 15;37(6):989-995 Interaction of flavonoids
with 1,1-diphenyl-2-picrylhydrazyl free radical, liposomal membranes and
soybean lipoxygenase-1. Ratty AK, Sunamoto J, Das NP The interaction of the
antiperoxidative flavonoids namely, quercetin, quercetrin, rutin, myricetin,
phloretin, phloridzin, catechin, morin and taxifolin with the
1,1,-diphenyl-2-picrylhydrazyl (DPPH) free radical was demonstrated.
Flavonoid-DPPH interaction was looked at in the absence and presence of
liposomes so as to reveal some information on bilayers. Perturbations in the
lipid bilayers were monitored with the fluorescent probe,
dansylhexadecylamine (DSHA). It was observed that the interaction of the
flavonoids on the lipid bilayer occurred in the polar zone of the lipid
bilayers. The flavonoids were able to scavenge free radicals and could do so
in biomembranes. It is suggested that the DPPH free radical abstracts the
phenolic hydrogen of the flavonoid molecule and that this could be the
general mechanism of the scavenging action of the antiperoxidative
flavonoids. The effects of the flavonoids on soybean lipoxygenase-1 were
investigated both in buffer and also in liposomal suspension. All the
flavonoids studied showed inhibition of the enzyme in both systems but the
inhibition was greater in the liposomal suspension. Quercetin was the most
potent and it inhibited the lipoxygenase in the liposomal suspension by
about 42% while the other flavonoids inhibited the enzyme by about 14-23%.
We observed that the effect of myricetin and quercetin on the enzyme was pH
dependent.
Biosci Biotechnol Biochem 1996 Jun;60(6):945-948 Protection against
oxidative damage by dihydroflavonols in Engelhardtia chrysolepis. Haraguchi
H, Mochida Y, Sakai S, Masuda H, Tamura Y, Mizutani K, Tanaka O, Chou WH
Dihydroflavonol taxifolin and its glycoside, astilbin, from Engelhardtia
chrysolepis were evaluated as antioxidants and radical scavengers. These
dihydroflavonols inhibited superoxide anion production in the xanthine/xanthine
oxidase system. Microsomal lipid peroxidation induced by NADPH-cytochrome
P-450 reductase was also inhibited by these flavonoids. Mitochondrial lipid
peroxidation was inhibited only by the aglycon. Taxifolin protected peroxy
radical-damaged mitochondria with no effect on enzyme activity.
Furthermore, taxifolin and astilbin protected red cells against oxidative hemolysis.
These dihydroflavonols were found to be effective for protecting subcellular
systems and red blood cells against oxidative stress in vitro.
Biochem Med Metab Biol 1988
Feb;39(1):69-79 Effects of flavonoids on nonenzymatic lipid peroxidation:
structure-activity relationship. Ratty AK, Das NP The in vitro effects of
several flavonoids on nonenzymatic lipid peroxidation in the rat brain
mitochondria was studied. The lipid peroxidation was indexed by measuring
the MDA production using the 2-thiobarbituric acid TBA test. The flavonoids,
apigenin, flavone, flavanone, hesperidin, naringin, and tangeretin promoted
the ascorbic acid-induced lipid peroxidation, the extent of which depended
upon the concentration of the flavonoid and ascorbic acid. The other
flavonoids studied, viz., quercetin, quercetrin, rutin, taxifolin, myricetin,
myricetrin, phloretin, phloridzin, diosmetin, diosmin, apiin, hesperetin,
naringenin, (+)-catechin, morin, fisetin, chrysin, and 3-hydroxyflavone, all
showed varying extents of inhibition of the nonenzymatic lipid peroxidation,
induced by either ascorbic acid or ferrous sulfate. The flavonoid aglycones
were more potent in their antiperoxidative action than their corresponding
glycosides. Structure-activity analysis revealed that the flavonoid molecule
with polyhydroxylated substitutions on rings A and B, a 2,3-double bond, a
free 3-hydroxyl substitution and a 4-keto moiety, would confer upon the
compound potent antiperoxidative properties. - inhibition of
ferments (mieloperoxinase) supporting peroxidation
Chem Biol Interact
1990;73(2-3):323-335 How flavonoids inhibit the generation of luminol-dependent
chemiluminescence by activated human neutrophils. Hart BA, Ip Via Ching TR,
Van Dijk H, Labadie RP The mechanism by which (a panel of) flanonoids
inhibit the production of luminol-dependent chemiluminescence (CLlum) by
activated human neutrophils is subject to this study. CLlum is frequently
used as a bio-assay to quantify the effect of xenobiotics on the production
of reactive oxygen species (ROS). Most of the flavonoids decreased CLlum by
inhibition of ROS production by the cells. Four selected flavonoids (Taxifolin,
Eriodictyol, Hesperetin and Luteolin), inhibited myeloperoxidase (MPO)
release, while two of these (Taxifolin and Eriodictyol) strongly inhibited
MPO activity. Because CLlum is a MPO-dependent process these activities
might mask effects of the flavonoids on ROS production. Finally, our results
provide evidence that essential determinants for inhibition of O2(-)-release
are the OH-groups located in the B-ring of the flavonoid molecule.
Flavonoids methylated at a single OH-group in the B-ring are only inhibitory
when they react with activated neutrophils in the presence of
myeloperoxidase. - increasing of skin resistance from the
influence of active oxygen groups and oxidation products
Environ Mutagen 1981;3(4): 401-419 Mutagenicities of 61
flavonoids and 11 related compounds. Nagao M, Morita N, Yahagi T, Shimizu M,
Kuroyanagi M, Fukuoka M, Yoshihira K, Natori S, Fujino T, Sugimura T The
mutagenicities of 61 flavonoids (naturally occurring flavonoid aglycones and
flavonal glycosides and synthetic flavonoids) and those of 11 compounds
structurally related to flavonoids were tested with Salmonella typhimurium
strains TA100 and TA98. Among the 22 flavone derivatives tested, only
wogonin was strongly mutagenic, while five derivatives, apigenin triacetate,
acacetin, chrysoeriol, pedalitin, and pedalitin tetraacetate, were only
weakly mutagenic. Two bisflavonyl derivatives, neither of which has a
3-hydroxyl group, were not mutagenic. Of the 16 flavonol derivatives tested,
all except 3-hydroxyflavone and the tetra- and penta-methyl ethers of
quercetin were mutagenic. Of the five flavanone derivatives tested, only
7,4-dihydroxyflavanone was mutagenic, showing weak activity. Of the four
flavanolol derivatives tested, hydrorobinetin and taxifolin were weakly
mutagenic. Of the six isoflavone derivatives tested, tectorigenin was weakly
mutagenic. Of the 11 compounds in the miscellaneous group structurally
related to flavonoids, only isoliquiritigenin was mutagenic, showing weak
activity. For the emergence of strong mutagenicity, the double bond between
positions 2 and 3 and the hydroxyl group at position 3 are required, except
in wogonin, which does not have a hydroxyl group at position 3 but is
strongly mutagenic to TA100. The 3-O-acetyl ester of flavonol, quercetin,
was mutagenic with S9 mix, but 3-O-methyl ethers were not. Six flavonol
glycosides, three quercetin glycosides and three kaempferol glycosides were
mutagenic after preincubation with "hesperidinase," a crude extract of
Aspergillus niger. Of 66 flavonoid agylcones and compounds structurally
related to flavonoids, quercetin was the strongest mutagen. The
carcinogenicity of this compound should be clarified because it is
ubiquitously found in vegetables.
Reduction of content of low density lipoproteins in liver and serum
Biosci Biotechnol Biochem 1996 Mar;60(3):513-515 Effect of astilbin in
tea processed from leaves of Engelhardtia chrysolepis on the serum and liver
lipid concentrations and on the erythrocyte and liver antioxidative enzyme
activities of rats. Igarashi K, Uchida Y, Murakami N, Mizutani K, Masuda H
The effects of astilbin in Kohki tea, which is produced from the leaves of
Engelhardtia chrysolepis Hance (Chinese name, huang-qui), and of an aglycone
of astilbin, taxifolin, on the serum and liver lipid concentrations, and on
the erythrocyte and liver antioxidative enzyme activities were determined
with rats fed on a cholesterol-free diet. The total liver cholesterol
concentration tended to be decreased by feeding with astilbin, and
significantly decreased by feeding with taxifolin. The liver phospholipid
concentration was decreased by feeding with both astilbin and taxifolin. In
addition, astilbin and taxifolin lowered the serum and liver TBARS
concentrations, but did not influence the serum and liver antioxidative
enzyme activities, suggesting the possibility that these compounds acted to
lower the TBARS concentration by their direct antioxidative action in vivo,
almost without influencing the antioxidative enzyme activities.
Chem.-Farm. Jornal 1995 Sept. P.61 - Diquertin - new antioxidant and
vasoprotector. - Kolhir V.K., Tyukavkina N.A.,Bykov V.A. and others
Antitumor effect - inhibition of reverse transcriptase- an
important factor of cancergenesis
J Nat Prod 1992 Feb;55(2): 179-183 Inhibitory effects of flavonoids on
Moloney murine leukemia virus reverse transcriptase activity. Chu SC, Hsieh
YS, Lin JY Several flavonoids were tested for their effects on Moloney
murine leukemia virus reverse transcriptase activity. Four groups of
flavonoids, namely flavones, flavanones, flavonols, and flavanonols, were
studied, and it was found that flavonols and flavanonols were very active in
this regard while flavones and flavanones displayed very low activity.
Among
the flavonoids tested, fisetin, quercetin, myricetin, kaempferol, morin,
(+/-)-taxifolin, (+)-catechin, and (-)-epicatechin were shown to be highly
effective in inhibiting the reverse transcriptase activity.
Structure-activity relationship analysis of these flavonoids revealed that
the simultaneous presence of free hydroxyl groups at positions 3 and 4'
enhanced the reverse transcriptase inhibitory activity. Replacement of the
3-hydroxyl group with a monosaccharide or of the 4'-hydroxyl group with a
methyl group reduced inhibitory activity. The double bond at position 2 and
3 of the flavonoid's pyrone ring is not essential for inhibiting reverse
transcriptase activity. The flavonoids studied demonstrated ability to
inhibit the reverse transcriptase activity using either (rA)n(dT)12-18 or
(rC)n(dG)12-18 as template-primers. - different tumor cells
antiproliferative effect
Anticancer Drugs 1992 Oct;3(5):525-530 Differential inhibition of
proliferation of human squamous cell carcinoma, gliosarcoma and embryonic
fibroblast-like lung cells in culture by plant flavonoids. Kandaswami C,
Perkins E, Drzewiecki G, Soloniuk DS, Middleton E Jr We investigated the
antiproliferative effect of two polyhydroxylated (quercetin and taxifolin)
and two polymethoxylated (nobiletin and tangeretin) flavonoids against three
cell lines in tissue culture. Tangeretin and nobiletin markedly inhibited
the proliferation of a squamous cell carcinoma (HTB 43) and a gliosarcoma
(9L) cell line at 2-8 micrograms/ml concentrations. Quercetin displayed no
effect on 9L cell growth at these concentrations, while at 8 micrograms/ml
it inhibited HTB 43 cell growth. Taxifolin slightly inhibited HTB 43 cell
growth at 8 micrograms/ml, while moderately inhibiting HTB 43 cell growth at
2-8 micrograms/ml. The proliferation of a human lung fibroblast-like cell
line (CCL 135) was relatively insensitive to low concentrations of the above flavonoids. - possible inhibition of malignant transformation of
lymphocytes.
Cancer Lett 1993 May 14;69(3):191-196 In vitro effects of natural plant
polyphenols on the proliferation of normal and abnormal human lymphocytes
and their secretions of interleukin-2. Devi MA, Das NP The growth of two
human lymphoid tissue derived cell lines, IM-9 and Molt-4 cells together
with normal lymphocytes was studied in the presence of several plant natural
products. Amongst the 11 test compounds studied, the flavonoids (fustin,
taxifolin, phloretin) and the polyphenol tannic acid were potent inhibitors.
At concentrations ranging from 10-50 microM they exerted varying degrees of
inhibition on Molt-4 cell and normal lymphocyte cell proliferation but not
on the non-malignant (IM-9) cells. The order of potency was tannic acid >
phloretin > taxifolin > fustin. The IL-2 level was also enhanced in the
Molt-4 but inhibited in normal lymphocytes. However, its level remained
unchanged in the IM-9 cells. The amount of IL-2 secreted could be directly
correlated to the percentage cell growth inhibition for only Molt-4 cells.
Interestingly, our findings suggest the possibility of exploiting the
natural plant polyphenols for their possible use in the treatment of
lymphocyte malignancy.
Antimutagenic effect
plant flavonoids. Huang MT, Wood AW, Newmark HL, Sayer JM, Yagi H, Jerina
DM, Conney AH Myricetin, robinetin and luteolin inhibited the mutagenic
activity resulting from the metabolic activation of benzo[a]-pyrene and
(+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]-pyrene by rat liver microsomes.
These naturally occurring plant flavonoids and seventeen additional
flavonoids and related derivatives with phenolic hydroxyl groups inhibited
the mutagenic activity of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10
alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (B[a]P
7,8-diol-9,10-epoxide-2), which is an ultimate mutagenic and carcinogenic
metabolite of benzo[a]pyrene. Several flavonoids without phenolic hydroxyl
groups or with methylated phenolic hydroxyl groups were inactive. The
mutagenic activity of 0.05 nmol of BP 7,8-diol-9,10-epoxide-2 towards strain
TA 100 of S. typhimurium was inhibited 50% by incubation of the bacteria and
the diol-epoxide with myricetin (2 nmol), robinetin (2.5 nmol), luteolin (5
nmol), quercetin (5 nmol), 7-methoxyquercetin (5 nmol), rutin (5 nmol),
quercetin (5 nmol), delphinidin chloride (5 nmol), morin (10 nmol),
myricitrin (10 nmol), kaempferol (10 nmol), diosmetin (10 nmol), fisetin (10
nmol), or apigenin (10 nmol). Considerably less antimutagenic activity was
observed for dihydroquercetin, naringenin, robinin, D-catechin, genistein,
kaempferide and chrysin. Pentamethoxyquercetin, tangeretin, nobiletin,
7,8-benzoflavone, 5,6-benzoflavone, and flavone, which lack free phenolic
groups, were inactive. The antimutagenic activity of hydroxylated flavonoids
results from their direct interaction with B[a]P 7,8-diol-9,10-epoxide-2
since the rate of disappearance of the diol-epoxide from cell-free solutions
in 1:9 dioxane:water was markedly stimulated by myricetin, robinetin and
quercetin. Myricetin was a highly potent inhibitor of the mutagenic activity
of bay-region diol-epoxides of benzo[a]pyrene, dibenzo[a,h]pyrene and
dibenzo[a,i]pyrene, but higher concentrations of myricetin were needed to
inhibit the mutagenicity of the chemically less reactive benzo[a]pyrene
4,5-oxide and bay region diol-epoxides of benz[a]anthracene, chrysene and
benzo[c]phenanthrene.
Radioprotective effect
Pharmacology and toxicology 1975. V.38(5) P.607 Pharmacological and
radioprotective properties of some gamma-pyrone derivatives (flavonons and
flavonols). T.Y.Iluchenok, A.I. Homenko, L.M. Frigidova et al. The gamma-pyron
derivatives obtained on the base of quercetin extracted from Daur and
Siberian larch timber are low toxic compounds and don’t significantly change
either arterial pressure or breath, causes no oppression effect on the
central nerve system, shows a markedly anti-inflammatory effect on healthy
and irradiated animals, displays a radioprotective and antihistaminic
activity, and also controls noradrenalin, dophamin and homovanilin acid
metabolism in the mouse cerebrum. Investigations of biologically active
compositions and anti-radiate means among the gamma-pyrone are perspective.
Voprosy Pitaniya 1996 Feb. P.33 - Natural flavonoids - food antioxidants and
biologically active additives. - N.A. Tukavkina, I.A. Rulenko, Y.A. Kolesnik
Antiviral effect
J Med Virol 1987 May;22(1):57-66 Effect of antiviral substances on
hepatitis A virus replication in vitro. Biziagos E, Crance JM, Passagot J,
Deloince R The effect of protamine, atropine, selenocystamine, taxifolin,
and catechin on the infectivity and antigenicity of the cell culture-adapted
hepatitis A virus (HAV) strain CF 53 was studied. The toxicity on uninfected
PLC/PRF/5 cells was examined for each antiviral compound by morphological
and biochemical methods, in order to determine concentrations without
cytotoxic effect.
At these concentrations, protamine and taxifolin, added to
infected cells for a 15-day period, caused concentration-dependent
reductions in the infectivity and antigenicity of HAV. Atropine also caused
a concentration-dependent reduction of HAV infectivity but did not affect
the antigenicity of the virus. At the highest concentration used, 50
micrograms/ml of protamine, 59 micrograms/ml of taxifolin, and 50
micrograms/ml of atropine, the infectious viral titer reduction was 1.56,
0.77, and 0.68 log10, respectively. Selenocystamine and catechin had no
effect on HAV replication.
Immuno-regulative (anti-allergic)and anti-inflammatory effect
Chem.-Farm. Jornal 1995 Sept. P.61 - Diquertin - new
antioxidant and vasoprotector. - Kolhir V.K., Tyukavkina N.A.,Bykov V.A. and
others - antihistaminic effect Agents Actions 1985
Apr;16(3-4):147-151 Kinetics of the inhibitory effect of flavonoids on
histamine secretion from mast cells. Bronner C, Landry Y The effect of
cromoglycate and of natural flavonoids on histamine release from peritoneal
rat mast cells induced by compound 48/80 and ionophore A23187 was studied
according to preincubation time of mast cells with drugs and to incubation
time of cells with the triggering agent. Preincubation of cells with
cromoglycate, dihydroquercetin and amentoflavone, a biflavonoid, decreased
the potency of drugs to inhibit the ionophore-induced release; the optimal
inhibitions were observed when drugs were added simultaneously with the
ionophore A23187. In contrast, a short preincubation (2 min) of cells with
quercetin or luteolin decreased their inhibitory effect on the ionophore-induced
release, whereas a longer preincubation increased the inhibition. When
compound 48/80 was used to trigger histamine secretion, the inhibitory
potencies of all the compounds used were decreased according to
preincubation time. Dihydroquercetin (taxifolin), previously considered as
inactive, showed an interesting cromoglycate-like behaviour.
Pharmacology and toxicology 1975. V.38(5) P.607 - Pharmacological and
radioprotective properties of some gamma-pyrone derivatives (flavonons and
flavonols). - T.Y.Iluchenok, A.I. Homenko, L.M. Frigidova et al.
Immunopharmacology 1984 Apr;7(2):115-126 Comparison of
the effects of quercetin with those of other flavonoids on the generation
and effector function of cytotoxic T lymphocytes. Schwartz A, Middleton E Jr
In previous studies (Schwartz et al., 1982) we showed that the naturally
occurring plant flavonoid quercetin can inhibit both the in vitro generation
and effector function of alloantigen specific cytotoxic T lymphocytes (CTL).
In the present studies, several additional flavonoids of different chemical
classes were tested similarly to determine whether structure-function
relationships exist. We have found that some other flavonoids, e.g. apigenin
, fisetin , hesperetin and chalcone also can inhibit both CTL generation and
effector function, with the effective concentration varying with the
specific flavonoid tested. On the other hand, flavonoids such as rutin,
naringin and catechin were inactive in both systems. Taxifolin (
dihydroquercetin ) differed from all the other flavonoids in that it was a
relatively active inhibitor of CTL generation, but was essentially unable to
inhibit CTL effector function. The presence of a double bond at position
C-2-3 in the flavone and flavonol aglycones, a keto group at C-4, B ring
hydroxylation and/or a free hydroxyl group at C-3 may be associated with
activity. We also show that the effects of some, but not all, of the
flavonoids active in our systems can be blocked by Cu2+ ions. Therefore,
chelation of divalent cations such as Cu2+ cannot explain the function of
all flavonoids in these systems.
Normalizing
influence on cell enzyme systems
- endocytosis and lisosomal enzyme activity regulation Life Sci 1986 Aug
25;39(8):717-726 Effects of flavonoids on enzyme secretion and endocytosis
in normal and mucolipidosis II fibroblasts. Vladutiu GD, Middleton E Jr The
effect of flavonoids on beta-hexosaminidase transport and endocytosis has
been studied in cultured human skin fibroblasts. In mucolipidosis II
fibroblast cultures, characterized by their preferential secretion of most
newly synthesized hydrolases, quercetin and phloretin (200 microM) inhibited
beta-hexosaminidase synthesis as well as total culture-associated enzyme
activity. Taxifolin induced a 2.4-fold increase in the total enzyme activity
without altering the intra- and extracellular distribution of the enzyme.
Rutin, although less effective, also stimulated an overall increase in total
enzyme. The flavonoid effects were all concentration-dependent. Very little
effect was observed in either the distribution or the total beta-hexosaminidase
activity in normal fibroblast cultures. Taxifolin and hesperitin inhibited
receptor-mediated endocytosis of beta-hexosaminidase by fibroblasts up to
50% of control uptake. Naringin, quercetin, and phloretin moderately
inhibited uptake by 30% while rutin and fisetin had no effect. The results
demonstrate that certain naturally occurring flavonoids affect the secretion
of lysosomal enzymes as well as their endocytosis by fibroblasts. Since most
individuals ingest up to one gram per day of these substances, flavonoids
may prove to have significant effects on normal lysosomal enzyme physiology.
Cholesterol
Lowering Activities
In a study of rats, Krecman et al. [2] studied found that pure silybin
was not as effective as silymarin. This suggested that other constituent(s)
of silymarin, in addition to silybin, also have hypocholesterolemic effects.
Subsequently, the minor constituent of silymarin, taxifolin, has attracted
Andre TheriaultÂ’s attention, because taxifolin constitutes the flavonoid
moiety in the flavolignan silybin. Hence, Andre Theriault and coworkers
investigated how taxifolin affected lipid profiles in a study using human
hepatoma cell- line, HepG2, as the model system. They had a few key
findings: (1) taxifolin inhibits cholesterol synthesis in a dose- and time-
dependent manner, (2) taxifolin suppresses HMG-CoA reductase activity and
cholesteryl ester formation (3) taxifolin inhibits the synthesis and
secretion of triacylglycerol and phospholipids and (4) taxifolin decreases
the secretion of apoB into LDL-like particles. [1] Morazzoni, P.,
Bombardelli, E. 1995. Silybum marianum. Cardus marianus Fitoterapia.
66:6-42. [2] Krecman, V., Skottova, N., Walterova, D., Ulrichova, J.,
Simanek, V. 1998. Silymarin inhibits the development of diet-induced
hypercholesterolemia in rats. Planta Med. 64:138-142. [3] Casaschi A et al,
Inhibitory activity of diacylglycerol acyltransferase (DGAT) and microsomal
triglyceride transfer protein (MTP) by the flavonoid, taxifolin, in HepG2
cells: potential role in the regulation of apolipoprotein B secretion.
Atherosclerosis. 2004 Oct;176(2): 247-53. [4] Wang YH Prevention of
macrophage adhesion molecule-1 (Mac- 1)-dependent neutrophil firm adhesion
by taxifolin through impairment of protein kinase-dependent NADPH oxidase
activation and antagonism of G protein- mediated calcium influx. Biochem
Pharmacol. 2004 Jun 15;67(12):2251-62.
