All about Taxifolin
The bioflavonoid dihydroquercetin (taxifolin) is the most promising natural antioxidant. The initial
raw material is the wood of Siberian and Dahurian larches which grow abundantly and can provide
steady supply.
The antioxidative activity of taxifolin exceeds that of most common antioxidants such
as tocopherols (vitamin E) and carotenoids (vitamin A). In addition, taxifolin is much more resistant
to the effects of oxidation and light.
Health benefits of taxifolin include capillary, liver, and radiation protection. By «trapping» free
radicals, taxifolin helps to protect the body against adverse environmental factors. Regular
consumption of taxifolin helps to sustain antioxidant reserves in the human body. Exhaustion
of these reserves may be caused by an unbalanced diet and environmental factors.
As a consequence, the human organism experiences oxidative stress, which may result in different
pathologies.
The daily physiological need for bioflavonoids (natural antioxidants) equates to 150-250 mg for
children over 7 years of age and 200-250 mg for adults (according to Guidelines MR 2.3.1.2432
−08 Physiological Needs for Energy and Nutrition of Different Population Groups within the
Russian Federation).
Toxicological studies demonstrated that taxifolin is non-toxic and produces no side effects
in human organism.
Daily consumption of taxifolin helps to maintain the body’s physiological functions at high levels.
Taxifolin Activity
Dihydroquercetin (taxifolin, 3,5,7,3’,4’-pentahydroxyffavanone) /CAS No. 480-18-2/ is one of the
most powerful antioxidants of natural origin.
Dihydroquercetin was discovered in 1936, by Albert, an American biochemist. Since then, its
biological and antioxidative activities have been studied for several decades. More active than
tocopherol and carotene, it is also more stable. Dihydroquercetin belongs to a limited flavanone
class of flavonoid compounds. It is a fine crystalline or amorphous powder of white to white-cream
color depending on the method of preparation and the presence of other substances.
Dihydroquercetin has a good solubility in acetone, methyl and ethyl alcohol, 1,2-propylene glycol,
acetic ether, and hydrocarbons, but is insoluble in chloroform, sulphuric ether, and hydrocarbons.
The solubility in water increases when more pure dihydroquercetin is used. While conventional
commercial products have a solubility of 0.1 percent by weight at 20oC and 5.20 percent by weight
at 90oC, highly purified dihydroquercetin provides more than threefold increase over these
solubility levels (see below).
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Basic Physical and Chemical Properties of Taxifolin
Molecular formula — С15Н1207
Molecular weight — 304.25 daltons
Melting point: 222 — 224oС. Buchi, Melting Point B-250
UV spectrum: λmax=289±2nm, log Emax=4.25±0.05.
A solution of 0.1 g of dihydroquercetin in 5 ml of 95% alcohol, with 0.5 ml of concentrated
chlorohydric acid and 0.05 g of granulated zinc added, yields a crimson color, signifying the
presence of the flavanoid (flavonoid qualitative test).
Although there are a considerable number of patents related to the extraction of dihydroquercetin,
no adequate technology has been available to achieve the high purification of the substance until
now. Solvent reprecipitation methods result in an amorphous product with a tar-like residue, which
is impossible to identify. This is responsible for the low solubility of dihydroquercetin even in hot
water.
Standard Chromatogram of Highly Purified Taxifolin
Dihydroquercetin 99.6%
Aromadendrin 0.40%
Eriodictyol 0%
Naringenin 0%
Analysis Conditions:
Column: 4.6×250 mm, Kromasil-100-C18, 5 µm
Eluent: A — ACN/2%CH3COOH (30:70), B — 100% ACN
Gradient: from 100% A to 100% B in 13 min
Detection: UV-288 nm
Flow rate: 1 ml/min
Injection — 10 µl
Higher purity of dihydroquercetin result to significant impact on its physical and chemical
properties. Dihydroquercetin, as part of bioflavonoid complex, differs from the other known
products because of its ability to become crystallized in highly pure state.
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Taxifolin Crystals:
The removal of foreign substances improves significantly its solubility as compared to the solubility
of the other known products. Such significant modifications in physical and chemical properties
show that dihydroquercetin manufactured using this new technology can be considered as new
generation product with new technological possibilities and expanded applications.
Taxifolin — new possibilities in sports nutrition
Performance and endurance training, required in professional sports, is closely related to the
training of one’s cardiovascular system in order to adapt it to exercise workload. This is especially
important during the competition period, when physical demands are at their peak and athletes
strive to push their limits.
An individual, undergoing intense physical training, utilizes oxygen at levels exceeding 75%
of maximum values. The challenge here is that sustained physical exercise may result
in an inadequate supply of oxygen to working muscles (known as tissue hypoxia), a result
of insufficient blood supply to the tissues due to poor microcirculation.
Moreover, during maximal exercise, the metabolism of the tissue is violated. Muscles accumulate
lactic acid, which causes fatigue and complicates recovery after training.
Studies show that the application of taxifolin is able to solve these problems very efficiently.
Specifically, taxifolin is able to:
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Improve intracardial hemodynaimcs and intensify blood flow to the myocardium
Help to return pathologic microcirculation to normal, thus, optimizing tissue blood flow
Contribute to the redistribution of blood flow within small arteries, thus, enhancing blood
supply to ischemia-affected tissues
Enhance blood flow to muscles
Enhance pulmonary mechanics and improve lung ventilation and blood gas composition
Help to increase РО2 (oxygen partial pressure) and blood oxygenation
Studies of taxifolin were conducted during the training period of the Russian Olympic Team prior
to the 2008 Olympic Games. The studies were supervised by S. A. Parastaev, M. D., a member
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of the medical commission of the Russian Olympic Committee, Professor of Physical Therapy,
Sports Medicine, and Physical Education of the Russian State Medical University.
The studies showed that taxifolin can be utilized by professional athletes in daily doses
of up to 100-200 mg during the training period, which requires aerobic and anaerobic endurance,
as well as during the competition period when the workload is at its maximum.
When dissolved, taxifolin is rapidly and completely absorbed by the human body (bioavailability),
thus promoting antioxidative activity.
We provide our own methods of qualitative and quantitative testing of taxifolin in premixes and
in any type of end products. End product control is performed utilizing ultraviolet
spectrophotometry and high performance liquid chromatography (HPLC) subject to the state
reference standard (GSO No. 9054-20080).
Federal State Educational Institution of Higher Professional Training
RUSSIAN STATE UNIVERSITY OF PHYSICAL EDUCATION, SPORT AND TOURISM
(RGUFKSMIT)
Sport Research Institute
RESEARCH REPORT
Effect of Taxifolin (Dihydroquercetin) on physical work capacity in top athletes practicing
cyclic sports
Project Director S.K. Sarsania, M.D., Prof.
INTRODUCTION
Topicality of the research. Professional sport training and participation in competitions involve
strenuous efforts and constantly growing training loads to be executed by athletes. For this reason
we feel the need to detect and investigate specific factors, which may help improve physical work
capacity in top athletes and speed up the recovery after training exertion. On the one hand, these
factors are related to optimal planning of both competition and training loads according to
biological adaptation laws with the use of pharmacological support. On the other hand, these factors
comprise efficient recovery of the organism after physical training. The recovery process is based
on well-balanced nutrition and intake of food supplements of high biological value and high
metabolic capacity, which intensify the synthesis of morphological structures and activate
favourable physiological reactions. In a long list of biologically active additives, we found it
interesting to study a product with the trade name Taxifolin, chemical name (Dihydroquercetin)98%, produced by the company "Taxifolia" Ltd., Belgorod (Registration #77.99.11.3.У.7914.8.09;
date of registration 24.08.2009). A preliminary information study showed that this product might be
called a model antioxidant free of admixtures (pitches, essential oils), its purity being not less than
98%. The base substance is found in the bottom part of Siberian larch and Dahurian larch [18].
Principal properties of Taxifolin:
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improvement of microcirculation;
preventing thrombus formation;
enhancement of work capacity and intensification of recovery processes after high physical
and psycho-emotional loads;
strengthening of capillary walls;
bringing triglycerides and cholesterol concentrations in blood to normal level;
improvement of coronary blood flow and myocardial contractility, normalization of
excitability and conductivity in cardiomyocytes.
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Hypothesis. Taking into account the ability of Taxifolin to protect capillaries and improve
microcirculation, we suggest that the use of Taxifolin increases oxygen supply and utilization in
skeletal muscles, thus resulting in development of aerobic capacities and growth of results in
endurance sports.
Purpose. The purpose of our research was to estimate short-term and long-term effects of Taxifolin
intake on aerobic capacity of working muscles, functional capacity of the cardiovascular system,
and short-term recovery after maximal physical exertion.
Subjects. 5 top-class male athletes (Masters of Sport; Masters of sport, International Class)
participated in the research. The age of the subjects varied from 23 to 28 years; all the subjects have
been practicing skiing, cycling, and mountain running for many years.
Object of investigation: aerobic capacity of skeletal muscles and functional capacity of the
cardiovascular system.
Principal tasks:
1. estimate short-term adaptive effects of Taxifolin intake on 1) functional capacity of the
cardiovascular system at rest and 2) immediate recovery of physiological parameters after physical
exertion;
2. estimate long-term adaptive effects of Taxifolin intake on 1) functional capacity of the
cardiovascular system at rest and 2) immediate recovery of physiological parameters after physical
exertion;
3. estimate short-term adaptive effects of Taxifolin intake on aerobic capacity of skeletal muscles;
4. estimate long-term adaptive effects of Taxifolin intake on aerobic capacity of skeletal muscles.
Expiration date — 3 years.
Application of Flavomix Taxifolin Premixes in Food
1. Antioxidant for various fat-containing food products (dairy, fish, meat, confectionary, etc.)
2. Therapeutic dietary supplements
Application of Flavomix Taxifolin Premixes in Dairy Products
Taxifolin (dihydroquercetin), registered in the RF National Standard — GOST R 52791-2007, has
been approved for application in dairy products.
Taxifolin (dihydroquercetin), when used as an antioxidant in dairy products, performs two functions
simultaneously:
ü Consumed with food, Taxifolin slows the body’s oxidation processes
ü Taxifolin also slows the oxidation process in foods, doubling or tripling normal shelf life.
Studies, conducted in the RF Dairy Research Institute, show that taxifolin, added to dairy products
in amounts of 0.08% to 0.2% of the product’s fat mass, slows the oxidation process thus, reducing
the accumulation of toxic substances resulting from oxidation. As a result, dairy products acquire
more stability and a more than twofold increase of shelf life without alteration in their organoleptic
properties. Only highly-purified taxifolin (≥98%), free from foreign substances, may be utilized
in the dairy industry.
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Dissolved taxifolin (premix) is convenient for integration in products at any stage of production.
A dairy product combined with 40 — 100 mg of dihydroquercetin acquires medicinal properties
Bibliography:
1. RF National Standard GOST R 52791-2007 ‘Canned Dairy Products. Powdered Milk.’
Specifications. Effective since 01/01/2009, eligible for early application.
2. Process Regulations. Osoboye Whole Cow’s Milk. Istra-Nutritsiya, RF, 1998
3. Dihydroquercetin protection of powdered milk against free radical oxidation.
I. V. Babenkova, G. I. Klebanov, Yu. A. Kolesnik, and others. Biotechnology and
Management periodical, 1994, No. 3-4, p. 254-256
4. Inhibition of free radical lipid oxidation in powdered milk by dihydroquercetin.
I. V. Babenkova, G. I. Klebanov, Yu. A. Kolesnik, I. A. Radayeva, and others.
Biotechnology and Management periodical,1995, No. 1, p. 36-39
Application of Flavomix Taxifolin Premixes in Confectionary
Studies, conducted jointly by the Red October Moscow Confectionary Factory and the Sechenov
Moscow Medical Academy, demonstrated that:
The inhibitory effect on lipid peroxidation, produced by a taxifolin dosage of 0.05% to 0.2% of the
fat mass of the confection, will extend product shelf life by 250%.
The studies included the following products:
1. Primary components of sugar-based fat-containing confections (confectionary fat, cocoa
butter, lipids of grated cocoa, lipids of cocoa powder, lipids of grated nut kernels, lipid
fraction of powdered milk)
2. Finished confectionary products: chocolate (Pushkin’s Fairy Tales, Alenka, Jubilee
Chocolate, Red October) and candies. The components listed under item a) constitute a part
of these products in various proportions depending upon the recipe, i.e. the composition and
quantities of lipid mass in the products varied.
The studies also showed that the confections containing taxifolin in amounts up to 1% of their fat
mass, acquire distinctive medicinal effects, thus, chocolate becomes a parapharmaceutical product
(e.g., Sibirsky chocolate with a taxifolin content of 0.75%).
Findings:
 Taxifolin antioxidative activity is manifested regardless of the nature or composition
of lipid fractions in the confectionary components.
 Taxifolin antioxidative activity is not affected by confectionary components of a non-lipid
nature.
 Taxifolin content in confections does not diminish over time with storage (Taxifolin
catalytic effect).
 The presence of Taxifolin in confections in the amount up to 1% of the product’s fat mass
does not affect organoleptic properties of the product.
 Only highly-purified taxifolin (≥96%) free from foreign substances (resins) may be utilized
in confectionary.
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Bibliography:
1. Confections containing dietary supplements. 1. Dihydroquercetin. Yu. A. Kolesnik, I. A.
Rulenko, N. A. Tyukavkina, and others. Biotechnology and Management periodical, 1993,
No. 3-4, p. 24-43.
2. Application of dihydroquercetin as antioxidative agent in confectionary products designed
for medicinal purposes. A. M. Daursky, Yu. A. Kolesnik, I. A. Rulenko, and others. The 3rd
International Symposium ‘Human Ecology: Challenges and Status of Therapeutic
Nutrition’, Moscow, 1994, p. 189-192.
3. Biological activity of dihydroquercetin-containing confectionary products. A. M. Daursky,
Yu. A. Kolesnik, I. A. Rulenko, and others. The 3rd International Symposium ‘Human
Ecology: Challenges and Status of Therapeutic Nutrition’, Moscow, 1994, p. 198-200.
4. Sibirsky Chocolate — New Type of medicinal confection. The 3rd International Symposium
‘Human Ecology: Food and Food Processing’, Moscow, 1995, p. 293-294.
Application of Flavomix Taxifolin Premixes in Cosmetics and Perfumes
The Flavomix taxifolin premixes can be utilized in cosmetics and perfumes, specifically, to:
 Preserve raw material, oil and fat components, as well as the finished products
 Render therapeutic effects to products
The Flavomix taxifolin premixes, utilized in cosmetics:
 Enhance protective functions of the skin against external and internal toxicity, radiation,
germs, and other environmental factors.
 Normalize general metabolic processes through topical application, specifically, those
in lymphatic and blood system, thus, slowing skin aging.
The Flavomix taxifolin premixes are a promising component to be utilized in cosmetics intended for
intensive care after:
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Dry and aging body and facial skin
Sensitive skin prone to irritation and allergy
Skin with weakened microcirculation
Capillaropathy
The Flavomix taxifolin premixes, introduced in creams and shampoos, help to renew skin.
Taxifolin-based hair conditioners contribute to the general health of hair and hair growth.
The Flavomix taxifolin premixes are quickly and completely absorbed by the skin, which
maximizes their antioxidative effect.
Bibliography:
1. Use of flavonoids in hair protection and (or) enhancement of its mechanical properties.
L’OREAL,FR 949405539,05.05.94.
2. Bioflavonoid-based hair cosmetics. L`OREAL.FR94905540 05.05.94.
3. Use of flavonoids to protect unstable active substances and ingredients in cosmetic and
dermatologic products. Beiersdorf AG, DE944444238,13.12.94.
4. Substances curing hyperactive and hypoactive skin conditions and dermatitis. Beiersdorf
AG, DE944444238, 13 Dec 94.
5. Use of flavonoids as immunomodulators or immune protectors in cosmetic and
dermatologic products. Biersdorf AG, DE944444238, 13.12.94.
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6. Cosmetic and medical preparations containing flavonoid-phospholipid complex. Enr.Pa+
Appl EP275.005(CL,CO779)10,20.07.88.) Bombardeli et al. Chem.Ab,v.111,1989. Gen.S
u b Ind, 45279Z
7. Clinical studies of the dihydroquercetin-enriched drinking water efficiency. ‘Beauty
Institute’ cosmetic center, Moscow, 2006
8. Assessing dynamics of blood microcirculation by laser Doppler flowmetry upon application
of taxifolin-enriched body cream. The Peoples’ Friendship University of Russia, Moscow,
2004.
9. Studies of cosmetic and perfume products efficiency. ‘Cosmetology’ laboratory testing
center, Moscow, 2006.
Application of Flavomix Taxifolin Premixes in Dietary Supplements
and Pharmaceutical Products
Due to its powerful antioxidative and capillary protection activities taxifolin is most widely used
in dietary supplements and pharmaceutical products. Taxifolin is compatible with vitamins, mineral
complexes, and medicinal plant extracts.
Taxifolin’s proven biological effects include:
Antioxidative activity
Vitamin P activity
Capillary protection: improving microcirculation and blood flow at the capillary level,
promoting the development of new capillaries
 Helping to maintain blood pressure at physiological levels, providing a mild hypotension
effect
 Improvement of the elasticity of red blood cells, reduction of blood viscosity
 Improvement of the coronary blood flow and myocardial contractility, reduction of the
affected zone of the cardiac muscle
 Anti-ischemic effect
 Antidepressant effect
 Reduction of the low density lipoprotein levels in blood plasma
 Stomach protection
 Liver protection
 Immune system regulation
 Inactivation of cytotoxic substances
 Radiation protection
 Synergist to vitamins А, С, Е
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Bibliography:
Free radicals scavenging and protection from peroxidation (extending life of cell membranes
and organelles):
1. Dihydroquercetin — new antioxidant and capillary protector. V. K. Kolkhir, N. A.
Tyukavkina, V. A. Bykov, and other. Chemical & pharmaceutical periodical, 1995, No. 9, p.
61-64.
2. Antioxidative activity of dihydroquercetin. Yu. O. Teselkin, B. A. Zhambalova,
I. V. Babenkova, G. I. Klebanov, N. A. Tyukavkina, Biophysics guide, 1996, Vol. 41, No. 3,
p. 620-624.
3. Natural flavonoids as food antioxidants and dietary supplements. N. A. Tyukavkina, I. A.
Rulenko, Yu. A. Kolesnik. Nutrition Issues periodical, 1996, No. 2, p. 33-38.
4. Interaction of flavonoids with 1,1-diphenyl-2-picrylhydrazyl free radical, liposomal
membranes and soybean lipoxygenase-1. Ratty A.K, Sunamoto J., Das N.P., Biochem.
Pharmacol., 1988, Mar 15;37(6), p.989-995.
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5. Protection against oxidative damage by dihydroflavonols in Engelhardtia chrysolepis.
Haraguchi H., Mochida Y., Sakai S., Masuda H., Tamura Y., Mizutani K., Tanaka O., Chou
W.H., Biosci. Biotechnol. Biochem., 1996 Jun;60(6), p.945-948.
6. Effects of flavonoids on nonenzymatic lipid peroxidation: structure-activity relationship.
Ratty A.K., Das N.P., Biochem. Med. Metab. Biol. 1988, Feb;39(1), p.69-79.
7. How flavonoids inhibit the generation of luminol-dependent chemiluminescence
by activated human neutrophils. Hart B.A., Ip Via Ching T.R., Van Dijk H., Labadie R.P.,
Chem. Biol. Interac.t 1990, 73(2-3), p.323-335.
8. 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., Environ. Mutagen., 1981, No 3(4), p.401-419
Inactivation of cytotoxic substances
1. Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis factor-alpha in L929 tumor cells. Habtemariam S., J. Nat. Prod., 1997, Aug;60(8), p.775-778.
2. Differences in the serum levels of acetaldehyde and cytotoxic acetaldehyde-albumin
complexes after the consumption of red and white wine: in vitro effects of flavonoids,
vitamin E, and other dietary antioxidants on cytotoxic complexes. Wickramasinghe S.N,
Hasan R., Khalpey Z., Alcohol. Clin. Exp. Res., 1996 Aug, No 20(5), p.799-803.
Antidiabetic Activity
1. 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 W.H., Biosci. Biotechnol. Biochem., 1997, Apr,
No 61(4), p.651-654.
2. An intensely sweet dihydroflavonol derivative based on a natural product lead compound.
Nanayakkara N.P., Hussain R.A., Pezzuto J.M., Soejarto D.D., Kinghorn A.D., J. Med.
Chem. 1988, Jun, No 31(6), p. 1250-1253.
Reduction of low-density lipid concentrations in liver and blood plasma without affecting
body’s own antioxidant enzyme systems
1. 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., Biosci. Biotechnol.
Biochem., 1996, Mar, No 60(3), p.513-515.
Antitumor activity
1. Inhibitory effects of flavonoids on Moloney murine leukemia virus reverse transcriptase
activity. Chu S.C., Hsieh Y.S., Lin J.Y., J. Nat. Prod., 1992. Feb., No 55(2), p.179-183.
2. 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 D.S., Middleton E. Jr., Anticancer. Drugs, 1992, Oct.,
No 3(5), p.525-530.
3. In vitro effects of natural plant polyphenols on the proliferation of normal and abnormal
human lymphocytes and their secretions of interleukin-2. Devi M.A., Das N.P., Cancer.
Lett., 1993, May, No 69(3), p.191-196.
Antimutagenic effect
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1. Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic
hydrocarbons by phenolic plant flavonoids. Huang M.T., Wood A.W., Newmark H.L.,
Sayer J.M., Yagi H., Jerina D.M., Conney A.H., Carcinogenesis, 1983, Dec. No4(12),
p.1631-1637.
Radiation protection
1. Pharmacological and radiation protection activities of some gamma-pyrone derivatives
(flavanones and flavanols). T. Yu. Il’yuchenok, A. I. Khomenko, L. M. Frigidova, and
others, Pharmacology and Toxicology periodical, 1975, 38, № 5, с.607-612.
Antiviral effect
1. Effect of antiviral substances on hepatitis A virus replication in vitro. Biziagos E, Crance
J.M., Passagot J., Deloince R., J. Med. Virol., 1987, May, No22(1), p.57-66.
Immune regulation (anti-allergy effect) and anti-inflammatory activity
1. Kinetics of the inhibitory effect of flavonoids on histamine secretion from mast cells.
Bronner C., Landry Y., Agents Actions, 1985, Apr. No16(3-4), p.147-151.
2. T. Yu. Il’yuchenok, A. I. Khomenko, L. M. Frigidova, and others, Pharmacology and
Toxicology, 1975, Volume 38, No. 5, p. 607.
3. 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.,
Immunopharmacology, 1984, No 7(2), p.115-126.
Normalizing influence on cell enzyme systems
1. Effects of flavonoids on enzyme secretion and endocytosis in normal and mucolipidosis
II fibroblasts. Vladutiu G.D., Middleton E. Jr., Life Sci., 1986, Aug, No 25;39(8), p.717726.
Low mutagenic activity and toxicity:
1. Pharmacological and radiation protection activities of some gamma-pyrone derivatives
(flavanones and flavanols). T. Yu. Il’yuchenok, A. I. Khomenko, L. M. Frigidova, and
others, Pharmacology and Toxicology periodical, 1975, 38, No. 5, p. 607-612.
2. Natural flavonoids as food antioxidants and dietary supplements. N. A. Tyukavkina, I. A.
Rulenko, Yu. A. Kolesnik. Nutrition Issues periodical, 1996, No. 2, p. 33-38.
3. Study on the mutagenic activity of 13 bioflavonoids with the Salmonella Ara test. Jurado J.,
Alejandre-Duran E., Alonso-Moraga A., Pueyo C., Mutagenesis, 1991, Jul., No6(4), p. 289295.
4. 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., Environ. Mutagen., 1981, No3(4), p. 401-419.
5. Quercetin and DNA in solution: analysis of the dynamics of their interaction with a linear
dichroism study. Solimani R., Int. J. Biol. Macromol., 1996, No18(4), p. 287-295.
6. Mutagenic activity of quercetin and related compounds. Bjeldanes L.F., Chang G.W.,
Science, 1977, Aug., No 5, 197(4303).,p.577-578.
Application of Flavomix Taxifolin Premixes in Agriculture
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The Flavomix taxifolin premixes may be utilized as a plant growth regulator.
The premixes used in animal feed not only serve as a dietary supplement improving
cardiovascular and immune systems, but also act as an antioxidant for fats and oils contained in the
feed.
Bibliography:
1. Vitamins / under the editorship of M. I. Smirnov — M.: Medicine, 1974 — p. 495
2. Encyclopedia of chemistry: Vol. 5 — M.: Soviet Encyclopedia, 1988. — Vol. 1. — p. 556557
3. Livestock feeding norms and rations: Reference guidelines / under the editorship
of A. P. Kalashnikov, V. I. Fisin, V. V Shcheglov, N. I. Kleimenova — 3rd edition revised
and amended — M., 2003 — p. 456
4. A. D. Orlov. Normal physiology /A. D Orlov, A. D. Nozdrachev. M.: GEOTAR Media,
2006 — p. 696
5. D. K. Kozyrev. Effect of milk, acidified with formic acid and enriched with chitosan, polisin
(mixture of amino acids, vitamins, and minerals), and dihydroquercetin, on the calf growth
and immunity during the milk-sustained growth period. Abstract of scientific paper
by D. K. Kozyrev, Biology Ph.D. — M., 2007 — p. 24
6. A. D. Belov. Veterinary radiobiology / A. D. Belov, V. A. Kirshin. M.: Agropromizdat,
1987 — p. 287
7. S. P. Yarmonenko. Human and animal radiobiology: Textbook for biological institutes /
S. P. Yarmonenko — 3rd edition revised and amended — M.: Vysshaya shkola, 1988 —
p. 424
Flavomix Taxifolin Premixes
The physical and chemical properties of dihydroquercetin render
it nearly insoluble in water and edible liquids (juices, milk,
sunflower oil, dairy products, fat-containing canned food, etc.).
Therefore, integration of dihydroquercetin into a finished product
is extremely challenging.
Our premixes contain dihydroquercetin (taxifolin) without foreign substances (resin) and
of a purification level exceeding 98%. This product has a higher-order crystal structure and all the
attributes of a nanosystem. Specifically, it has a good solubility in water (up to 2 g/l) and stability
in a water solution, ensuring its high bioavailability. These properties of high-purity taxifolin,
combined with its strong antioxidative and capillary protection effects, make it attractive for food
industry, including its application in the fabrication of water-based products.
Integration of taxifolin into a finished product in liquid form has an absolute advantage over
the weight method.
The technology, developed by our specialists, allows for application of taxifolin in your production
processes and facilitates the production of a standardized end product.
Drinking water properties:
1. Standard color (yellowy-orange)
2. No precipitate
3. Unaltered taste
Additionally, water may be boiled or frozen with no effect on the above properties.
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Our premixes, utilized in other food products, allow integration of any required dose of taxifolin,
thus, giving new therapeutic effects to these products.
Integration of taxifolin in fat-containing products will extend their shelf life by 50 — 100%.
Highly technological production process of natural antioxidant from Larix sibirica based on modern
chromatography purification technique gives the products with content of target compounds more
than 99%.
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
Highly purified "mono-component" Taxifolin (Dihydroquercetin) with the purity at least
99% for the production of pharmaceuticals;
Taxifolin (Dihydroquercetin) with the purity at least 98% for the production of
pharmaceuticals and foodstuffs;
Taxifolin (Dihydroquercetin) containing Taxifolin at not less than 97% for beverages,
dietary supplements and food products;
Bioflavonoid complex «Taxifolia®», containing the amount of related bioflavonoids of 98-99%
(content of Taxifolin is 95-96,9%) for the production of dietary supplements, cosmetics and food.
ARKHYZ
Taxifolin-Enriched Beverage
Water with taxifolin — key to long and healthy life
ARKHYZ, a new antioxidant enriched beverage (taxifolin content — 80 mg per liter) — is the first
drinking water available to contain a natural vitamin and mineral complex with a pure plant extract
of taxifolin (dihydroquercetin content ≥98%).
The major advantage of taxifolin, dissolved in beverages, is its rapid and complete absorption
by human body (bioavailability), which promotes antioxidative activity of the substance.
As demonstrated by ultrasonic dopplerography of capillary blood flow, within a few minutes
of ingesting 150-200 ml of taxifolin water solution (80 m per liter), the capillary blood flow
velocity doubles.
Our odorless and tasteless beverage has a saturated orange color. When boiled, taxifolin retains its
antioxidant properties, making it suitable for cooking and hot drinks (tea, coffee, soups, second
courses, etc).
Daily consumption of taxifolin helps to maintain the body’s physiological functions at high levels.
According to L. Polling, the Nobel prize winner, regular consumption of food products with
a preparation of vitamin P properties (dihydroquercetin) added to them would prolong the life
significantly. The daily physiological need for bioflavonoids (natural antioxidants) equates to 150250 mg for children over 7 years of age and 250 mg for adults (according to Guidelines
MR 2.3.1.2432 −08 Physiological Needs for Energy and Nutrition of Different Population Groups
within the Russian Federation).
Quality
12
Taxifolin from our company is produced by Taxifolia factory (State Registration
Certificate 77.99.11.3.У.7914.8.09., 24 Aug 09) to utilize for development of premixes and
therapeutic beverages. Taxifolin possesses a purification degree of at least 98% and is completely
free from foreign substances (resins and ether oils), thus, enabling its application in the food
industry without modifying organoleptical properties of the food products.
Until now, taxifolin production had several considerable shortcomings, mostly related to the
presence of non-flavonoid substances in taxifolin: resins, ether oils, etc. This resulted in peculiar
and unpleasant taste, which limited application of non-purified taxifolin in food. Dihydroquercitin
content in these products did not exceed 90-92%.
The innovative nature of the technology, developed by Taxifolia company, has been certified
by patents and honored with a gold medal at the IDEEN-ERFINDUNGEN-NEUHEITEN
International Exhibition in Germany.
13
Propylene glycol, utilized to manufacture our premixes, is a product of the German company —
DOW EUROPE GmbH, (State Registration Certificate 77.99.26.9.У.7846.9.08, 15 Sep 2008).
It complies with the Sanitary Regulations and Standards SANPIN 2.3.2.1293-03 Hygiene
Requirements for Application of Dietary Supplements.
Water
To manufacture taxifolin-enriched beverages we utilize Arkhyz water. Arkhyz, the only mineral
drinking water of natural origin, is produced and bottled in the North Caucasus mountains at the
elevation of 1,507 m. Flowing through the mountain filter, this water becomes lightly mineralized,
acquiring beneficial properties and amazing taste. Bacteriological purity within the water well
is similar to that of vacuum, i.e. Arkhyz water is perfectly pure. The water is bottled on-site with its
original nature preserved. Thus, we can rightfully say that Arkhyz is the water of original natural
quality, providing considerable health benefits, as opposed to artificially mineralized water and
regular water being purified almost to the level of distilled water. Arkhyz has been collaborating
for 9 years with the Federal Agency for Physical Education and Sports of Russia and has been
a partner of such events as Ski-Track of Russia (all-Russia amateur ski racing), Nation’s CrossCountry Run (amateur running race), and others. Arkhyz is the official partner of the Zenit Football
Club.
Cardiovascular Pathology
TAXIFOLIN AND blood PRESSURE
The prevalence of hypertension shows continuous growth. By 2025, adult hypertension will
increase by approximately 60%, affecting 1.56 billion people worldwide.
Hypertension affects both developed and developing nations. This is precursor to the global
epidemic of cardiovascular diseases.
In 2000, 26.4% of the world’s total adult population (972 million people) suffered from
hypertension, including 333 million in developed countries and 639 million in developing countries.
It is expected that by 2025, the global hypertension rates among adult population will rise to 29.2%
and it means that 1.54-1.58 billion people will suffer from high blood pressure. These rates reflect
an increase of 24% in developed countries and of 80% in developing countries.
This forecast becomes all the more horrifying if one considers the fact that hypertension is currently
responsible for 40% of the total death rate, 69 % of cerebral strokes, and 49% of coronary
conditions.
Clinical studies were conducted among 40 second-degree hypertensive patients (all males). The
individuals mentioned were undergoing the in-patient period of rehabilitation due to a hypertensive
crisis and unstable blood pressure with astheno-neurotic syndrome. The average age of these
patients was 49.6±4.5 years, while the average duration of hypertension was 8.8±1.9 years.
A control group of 20 patients received standard treatment, while an experimental group
(20 persons as well) received a daily dose of 80 mg of taxifolin in addition to the standard therapy.
14
The patients’ risk factors included the following:
The rehabilitation of all the hypertensive patients at the end of the treatment was successful in both groups; however,
it was more effective in the experimental group.
The rehabilitation of the individuals receiving taxifolin as part of the therapy was characterized by:







Improvement of respiratory function
Improvement of central and peripheral hemodynamics
Enhancement of blood oxygenation
Improvement of microcirculation
Improvement of exercise tolerance
Improvement of the emotional and psychological state of the patients
Enhancement of rehabilitation efficiency
Upon completion of treatment, both systolic and diastolic pressures decreased considerably in both groups. However,
this decrease was more significant in the experimental group receiving taxifolin.
15
HEALTHY
HEART
AND
VESSELS
–
the
simple
secret
to
a
long
life
According to the WHO, more than 17 million people die due cardiovascular diseases each year, including over
7 million individuals with ischemic heart disease (IHD). By 2020, IHD is expected to become a killer of more than
11 million people every year.
For example, 5-6 million Americans are diagnosed with IHD each year and one third of total middle-aged deaths (in 3564 age group) is attributed to coronary atherosclerosis, claiming the lives of more than 1 million people every year.
Acute myocardial infarction alone is the reason for hospitalizing over 200,000 people per year in the age group
of 65 and over in the US.
Currently, myocardial infarction affects an estimated 900,000 people every year in the US, approximately 225,000
of them do not survive.
In Europe, IHD is one of the leading causes of death, with approximately 2 million cases annually. The percentage
of deaths from this disease reaches 22% among European women and 21% among European men.
Changes in the blood microcirculation underlie the IHD pathogenesis. Therefore, the search for new medical
preparations facilitating blood microcirculation remains of great importance.
Dihydroquercetin (taxifolin), being one of such preparations, has a stimulating effect on the tissue blood flow,
stabilizing the barrier function of microvessels and reducing the permeability of the capillary walls, thus reducing stasis
in the microcirculatory bloodstream.
Active life after heart surgery
An experimental group* included 30 patients aged 32-68 years (average age 47.6 ±3.2 years), who underwent coronary
artery bypass surgery.
Patients consumed 80 mg of taxifolin daily for a 21 day period.
The most common complaints in these patients during the rehabilitation period included shortness of breath, caused
by regular physical workload, and general weakness, which altered considerably the quality of their lives.
The rehabilitation of the taxifolin taking patients resulted in improved central and peripheral hemodynamics, blood
oxygenation, and microcirculation.
It’s remarkable that the most significant subjective improvement was the increased tolerance to exercise. This resulted
in the patients‘ better emotional and psychological state which finally improved the rehabilitation outcome.
LIFE AFTER A HEART ATTACK
Studies were conducted among 30 patients, hospitalized for rehabilitation after acute myocardial infarction. The
rehabilitation period lasted for 16- 28 days. All subjects were males aged 47-68 years (average age 57.6В±3.2 years). A
substantial majority of the group was comprised of individuals whose work was associated with high emotional charge
16
and mental labor.
53.3% of patients experienced angina attacks when they walked rapidly on horizontal surface or climbed upstairs, while
39.8% experienced angina attacks while walking on a level surface or ascended less than two flights of stairs at a
moderate pace. Some patients (6.6%) experienced angina attacks at rest.
Repeated angina episodes (chest pains) often frighten patients who have recently experienced a potentially fatal heart
attack. Their fear of a recurrent attack makes them emotionally suppressed.
The number of angina attacks was significantly reduced among the experimental group patients receiving taxifolin.
This increased the number of patients who were able to cope psychologically with the disease or had minor difficulties
with adaptability.
Thus, rehabilitation programs using taxifolin can be considered to be more efficient.
The positive dynamics in the control group was insignificant.
Taxifolin and ischemic heart disease
These studies were conducted among IHD male patients.
The average age of patients was 54.3 ± 2.3 years in the experimental group and 55.3 ± 1.9 years in the control group
The experimental group consumed 80 mg of taxifolin daily for a 21 day period, in an addition to the standard treatment.
The control group received the standard treatment only.
The studies showed that taxifolin consumption prevented and relieved spasms in both the normal and
atherosclerotic coronary arteries, thus helping to eliminate microangiopathy.
The rehabilitation program which included taxifolin resulted in improved rheological parameters, specifically:






Increased blood flow velocity in microvessels
Reduced stippling of the red blood cells and decreased aggregations of the cells
In general, no focal stasis areas
Improved hemodynamics
Increased number of functioning capillaries
Mitigated arteriolar spasm
17

Normalizing arteriolar-to-venular diameter ratio
Additionally, the emotional state of the taxifolin taking patients improved significantly.
Combination of the above positive changes in




Microcirculation system
Hemorheology
Cardiorespiratory system
Emotional and psychological state
finally resulted in the reduction or elimination of respiratory and heart insufficiency and a rapid recovery in patients.
Taxifolin improved intracardial hemodynamics, systemic and pulmonary circulations, respiratory function, and gas
composition.
The preparation produces a positive effect on the peripheral microhemodynamics and facilitates the normalization
of the pathological microcirculation, thus optimizing the tissue microflow.
Taxifolin facilitates the redistribution of the blood flow within the small arteries and enhances blood supply
of ischemia-affected tissues such as myocardium. It also eliminates artery spasms which can alter the coronary
arteries.
All patients reported good tolerance of the preparation and improved well-being, specifically:




Reduction or elimination of the shortness of breath
Reduction of retrosternal chest pain
Increased activity level
Improved sleep
Clinical Tests of DHQ in IHD Patients
Gerontology Center.
Objective:В evaluation of DHQ antioxidative activity in medical patients.
Utilized materials and methods: 50 individuals participated in the studies. The first experimental group was
comprised of 10 patients aged 50-73 years. The main medical condition of the patients was IHD often combined with
hypertension, diabetes, and obesity. The control group included 20 individuals.
Therapeutic approach: prior to application of DHQ, a complete clinical examination of the patients was conducted.
The patients consumed 250 mg of the preparation daily for a 10 day period.
The first control group included 14 people, matched by gender, age, and diseases.
Studied parameters: cholesterol, triglyceride, conjugated dienes, conjugated trienes, Schiff base, and antioxidative
activity index. The specified parameters were recorded within the timeline in accordance with the clinical observation
protocols containing patients’ feedback as well as diagnosis of their primary diseases and co-morbid conditions.
Research approach: dynamics of lipid peroxidation resulting from the treatment was measured by the
chemiluminescence method.
18
Results:within 10 days, the consulting physicians recognized the improved well-being and reduced intensity of cardiac
chest pain and headache in the experimental group as compared to the control group. The evaluation of lipid
peroxidation at elevated levels of molecular products (primary products — conjugated dienes, secondary products —
conjugated trienes, final products — Schiff bases) showed prominent decrease in peroxidation against the
chemiluminescence intensity rate. This decrease was expressed in a reduction of both Imax index and light sum (S), and
was attributed to the reduced metabolic activity accompanied by the free-radical reactions. The Imax/S coefficient
characterizing general antioxidative activity also decreased. After the DHQ therapy, none of the lipid peroxidation
parameters analyzed deviated significantly from the norm (Table 1), while the same parameters in the control group
patients not receiving the preparation treatment, demonstrated no marked changes (Table 2). Additionally, patients
receiving DHQ treatment had a more significant decrease of cholesterol, triglyceride, and uric acid levels, and
prothrombin time, which are crucial elements of the pathogenesis of the specified diseases. This demonstrates that the
preparation is able to affect deep metabolic processes in the liver.
Table 1
Dynamics of Parameters in the Experimental Group of Atherosclerosis Patients Resulting from the DHQ Treatment
19
Table 2
Control Group
Application of taxifolin in treatment of the IHD patients. Several studies [1-3] have demonstrated that the IDH patients
have both enhanced lipid peroxidation and reduced antioxidative protection levels, which suggests that these disorders
constitute a link in the chain of the IHD pathogenesis. A significant amount of data regarding the crucial role of lipid
peroxidation in the atherosclerosis pathogenesis is also available now [4]. In this connection, antioxidants become
an important part of the comprehensive treatment of atherosclerosis and IHD, as they slow the lipid peroxidation and,
thus, produce a positive effect on cell membrane and vessel wall health [5]. At the same time, antioxidative therapy for
IHD patients is directly related to the lipid peroxidation levels and the antioxidative protection activity. The quicker
membrane lipid peroxidation occurs and the weaker the level of the antioxidative protection, the lesser the therapeutic
effect on the patient. [Р±].
Taxifolin is a bioflavanoid preparation [9]. Its antioxidative and capillary protective properities combine with the lipidlowering, liver protective, and diuretic ones [10]. The DHQ produces neither allergic reaction, nor immunodepressive,
embryotoxic, teratogenic, or mutagenic effects [II].
The objective of the above mentioned research was to justify the application of the DHQ as an antioxidant preparation
in combination with the IHD therapy.
20
Materials and Methods
The data accumulated during the studies result from the observation of more than 56 IHD patients. The IHD diagnosis
was developed on the basis of the WHO criteria, while angina functional class was determined in accordance with the
Canadian Cardiovascular Society grading scale. Eighteen patients out of 56 (45 males and 11 females; average age 61.2
±1.6 years) had a medical history of myocardial infarction. All the patients suffered from a stable exertional angina
of the II or III functional class, which was diagnosed on the basis of the clinical symptoms and bicycle exercise test.
The second-degree hypertensive disease has been diagnosed in 21 patients.
The patients received therapy including nitrates of long-lasting action, β-adrenergic receptor blocking agents, and
angiotensin-converting enzyme inhibitors. Medication dosages were constant during the entire research process. All the
patients continued to experience angina attacks during the therapy. Additionally, all the patients received taxifolin
according to the following scheme: 0.04 g four times a day for 6 days; 0.04 g three times a day for 10 days; and 0.02 g
three times a day for the remainder of the period. The therapy course continued for 40 days.
Examination of the IHD patients was performed prior to and after a 40-day taxifolin course which took place in parallel
with the standard treatment. The evaluations included the patient’s general well-being, frequency of angina attacks,
electrocardiographic examination data, and exercise tolerance as determined by the bicycle exercise test. The protocol
of this test provided for a stepwise increasing workload (one workload level −25 Watt, duration — 3 min) until either
the critical level (rhetrostanal chest pain and/or ischemic ST-segment displacement by 1 mm or more) or submaximal
level (85 % of maximal heart rate) was reached.
Moreover, the blood lipid spectrum (total cholesterol), low-density lipoproteins, and triglycerides were measured
in accordance with the unified procedure. Blood was obtained for analysis at the morning time following a 12-hour
fasting period. The above study was combined with the diagnostic of thymus-dependant disregulatory immune
deficiency, since this immune deficiency is recognized as one of the pathogenic components of most internal organ
diseases, including IHD. Immune deficiency was determined through the method co-authored by M. V. Vogralik
(1986). This method uses a thermal imager to scan the skin surface in the upper sternum area and the medial surface
of the big toe in order to identify zones of reduced infrared radiation.
A decrease rate expressed in degrees demonstrates a statistically significant correlation with the decrease of quantitative
and functional parameters of the T-cells. Additionally, the temperature gradient value has a negative correlation with
the helper T-cells/suppressor T-cells ratio. Immune deficiency diagnosis was conducted with the help of the Helper
device.
Clinical effect was evaluated on the basis of frequency of angina attacks, number of nitroglycerin pills consumed, and
increase of the exercise tolerance. The effect was confirmed when less frequent or weaker angina attacks occurred,
consumption of nitroglycerine was reduced by 50 % or more, pain thresholds decreased by 10% or more (as compared
to the original levels), immunity increased, and blood lipids showed a marked reduction.
Results and Discussion
78% of the patients receiving taxifolin had mild symptoms of coronary failure. Specifically, the rate of angina attacks
occurrence decreased by 50 %, resulting in a decrease of nitroglycerine consumption (Table 1). The data obtained
confirm the crucial role of oxidative stress for the development of nitrate tolerance and, consequently, the beneficial
effects of antioxidants included in the treatment.
Table 1. Dynamics of Angina Episodes in DHQ Patients
*СЂ<0.05
A significant increase of exercise tolerance was observed — from 76.4 ± 3.9 Watt to 112.3 ± 7.2 Watt at СЂ < 0.05
(Figure 1)
21
Upon completion of taxifolin therapy total cholesterol levels decreased by 25.7 %, low-density lipoproteins — by 23 %,
and triglycerides — by 4.4 %
Table 2. Dynamics of Blood Lipid Levels
СЂ < 0.05 between the before- and after-treatment parameters
Most IHD patients (94 %) had been diagnosed with thymus-dependant disregulatory immune deficiency, the
development of which might possibly be attributed not only to IHD, but also to age, stress, and environmental factors.
Upon completion of treatment, positive visible changes were observed in the immune system and the body’s reactivity
increased (Table 3).
Table 3. Dynamics of Temperature Gradient of Reflexogenic Zones
СЂ< 0,05.
Other studieswere conducted among 40 second-degree hypertensive patients (all males). The above individuals were
undergoing the in-patient stage of rehabilitation due to a hypertensive crisis and unstable blood pressure with
asthenoneurotic syndrome. The age of these patients averaged 49.6±4.5 years, while the average afflicted duration
of hypertension was 8.8±1.9 years.
A control group of 20 patients received standard treatment, while an experimental group (20 persons as well) received
a daily dose of 80 mg of taxifolin in addition to the standard therapy.
The patients’ risk factors included the following:
Upon completion of treatment, both systolic and diastolic blood pressures decreased in both groups.
The rehabilitation of hypertensive patients at the end of the treatment was successful in both groups; however, it was
considered to be more efficient in the experimental group.
22
Findings:
1.
2.
3.
4.
DHQ decreases nitrate tolerance in IHD patients by reducing oxidative stress.
DHQ consumption combined with the standard therapy, including nitrates, β-adrenergic receptor blocking
agents, and angiotensin-converting enzyme inhibitors, increases exercise tolerance and immunity levels in IHD
patients.
DHQ reduces total cholesterol levels and low-density lipoprotein concentrations in IHD patients.
Taxifolin as an antioxidative agent is practical for introduction into the standard therapy of IHD patients.
Taxifolin in Diabetes
METABOLIC SYNDROME
The term «metabolic syndrome» was first suggested in1988. Around that time,
specialists first noticed that a combination of arterial hypertension, obesity, diabetes,
and increased cholesterol levels lead to a high risk of development of cardiovascular
diseases, including potentially fatal myocardial infarction and stroke. Consequently,
the metabolic syndrome was referred to as «the deadly quartet».





Waist circumference: more than 88 cm for women and more than 102 cm for
men
Blood pressure: more than 130\85 mm Hg
Fasting plasma glucose: more than 6.1 mmol\L
Raised triglyceride level: more than1.7 mmol\L
Reduced high-density lipoproteins: less than 1mmol/L for men and 1.3 mmol\l
for women
According to the WHO, the number of people affected with metabolic syndrome
in Europe
is 40-60
million.
Prevalence of the metabolic syndrome in adults over 30 years of age reaches 10-20%
in developed countries (25% in the US).
The studies conducted by the American Diabetes Association show a continuous
increase of metabolic syndrome among teenagers and young adults. During the
period of 1994 through 2000, the metabolic syndrome prevalence among teenagers
23
increased from 4.2% to 6.4%. In the US, the number of teenagers and young adults
affected by metabolic syndrome is estimated to exceed two million people.
The studies included 40 patients (16 males and 24 females) aged 56.2±8.5 years with
an average afflicted duration of diabetes of 0.4±0.12 years and a body mass index
of 33.3±6.3 kg/m2.
The patients were randomly assigned for experimental or control group.
The experimental group received a daily dose of 120 mg of taxifolin for 12 weeks
in addition to the standard glucose-lowering therapy. The control group received only
the standard glucose-lowering therapy.
24
The specified results provide grounds for considering taxifolin as a promising component for the therapeutic
preparations for the metabolic syndrome patients.
DIABETIC RETINOPATHY
The diabetic retinopathy is one of the most common age-related pathologies.
Clinical research on taxifolin revealed protective and even therapeutic effects for the development of diabetic
retinopathy.
The studies included 40 patients (16 males and 24 females) aged 56.2±8.5 years with an average afflicted duration
of diabetes of 0.4±0.12 years and a body mass index of 33.3±6.3 kg/m2.
The patients were randomly distributed between the experimental and control groups.
The experimental group received a daily dose of 120 mg of taxifolin for 12 weeks in addition to the standard glucoselowering therapy (2,000-2,500 mg of metformin daily).
The control group received only the standard glucose-lowering therapy.
TYPE 2 DIABETES. BLOOD SUGAR
Type 2 diabetes is one of the most common diseases affecting both developed and developing nations.
According to the WHO, diabetes prevalence worldwide is in excess of 100 million people (3% of the world population).
Each year this number increases by 5-7% and every 12-15 years it doubles.
Over the last ten years, the prevalence of diabetes among young adults aged 30-39 increased by 70%. Hence, the
American
Diabetes
Association
is stating
that
this
disease
is reaching
epidemic
proportions.
Currently, an estimated 16 million Americans suffer from type 2 diabetes. Another alarming fact is that the earlier
diabetes occurs, the higher the risk of such grave complications as blindness and limb amputation.
The study included 40 patients (16 males and 24 females) aged 56.2±8.5 years with an average afflicted duration
of diabetes of 0.4±0.12 years and a body mass index of 33.3±6.3 kg/m2.
The patients were randomly assigned to the experimental and control groups.
The experimental group received a daily dose of 120 mg of taxifolin for 12 weeks in addition to the standard glucoselowering therapy (2,000-2,500 mg of metformin daily).
25
The control group received only the standard glucose-lowering therapy.
A decrease of basal glycemia means that the total blood sugar levels are decreasing.
A decrease of basal glycemia while dosages of glucose-lowering medications remain constant, suggests that the
sensitivity of peripheral tissues and, primarily, the liver sensitivity to circulating insulin have increased, which resulted
in reduced gluconeogenesis.
A decrease of the postprandial (after meal) glycemia demonstrates that the body is coping better with carbohydrates.
In general, a decrease of glycemia reduces the risk of developing diabetes-related complications and retards the
progression of micro and macroangiopathy.
26
Levels of glycated hemoglobin showed prominent decrease as compared to the start of treatment and as opposed to the
control group. Thus, taxifolin allows a significant improvement of diabetes compensation.
Increased sensitivity to insulin and reduced insulin resistance indicate the increased sensitivity of cells to insulin and,
as a result, the increased ability of cells to assimilate glucose. This leads to reduced total blood sugar and improved
metabolism.
Most patients who have been suffering from diabetes for more than 10 years, have various damages to the retina. Close
control of blood glucose levels, special diet, and healthy life style help to reduce risk of blindness resulting from
diabetes-related eye complications.
CHOLESTEROL-LOWERING EFFECT
The study included 40 patients (16 males and 24 females) aged 56.2±8.5 years with an average afflicted duration
of diabetes of 0.4±0.12 years and a body mass index of 33.3±6.3 kg/m2.
The patients were randomly assigned to the experimental and control groups.
The experimental group received a daily dose of 120 mg of taxifolin for 12 weeks in addition to the standard glucoselowering therapy.
The control group received only the standard glucose-lowering therapy.
Prior to the study, all the patients, both in experimental and control groups, were diagnosed with dyslipidemia
(hypercholesterolemia and hypertriglyceridemia), increased low-density lipid (LDL) concentrations and reduced highdensity lipid (HDL) concentrations, as compared to the normal levels of these concentrations.
Taxifolin consumption resulted in a marked decrease of MDL in plasma lipoproteins and the reduction of cholesterol
and triglyceride levels to nearly normal levels.
27
Normalized lipid spectrum of blood, including significantly reduced levels of cholesterol and triglyceride and
an increase of HDL concentrations in parallel with a decrease of LDL, indicate the hypolipidemic activity of taxifolin.
Taxifolin Nootropic Properties
BRAIN EFFICIENCY
Chronic cerebral circulation insufficiency is the most common pathology of the cerebrovascular
system, primarily affecting individuals aged 30–50 years, i.e., potentially the largest working-age
group.
Most often, these patients report headaches, dizziness, feeling shaky and unsteady when walking,
weakness and awkwardness of the extremities, failing memory, decreased intellectual performance,
and emotional disorder. This significantly decreases the quality of life for these individuals.
Therefore, optimized treatment and rehabilitation of these patients is crucial. Mild and highly
efficient multifunctional bioregulators included in the treatment will yield very promising results.
Clinical studies demonstrated significant positive effects of taxifolin on the overall condition and quality of life
of individuals afflicted with cerebral circulation insufficiency. These improvements are attributed to the following
taxifolin efficiency:


Improving microcirculation and blood flow at the capillary level and promoting the development of new
capillaries
Improving the elasticity of the red blood cells and decreasing blood viscosity
Studies of taxifolin efficiency in patients with chronic cerebral circulation insufficiency conducted by the
Institute of Human Brain of the Russian Academy of Sciences
The group receiving taxifolin included 29 individuals (7 males and 22 females) aged 56-78 (average age 67.6±7.5 year).
All patients were diagnosed with dyscirculatory encephalopathy of II and III stages.
Patients received a daily dose of 80 mg of taxifolin for 21 day period.
28
Comment: 0 — no symptom; 1 — mild symptom; 2 — moderate symptom; 3 — distinct symptom; 4 — severe
symptom.
According to patient-reported results and clinical neurological examinations, the use of taxifolin can be considered
to be efficient in elderly people with dyscirculatory encephalopathy.
This efficiency is demonstrated in the following results: reduction of asthenic disorders, general cerebral disorders
(headache, dizziness), and emotional neurotic disorders.
Comment: short-term memory capacity was evaluated through the Digit Span test, attention skills through Digit
Symbol-Coding test.
Thus, the effects of taxifolin included the improvement in attention level, short-term memory, intellectual performance,
and associative activity.
Other studies included 21 patients aged 45- 65 years (average age 60.4±4.8 years). All patients were diagnosed with
dyscirculatory encephalopathy of I and II stages.
The patients received taxifolin for a 21 day period according to the following scheme: first week — 120 mg daily,
second and third weeks — 60 mg daily.
29
Comment: short-term memory was evaluated through Ten Numbers test, attention skills through Serial Sevens test.
Upon completion of the taxifolin treatment course, significant improvement in short-term memory, concentration skills,
and quicker mental processes were observed in all patients.
Comment: motor coordination was evaluated by hand grip test.
Upon completion of the taxifolin treatment course, subjects demonstrated improved motor coordination, when
performing complicated standard voluntary movements.
POTENTIAL ANTIDEPRESSANT AND ANTIPARKINSONIC EFFECTS OF TAXIFOLIN
The majority of compounds which impact the functioning of central nervous system, also affect the bioelectric activity
of the brain, altering its electroencephalogram. These changes, induced by neurotropic agents, vary depending upon the
properties of the agent (pharmaceutical ingredient, medication, natural compound).
The studies showed that electropharmacograms of preparations having similar properties are similar as well.
Tele-Stereo-EEG in conscious rats was utilized to research highly-purified taxifolin (98%) in the amount of 20 mg/kg
of the rat’s weight (equal to — 3.4 mg/kg of human weight).
A comparison of taxifolin electropharmacograms with other available data showed similarity with those of amantadin,
amitriptylin, imipramin, and memantin.
Therefore, taxifolin in the amounts studied may be regarded as a compound with antidepressive and antiparkinsonic
30
properties.
Taxifolin in ophthalmology
TAXIFOLIN when THE EYES NEEDS THE rest Today many actively working people,
especially those who spend a lot of time at a computer, suffer from asthenopia syndrome (eye
strain), including the following:







Eye fatigue
Blurred vision
Occasional double vision
Eye redness, sandpaper feeling, burning sensation
Frequent eye blinking, lacrimation
Pain in the eyes, eyelids, and temples
Difficulty focusing
Most of us are familiar with these symptoms. Today, specialists view asthenopia syndrome
as a anifestation of the chronic fatigue syndrome.
Eye strain (asthenopia) occurs after intense visual efforts in 68%-72% of people who otherwise
have absolutely healthy vision. Eventually, this condition may lead to unreliable job performance.
In this regard, medicinal plant extracts play an important role, as they are safe to use, do not
produce side effects and, if used correctly, can produce therapeutic effects eligible for clinical
diagnosis.
Studies confirm the practicability and necessity of drug-free treatment for patients suffering from
visual
fatigue.
The study included 30 patients with asthenopia (aged 19-38 years) and 122 individuals whose
professional occupation is associated with tedious visual tasks: 30 professional drivers (aged 19-42
years), 30 professional computer users (aged 22-36 years), and 62 individuals — pilots and flight
personnel of fighter planes (aged 22-36 years).
31
An experimental group received three capsules of DHQ daily for a 21 day period. A control group
proceeded with their normal professional activity, not taking any medications.
It is especially important to note the opposite dynamics of the examined parameters — the control group had a negative
dynamics, while the experimental group experienced positive changes.
The visual performance of the taxifolin patients improved by 1.2%-8.4% based on various parameters (average
increase — 4.8%, p<0.05).
These results justify DHQ application for recovery and preventive treatment of patients (whose occupation requires
visual efforts), suffering from acute or chronic eye strain.
32
33
Following the taxifolin treatment, over 90% of the patients reported improved eyesight
(objective — according to eye charts), improved resistance to eye fatigue, as well as a general
improvement in well-being (subjective — according to the opinions of adult patients and parents
of child patients). When comparing data of the control and experimental groups, the improvement
of visual functions was more distinctive in those patients who received DHQ in addition to the
standard therapy.
Evidently, these improvements are attributable to taxifolin, a powerful antioxidant and capillary
protector.
All adolescent and adult patients diagnosed with myopia and accommodation spasm
reported improved distance vision and general well-being. Additionally, an improved
contrast sensitivity based on a red-black gratings test was observed, which indicates
the improvement of metabolic processes in the macular area.
DIFFERENTS PROPERTIES & BIOLOGICAL EFFECTS OF FLAVONOIDS
P.B. Tsydendambayev, B.S. Khyshiktuyev, S.M. Nikolayev
Chita State Medical Academy, Chita
Institute of General and Experimental Biology SB RAS, Ulan Ude
Modern ideas about biological and pharmacological effects of the flavonoids have been isolated
from different plant sources are summarized in the review. Some of these molecules show various
interesting biological activities, such as removal of oxygen radical, immunostimulating, pro and
antiapoptotic, anticancer, antibacterial, viricidal, hypolipidaemic actions and other numerous
features of a biological potency of studied substances are demonstrated. The basic directions of
pharmacological application of flavonoids are detected.
Key words: flavonoids, biological pharmacological action
34
Dicvertase potential for the treatment of osteoarthrosis in the geriatric practice
Gridneva T.D., Dobrynina A.L., Plotnikov M.B., Oudut V.V.
Complex treatment of aged and old patients (n = 60) suffering from deforming osteoarthrosis
complicated with reactive synovitis in combination with associated pathology of cardiovascular
system is studied. Natural antioxidant dicvertase introduced by ultrasonic waves was used. Positive
combined action of ultraphonophoresis by dicvertase was revealed which resulted in lowering pain
syndrome, increasing motions range in the affected joint, normalizing of immunity status which
allows to broaden indications for the treatment of these patients by lowering the risk of
development of pathologic response of the organism on the treatment and facilitates lowering drug
loading on patients.
Key words:
osteoarthrosis, antioxidant dicvertase, ultraphonophoresis.
Mutagenesis 1991 Jul;6(4): 289-295
Study on the mutagenic activity of 13 bioflavonoids with the Salmonella Ara test.
Jurado J, Alejandre-Duran E, Alonso-Moraga A, Pueyo
The mutagenicity of 13 flavonoids has been investigated with the L-arabinose forward mutation
assay of Salmonella typhimurium. Each flavonoid was tested by both plate incorporation and
preincubation mutagenesis protocols in the presence or the absence of mammalian metabolic
activation (S9 mixture). All flavonoids gave a dose-response relationship and induced a number of
AraR mutants considered statistically significant. Their minimum mutagenic doses (MMD) differed
markedly in the Ara test, covering a 400-fold range: from 4 nmol for quercetin to 1626 nmol for
taxifolin. Flavonols were the strongest mutagens, with mutagenic potencies (MMD-1) representing
from 27 to approximately 2% that of quercetin. Comparatively, the mutagenicities of other
flavonoids represented only less than or equal to 1%. The data reported in this paper for the Ara
forward mutation test suggest structural requirements for mutagenicity of bioflavonoids like those
previously reported for the His reverse mutation assay: (i) flavonols with a free hydroxyl at position
3 are the strongest mutagenic flavonoids, (ii) saturation of the 2,3 double bond diminishes the
mutagenic potency, and (iii) free hydroxyl groups at positions 3' and 4' influence the nonrequirement for metabolic activation. The mutagenic properties of quercetin and rutin in the Ara test
support the idea that these flavonols are not the major putative mutagens in complex mixtures such
as wine.
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
35
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.
Int J Biol Macromol 1996 Jun;18(4):287-295
Quercetin and DNA in solution: analysis of the dynamics of their interaction with a linear
dichroism study.
Flow-Linear Dichroism (LD) spectra on quercetin-DNA solutions (buffer-ethanol 30%) showed
evidence that the flavonol can intercalate the biopolymer. There is no electrostatic component in the
formation of the quercetin-DNA complex. The DNA concentration and the planarity of the
chromophore are limiting factors in the interaction. There are no induced LD signals for
concentrations of the biopolymer less than 7.8 x 10(-3) M phosphate. The interaction is most
probably of a hydrophobic nature between the most hydrophobic segment of the quercetin
(benzopyran-4-one) and the intercalation site, which allows the chromophore to penetrate the DNA
helix and to arrange its planar structure more or less parallel to the adjacent planes of the
nitrogenous bases. A comparison between the planar and hydrophobic flavonol quercetin, and the
non-planar and hydrophilic flavanone dihydroquercetin, showed that the interaction of the latter
with DNA was strongly limited. The notable biological activity of the quercetin compared to the
'weaker' activity of the dihydroquercetin could also be derived from the different planarity (and
probably hydrophobicity) of the two flavonoids. The very low concentration of the quercetin-DNA
complex was efficiently shown by the high sensitivity of the LD technique, whereas it could not be
resolved by isotropic UV-Vis and induced circular dichroism spectra. The hypothesis of a frame
shift mutagenicity activity of quercetin (Science 1977; 197: 577-578) is highly improbable. In fact,
the affinity of quercetin for DNA, which emerges from this study, is very low compared with that of
a typical intercalator agent (Q. Rev. Biophys. I 1992; 25: 51-170).
Science 1977 Aug 5;197(4303):577-578
Mutagenic activity of quercetin and related compounds.
Bjeldanes LF, Chang GW
The mutagenic activities of several flavonoids and flavonoid metabolites were examined by means
of Salmonella typhimurium mutants that reveal base-pair substitution and frameshift mutagens. Of
the compounds tested (naringin, rutin, neohesperetin, hesperetin, dihydroquercetin, quercetin,
quercetin pentaacetate, permethylquercetin, m-hydroxyphenylacetic acid, and m,pdihydroxyphenylacetic acid), only quercetin was mutagenic without microsomal activation. With
activation, however, the mutagenic activity of quercetin was increased significantly and that of
quercetin pentaacetate was revealed. The health implications of these findings and aspects of
flavonoid structural requirements for mutagenic activity are discussed.
Mutagenesis 1991 Jul;6(4): 289-295
Study on the mutagenic activity of 13 bioflavonoids with the Salmonella Ara test.
Jurado J, Alejandre-Duran E, Alonso-Moraga A, Pueyo
The mutagenicity of 13 flavonoids has been investigated with the L-arabinose forward mutation
assay of Salmonella typhimurium. Each flavonoid was tested by both plate incorporation and
preincubation mutagenesis protocols in the presence or the absence of mammalian metabolic
activation (S9 mixture). All flavonoids gave a dose-response relationship and induced a number of
AraR mutants considered statistically significant. Their minimum mutagenic doses (MMD) differed
markedly in the Ara test, covering a 400-fold range: from 4 nmol for quercetin to 1626 nmol for
taxifolin. Flavonols were the strongest mutagens, with mutagenic potencies (MMD-1) representing
from 27 to approximately 2% that of quercetin. Comparatively, the mutagenicities of other
flavonoids represented only less than or equal to 1%. The data reported in this paper for the Ara
forward mutation test suggest structural requirements for mutagenicity of bioflavonoids like those
previously reported for the His reverse mutation assay: (i) flavonols with a free hydroxyl at position
3 are the strongest mutagenic flavonoids, (ii) saturation of the 2,3 double bond diminishes the
36
mutagenic potency, and (iii) free hydroxyl groups at positions 3' and 4' influence the nonrequirement for metabolic activation. The mutagenic properties of quercetin and rutin in the Ara test
support the idea that these flavonols are not the major putative mutagens in complex mixtures such
as wine.
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.
Int J Biol Macromol 1996 Jun;18(4):287-295
Quercetin and DNA in solution: analysis of the dynamics of their interaction with a linear
dichroism study.
Flow-Linear Dichroism (LD) spectra on quercetin-DNA solutions (buffer-ethanol 30%) showed
evidence that the flavonol can intercalate the biopolymer. There is no electrostatic component in the
formation of the quercetin-DNA complex. The DNA concentration and the planarity of the
chromophore are limiting factors in the interaction. There are no induced LD signals for
concentrations of the biopolymer less than 7.8 x 10(-3) M phosphate. The interaction is most
probably of a hydrophobic nature between the most hydrophobic segment of the quercetin
(benzopyran-4-one) and the intercalation site, which allows the chromophore to penetrate the DNA
helix and to arrange its planar structure more or less parallel to the adjacent planes of the
nitrogenous bases. A comparison between the planar and hydrophobic flavonol quercetin, and the
non-planar and hydrophilic flavanone dihydroquercetin, showed that the interaction of the latter
with DNA was strongly limited. The notable biological activity of the quercetin compared to the
'weaker' activity of the dihydroquercetin could also be derived from the different planarity (and
probably hydrophobicity) of the two flavonoids. The very low concentration of the quercetin-DNA
complex was efficiently shown by the high sensitivity of the LD technique, whereas it could not be
resolved by isotropic UV-Vis and induced circular dichroism spectra. The hypothesis of a frame
shift mutagenicity activity of quercetin (Science 1977; 197: 577-578) is highly improbable. In fact,
the affinity of quercetin for DNA, which emerges from this study, is very low compared with that of
a typical intercalator agent (Q. Rev. Biophys. I 1992; 25: 51-170).
Science 1977 Aug 5;197(4303):577-578
37
Mutagenic activity of quercetin and related compounds.
Bjeldanes LF, Chang GW
The mutagenic activities of several flavonoids and flavonoid metabolites were examined by means
of Salmonella typhimurium mutants that reveal base-pair substitution and frameshift mutagens. Of
the compounds tested (naringin, rutin, neohesperetin, hesperetin, dihydroquercetin, quercetin,
quercetin pentaacetate, permethylquercetin, m-hydroxyphenylacetic acid, and m,pdihydroxyphenylacetic acid), only quercetin was mutagenic without microsomal activation. With
activation, however, the mutagenic activity of quercetin was increased significantly and that of
quercetin pentaacetate was revealed. The health implications of these findings and aspects of
flavonoid structural requirements for mutagenic activity are discussed.
gents Actions 1985 Apr;16(3-4):147-151
Kinetics of the inhibitory effect of flavonoids on histamine secretion from mast cells.
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.
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.
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
38
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.
Carcinogenesis 1983 Dec;4(12):1631-1637
Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic
hydrocarbons by phenolic 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-9,10epoxide-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 cellfree 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.
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 templateprimers.
39
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 fibroblastlike cell line (CCL 135) was relatively insensitive to low concentrations of the above flavonoids.
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.
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.
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
40
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 3hydroxyl substitution and a 4-keto moiety, would confer upon the compound potent
antiperoxidative properties.
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.
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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.
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.
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Dihydroflavonol derivatives 1-3 represent a new class of potentially noncaloric and noncariogenic
intense sweeteners.
J Nat Prod 1997 Aug;60(8):775-778
Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis factor-alpha in L-929
tumor cells.
Habtemariam S
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.
Alcohol Clin Exp Res 1996 Aug;20(5):799-803
Differences in the serum levels of acetaldehyde and cytotoxic acetaldehyde-albumin complexes
after the consumption of red and white wine: in vitro effects of flavonoids, vitamin E, and
other dietary antioxidants on cytotoxic complexes.
Wickramasinghe SN, Hasan R, Khalpey Z
After the consumption of ethanol, acetaldehyde levels increase in the serum, and the serum
develops a nondialyzable cytotoxic activity caused by the formation of unstable acetaldehydealbumin complexes. The concentration of acetaldehyde in the serum and the cytotoxic activity in
serum albumin 8.5 hr after six healthy volunteers began to drink 94 g of ethanol were significantly
less when the ethanol was consumed as red wine than as white wine. The serum acetaldehyde was
measured by a fluorigenic HPLC assay, and the cytotoxic activity in albumin was determined using
two different assays based on dissimilar endpoints: (1) detachment of adherent A9 cells and (2)
impairment of the ability of A9 cells to reduce tetrazolium. When serum obtained from five other
healthy volunteers after the consumption of white wine was incubated at 37 degrees C for 3 hr with
a number of dietary antioxidants at a concentration of 100 mumol/liter, the cytotoxicity of the
albumin was markedly reduced. The antioxidants studied consisted of six flavonoids (kaempherol,
fisetin, quercetin catechin, taxifolin, and coumarin) and three nonflavonoids (salicylic acid, tannic
acid, and alpha-tocopherol). In the cases of alpha-tocopherol, a statistically significant reduction of
cytotoxicity was observed at a concentration of 10 mumol/liter. In addition, the cytotoxicity of
artificially prepared acetaldehyde-albumin complexes was significantly reduced when such
complexes were incubated with 50 to 100 mumol/liter of kaempherol, fisetin, quercetin, coumarin
or salicylic acid, or 10 mumol/liter of alpha-tocopherol at 37 degrees C for 3 hr. Evidently, in vitro,
flavonoid and nonflavonoid dietary constituents reduce the amount of unstable acetaldehydealbumin complexes found in both postalcohol serum and in artificially produced acetaldehydealbumin complexes. The difference in the amount of unstable acetaldehyde-albumin complexes
found in serum after the consumption of red and white wine may therefore be caused by the higher
concentration of antioxidants, including flavonoids, in red wine than in white wine. Because
acetaldehyde and acetaldehyde-albumin complexes have been implicated in the pathogenesis of
alcohol-mediated tissue damage, these data suggest that dietary antioxidants may influence the
biological consequences of excess alcohol consumption.
Technology
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Raw material for production of Taxifolin is waste of timber (butt part) Siberian larch Larix sibirica
Ledeb. and L.gmelini Rupr. (Rupr.), grown in ecologically clean regions of Siberia and the Far
East.
Source of raw materials is stable and virtually inexhaustible. Taxifolin content in the raw material is
1-3%.
The first stage of the technological process of obtaining Taxifolin is the extraction chips butt of
larch by organic solvents. Along with the desired product extract contains a rich mixture of natural
compounds of different chemical nature (terpenoids, essential oils, pitch and pitch acids).
The main step of the technology is based on the chromatographic process that allows, depending on
the conditions of its implementation, to obtain an individualized "mono-component" Taxifolin with
the content of the base material 98 or 99% or bioflavonoid complex «Taxifolia ®», which along
with Taxifolin, contains related compounds: aromadendrin, eriodictiol and naringenin.
The basis of the technological process is the chromatographic column axial compression 900 mm in
diameter, developed by our specialists.
Specially designed for this technology, modified sorbent and original technological mode
chromatographic purification can achieve record load characteristics and high performance
purification process.
Managing and monitoring the cleaning process is carried out with the use of specialized software
based on modern CAN-technology.
Control of raw materials, intermediate and final products is carried out
by modern physical and chemical methods.
The planned capacity of the enterprise - 3000 kg of high-purity
substances in the month.
Kutafya Bashnya LLC
General director Andrey Y. Ayvazov
info@kutbash.ru
+7-495-2316703 mob.
By amiable authorization from Flavomix LLC
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