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Abstract

Phytoestrogens are a diverse group of plant-derived compounds that structurally or functionally mimic mammalian estrogens and show potential benefits for human health. They can serve as potential alternatives to the synthetic selective estrogen receptor modulators which are currently being used in hormone replacement therapy. Estrogens play many important physiological roles in men and women. In women, life is severely affected by a variety of estrogen-related conditions such as osteoporosis, cognitive and cardiovascular disease, increased risk of breast cancer and other symptoms that decrease the overall quality of life. Phytoestrogens are effective in maintaining bone mineral density, prevent bone loss, and help in the prevention and/or treatment of such health related problems. They can be classified as flavonoids, isoflavonoids, coumestans, stilbenes, lignans and terpenoids. The main isoflavones, genistein and daidzein found in soybean, can exist as glucosides or as aglycones, and are readily hydrolyzed in the gut to their aglycones. The aglycones are easily transported across intestinal epithelial cells. Terpenoids (ferutinine, tschimgine, and tschimganidine) found in the Umbelliferae family have estrogenic activities. The main dietary source of phytoestrogenic stilbenes is trans-resveratrol from red wine and peanuts. Plant-derived foods may be an adequate source for a variety of phytoestrogens capable of producing a range of pharmacological effects and protection from various life threatening diseases. This article provides the comprehensive information about the main groups of phytoestrogens, their food as well as herbal or botanical sources, potential health benefits and probable health hazards.
Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-2-127
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
Phytoestrogens as Pharma Foods
Charu Gupta, PhD1*; Dhan Prakash, PhD1; Sneh Gupta, MSc2
1Amity Institute for Herbal Research and Studies, Amity University-UP, Sector-125
Noida 201313, India
2Department of Zoology, RGPG college, Chippi Tank, Meerut 250001, India
*Corresponding author
Charu Gupta, PhD
Assistant Professor
Amity Institute for Herbal Research
and Studies (AIHRS)
Amity University UP, Sector-125
Noida 201303, India
Tel. +91-120-4392549
Fax: +91-120-4392502
E-mail: charumicro@gmail.com
Article History
Received: June 10th, 2016
Accepted: June 30th, 2016
Published: July 1st, 2016
Citation
Gupta C, Prakash D, Gupta S.
Phytoestrogens as pharma foods.
Adv Food Technol Nutr Sci Open
J. 2016; 2(1): 19-31. doi: 10.17140/
AFTNSOJ-2-127
Copyright
©2016 Gupta C. This is an open
access article distributed under the
Creative Commons Attribution 4.0
International License (CC BY 4.0),
which permits unrestricted use,
distribution, and reproduction in
any medium, provided the original
work is properly cited.
Volume 2 : Issue 1
Article Ref. #: 1000AFTNSOJ2127
Research
Page 19
ABSTRACT
Phytoestrogens are a diverse group of plant-derived compounds that structurally or functionally
mimic mammalian estrogens and show potential benets for human health. They can serve as
potential alternatives to the synthetic selective estrogen receptor modulators which are currently
being used in hormone replacement therapy. Estrogens play many important physiological
roles in men and women. In women, life is severely affected by a variety of estrogen-related
conditions such as osteoporosis, cognitive and cardiovascular disease, increased risk of breast
cancer and other symptoms that decrease the overall quality of life. Phytoestrogens are effective
in maintaining bone mineral density, prevent bone loss, and help in the prevention and/or
treatment of such health related problems. They can be classied as avonoids, isoavonoids,
coumestans, stilbenes, lignans and terpenoids. The main isoavones, genistein and daidzein
found in soybean, can exist as glucosides or as aglycones, and are readily hydrolyzed in the
gut to their aglycones. The aglycones are easily transported across intestinal epithelial cells.
Terpenoids (ferutinine, tschimgine, and tschimganidine) found in the Umbelliferae family have
estrogenic activities. The main dietary source of phytoestrogenic stilbenes is trans-resveratrol
from red wine and peanuts. Plant-derived foods may be an adequate source for a variety of
phytoestrogens capable of producing a range of pharmacological effects and protection from
various life threatening diseases. This article provides the comprehensive information about
the main groups of phytoestrogens, their food as well as herbal or botanical sources, potential
health benets and probable health hazards.
KEYWORDS: Phytoestrogens; Pharma foods; Nutraceuticals; Estrogen antagonists; Flavonoids;
Isoavonoids.
ABBREVIATIONS: DES: Diethylstilbestrol; SECO: Secoisolariciresinol; ER: Estrogen
receptors; SHBG: Soy-based infant formulas; PPARs: Peroxisome proliferator-activated
receptors; CV: Corn oil vehicle; G: Genistein; SBIFs: Soy-based infant formulas; BD: Beta-
defensin-2; S1P: Sphingosine-1-phosphate; CAMP: Cathelicidin antimicrobial peptide; VDR:
Vitamin D receptor; SERM: Selective Estrogen Receptor Modulator; CVD: Cardiovascular
disease; LDL: Low Density Lipoprotein; HRT: Hormone Replacement Therapy; BMD: Bone
Mineral Density; AD: Alzheimer’s Disease.
INTRODUCTION
It was observed that Asian populations have lower rates of cardiovascular disease, menopausal
symptoms, breast cancer (and other hormone dependent cancers), diabetes and obesity than
Western populations.1 The diet of Asian populations revealed that soy is the major part of
food in an Asian diet. This observation has fueled the widely held belief that consumption of
soy foods reduces the risk of disease. Phytoestrogens were rst observed in 1926,2 but it was
unknown if they could have any effect in human or animal metabolism. In the 1940s, it was
noticed for the rst time that red clover (a phytoestrogens-rich plant) pastures had effects on
the fecundity of grazing sheep.2,3
Phytoestrogens as the name suggests are the estrogens (xenoestrogens) that are derived
from the plants and not generated within the endocrine system. They can be consumed by
Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-2-127
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
Page 20
Food items Total phytoestrogens (μg/100g)
Vegetables
Soy bean sprouts 790
Garlic 604
Winter squash 115
Green beans 106
Broccoli 94
Cabbage 80
Fruits
Dried prunes 184
Peaches 65
Strawberry 52
Raspberry 48
Watermelon 2.9
Nuts and other legume seeds
Pistachios 383
Chestnuts 210
Walnuts 140
Cashews 122
Hazel nuts 108
Lentils 37
Beverages
Red wine 54
Green tea 13
White wine 12.7
Black tea 8.9
Coffee 5.5
Beer 2.7
eating phytoestrogenic plants and so are also known as “dietary
estrogens”. A phytoestrogen is a plant nutrient that is somewhat
similar to the female hormone estrogen. Due to this similarity,
lignans may have estrogenic and/or anti-estrogenic effects in the
body.
They are a diverse group of naturally occurring non-
steroidal plant compounds that because of their structural
similarity with estradiol (17-β-estradiol), have the ability to
cause estrogenic or/and anti-estrogenic effects,2 by sitting in and
blocking receptor sites against estrogen. Research has shown that
phytoestrogens have many health benets such as reduction in
incidence of cardiovascular diseases, prostate cancer and breast
cancer. They also provide protection against post menopausal
diseases including osteoporosis. Besides, both phytoestrogens
such as avonoids and lignan also possess antioxidant activity.
The major groups of phytoestrogens include avones,
isoavones, coumestans and lignans. The former three chemically
are avonoids. Phytoestrogens in particular isoavones are
found in high amounts in soybean and their products like tofu
whereas lignans are mainly found in ax seed.
Dietary estrogen (phytoestrogen) are found in wide va-
riety of food products (including herbs), even though the level
varies depending on the source. The food products with the high-
est total phytoestrogen content are nuts and oil seeds followed by
soy products (Tables 1 and 2). The total phytoestrogen content
presented is the sum of isoavones (genistein, daidzein, glycit-
ein, formononetin), lignans (secoisolariciresinol, matairesinol,
pinoresinol, lariciresinol), and coumestan (coumestrol).
Food Sources of Phytoestrogens
The main food sources rich in phytoestrogens are nuts
and oilseeds, followed by soy products, cereals and breads, le-
gumes, meat products and other processed foods that may con-
tain soy, vegetables, fruits, alcoholic and nonalcoholic bever-
ages. Flax seed and other oilseeds contained the highest total
phytoestrogen content, followed by soybeans and tofu.4 The
highest concentrations of isoavones are found in soybeans and
soybean products followed by legumes, whereas lignans are the
primary source of phytoestrogens found in nuts and oilseeds
(e.g. ax) and also found in cereals, legumes, fruits and veg-
etables.
Phytoestrogen (PE) content varies in different foods,
and may vary signicantly within the same group of foods (e.g.
soy beverages, tofu) depending on processing mechanisms and
type of soybean used.5 Legumes (in particular soybeans), whole
grain cereals, and some seeds are high in phytoestrogens. Some
other examples of foods that contain phytoestrogens are linseed
(ax), Sesame seeds, Wheat berries, Fenugreek, Oats, Barley,
Phytoestrogen food sources Phytoestrogen content (μg/100g)
Flax seed 379380
Soy beans 103920
Tofu 27151
Soy yogurt 10275
Sesame seed 8008
Flax bread 7540
Multigrain bread 4799
Soy milk 2958
Hummus 993
Garlic 604
Mung bean sprouts 495
Dried apricots 445
Alfalfa sprouts 442
Dried dates 329
Sunower seed 216
Chestnuts 210
Olive oil 181
Almonds 131
Green bean 106
Peanuts 34.5
Onion 32
Blueberry 17.5
Corn 9
Coffee regular 6.3
Water melon 2.9
Milk (cow) 1.2
Table 1: Foods high in phytoestrogen content. Table 2: Total phytoestrogen content in vegetables, fruits, nuts and drinks.
Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-2-127
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
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Beans, Lentils, Yams, Alfalfa, Mung beans, Apples, Carrots,
Pomegranates, Wheat germ, Rice bran, Lupin, Kudzu, Coffee,
Licorice root, Mint, Ginseng, Hops, Bourbon, Beer, Fennel and
Anise, Red clover (sometimes a constituent of green manure).
Due to the molecular similarities with estrogens, phy-
toestrogens mildly mimic and sometimes act as antagonists
of estrogen. Studies have proved that phytoestrogens play an im-
portant role in the regulation of cholesterol and the maintenance
of proper bone density post-menopause. Evidence is accruing
that phytoestrogens may have protective action against diverse
health disorders, such as prostate, breast, bowel and other can-
cers, cardiovascular disease, brain function disorders and osteo-
porosis.2,3,6 However, phytoestrogens cannot be considered as
nutrients, since the lack of these in the diet does not produce any
characteristic deciency syndrome nor do they participate in any
essential biological function.2
Phytoestrogens Structure
Chemically phytoestrogens belong to a large group of substituted
natural phenolics compounds: the coumestans, prenyl-avanoids
and Isoavones. These are the three most active estrogenic
compounds in this class. Isoavones are the most researched
phytoestrogens and is commonly found in soy and red clover.
Apart from this, lignans, stilbenes and terpenoids have also
been identied as phytoestrogens but they are not avonoids.2
Another term ‘mycoestrogens’ refers to the mold metabolites
of fungus Fusarium that is frequently found in pastures as well
as in alfalfa and clover.7,8 The major phytoestrogens along with
their food sources are given in Table 3.
The Major Classes of Phytoestrogens are Discussed below:
Isoavones
Isoavones are found exclusively in the family Fabaceae (Le-
guminosae) and soybeans are a very rich source of them. The
isoavonoids encompass several structurally and biosyntheti-
cally related classes such as avonols, anthocyanins, avanones,
coumestans, and chalcones. Isoavonoids differ structurally
from other classes of avonoids in having the phenyl ring at-
tached at the 3- rather than at 2-position of the heterocyclic ring.
They have similar structure to estrogen and have the capacity to
exert both estrogenic and anti-estrogenic effects, they may block
the effects of estrogen in some tissues e.g. the breast and womb
lining but act like an estrogen in providing possible protection
against bone loss and heart diseases. In this subclass, the most
thoroughly investigated and interesting compounds with regard
to estrogenicity are genistein, daidzein, biochanin A and for-
mononetin. The estrogen effect of isoavones is much less pow-
erful than the estrogen hormones. This is why isoavones and
phyto-estrogens exercise a balancing effect when the level of
estrogens is low, such as during the menopause, and cause less
menopause symptoms. A closely related compound to the isoa-
vonoids is 8-prenyl-naringenin, an isoavanone, found in hops
(Humulus lupulus), an ingredient used in beer. Populations in
China, Japan, Taiwan and Korea are estimated to consume high
quantities of isoavones and women of these countries complain
fewer incidences of osteoporosis and related health problems,
especially hot ushes, cardiovascular diseases, lower incidence
of hormone dependent breast and uterine cancer.9
Flavones
The avones are a group of naturally occurring chemical
compounds widely distributed in the plants. Natural avones
include apigenin, chrysin, quercetogetin, luteolin, and tricetin.
Their major food sources are parsley, celery, citrus peels,
capsicum, and pepper. Apigenin (4,5,7-trihydroxyavone)
commonly present in fruits and vegetables with proven anti-
inammatory and anticarcinogenic effects in various animal
tumor model systems. It has been shown to suppress angiogenesis
in melanoma and carcinoma of the breast, skin and colon.10,11
Apigenin has shown potential to inhibit growth in several human
cancer cells, including breast, colon, skin, thyroid, leukemia, and
prostate.9
Stilbenes
Stilbenes belong to the family of phenylpropanoids and share
most of their biosynthesis pathway with chalcones.12 An ex-
ample of stilbene is resveratrol found in grapes and has several
health benets. It exists in 2 structural isomeric forms, cis and
trans, with the trans form being more common and possessing
greater biological activity. One of the richest sources of this is
Table 3: Phytoestrogens of human interest and their food sources.9
Class Phytoestrogens Food sources
Isoavones Genistein, biochanin A, diadzein (with its metabolites:
O-DMA and equol), formononetin, glycetin
Soy, peanut, clover,
sunower seed, walnut
Flavones Apigenin, chrysin, quercetogetin, luteolin, tricetin Parsley, celery, citrus peels,
capsicum, pepper
Stilbenes Resveratrol Grape, peanuts
Lignans
Secoisolariciresinol,
matairesional, enterodiol,
enterolactone
Soybean, peanut, broccoli, cashew
nut, kiwi, pomegranate,
triticale straw, axseeds, cereals
Coumestans Coumestrol Mung beans or soy sprouts,
alfalfa sprouts, clover
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Polygonum cuspidatum, a weed that is used in traditional Chi-
nese and Japanese medicines. The primary dietary sources in the
human diet are peanuts, grapes and wine. It has exhibited anti-
oxidant, cardio-protective, chemo-preventative, anti-inamma-
tory, and estrogenic properties, as well as interaction with signal
transduction pathways. It has shown to inhibit oxidative-induced
apoptosis in a variety of cell lines and reduced oxidative stress
in RPE cells. The antioxidant activity of resveratrol may also
be associated with protection against the progression of athero-
sclerosis. The structural similarity of resveratrol to the synthetic
estrogen diethylstilbestrol (DES) suggests that it may have es-
trogenic activity, cardio-protection and prevention of estrogen-
dependent cancers. The estrogenic activity of resveratrol may
also help prevent bone loss in post-menopausal women.9,11
Lignans
The lignan family is a large group of naturally abundant molecules
that can be found in a plethora of superior plants where axseed
is a particularly rich source. Lignans, along with isoavones and
coumestans, comprise the three major classes of phytoestrogens.
When plant lignans are consumed, intestinal bacteria convert
some into two mammalian lignans, enterolactone and enterodiol.
These compounds are absorbed from the digestive tract, circulate
and are excreted in the urine.13-16
Among lignans, secoisolariciresinol (SECO) and
matairesinol are of particular interest. Secoisolariciresinol and
matairesinol are two lignan dimers which are not estrogenic
by themselves, but readily convert to the mammalian lignans,
enterodiol and enterolactone, respectively, which are estrogenic.
These are of great interest because of their estrogenic, anti-
estrogenic, anti-carcinogenic, antiviral, antifungal and
antioxidant activities. Particularly abundant in axseed, these
molecules can also be found, for example, in soybean, peanut,
broccoli, cashew nut, kiwi17 and pomegranate,14 triticale straw,15
greater burdock18 or Forsythia intermedia, asparagus, whole
grains and tea.9 Due to the structural similarity of enterolignans
with mammalian oestrogens, these compounds are potentially
interesting for combating some hormone-dependent cancers.19-22
Some epidemiologic investigations have shown that the risk of
breast, prostate and colon cancers is lower in countries or regions
in which the diet is particularly rich in lignans.
Coumestans
Coumestans are another important group of plant (family
Fabaceae) phenols that show estrogenic activity. The main
coumestans with phytoestrogenic effects are coumestrol and
4′-methoxycoumestrol. Coumestrol was rst isolated from
ladino clover (Trifolium repens L.), strawberry clover (Trifolium
fragiferum L.) and alfalfa (Medicago sativa L.). Coumestrol
and genistein have higher binding afnities to ER-β than the
other phytoestrogen compounds. Under in vitro conditions,
coumestrol has been reported to inhibit bone resorption and to
stimulate bone mineralization. Coumestans are less common in
the human diet than isoavones yet similar to isoavones, in that
they are also found in legumes, particularly sprouts of alfalfa
and mung bean (Vigna radiata) and they are especially high in
clover however, low levels have been reported in brussel sprouts
and spinach.9
Terpenoids
Ikeda et al23 surveyed estrogenic and antiestrogenic activities of
terpenoids phytochemicals found in the Umbelliferae family and
revealed that three compounds tschimgine, tschimganidine and
ferutinine have agonistic and/or antagonistic activities for ER-α
and ER-β. Ferutinine and tschimganidine are sesquiterpenoids
and tschimgine is a monoterpenoid. Ferutinine isolated from
Ferula jaeschkeana was reported to increase uterine weight
and prevent pregnancy when administered orally in rats. It
may modulate estrogen signaling similar to phytoestrogens
specically, estrogen receptor subtype selective PE and may be
useful as natural SERMs.9,24,25
MODE OF ACTION
Phytoestrogens bind to the specic receptor sites known as
estrogen receptors (ER). These receptor sites are of two types,
alpha (ER-α) and beta (ER-β). Generally phytoestrogens display
higher afnity for ER-β compared to ER-α.26 The high afnity
of phytoestrogens to estrogen receptors is due to their unique
structural conguration that enables them to display estradiol-
like effects.2
1. Phytoestrogens possess a phenolic ring for binding to
estrogen receptor.
2. They have a low molecular weight similar to estrogens
(mol. wt. 272).
3. Phytoestrogens possess a ring of isoavones that mimics
the ring of estrogens at the receptors binding site.
4. The distance between two hydroxyl groups at the isoavones
nucleus is similar to that occurring in estradiol.
5. There is an optimal hydroxylation pattern that favours
binding with estrogen receptors.
Phytoestrogens also modulate the concentration of
endogenous estrogens by binding or inactivating some enzymes
and also affect the bioavailability of sex hormones by depressing
or stimulating the synthesis of sex hormone binding globulin
(SHBG).3 Research has shown that phytoestrogens bind and
transactivate peroxisome proliferator-activated receptors
(PPARs). Both ERs and PPARs inuence each other and
therefore, induce differential effects in a dose-dependent way.
The nal biological effects of genistein are determined by the
balance among these pleiotrophic actions.27
Ecology of Phytoestrogens
Phytoestrogens are naturally occurring substances since ancient
times and are involved in plant defense systems particularly
against fungi. They function as dietary phytochemicals and are
considered co-evolutive with mammals.9 besides phytoestrogens,
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there are some man-made novel exogenous estrogens known as
xenoestrogens. They are used as food additives and in ingredients
like cosmetics, plastics and insecticides. Xenoestrogens have
environmentally similar effect as phytoestrogens as proved in a
study of populations.28
Phytoestrogens and Birds
Studies have shown that consumption of plants containing
unusual content of phytoestrogens under drought conditions
decreases the fertility in quail. It has been found that parrot food
available in nature possess weak estrogenic activity. Studies
are being conducted on screening methods for environmental
estrogens present in manufactured supplementary food, with the
purpose to enable reproduction of endangered species.29
In another, it was found that developmentally
inappropriate exposures to estrogenic compounds are known to
alter morphology and function of the reproductive tract in various
species. Chickens are continually exposed to the relatively potent
estrogenic soy isoavones through the diet. Previous experiments
have demonstrated that the primary soy isoavone genistein
induces proliferation of the chick oviduct. However, information
is lacking as to specic reproductive tract developmental effects
of genistein exposure in chicks. Experiments were done to
compare specic oviduct morphological and functional responses
to genistein exposure with responses elicited by a classical
estrogen, diethylstilbestrol (DES). To avoid the effects of dietary
soy isoavones, the experimental diets were formulated with
dried egg white, rather than the usual soybean meal, as a protein
source. 100 one day-old female chicks were assigned evenly to
10 treatments: egg white based diet with daily oral gavages of
corn oil vehicle (CV); 1 mg DES; 2.0 mg genistein (G2); 20 mg
genistein (G20); or 40 mg genistein (G40). At 15 days of age,
half the birds from each treatment received a single injection
of 2 mg progesterone in a corn oil vehicle to induce ovalbumin
synthesis in the oviduct. The classical oviduct responses to
estrogen, induction of progesterone receptor and initiation of
ovalbumin synthesis, were examined by immune-histochemistry.
At 16 days of age, DES treatment increased oviduct weight
and percentage of nal body weight as compared to all other
treatments (p<0.05). Immunohistochemistry of formalin xed
oviduct samples revealed that the DES, G20, and G40 treatments
signicantly increased specic staining for progesterone receptor
and ovalbumin in the chick oviduct as compared to CV and G2
treatments. It was concluded that genistein can function as a
classical estrogen in the chick oviduct and that dietary exposures
to genistein may alter oviduct development.30
Effect of Phytoestrogens on Humans
Phytoestrogens are readily absorbed and circulated in plasma
and the unabsorbed portion is nally excreted in the urine. The
metabolic pathway of phytoestrogens is completely different
in humans as compared in grazing animals. This is due to their
difference in digestive systems.9
Clinical trials on males have shown no observable
changes in testicular or ejaculate volume when their diet was
supplemented with isoavone. A meta-analysis of 15 placebo-
controlled studies has also shown that the incorporation of soy
foods does not alter the bioavailability of testosterone concentra-
tions in men.31
Contrary to this, some epidemiological studies have
shown the protective effects of phytoestrogens in females against
breast cancer. It has also been found that females with history of
breast cancer should consume the soya products with caution since
soybean can stimulate the growth of estrogen receptor-positive
cells in vitro. However, the potential for tumour growth is related
only with small concentration of genistein and the protective
effect was found to be related with larger concentrations of same
phytoestrogens.5 Although not much information is available on
the mechanism of action of isoavones to inhibit tumour growth,
but the in vitro studies justify the need to evaluate the impact of
isoavones on breast tissue in females.32 Epidemiologic studies
suggest that consumption of soy estrogens is safe for patients
with breast cancer and that it may in fact decrease mortality and
recurrence rates.33 It has been reported that phytoestrogens such
as genistein may help to prevent photo aging in human skin and
promote formation of hyaluronic acid.34
Effect of Phytoestrogens on Infants
It has been found that there are no adverse effects of
phytoestrogens on infants.35 Research has shown that there
are no adverse effects on human growth, development, or
reproduction due to the consumption of soy-based infant formula
as compared to conventional cow-milk formula.36-37 In a clinical
studies of infants fed SBIFs [soy-based infant formulas] have
resolved questions and raised no clinical concerns with respect
to nutritional adequacy, sexual development, neurobehavioral
development, immune development, or thyroid disease. SBIFs
provide complete nutrition that adequately supports normal
infant growth and development. FDA has accepted SBIFs as
safe for use as the sole source of nutrition. Although clinical
guidelines published by American Academy of Pediatrics stated
that isolated soy protein-based formulas may be used to provide
nutrition for normal growth and development, but there are few
indications for their use in place of cow milk-based formula.
These indications are especially for infants with galactosemia
and hereditary lactase deciency (rare) and in situations where a
vegetarian diet is preferred.38
Ethnopharmacology of Phytoestrogenic Plants
Phytoestrogenic plants are used in the treatment of menstrual,
menopausal and including fertility problems. Phytoestrogen
containing plants are Pueraria mirica and its close
relative, kudzu, Angelica, fennel and anise. In an another study,
phytoestrogens rich plant red clover has been shown to be
safe, but ineffective in relieving menopausal symptoms, black
cohosh is also used for menopausal symptoms, but does not
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Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
Page 24
contain phytoestrogens. Panax Ginseng contains phytoestrogens
and has been used for menopausal symptoms.39
Biological Activities of Phytoestrogens
Antimicrobial activity and Phytoestrogens
In a study, synergistic antimicrobial activities of phytoestrogens
were observed in crude extracts of two sesame species against
some common pathogenic microorganisms. Methanolic and
ethanolic extracts exhibited broad spectrum antimicrobial ef-
fect against all the tested pathogenic micro-organisms except
Streptococcus pneumoniae and Staphylococcus aureus respec-
tively, while the aqueous extract exhibited inhibitory activity on
Staphylococcus aureus, Streptococcus pneumoniae and Candida
albicans. The result conrmed the folkloric claims of the antimi-
crobial effectiveness of locally consumed sesame leaves extracts
especially against bacterial and common skin infection in many
areas of Nigeria.40
In another study, it was found that soybean phytoestrogen
enhances the antimicrobial peptides beta-defensin-2 (BD)
synthesis in endometrial epithelial cells with lipopolysaccharides
and polyinosinic-polycytidylic acid stimulation. This study
provided the rst evidence and a role of BD in mucosal defense
against pathogen in glandular endometrial epithelium. The
differential modulation of the expression and secretion of BD by
soybean phytoestrogen could be applied for protection of female
reproductive tract from pathogen invasions.41
In an another study, it was discovered that a signaling
lipid, sphingosine-1-phosphate (S1P), generated by sphingosine
kinase 1, regulates a major epidermal antimicrobial peptide’s
cathelicidin antimicrobial peptide (CAMP)] expression via an
NF-κB→C/EBPα-dependent pathway, independent of vitamin
D receptor (VDR) in epithelial cells. Activation of estrogen
receptors (ERs) by either estrogens or phytoestrogens also is
known to stimulate S1P production, but it is unknown whether
ER activation increases CAMP production. The researchers
investigated whether a phytoestrogen, genistein, simulates CAMP
expression in keratinocytes, a model of epithelial cells, by either
a S1P-dependent mechanism(s) or the alternate VDR-regulated
pathway. Exogenous genistein, as well as an ER-β ligand,
WAY-200070, increased CAMP mRNA and protein expression
in cultured human keratinocytes, while ER-β antagonist,
ICI182780, attenuated the expected genistein and WAY-
200070-induced increase in CAMP mRNA/protein expression.
Genistein treatment increased acidic and alkaline ceramidase
expression and cellular S1P levels in parallel with increased S1P
lyase inhibition, accounting for increased CAMP production. In
contrast, siRNA against VDR did not alter genistein-mediated
up-regulation of CAMP. Taken together, genistein induces
CAMP production via an ER-β→S1P→NF-κB→C/EBPα-
rather than a VDR-dependent mechanism, illuminating a new
role for estrogens in the regulation of epithelial innate immunity
and pointing to potential additional benets of dietary genistein
in enhancing cutaneous antimicrobial defense.34
Phytoestrogens for Cancer Prevention
Phytoestrogens display an array of pharmacologic properties and
investigation of their potential as anticancer agents has increased
dramatically. Phytoestrogens have been investigated as natural
alternatives to hormone replacement therapy and their potential
as chemopreventive agents. Scientists have investigated the
effects of equol, genistein and coumestrol on cell growth in
fully estrogenized MCF-7 cells, simulating the peri-menopausal
state and long term estrogen deprived MCF7:5C cells which
simulate the postmenopausal state of a woman after years
of estrogen deprivation and compared the effects to that of
steroidal estrogens: 17 β-estradiol (E2) and equilin present in
conjugated equine estrogen. Steroidal and phytoestrogens induce
proliferation of MCF-7 cells at physiologic concentrations
but inhibit the growth and induce apoptosis of MCF7:5C
cells. Although steroidal and phytoestrogens induce estrogen
responsive genes, their anti-proliferative and apoptotic effects
are mediated through the estrogen receptor. Knockdown of
ER-α using siRNA blocks all estrogen induced apoptosis
and growth inhibition. Phytoestrogens induce endoplasmic
reticulum stress and inammatory response stress related genes
in a comparable manner as the steroidal estrogens. Inhibition of
inammation using dexamethasone blocked both steroidal and
phytoestrogen induced apoptosis and growth inhibition as well
as their ability to induce apoptotic genes. Together, this suggests
that phytoestrogens can potentially be used as chemopreventive
agents in older postmenopausal women but caution should
be exercised when used in conjunction with steroidal anti-
inammatory agents due to their anti-apoptotic effects.42
In yet another study, it was proved that some
phytoestrogenic compounds are associated with reduced risk of
endometrial cancer. The development of endometrial cancer is
largely related to prolonged exposure to estrogens without cyclic
exposure to progesterone. Unopposed estrogens increase mitotic
activity in endometrial cells, whereas progesterone reduces this
activity. The identication of factors that lower endogenous
estrogen levels is therefore, important in efforts to prevent this
disease.43
Estrogens found in plant foods (phytoestrogens),
such as isoavones found in soybeans and lignans found in
whole grains, seeds, and dried fruit, have been shown to lower
endogenous estrogen levels. They also stimulate the production
of sex hormone–binding globulin (SHBG) by the liver. Higher
SHBG levels result in more bound and thus less free estradiol,
reducing the amount of estrogens available for binding with
estrogen receptors. Phytoestrogens also bind competitively to
estrogen receptors, thereby blocking binding by estradiol and
other estrogens. Because of their weak estrogenic potential
(0.1% that of estradiol), phytoestrogens do not elicit a strong
estrogenic response and thus have an antiestrogenic effect that
inhibits the growth and proliferation of estrogen-dependent
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cancer cells.43
Phytoestrogens for Breast Cancer Treatment
Flaxseed is the richest dietary source of lignans, a type of
phytoestrogen. They are found in a variety of foods, including
soy, axseeds, other nuts and seeds, whole grains, and some
vegetables and fruit. Most of the research regarding axseed
and breast cancer focuses on the lignans found in axseeds,
and their potential for weak estrogenic or anti-estrogenic
effects in a woman’s body.44 Lignans, can also change estrogen
metabolism. In postmenopausal women, lignans can cause the
body to produce less active forms of estrogen. This is believed
to potentially reduce breast cancer risk. There are evidences that
adding ground axseeds into the diet decreases cell growth in
breast tissue as well. This would be the type of change that would
be expected to decrease breast cancer risk.8 It is well known that
all cells have the ability to go through a process called apoptosis,
or programmed cell death. It is believed that through this
process, the body can prevent damaged cells from reproducing,
and eventually developing into cancer. Researchers have shown
that axseed sprouts can increase apoptosis. Some cell and
animal studies have shown that two specic phytoestrogens
found in lignans, named enterolactone and enterodiol, may help
suppress breast tumor growth. Animal studies have shown that
both axseed oil and lignans can reduce breast tumor growth
and spread, even for ER- cancer cells. This result suggests that
axseeds may have anti-cancer benets that are unrelated to any
type of effect on estrogen or estrogen metabolism.45
Tamoxifen is a medication known as a Selective
Estrogen Receptor Modulator (SERM). It binds with estrogen
receptors, without activating growth in breast cancer cells. In
this way, tamoxifen prevents a women’s own estrogen from
binding with these cells. As a result, breast cancer cell growth is
blocked.46 One study in mice concluded that axseed inhibited
the growth of human estrogen-dependent breast cancer, and
strengthened the tumor-inhibitory effect of tamoxifen. Multiple
other studies with mice have shown that dietary axseed works
with tamoxifen to inhibit breast tumor growth.47 Researchers
are not conrmed about the results will apply to women with
breast cancer, but this approach of adding axseeds to the diet
looks promising. And several studies in women have shown that
higher intake of lignans, the key phytoestrogen in axseeds, is
associated with reduced risk of breast cancer.48 Further, lignans in
the diet are associated with less aggressive tumor characteristics
in women who have been diagnosed with breast cancer. In other
words, women who have already been eating lignans at the time
of diagnosis seem to have tumors that are less aggressive.49
Phytoestrogens for Preventing Post Menopausal Osteoporosis
Aging causes the progressive loss of bone-mineral density, a
process that accelerates during pre-menopause and increases
fracture risk. Postmenopausal osteoporosis has become a social
problem and it requires appropriate management strategies.
Replacement therapy is effective for both prevention and therapy,
but recent ndings have shown that its long term administration
is not as safe as was previously thought, so alternative treatments
are urgently needed. Dietary phytoestrogens are emerging as a
valid alternative to estrogens in the treatment of menopause-
related diseases, such as the climacteric syndrome, cardiovascular
diseases, osteoporosis, and dementia. Research has shown that
dietary changes in Western habits favoring an increased intake
of phytoestrogens-rich foods, could contribute to prevent and
to reduce the incidence of postmenopausal osteoporosis in this
population.9
Phytoestrogens promote estrogenic actions in
mammals. They not only act estrogenically as estrogen agonists,
but also anti-estrogenically as antagonists by blocking or
altering ERs, thus they more closely resemble natural Selective
Estrogen Receptor Modulators (SERMS). In short, they perform
a complex function as agonists or antagonists depending on
the tissue, ER type and quantity and the endogenous hormonal
milieu.5
In vitro studies have shown that phytoestrogens can be
the ideal candidates for treatment of osteoporosis because they
are able to stimulate osteoblastic activity and inhibit osteoclast
formation. This double positive action is obtained at a range of
concentrations (10-5 to10-7 M) consistent with human ingestion
of genistein.50 The discovery of ERα and ERβ receptors in the
bone, the positive effect of selective SERMs such as raloxifene
in animals and in humans, and the fact that by virtue of their
similarity to raloxifene in forming bonds with the estrogen
receptors, phytoestrogens such as genistein, have selective
effects on the bone. This protective effect of the phytoestrogens
on the bone is produced through the binding of these substances
to the estrogen receptors and particularly ER-β ER-β expression
is increased during bone mineralization and the high afnity
of genistein towards ER-β could make its action efcient at
physiological levels.9 Animal studies have shown that numerous
phytoestrogens including coumestrol, genistein, daidzein and
others have bone sparing effects in the rat.51
Evidence for measurable effects in humans is equally
mixed. At least one study has found that post-menopausal women
consuming high quantities of soy foods have better femoral and/
or lumbar spine density compared to women who consume
less soy.52 A 2009 meta-analysis of randomized clinical trials
conducted in humans, however, found only a weak association
between increased consumption of soy isoavones and improved
bone-mineral density, leading the authors to conclude that soy
isoavones were unlikely to meaningfully reduce the risk of
osteoporosis.53 Thus adding soya to diet can help stave off bone
loss in mid-life especially for women.
Phytoestrogens for Prostate Cancer
Worldwide disparities exist between geographic regions with
regard to prostate cancer incidence and mortality. Countries in
East Asia have lower rates of prostate cancer compared with
Western countries such as Canada and the US. Some suggest
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that dietary differences between the two geographic regions,
particularly the higher amount of phytoestrogens consumed in
East Asia, is responsible for the difference in prostate cancer
incidence. Phytoestrogens are hormonally active compounds
present in plant foods that are being studied extensively for
their potential roles in hormonally-sensitive neoplasms such as
prostate cancer. The mechanism of action of the soy isoavones
is incompletely understood, but in regards to prostate
carcinogenesis likely involves estrogenic effects, cell cycle
inhibition, anti-angiogenesis and induction of apoptosis. Recent
clinical studies have provided mixed results with regard to a clear
association between prostate cancer and soy consumption.54
The evidence for a protective role of phytoestrogens
is not conclusive enough for a general recommendation for
their use as dietary supplements, but phytoestrogens can be
considered for therapeutic use in prostate cancer patients under
certain circumstances. A literature review was performed to
study the evidence regarding the chemo-preventive role of
phytoestrogens in healthy men, the protective role in early
prostate cancer, and a possible therapeutic role in advanced
prostate cancer patients. Dietary supplementation with
phytoestrogens for chemoprevention of prostate cancer is still
a debatable subject. Numerous pre-clinical in vitro studies have
been promising, and novel molecular mechanisms of action
for phytoestrogens continue to be identied. However, human
clinical trials including studies done on prostate biomarkers
and on the effects of phytoestrogens on steroid hormones
are complicated by the possibility of local paracrine effects
in prostatic tissue by phytoestrogens that are steroid-like in
structure. Their interaction with multiple enzymes represents
a paradigm for the complexity of phytoestrogen effects and a
window into a potential reason that study results are inconsistent
or difcult to explain. A nal outcome of the phytoestrogen
effect in the intact human may be difcult to discern because
these agents can inhibit or induce enzymes, destroy cancer cells,
yet will have intrinsic estrogenic effects themselves. Larger
multi-center, multi-national, randomized controlled trials are
needed before denitive recommendations can be made on the
usefulness of phytoestrogens for chemoprevention and therapy
for prostate cancer. However, combinations of phytoestrogens
with radiation therapy and other antioxidants in advanced or
metastatic prostate cancer can be considered because there are
limited effective therapy options for this group of patients.55
In a study, a large meta-analysis suggests that both
fermented and non-fermented soy is protective against cancer.56
While tofu was the only individual food showing a protective
effect, the phytoestrogens genistein and daidzein were also
associated with a lower risk of prostate cancer. Further evidence
of the protective effect of genistein can be concluded from
studies using rodent models and human cell lines.
Mentor-Marcel et al57 investigated the effects of
genistein on the progression of prostate cancer in the TRAMP
mouse model. When dietary genistein was used to elevate mouse
serum genistein to levels comparable to that of Asian men, the
rate of poorly differentiated adenocarcinoma decreased in a
dose-dependent manner, while survival improved as a function
of decreased tumor burden.57
In yet another study, using a rat hormonal carcinogenesis
model has shown that a soy isoavone mixture that includes
genistein and diazein is able to protect against carcinogenesis
in the dorsolateral and anterior prostate lobes.58 In vitro studies
revealed that genistein inhibited growth of two prostate cancer
cell lines alone or in combination with selenium.59 The treatment
also induced apoptosis through caspase-dependent pathways
and reduced expression of matrix metalloproteinase 2, which
has been associated with active invasion and metastases.
Phytoestrogens for Cardiovascular Diseases
Cardiovascular disease (CVD) is the number one cause of
morbidity and mortality in men and women worldwide.
According to the WHO, by 2015, almost 20 million people will
die from CVD each year.60 In menopause the risk of CVD greatly
increases due to the loss of estrogen. Lipid proles, vascular
reactivity, cellular proliferation and thrombosis are factors that
affect CVD and on which phytoestogens have shown benecial
effects.61 Mechanisms suggested explaining the prevention of
CVD and the reduction of atherosclerosis are: improvement of
plasma lipid concentrations, reduction of thrombus formation
such as inhibition of platelet action, improvement of systemic
arterial compliance and antioxidant activity. Studies suggest that
isoavones as antioxidants may affect atherogenesis by reducing
the oxidation of LDL. Phytoestrogens are a subcategory of
compounds called avonoids, a group composed of hundreds or
more types of molecules. The 2 classes of phytoestrogens are
isoavones, notably found in soy products and lignans, present in
nuts, fruits, cereal grains, tea, and coffee.62 Hwang et al63 reported
that extracts of soy, alfalfa and acerola cherry (Malpighia glabra
L., Malpighiaceae) may synergistically interact to prevent LDL
oxidation. Because of their assumed health benet, isoavone
content is advertised in many foods that contain soybeans, and
isoavones are sold as nutritional supplements.
Phytoestrogens for Relief from Menopausal Symptoms
This is the most widely attributed health benet of phytoestrogen
consumption. Research has shown that intake of phytoestrogens
provides relief from menopausal symptoms including hot ushes
and night sweats. Studies have shown that there is a slight
reduction in hot ushes and night sweats with phytoestrogen-
based treatment. Extracts containing high levels of genistein
appeared to reduce the number of daily hot ushes but it needs
to be investigated further. Overall no indication suggested that
other types of phytoestrogens work any better than no treatment.
Moreover, no evidence was found of harmful effects on the lining
of the womb, stimulation of the vagina or other adverse effects
with short-term use.64
The association between phytoestrogen intake and breast
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cancer risk in a large prospective study in a Dutch population
with a habitually low phytoestrogen intake was investigated and
it was concluded that in Western populations, a high intake of
isoavones or mammalian lignans is not signicantly related to
breast cancer risk. Despite this uncertainty, dietary supplements
continue to be popular, particularly among women seeking a
“natural” alternative to hormone replacement therapy.65 In yet
another review it was concluded that no evidence shows a benet
of phytoestrogens enriched or-derived products for menopausal
vasomotor symptoms with the exception of products containing
a minimum of 30 mg per day of genistein which have been
evaluated for upto two years in four studies.66
Phytoestrogens for Bone Health and Osteoporosis
Estrogen deciency is a major risk factor for osteoporosis in
postmenopausal women. Although hormone replacement therapy
(HRT) has been rampantly used to recompense for the bone loss,
but the procedure is coupled with severe adverse effects. Hence,
there is a boost in the production of newer synthetic products
to ward off the effects of menopause-related osteoporosis. As
of today, there are several prescription products available for
the treatment of postmenopause osteoporosis; most of these
are estrogenic agents and combination products. Plant-derived
natural products, mostly phytoestrogens (isoavones, lignans,
coumestanes, stilbenes, and avonoids) are used to prevent
menopause-related depletion in bone mineral density (BMD).
Although, a number of papers are published on menopause-
related general symptoms, sexual dysfunction, cardiovascular
diseases, Alzheimer’s disease, diabetes, colon and breast
cancers, there is paucity of literature on the accompanying
osteoporosis and its treatment.67 In a recent study, the effect of
soy protein with and without phytoestrogens on bone turnover
was determined in post menopausal women i.e. within two years
of the onset of menopause when the bone loss is at its greatest.
It was found that there was a signicant decrease in bone turn
over markers of resorption and formation after supplementation
with 15 g soy protein and phytoestrogens for 6 months. An
initial effect on osteoclast followed by decreased osteoblast
function may have benecial effects on bone health. There was
no signicant change in bone turn over makers with 30 g soy
protein alone for 6 months.68
Phytoestrogens and Cognition
Cognition and memory functioning have been reported
to decrease around menopause and therefore, studies have inves-
tigated the association of ERT and cognition, as well as phytoes-
trogens and cognition. However, limited studies are available
on the effects of phytoestrogens on cognitive functioning. The
mechanisms are not understood, but it has been suggested that
phytoestrogens act as estrogen agonists and may increase spine
density and synapse formation in the hippocampus of adults. In
addition, phytoestrogens may interact with the transcription of
neurotrophin genes.69
Neuroprotective effects of phytoestrogen compounds
found in soy have been demonstrated in animal research and
cell culture studies. In particular, phytoestrogens have been
shown to reduce Alzheimer’s Disease (AD) related pathology,
potentially alleviating risk of AD progression. In addition to
their antioxidant properties, soy products also have the ability
to affect cognition via interaction with estrogen receptors.
However, observational studies and randomized controlled trials
in humans have resulted in inconclusive ndings within this
domain. There are several possible reasons for these discrepant
data. Studies which report no effect of phytoestrogens on
cognition have mainly been carried out in European cohorts, with
an average low dietary consumption. In contrast, investigation
of Asian populations, with a higher general intake of tofu (a non-
fermented soy product) has shown negative associations with
cognitive function in those over the age of 65. Consideration
of type of soy product is important, as in the latter sample,
protective effects of tempeh (fermented soy) were also observed.
Limited data provide evidence that effects of phytoestrogens on
cognition may be modied by dosage, duration of consumption
and cognitive test used. Additionally, characteristics of the study
population including age, gender, ethnicity and menopausal
status appear to be mediating variables. Phytoestrogen treatment
interventions have also shown time-limited positive effects on
cognition. These ndings are consistent with estrogen treatment
studies, where initial positive short-term cognitive effects may
occur, which reverse with long-term continuous use in elderly
women. Well controlled, large scale studies are needed to assess
the effects of phytoestrogens on the aging brain and provide
further understanding of this association.70
Phytoestrogens: Side Effects
As it is already known, phytoestrogens are structurally similar to
endogenous estrogens such as 17 β-estradiol and are produced
by plants. The most well-understood phytoestrogen action on
animal physiology, due to ingestion or exposure to contaminated
water, involves competitive binding to estrogen receptors.
Because of this ability, some phytoestrogens have documented
medicinal potential,71 but in uncontrolled conditions they may
adversely affect reproduction.72 Furthermore, phytoestrogens
may also interfere directly with steroid biosynthesis, intracellular
signaling, cell proliferation, and gene expression,73 which has
raised concerns in the medical community about their safety.8
Consequences of exposure to these compounds are
still unclear, as phytoestrogens have been reported to have
estrogenic as well as anti-estrogenic effects on vertebrates.74
Generally, phytoestrogens are considered safe for humans at
common exposure levels, such as those found in soy products,
but the large-scale anthropogenic production of phytoestrogens
in runoff from agricultural areas, wood pulp mill discharge, and
sewage treatment plant efuent may still pose a threat to aquatic
ecosystems.75
In another study, a meta-analysis of side effects was
performed comparing phytoestrogen treatment with placebo or
no treatment in randomized controlled trials and it was found
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that phytoestrogen supplements have a safe side-effect prole
with moderately elevated rates of gastrointestinal side effects. It
was also found in the investigation studies that rates of vaginal
bleeding, endometrial hyperplasia, endometrial cancer and breast
cancer were not signicantly increased among phytoestrogen
users.76
CONCLUSION
Thus from the foregoing it is quite evident that diets rich in plant-
derived products may supply a variety of phytoestrogens capable
of producing a range of pharmacological effects in the human
body. As people live longer, women are spending more of their
lives in menopause, affected by a variety of estrogen-related
conditions such as osteoporosis, cognitive and cardiovascular
disease, increased risk of breast cancer and other symptoms
that decrease the overall quality of life. Epidemiological
evidence and experimental data from animal studies are highly
suggestive of the benecial effects of phytoestrogens on human
health and their potential to be used as pharma foods, but the
clinical data supportive of such effects are either not available,
or are awaiting design and execution of appropriate prospective
large-scale clinical studies. Due to the functional and structural
differences of phytoestrogens, their biological activities are
also highly variable and there may be other effects that have
not yet been studied. Future research should focus on specic
soy components, variability in phytoestrogen metabolism and
effects of phytoestrogens on specic target tissues.
ACKNOWLEDGEMENTS
Authors are grateful to Dr. Ashok K Chauhan, Founder President
and Mr. Atul Chauhan, Chancellor, Amity University UP, Noida,
India for the encouragement, research facilities and nancial
support.
ETHICAL ISSUES
There is none to be declared
CONFLICT OF INTEREST
The author(s) conrm that this article content has no conict of
interest.
REFERENCE
1. Adlercreutz H, Mazur W. Phytoestrogens and western
diseases. Ann Med. 1997; 29(2): 95-120. doi: 10.3109/078538
99709113696
2. Yildiz F. Phytoestrogens in Functional Foods. Taylor &
Francis Ltd; 2005: 3-5: 210-211.
3. Johnston I. Phytochem Functional Foods. Boca Raton,
Florida: CRC Press Inc.; 2003: 66-68.
4. Thompson LU, Boucher BA, Liu Z, Cotterchio M, Kreiger N.
Phytoestrogen content of foods consumed in Canada, including
isoavones, lignans, and coumestan. Nutr Cancer. 2006; 54(2):
184-201. doi: 10.1207/s15327914nc5402_5
5. Prakash D, Gupta C. Role of phytoestrogens as nutraceuticals
in human health. Pharmacology online. 2011; 1: 510-523. Web
site. http://pharmacologyonline.silae.it/les/newsletter/2011/vol
1/050.prakash.pdf. Accessed June 9, 2016
6. Zhao E, Mu Q. Phytoestrogen biological actions on mamma-
lian reproductive system and cancer growth. Sci Pharm. 2011;
79(1): 1-20. doi: 10.3797/scipharm.1007-15
7. Naz Rajesh K. Endocrine Disruptors: Effects on Male and
Female Reproductive Systems. Boca Raton, Florida: CRC Press
Inc; 1999: 90.
8. Patisaul HB, Jefferson W. The pros and cons of phytoes-
trogens. Front Neuroendocrinol. 2010; 31(4): 400-419. doi:
10.1016/j.yfrne.2010.03.003
9. Prakash D, Gupta C. Role of Phytoestrogens as Nutraceuticals
in Human Health. In: Phytochemicals of nutraceutical impor-
tance. Prakash D, Sharma G, eds. Oxfordshire, UK: CABI Inter-
national Publishers; 2014: 148-172.
10. Caltagirone S, Rossi C, Poggi A, et al. Flavonoids api-
genin and quercetin inhibit melanoma growth and meta-
static potential. Int J Cancer. 2000; 87(4): 595-600. doi:
10.1002/1097-0215(20000815)87:4<595::AID-IJC21>3.0.
CO;2-5
11. Liu LZ, Fang J, Zhou Q, Hu X, Shi X, Jiang BH. Apigenin
inhibits expression of vascular endothelial growth factor
and angiogenesis in human lung cancer cells: Implication of
chemoprevention of lung cancer. Molecular Pharmacology.
2005; 68(3): 635-643. doi: 10.1124/mol.105.011254
12. Sobolev VS, Horn BW, Potter TL, Deyrup ST, Gloer JB.
Production of stilbenoids and phenolic acids by the peanut plant
at early stages of growth. J Agric Food Chem. 2006; 54: 3505-
3511. doi: 10.1021/jf0602673
13. Beejmohun V, Fliniaux O, Hano C, et al. Coniferin dimeriza-
tion in lignan biosynthesis in ax cells. Phytochemistry. 2007;
68(22-24): 2744-2752. doi: 10.1016/j.phytochem.2007.09.016
14. Bonzanini F, Bruni R, Palla G, Serlataite N, Caligiani A.
Identication and distribution of lignans in Punica granatum L.
fruit endocarp, pulp, seeds, wood knots and commercial juices
by GC-MS. Food Chem. 2009; 117: 745-749. doi: 10.1016/j.
foodchem.2009.04.057
15. Hosseinian FS, Mazza G. Triticale bran and straw: Potential
new sources of phenolic acids, proanthocyanidins and lignans. J
Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-2-127
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
Funct Foods. 2009; 1(1): 57-64. doi: 10.1016/j.jff.2008.09.009
16. Attoumbre J, Bienaime C, Dubois F, Fliniaux MA, Chabbert
B, Baltora-Rosset S. Development of antibodies against
secoisolanciresinol- Application to the immunolocalization of
lignans in Linum usitatissimum seeds. Phytochemistry. 2010;
71(17-18): 1979-1987. doi: 10.1016/j.phytochem.2010.09.002
17. Milder IEJ, Arts ICW, van de Putte B, Venema DP, Hollman
PC. Lignan contents of Dutch plant foods: A database including
lariciresinol, pinoresinol, secoisolariciresinol and matairesinol.
Br J Nutr. 2005; 93(3): 393-402. doi: 10.1079/BJN20051371
18. Cai YZ, Mei S, Jie X, Luo Q, Corke H. Structure-radical
scavenging activity relationships of phenolic compounds from
traditional Chinese medicinal plants. Life Sciences. 2006;
78(25): 2872-2888. doi: 10.1016/j.lfs.2005.11.004
19. Apers S, Vlietinck A, Pieters L. Lignans and neolignans as
lead compounds. Photochemistry Reviews. 2003; 2(3): 201-217.
doi: 10.1023/B:PHYT.0000045497.90158.d2
20. Duncan AM, Phipps WR, Kurzer MS. Phyto-estrogens. Best
Pract Res Clin Endocrinol Metab. 2003; 17(2): 253-271. doi:
10.1016/S1521-690X(02)00103-3
21. Boccardo F, Puntoni M, Guglielmini P, Rubagotti A. En-
terolactone as a risk factor for breast cancer: a review of the
published evidence. Clinica Chimica Acta. 2006; 365(1-2): 58-
67. doi: 10.1016/j.cca.2005.07.026
22. Albertazzi P, Purdie DW. The nature and utility of the
phytoestrogens: A review of the evidence. Maturitas. 2002;
42(3): 173-185. doi: 10.1016/S0378-5122(02)00024-5
23. Ikeda K, Arao Y, Otsuka H, et al. Terpenoids found
in the Umbelliferae family act as agonists/antagonists for
ER(alpha) and ER(beta): Differential transcription activity
between ferutinine-liganded ER(alpha) and ER(beta). Biochem
Biophys Res Commun. 2002; 291(2): 354-360. doi: 10.1006/
bbrc.2002.6446
24. Cherdshewasart W, Sutjit W, Pulcharoen K, Chulasiri M.
The mutagenic and anti-mutagenic effects of the traditional
phytoestrogen-rich herbs. Pueraria mirica and Pueraria lobata.
Braz J Med Biol Res. 2009; 42(9): 816-823. doi: 10.1590/S0100-
879X2009000900008
25. Ibarreta D, Daxenberger A, Meyer HH. Possible health
impact of phytoestrogens and xenoestrogens in food. Acta
Pathologica, Microbiologica et Immunologica. 2001; 109(3):
161-184. doi: 10.1034/j.1600-0463.2001.090301.x
26. Turner JV, Agatonovic-Kustrin S, Glass BD. Molecular
aspects of phytoestrogen selective binding at estrogen
receptors. J Pharm Sci. 2007; 96 (8): 1879-1885. doi: 10.1002/
jps.20987
27. Dang ZC. Dose-dependent effects of soy phytoestro-
gen genistein on adipocytes: Mechanisms of action. Obes Rev.
2009; 10(3): 342-349. doi: 10.1111/j.1467-789X.2008.00554.x
28. Amadasi A, Mozzarelli A, Meda C, Maggi A, Cozzini P.
Identication of xenoestrogens in food additives by an integrated
in Silico and in vitro approach. Chem Res Toxicol. 2008; 22(1):
52-63. doi: 10.1021/tx800048m
29. Dusza L, Ciereszko R, Skarzynski DJ, et al. Mechanism of
phytoestrogen action in reproductive processes of mammals and
birds. Reproductive Biology. 2006; 6(1): 151-174. Web site.
http://europepmc.org/abstract/med/16967096. Accessed June 9,
2016
30. Stevenson LM, Oates SH, Doernte AL, Hess JB, Berry
WD. Soy phytoestrogen effects on progesterone receptor and
ovalbumin synthesis in the chick oviduct. EPC 2006 - 12th
European Poultry Conference, Verona, Italy, 10-14 September,
2006 pp. paper 47. Record no. 20093210252. Web site. http://
cabdirect.org/abstracts/20093210252.html;jsessionid=7251C31
21F94427FE9BA11889FB50B73
31. Hamilton-Reeves JM, Vazquez G, Duval SJ, Phipps WR,
Kurzer MS. Clinical studies show no effects of soy protein or
isoavones on reproductive hormones in men: Results of a meta-
analysis. Fertil Steril. 2010; 94(3): 997-1007. doi: 10.1016/j.
fertnstert.2009.04.038
32. Messina M, McCaskill-Stevens W, Lampe JW. Addressing
the soy and breast cancer relationship: Review, commentary, and
workshop proceedings. Journal of National Cancer Institute.
2006; 98(18): 1275-1284. doi: 10.1093/jnci/djj356
33. Shu XO, Zheng Y, Cai H, et al. Soy food intake and breast
cancer survival. JAMA. 2009; 302(22): 2437-2443. doi: 10.1001/
jama.2009.1783
34. Park K, Kim Y-Il, Shin K-Oh, et al. The dietary ingredient,
genistein, stimulates cathelicidin antimicrobial peptide expres-
sion through a novel S1P-dependent mechanism. J Nutr Bio-
chem. 2014; 25(7): 734-740. doi: 10.1016/j.jnutbio.2014.03.005
35. Chen A, Rogan WJ. Isoavones in soy infant formula:
A review of evidence for endocrine and other activity in
infants. Annu Rev Nutr. 2004; 24(1): 33-54. doi: 10.1146/
annurev.nutr.24.101603.064950
36. Giampietro PG, Bruno G, Furcolo G, et al. Soy protein
formulas in children: no hormonal effects in long-term feeding. J
Pediatr Endocrinol Metab. 2004; 17(2): 191-196. doi: 10.1515/
JPEM.2004.17.2.191
37. Merritt RJ, Jenks BH. Safety of soy-based infant formulas
containing isoavones: the clinical evidence. J Nutr. 2004;
134(5): 1220S-1224S.
Page 29
Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-2-127
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
38. Bhatia J, Greer F. Use of soy protein-based formulas in infant
feeding. Pediatrics. 2008; 121(5): 1062-1068. doi: 10.1542/
peds.2008-0564
39. Geller SE, Shulman LP, van Breemen RB, et al. Safety and
efcacy of black cohosh and red clover for the management of
vasomotor symptoms: A randomized controlled trial. Menopause.
2009; 16(6): 1156-1166. doi: 10.1097/gme.0b013e3181ace49b
40. Bankole MA, Shittu LAJ, Ahmed TA, et al. Synergistic
antimicrobial activities of phytoestrogens in crude extracts
of two sesame species against some common pathogenic
microorganisms. African Journal of Traditional Complementary
and Alternative Medicines. 2007; 4(4): 427-433. doi: 10.4314/
ajtcam.v4i4.31237
41. Srisomboon Y, Buathong N, Kiatprasert P, Poonyachoti S,
Deachapunya C. Soybean phytoestrogen enhances the
antimicrobial peptides beta-defensin-2 synthesis in endometrial
epithelial cells with lipopolysaccharides and polyinosinic-
polycytidylic acid stimulation. The FASEB Journal. 2014; 28(1)
Supplement 639.8. Web site. http://www.fasebj.org/content/28/
1_Supplement/639.8. Accessed June 9, 2016
42. Obiorah IE, Fan P, Jordan VC. Breast cancer cell apoptosis
with phytoestrogens is dependent on an estrogen deprived state.
Cancer Prevention Research. 2014. doi: 10.1158/1940-6207.
CAPR-14-0061
43. Horn-Ross PL, John EM, Canchola AJ, Stewart SL, Lee
MM. Phytoestrogen intake and endometrial cancer risk. J Natl
Cancer Inst. 2003; 95(15): 1158-1164. doi: 10.1093/jnci/djg015
44. Flaxseed. Natural Medicines Comprehensive Database.
Web site. http://naturaldatabase.therapeuticresearch.com/nd/
Search.aspx?cs=ONDPG&s=ND&pt=100&id=991&ds=&la
ng=0. Accessed March 24, 2013
45. Lee J, Cho K. Flaxseed sprouts induce apoptosis and inhibit
growth in MCF-7 and MDA-MB-231 human breast cancer
cells. In Vitro Cell Dev Biol Anim. 2012; 48(4): 244-250. doi:
10.1007/s11626-012-9492-1
46. Tamoxifen. U.S. National Library of Medicine, National
Institutes of Health. Web site. https://www.nlm.nih.gov/
medlineplus/druginfo/meds/a682414.html. Accessed March 24,
2013
47. Chen J, Power KA, Mann J, Cheng A, Thompson LU.
Dietary axseed interaction with tamoxifen induced tumor
regression in athymic mice with MCF-7 xenografts by down
regulating the expression of estrogen related gene products and
signal transduction pathways. Nutr Cancer. 2007; 58(2): 162-70.
doi: 10.1080/01635580701328271
48. McCann SE, Hootman KC, Weaver AM, et al. Dietary
intakes of total and specic lignans are associated with clinical
breast tumor characteristics. J Nutr. 2012; 142(1): 91-98. doi:
10.3945/ jn.111.147264
49. McCann SE, Thompson LU, Nie J, et al. Dietary lignan
intakes in relation to survival among women with breast cancer:
the Western New York Exposures and Breast Cancer (WEB)
Study. Breast Cancer Res Treat. 2010; 122(1): 229-235. doi:
10.1007/s10549-009-0681-x
50. Branca F. Dietary phytoestrogens and bone health. Proc Nutr
Soc. 2003; 62(4): 877-887. doi: 10.1079/PNS2003309
51. Cassidy A, Albertazzi P, Nielsen IL, et al. Critical review of
health effects of soybean phyto-oestrogens in post-menopausal
women. Proc Nutr Soc. 2006; 65(1): 76-92. doi: 10.1079/
PNS2005476
52. Yamori Y, Moriguchi EH, Teramoto T, et al. Soybean
isoavones reduce postmenopausal bone resorption in female
Japanese immigrants in Brazil: A ten-week study. Journal of
American College of Nutrition. 2002; 21(6): 560-563. doi:
10.1080/07315724.2002.10719255
53. Liu J, Ho SC, Su YX, Chen WQ, Zhang CX, Chen YM.
Effect of long-term intervention of soy isoavones on bone
mineral density in women: A meta-analysis of randomized
controlled trials. Bone. 2009; 44(5): 948-953. doi: 10.1016/j.
bone.2008.12.020
54. Goetzl MA, VanVeldhuizen PJ, Thrasher JB. Effects of
soy phytoestrogens on the prostate. Prostate Cancer Prostatic
Dis. 2007; 10(3): 216-223. doi: 10.1038/sj.pcan.4500953
55. Kolukula S, Anderson RJ. Phytoestrogens and their potential
roles in prostate cancer prevention and treatment. J Cancer Sci
Ther. 2011; S1. doi: 10.4172/1948-5956.S1-002
56. Hwang YW, Kim SY, Jee SH, Kim YN, Nam CM. Soy food
consumption and risk of prostate cancer: A meta-analysis of
observational studies. Nutr Cancer. 2009; 61(5): 598-606. doi:
10.1080/01635580902825639
57. Mentor-Marcel R, Lamartiniere CA, Eltoum IA, Greenberg
NM, Elgavish A. Dietary genistein improves survival and reduces
expression of osteopontin in the prostate of transgenic mice
with prostatic adenocarcinoma (TRAMP). J Nutr. 2005; 135(5):
989-995. Web site. http://jn.nutrition.org/content/135/5/989.
Accessed June 9, 2016
58. McCormick DL, Johnson WD, Bosland MC, Lubet
RA, Steele VE. Chemoprevention of rate prostate carcinogenesis
by soy isoavones and by Bowman–Birk inhibitor. Nutr Cancer.
2007; 57(2): 184-193. doi: 10.1080/01635580701277478
59. Kumi-Diaka J, Merchant K, Haces A, Hormann V, Johnson
M. Genistein-selenium combination induces growth arrest in
prostate cancer cells. J Med Food. 2010; 13(4): 842-850. doi:
Page 30
Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-2-127
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
10.1089/jmf.2009.0199
60. Bhupathy P, Haines CD, Leinwand LA. Inuence of sex
hormones and phytoestrogens on heart disease in men and
women. Summary Women’s Health. 2014; 6(1): 77-95. doi:
10.2217/whe.09.80
61. Van der Schouw YT, Kreijkamp-Kaspers S, Peeters PH,
Keinan-Boker L, Rimm EB, Grobbee DE. Prospective study on
usual dietary phytoestrogens intake and cardiovascular disease
in Western women. Circulation. 2005; 111(4): 465-471. doi:
10.1161/01.CIR.0000153814.87631.B0
62. Kris-Etherton PM, Hecker KD, Bonanome A, et al.
Bioactive compounds in foods: their role in the prevention of
cardiovascular disease and cancer. Am J Med. 2002; 113 (suppl
9B): 71S-88S. doi: 10.1016/S0002-9343(01)00995-0
63. Hwang J, Hodis HN, Sevanian A. Soy and alfalfa
phytoestrogen extracts become potent low-density lipoprotein
antioxidants in the presence of acerola cherry extract. J Agric
Food Chem. 2001; 49(1): 308-314. doi: 10.1021/jf0007028
64. Lethaby A, Marjoribanks J, Kronenberg F, Roberts H, Eden J.
Phytoestrogens for menopausal vasomotor symptoms. Cochrane
Database Syst Rev. 2013. doi: 10.1002/14651858.CD001395.
pub4
65. Keinan-Boker L, van Der Schouw YT, Grobbee DE, Peeters
PH. Dietary phytoestrogens and breast cancer risk. Am J Clin
Nutr. 2004; 79(2): 282-288. Web site. http://ajcn.nutrition.org/
content/79/2/282.short. Accessed June 9, 2016
66. Roberts H, Lethaby A. Phytoestrogens for menopausal
vasomotor symptoms: A Cochrane review summary. Maturitas
(Editorial). 2014; 78(2): 79-81. doi: 10.1016/j.maturitas.2014.
04.004
67. Al-Anazi AF, Qureshi VF, Javaid K, Qureshi S. Preventive
effects of phytoestrogens against postmenopausal osteoporosis
as compared to the available therapeutic choices: An overview.
Journal of Natural Science Biology and Medicine. 2011; 2(2):
154-163. doi: 10.4103/0976-9668.92322
68. Sathyapalan T, Kilpatrick ES, Aye M, et al. The Effect of Soy
Phytoestrogens on Bone Turn over Markers in Women during
Early Menopausal Period. Endocrine Disrupting Chemicals
Action in Physiology and Cancer, Endocrine Society’s 96th
Annual Meeting and Expo, June 21-24, 2014; Chicago. http://
press.endocrine.org/doi/abs/10.1210/endo-meetings.2014
ED.2.SAT-0360
69. File SE, Hartley DE, Alom N, Rattray M. Soya phytoestrogens
change cortical and hippocampal expression of BDNF mRNA
in male rats. Neuroscience Letters. 2003; 338(2): 135-138. doi:
10.1016/S0304-3940(02)01391-5
70. Soni M, Rahardjo TB, Soekardi R, et al. Phytoestrogens and
cognitive function: A review. Maturitas. 2014; 77(3): 209-220.
doi: 10.1016/j.maturitas.2013.12.010
71. Ullmann U, Metzner J, Frank T, Cohn W, Riegger C. Safety,
tolerability, and pharmacokinetics of single ascending doses
of synthetic genistein (Bonistein™) in healthy volunteers. Adv
Ther. 2005; 22(1): 65-78. doi: 10.1007/BF02850186
72. Wisniewski AB, Cernetich A, Gearhart JP, Klein SL.
Perinatal exposure to genistein alters reproductive development
and aggressive behavior in male mice. Physiology and Behavior.
2005; 84(2): 327-334. doi: 10.1016/j.physbeh.2004.12.008
73. Toyohira Y, Ueno S, Tsutsui M, Itoh H, Sakai N, Saito
N. Stimulatory effects of the soy phytoestrogen genistein on
noradrenaline transporter and serotonin transporter activity.
Mol Nutr Food Res. 2010; 54(4): 516-524. doi: 10.1002/mnf
r.200900167
74. Dixon RA. Phytoestrogens. Annu Rev Plant Biol. 2004; 55:
225-261. doi: 10.1146/annurev.arplant.55.031903.141729
75. Brown AC, Stevenson LM, Leonard HM, Nieves-Puigdoller
K, Clotfelter ED. Phytoestrogens β-sitosterol and genistein have
limited effects on reproductive endpoints in a female sh, Betta
splendens. BioMed Research International. 2014; Article ID
681396: 7. doi: 10.1155/2014/681396
76. Tempfer CB, Froese G, Heinze G, Bentz EK, Heer LA,
Huber JC. Side effects of phytoestrogens: A meta-analysis of
randomized trials. Am J Med. 2009; 122(10): 939-946. doi:
10.1016/j.amjmed.2009.04.018
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... łagodzić sympto-symptoms of menopause, prevent cardiovascular diseases, regulate glucose metabolism, reduce insulin resistance, improve cognitive functions of the brain, prevent osteoporosis or some cancers (6,7). There are also reports in the literature about the possible negative effects of phytoestrogens, including: fertility problems, feminization in men, the possibility of developing hormone-dependent neoplasms, vaginal bleeding or allergic reactions (7)(8)(9)(10). Although side effects occur only occasionally, the precautions are recommended in regard to the type of phytoestrogen taken and the body's response to it. ...
... Phytoestrogens, present in the diet, are found in popular plants that provide substances for the production of food products. Such plants are, for example, flax (Linum usitatissimum), Indian sesame (Sesamum indicum), soybean (Glycine max), sunflower (Helianthus annuus), olive (Olea europaea), edible lentil (Lens culinaris) or common hops (Humulus lupulus) (10). Phytoestrogens are also available as dietary supplements and over-the-counter (OTC) medications. ...
... The survey included questions referring to general knowledge about my menopauzy, zapobiegać chorobom sercowo-naczyniowym, regulować metabolizm glukozy, zmniejszać insulinooporność, poprawiać funkcje poznawcze mózgu, zapobiegać osteoporozie czy niektórym nowotworom (6,7). W literaturze pojawiają się również doniesienia o możliwych negatywnych skutkach stosowania fitoestrogenów m.in.: problemach z płodnością, feminizacją u mężczyzn, możliwością rozwoju nowotworów hormonozależnych, krwawieniach z dróg rodnych lub reakcjach alergicznych (7)(8)(9)(10). Mimo że działania niepożądane nie występują często, powinno się zwracać uwagę na rodzaj przyjmowanego fitoestrogenu oraz obserwować odpowiedź organizmu na jego działanie. ...
... Phytoestrogens are non-steroidal natural compounds produced by plants. There are several classes of phytoestrogens spanning innumerous compounds (for a review, see [109,110]). These compounds are chemically and structurally similar to E2, providing them with the capacity to bind in both ESR1 and ESR2 [111], although their affinity for ESR1 or ESR2 can be highly variable. ...
... After binding to ESR1 or ESR2, phytoestrogens can activate or block estrogen receptor ligand-binding domains, thus displaying estrogenic or antiestrogenic effects, respectively [110,111]. It is important to observe that some compounds are found in large amounts in some food sources, of which we ingest only small amounts (for example, nuts, seeds and spices); thus, their relative participation in our regular diets may be low (for a review, see [109]). The final true role of phytoestrogens in any estrogen biological effect is still a real challenge because at least the following must be considered: (1) the ESR1/ESR2 RBA, (2) the pattern of ESR1 and ESR2 expression in the target tissue, (3) the concentration of the compound in the food source and the respective amount of intake of this food and (4) the concomitant concentration of endogenous estrogens at the target tissue. ...
... ND, not determined. Data are based on[109,110]. ...
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Impaired circulating estrogen levels have been related to impaired glycemic homeostasis and diabetes mellitus (DM), both in females and males. However, for the last twenty years, the relationship between estrogen, glycemic homeostasis and the mechanisms involved has remained unclear. The characterization of estrogen receptors 1 and 2 (ESR1 and ESR2) and of insulin-sensitive glucose transporter type 4 (GLUT4) finally offered a great opportunity to shed some light on estrogen regulation of glycemic homeostasis. In this manuscript, we review the relationship between estrogen and DM, focusing on glycemic homeostasis, estrogen, ESR1/ESR2 and GLUT4. We review glycemic homeostasis and GLUT4 expression (muscle and adipose tissues) in Esr1−/− and Esr2−/− transgenic mice. We specifically address estradiol-induced and ESR1/ESR2-mediated regulation of the solute carrier family 2 member 4 (Slc2a4) gene, examining ESR1/ESR2-mediated genomic mechanisms that regulate Slc2a4 transcription, especially those occurring in cooperation with other transcription factors. In addition, we address the estradiol-induced translocation of ESR1 and GLUT4 to the plasma membrane. Studies make it clear that ESR1-mediated effects are beneficial, whereas ESR2-mediated effects are detrimental to glycemic homeostasis. Thus, imbalance of the ESR1/ESR2 ratio may have important consequences in metabolism, highlighting that ESR2 hyperactivity assumes a diabetogenic role.
... Phytoestrogens are polyphenolic non-steroidal compounds present naturally in several fruits, vegetables and leguminous plants such a soybean and flax [1][2][3] . Phytoestrogens include a wide variety of structurally different compounds such as flavones (Kaempferol and quercetin), isoflavones (genistein, daidzein and equol), coumestans (coumestrol), lignans (secoisolariciresinol, matairesinol, pinoresinol, and lariciresinol) and stilbenes (resveratrol) [3][4][5][6] . ...
... Phytoestrogens are polyphenolic non-steroidal compounds present naturally in several fruits, vegetables and leguminous plants such a soybean and flax [1][2][3] . Phytoestrogens include a wide variety of structurally different compounds such as flavones (Kaempferol and quercetin), isoflavones (genistein, daidzein and equol), coumestans (coumestrol), lignans (secoisolariciresinol, matairesinol, pinoresinol, and lariciresinol) and stilbenes (resveratrol) [3][4][5][6] . ...
... Phytoetrogens have a structural similarity with 17β-estradiol and can bind to the estrogen receptor sites 3,7,8 . Furthermore, there is evidence that phytoestrogens are directly responsible for the estradiol concentrations in circulation. ...
... Phytoestrogens are bioactive substances found in a large variety of fruits and vegetables. They belong to a wide group of chemical compounds such as isoflavones, coumestans and lignans [1][2][3][4] . The assessment of the benefits and the risks of phytoestrogens is a complex task due to inter-individual variation and the complexity in the absorption and metabolism 5 . ...
... Because of their structural similarity with endogenous estrogen, 17β-estradiol (E2), phytoestrogens may exert estrogenic or antiestrogenic actions by interacting with estrogen binding sites 4,15,16 . ...
... Phytoestrogens are found in a variety of plants, as Genistein, Kaempferol, Daidzen, Quercetin, and others. Genistein is a phytoestrogen that can boost osteoblast cell development and increase osterix expression (Gupta et al., 2016;Sirotkin & Harrath, 2014). ...
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... In conclusion, the authors reported that in as far as phytoestrogens have shown great epidemiological proofs in animal experimental studies and humans at large and have been used as pharmafoods, there is no much available data in the clinical utilization in large scale prospective execution by design. They recommend that further research on precise target tissues, various metabolism of phytoestrogens, and certain soy constituents should be worked upon for effective nutritional and pharmacological influence of the pharmafood [111]. ...
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This chapter has described detailed information on the application of pharmafood for a sustainable solution that could be used for the management of several chemicals and biological agents that could affect mankind’s. There is a need to emphasis also on some special techniques that could help in the identification of the bioactive constituents present in these pharmafoods. There is a need to carry out the structural elucidation of the active biological constituents present in these pharmafoods. The active constituents that have been validated to be responsible in pharamafood could also be included in some nutraceutical foods. There is also a need to increase public awareness of the health and nutritional benefits of these pharmafoods since they are easily accessible and could be easily accessible and utilized most especially by poor people leaving in rural areas who could not afford the cost and expensive drugs. The application of structural biology, informatics, chemoinformatics, and computational biology could help in the designing of a more active drug with more effectiveness for proper management of chemical and biological agents responsible for several diseases affecting mankind.
... Phytoestrogens are plant-derived compounds that structurally or functionally mimic mammalian estrogens and therefore are considered to play an important role in the prevention of menopause associated osteoporosis ( Gupta et al., 2016 ). Our earlier study on M. aboensis root showed that this plant exhibited good in vivo estrogenic activity with abundant phytoestrogens like genistein and daidzein in its ethyl acetate fraction ( Anwuchaepe et al., 2019 ). ...
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