Bee Pollen: Current Status and Therapeutic Potential

Abstract

Bee pollen is a combination of plant pollen and honeybee secretions and nectar. The Bible and ancient Egyptian texts are documented proof of its use in public health. It is considered a gold mine of nutrition due to its active components that have significant health and medicinal properties. Bee pollen contains bioactive compounds including proteins, amino acids, lipids, carbohydrates, minerals, vitamins, and polyphenols. The vital components of bee pollen enhance different bodily functions and offer protection against many diseases. It is generally marketed as a functional food with affordable and inexpensive prices with promising future industrial potentials. This review highlights the dietary properties of bee pollen and its influence on human health, and its applications in the food industry.

Full text

nutrients
Review
Bee Pollen: Current Status and Therapeutic Potential
Shaden A. M. Khalifa 1, *, Mohamed H. Elashal 2, Nermeen Yosri 2,3 , Ming Du 4, Syed G. Musharraf 5,
Lutfun Nahar 6, Satyajit D. Sarker 7, Zhiming Guo 3, Wei Cao 8, Xiaobo Zou 3, Aida A. Abd El-Wahed 9,
Jianbo Xiao 10 , Hany A. Omar 11 , Mohamed-Elamir F. Hegazy 12 and Hesham R. El-Seedi 2,13,14,*


Citation: Khalifa, S.A.M.; Elashal,
M.H.; Yosri, N.; Du, M.; Musharraf,
S.G.; Nahar, L.; Sarker, S.D.; Guo, Z.;
Cao, W.; Zou, X.; et al. Bee Pollen:
Current Status and Therapeutic
Potential. Nutrients 2021,13, 1876.
https://doi.org/10.3390/nu13061876
Academic Editors:
Christina Chrysohoou and
Konstantinos Tsioufis
Received: 7 May 2021
Accepted: 28 May 2021
Published: 31 May 2021
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Copyright: © 2021 by the authors.
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Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
1Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University,
SE-106 91 Stockholm, Sweden
2Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Kom 32512, Egypt;
m_h_elashal@yahoo.com (M.H.E.); nermeen.yosri@science.menofia.edu.eg (N.Y.)
3School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China;
guozhiming@ujs.edu.cn (Z.G.); zou_xiaobo@ujs.edu.cn (X.Z.)
4
School of Food Science and Technology, National Engineering Research Center of Seafood, Dalian Polytechnic
University, Dalian 116024, China; duming@dlpu.edu.cn
5H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences,
University of Karachi, Karachi 75270, Pakistan; musharraf@iccs.edu
6Laboratory of Growth Regulators, Institute of Experimental Botany ASCR & PalackýUniversity,
Šlechtitel˚u 27, 78371 Olomouc, Czech Republic; drnahar@live.co.uk
7Centre for Natural Products Discovery (CNPD), School of Pharmacy and Biomolecular Sciences, Liverpool
John Moores University, James Parsons Building, Byrom Street, Liverpool L3 3AF, UK; profsarker@live.com
8College of Food Science and Technology, Northwest University, Xi’an 710069, China; caowei@nwu.edu.cn
9Department of Bee Research, Plant Protection Research Institute, Agricultural Research Centre,
Giza 12627, Egypt; aidaabd.elwahed@arc.sci.eg
10 Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food
Science and Technology, University of Vigo—Ourense Campus, E-32004 Ourense, Spain; jianboxiao@uvigo.es
11 College of Pharmacy, University of Sharjah, Sharjah, P.O.Box 27272, United Arab Emirates;
hanyomar@sharjah.ac.ae
12 Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki,
Giza 12622, Egypt; me.fathy@nrc.sci.eg
13 International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
14 Pharmacognosy Group, Department of Pharmaceutical Biosciences, Biomedical Centre, Uppsala University,
Box 591, SE-751 24 Uppsala, Sweden
*Correspondence: shaden.khalifa@su.se (S.A.M.K.); hesham.el-seedi@farmbio.uu.se (H.R.E.-S.);
Tel.: +46-700-101-113 (S.A.M.K.); +46-700-434-343 (H.R.E.-S.)
Abstract:
Bee pollen is a combination of plant pollen and honeybee secretions and nectar. The Bible
and ancient Egyptian texts are documented proof of its use in public health. It is considered a gold
mine of nutrition due to its active components that have significant health and medicinal properties.
Bee pollen contains bioactive compounds including proteins, amino acids, lipids, carbohydrates,
minerals, vitamins, and polyphenols. The vital components of bee pollen enhance different bodily
functions and offer protection against many diseases. It is generally marketed as a functional food
with affordable and inexpensive prices with promising future industrial potentials. This review
highlights the dietary properties of bee pollen and its influence on human health, and its applications
in the food industry.
Keywords: bee pollen; metabolic syndromes; human health; functional food; nutritional value
1. Introduction
In ancient societies, mainly in Greece, China, and Egypt, bee products were widely
used in medicine. The ancient Egyptians portray pollen as “a life-giving dust” [
1
]. Bee
pollen (Figure 1) is a mixture of flower pollen with honeybee secretions and nectar. It
can be gathered at the entrance of the hives with the aid of traps (Figure 1) [
2
]. Bee
pollen is used in diets as supplementary nutrition due to its beneficial actions against
Nutrients 2021,13, 1876. https://doi.org/10.3390/nu13061876 https://www.mdpi.com/journal/nutrients

Nutrients 2021,13, 1876 2 of 15
human diseases. It is a potential source of vital nutrients like proteins, lipids, vitamins,
minerals, and carbohydrates, as well as trace elements and considerable amounts of
polyphenols, mainly flavonoids [
3
]. Plant and geographical origins besides other factors
like atmospheric conditions, soil nature, and behavior of the bees affects bee pollen chemical
composition [4,5].
Nutrients 2021, 13, x FOR PEER REVIEW 2 of 15
be gathered at the entrance of the hives with the aid of traps (Figure 1) [2]. Bee pollen is
used in diets as supplementary nutrition due to its beneficial actions against human
diseases. It is a potential source of vital nutrients like proteins, lipids, vitamins, minerals,
and carbohydrates, as well as trace elements and considerable amounts of polyphenols,
mainly flavonoids [3]. Plant and geographical origins besides other factors like atmos-
pheric conditions, soil nature, and behavior of the bees affects bee pollen chemical com-
position [4,5].
The current review aims to provide an overview of the dietary properties of bee
pollen and its impact on human health and recent applications in the food industry.
Figure 1. Bee pollen traps and multi-flora bee pollen.
2. Metabolites of Bee Pollen
Bee pollen metabolites including; proteins, amino acids, enzymes, co-enzymes,
carbohydrates, lipids, fatty acids, phenolic compounds, bio-elements, and vitamins
(Figures 2 and 3) [6]. The mean percent of protein in pollen is 22.7%, including vital
amino acids such as tryptophan, phenylalanine, methionine, leucine, lysine, threonine,
histidine, isoleucine, and valine. These amino acids are not synthesized in our bodies, but
they play an important role in optimal growth and health. And for their vital engagement
in gene expression, cell signaling pathways, digestion, and nutrient absorption, they
must be included in the diet [7]. Nucleic acids, particularly ribonucleic acid, are present
in considerable amounts. As a source of energy, carbohydrates exist in bee pollen at
30.8%, containing reducing sugars like glucose and fructose [8]. About 5.1% of lipids are
found in bee pollen as essential fatty acids like archaic, linoleic, and γ-linoleic acids,
phospholipids, and phytosterols (in particular β-sitosterol) [9]. Phenolic compounds
represent an average of 1.6% of pollen content, including leukotrienes, catechins, phe-
nolic acids (e.g., chlorogenic acid), and flavonoids (e.g., kaempferol, isorhamnetin, and
quercetin) [10].
The essential substances, including vitamins and bio-elements, are present in 0.7% of
the whole material. Bee pollen is a potential source of fat-soluble vitamins like vitamin E,
pro-vitamin A, vitamin D, and water-soluble vitamins such as vitamins B1, B2, B6, and C,
also a source of acids like biotin, rutin, pantothenic, nicotinic, inositol, and folic.
Bio-elements include macro-elements like sodium, magnesium, calcium, phosphorus,
and potassium, as well as micro-elements as zinc, copper, manganese, iron, and selenium
[6]. These metabolites contribute to the therapeutic potentials of bee pollen.
Figure 1. Bee pollen traps and multi-flora bee pollen.
The current review aims to provide an overview of the dietary properties of bee pollen
and its impact on human health and recent applications in the food industry.
2. Metabolites of Bee Pollen
Bee pollen metabolites including; proteins, amino acids, enzymes, co-enzymes, carbohy-
drates, lipids, fatty acids, phenolic compounds, bio-elements, and vitamins (
Figures 2and 3
) [
6
].
The mean percent of protein in pollen is 22.7%, including vital amino acids such as tryp-
tophan, phenylalanine, methionine, leucine, lysine, threonine, histidine, isoleucine, and
valine. These amino acids are not synthesized in our bodies, but they play an important
role in optimal growth and health. And for their vital engagement in gene expression,
cell signaling pathways, digestion, and nutrient absorption, they must be included in the
diet [
7
]. Nucleic acids, particularly ribonucleic acid, are present in considerable amounts.
As a source of energy, carbohydrates exist in bee pollen at 30.8%, containing reducing sug-
ars like glucose and fructose [
8
]. About 5.1% of lipids are found in bee pollen as essential
fatty acids like archaic, linoleic, and
γ
-linoleic acids, phospholipids, and phytosterols (in
particular
β
-sitosterol) [
9
]. Phenolic compounds represent an average of 1.6% of pollen
content, including leukotrienes, catechins, phenolic acids (e.g., chlorogenic acid), and
flavonoids (e.g., kaempferol, isorhamnetin, and quercetin) [10].
The essential substances, including vitamins and bio-elements, are present in 0.7% of
the whole material. Bee pollen is a potential source of fat-soluble vitamins like vitamin
E, pro-vitamin A, vitamin D, and water-soluble vitamins such as vitamins B1, B2, B6,
and C, also a source of acids like biotin, rutin, pantothenic, nicotinic, inositol, and folic.
Bio-elements include macro-elements like sodium, magnesium, calcium, phosphorus, and
potassium, as well as micro-elements as zinc, copper, manganese, iron, and selenium [
6
].
These metabolites contribute to the therapeutic potentials of bee pollen.

Nutrients 2021,13, 1876 3 of 15
Nutrients 2021, 13, x FOR PEER REVIEW 3 of 15
Figure 2. Different components of bee pollen [8,10–12].
Figure 2. Different components of bee pollen [8,10–12].

Nutrients 2021,13, 1876 4 of 15
Nutrients 2021, 13, x FOR PEER REVIEW 4 of 15
Figure 3. Chemical structure of active components in bee pollen.
Figure 3. Chemical structure of active components in bee pollen.

Nutrients 2021,13, 1876 5 of 15
3. Consumption of Bee Pollen
Although bee pollen contains a large amount of metabolites, previous studies indicate
a limited utilization of the bee pollen ingredients due to the presence of a robust outer
shell layer called exine [
13
]. Many methods were tested to enhance bee pollen’s nutritional
quality and consumption. Chemical treatment is one of the earliest techniques were used
to destroy the exine layer where the grains are subjected to monoethanolamine for three
hours at 97
◦
C to destroy the exine layer, but this approach is unacceptable when bee
pollen is used in food supplements [
14
]. Mechanical methods were effective as the exine
was broken via the action of shear forces generating heat i.e., the technique of High-
speed Shear Dispersing Emulsifier (HSDE), the action of shear force which generate a
large amount of heat, resulting in the loss of heat-sensitive nutrients [
13
]. On the other
hand, it caused nutritional loss. Physical treatment with ultrasound and supercritical
fluids was successful, but these methods are highly challenging in terms of time, cost,
and effort [
15
]. The supercritical carbon dioxide (CO
2
) technique was used to extract
essential oil from bee pollen using a supercritical CO
2
system at pressures of 13.2–46.8 MPa,
temperatures of 33.2–66.8
◦
C, and CO
2
flow rates of 6.6–23.4 L/h. Pressure, temperature,
and CO
2
flow rate all have a major impact on the yield output of lysed oil [
16
]. The use
of ultrasonic technology can effectively disrupt bee pollen walls by breaking the exine
and intine layers of bee pollen into tiny fragments, enabling nutrients to flow freely [
17
].
Finally, biotechnology processes produce remarkable results; fermentation and enzymatic
hydrolysis were the most examined techniques. They are efficiently utilized and a lot
more affordable than previous techniques [
13
]. Various articles refer to fermentation using
bacteria for exine dissolution such as lactic acid bacteria, Apilactobacillus kunkeei strains, and
Hanseniaspora uvarum [
18
–
20
]. Enzymatic treatment is a valuable technique with promising
results compared to fermentation as there are numerous enzymatic products commercially
available at reasonable prices such as some papain, protamex
TM
, protease, neutral protease,
cellulose, hemicellulose, or pectinase that allow the breaking of bee pollen wall down [
13
].
It was reported that proteases modified protein content by around 13–18%, phenolics
by 83–86%, and flavonoids by 85–96%, and antioxidant activity up to 68%, as well as
increasing all-important amino acids quantity. Protamex was the most efficient enzyme.
According to Zuluaga-Domínguez et al., the enzymatic hydrolysis could be performed by
the addition of the enzyme to the bee pollen- aqueous suspension at a stable temperature,
pH, and constant stirring (200 rpm) for 4 h. The enzymatic hydrolysis stopped by boiling
the suspension for 2 min [21].
When pollen reaches the gastrointestinal tract, the grains swell due to absorption of
water and activation of the enzymes. The components of pollen grain walls (pigments,
enzymes, and allergens) are diffused in the acid medium of the stomach. The inner layer of
the grain wall protrudes outside, forming a germination tube shape. Pollen grains break
and deliver starch grains that are coated by protein lamella Digestion of pollen proteins,
carbohydrates, and lipids occurs under the control of gastrointestinal (GI) enzymes. Fatty
acids, amino acids, vitamins, and sugars undergo normal desorption processes. Pollen can
enter blood flow directly from the GI tract [22].
Bee pollen is taken orally and is suitable for both children and adults. One dose is
noted to be 3–5 teaspoons for adults and 1–2 teaspoons for children, as a teaspoon is
7.5 g
of pollen. Using small doses of bee pollen with other medications is advised in chronic
ailments [10].
4. Bee Pollen Effect on Metabolic Syndrome Disorders
Metabolic syndrome disorders are a group of ailments that raise the risk of cardiovas-
cular diseases, strokes, and diabetes. These problems lead to elevated blood pressure, hy-
perglycemia, extra visceral fats, and anomalous levels of cholesterol and triglycerides [
23
].
Eating a healthy diet is the primary way for the prevention and treatment of metabolic
syndrome disorders. Dietary components which could be promoted include low saturated
and trans fats, balanced carbohydrates, and dietary fibers [
24
]. Bee pollen is a balanced

Nutrients 2021,13, 1876 6 of 15
healthy natural supplement that can protect against metabolic syndrome disorders as
described below [25–30].
4.1. Bee Pollen Ameliorates Blood Sugar
Intestinal enzymes (
α
-amylase and
α
-glucosidase) break down polysaccharides into
glucose to be transported into body cells. Glucose levels could be altered by impairing the
activity of these enzymes [
31
].
α
-Amylase and
α
-glucosidase inhibitors can induce glycemic
control. Still, these synthetic agents have undesirable side impacts such as liver disorders,
abdominal pain, flatulence, and renal tumors, so seeking natural inhibitors is warranted to
maintain blood glucose at normal levels [
32
]. Bee pollen aqueous-ethanol extracts exhibited
significant α-amylase inhibition (IC50 4.51 mg/mL) and was more potent than the control
(acarbose) (IC
50
6.52 mg/mL). Bee pollen water extracts inhibited
α
-glucosidase with the
lowest IC
50
0.60 mg/mL compared to IC
50
11.30 mg/mL of the control (acarbose) [
28
].
This revealed that bee pollen could act as a natural
α
-glucosidase inhibitor to ameliorates
blood sugar.
4.2. Bee Pollen Amends Diabetic Testicular-Pituitary System Dysfunction
Testicular dysfunction, impotence, and reduced fertility are symptoms manifested in
diabetic males and are correlated to decreased sperm count and defective sperm production,
reverse ejaculation, and erectile dysfunction [
33
]. Oxidative stress may relate to testicular
dysfunction and deterioration in animal models with diabetes [
34
]. Therefore, the quest
for diabetes treatment and its related sexual dysfunction in males with natural antioxidant
sources is a beneficial field of research [
35
]. When streptozotocin was induced to diabetic
male Wister rats orally following bee pollen and/or date palm pollen suspension intake at
dose levels of 100 mg/kg body weight daily for four weeks, significant improvements were
observed both for blood glucose levels and testicular nitric oxide (NO), and malondialde-
hyde (MDA) levels. Body weight, testis, serum insulin levels, pancreas weight, luteinizing
hormone (LH), testosterone, follicle-stimulating hormone (FSH), sperm motility, and viabil-
ity are all parameters that were interestingly improved compared to the control diabetic
group. Bee pollen and/or date palm pollen suspension treatment enhanced the testicular
antioxidant defense systems as observed by the elevated levels of glutathione-S-transferase
(GST), glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GP
X
).
Histopathological analysis showed an improvement in spermatogenesis characterized
by an increase in spermatids, spermatogonia, spermatocytes, and Sertoli cells compared
with the diabetic control. In addition, pancreatic cells appeared normal. Thus, it can be
hypothesized that suspensions of bee pollen and date palm pollen have a protective role
against diabetes-induced dysfunction of the pituitary testicular system and the related
adverse changes [29].
4.3. Bee Pollen Prevents Obesity and Combats Liver Disorders
Obesity is a health problem, and nonalcoholic fatty liver (NAFLD) is a common
ailment belonged to obesity. It is characterized by the accumulation of fat in the liver cells,
and the hepatocytes [
36
]. The latest evidence has shown that phenolic compounds can
enhance the absorption of nutrients, lipid metabolism, and weight loss [
37
]. Bee pollen
is rich in phenolic compounds that could play a crucial role in avoiding obesity and its
secondary health complications [
38
]. Obese mice were supplemented for eight weeks with
Schisandra chinensis bee pollen extracts (SCPE) at 7.86 and 15.72 g/kg body weight. The
body weight was decreased by 18.23% and 19.37%, respectively, and lipid accumulation in
the liver and serum was declined. SCPE inhibited the production of NAFLD by impacting
the expression of the liver-X receptor alpha (LXR-
α
), sterol regulatory element-binding
protein 1 (SREBP-1c), and the fatty acid synthase (FAS) gene [38].
In vivo
studies have shown that pectic bee pollen polysaccharides (homogalacturonan,
arabinogalactan, and rhamnogalacturonan I domains) in obese mice significantly improved
hepatic steatosis and triglyceride by increasing hepatic autophagy via an adenosine 5
0
-

Nutrients 2021,13, 1876 7 of 15
monophosphate-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR)
mediated signaling pathways and lipase expression [
39
]. Another study showed that
supplementing diets with ethanolic extract of bee pollen in doses of 0.1 g/kg body mass
and 1 g/kg body mass ameliorates the degenerative changes and liver steatosis in 56 female
mice via a decrease of total cholesterol (TC) by 31% and 35%, and the level of low-density
lipoproteins by 67% and 90%, respectively [
30
]. The rats were given chestnut bee pollen
(200 and 400 mg/kg/day) orally for seven days compared to the positive control (silibinin,
50 mg/kg/day, i.p.). Bee pollen protects the hepatocytes from oxidative stress and aids the
recovery of the liver damage induced by CCI4toxicity [40].
For 12 days, the rats were fed intragastrically different doses of ethanolic extract of
SCPE (400, 800, 1200 mg/kg/day) and vitamin C (400 mg/kg/day, positive control group).
A single intraperitoneal cisplatin injection (8 mg/kg) was used to cause liver and kidney
injury on the seventh day. As a result of high pollen doses, the activities of serum aspartate
aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and
creatinine (Cr) decreased. The pollen reduced cisplatin-induced liver and kidney damage
while increasing the activities of SOD, catalase (CAT), and GSH, and decreasing MDA and
inducible nitric oxide synthase (iNOS) [41].
4.4. Cardio-Protective Effects of Bee Pollen
In patients with acute myocardial infarction, antioxidant therapy may be an effective
tool for avoiding cardiac damage and myocardial dysfunction [
42
]. Research was planned
to determine the cardio-protective effects of Schisandra chinensis bee pollen extract (SCBPE)
in rats in this manner. SCBPE (600, 1200, 1800 mg/kg/day) and Danshen dropping pills
(270 mg/kg/day) were given intragastrically to rats for thirty days, after which they were
injected with isoprenaline (ISO). On the 29
th
and 30
th
days, ISO (65 mg/kg/day) was
injected subcutaneously. Medium and large doses of SCBPE reduced serum aspartate
transaminase, lactate dehydrogenase. Although can the development of SOD, GP
X
, and
CAT in myocardium. The SCBPE treated groups had less heart damage than the model
group, according to histopathological images of rat hearts. Among the groups with nearly
safe cardiac fibers, the high-dose SCBPE community had the least inflammatory infiltration.
The increased dose of SCBPE displayed the protein expression of nuclear factor-erythroid
2-related factor 2(Nrf-2), heme oxygenase-1 (HO-1), and B-cell lymphoma 2 (Bcl2) in the
heart. Whereas, BAX’s expression was decreased compared to the model group. The heart
protein expression of Nrf-2, HO-1, and Bcl2 was increased when the SCBPE dose was
increased. BAX expression, on the other hand, was reduced when compared to the model
population [26]. This confirmed the cardio-protective effect of bee pollen.
Atherosclerosis is a process of inflammation and oxidation in arteries modulated
by high serum lipid levels, oxidative stress, and blood clotting with a disrupted equi-
librium of renin-angiotensin-aldosterone systems. Fifty-four females of ApoE-Knockout
mice were supplemented for 16 weeks with diets enriched in bee pollen ethanolic extract
(dose
0.1 g/kg
body mass). Significant decrease in the levels of TC, asymmetric di-methyl-
arginine (ADMA), oxidized low-density lipoprotein (ox-LDL), angiotensin-converting en-
zyme (ACE), and angiotensin-
Π
were observed. Antioxidant metabolites namely polyphe-
nols and flavonoids (rutin, myricetin, quercetin, isorhamnetin, kaempferol, gallic acid,
cinnamic acid, hydroxycinnamic acid, ferulic acid, and caffeic acid) were identified in
the extract and believed to limit the growth of atherosclerotic plaques by different mech-
anisms [
43
]. Quercetin and catechin have inhibited platelet induction and increase NO
synthesis [
44
]. Catechin, trans-resveratrol, and caffeic acid can decrease the incidence of
atherosclerosis by lowering endothelin-1 expression, which could affect endothelial func-
tion [
45
]. The results showed that bee pollen-enriched diets could prevent atherosclerosis.
4.5. Bee Pollen Lowers Uric Acid
Five fractions were obtained after rape bee pollen was extracted with n-butanol and
purified by polyamide resin and AB-8 resin in a study to assess the hypouricemic effect

Nutrients 2021,13, 1876 8 of 15
of rape bee pollen from Qinghai, China. Fraction 5 had the highest inhibition
in vitro
(IC
50
= 0.21
±
0.02 mg/mL). Further purification of fraction 5, fraction 5
0
had lower uric
acid in serum in vivo and reduced BUN, Cr levels, and hepatic XO. Additionally, fraction
5
0
had increased CAT activity (chloramphenicol acetyltransferase) and GSH content in
hyperuricemic mice. HPLC-ESI-QTOF-MS/MS analysis showed that fraction 5
0
contained
higher coumaroylspermidines content (N,N”-di-p-coumaroylspermidine) (Figure 3), im-
plying that spermidines can be considered the efficient compounds with high antioxidant
ability. Other identified compounds were flavonoid glycosides, especially quercetin and
kaempferol glycosides. As for diet, taking 6.25–7.5 g of rape bee pollen per day is a good
supplement for hyperuricemia prevention. This study showed that rape bee pollen could
serve as a potential anti-hyperuricemia agent with dual xanthine oxidase inhibitory effect
and antioxidant activity with a potential clinical approach [46].
5. Bee Pollen Rectifies the Effects of Toxins
Propoxur (2-isopropoxyphenyl methylcarbamate) is a broad-spectrum carbamate
insecticide that acts against pests in food and is used against bugs, millipedes, fleas,
ants, mosquitoes, and cockroaches. It is toxic due to its ability to inhibit cholinesterase
enzymes [
47
,
48
]. Propoxur induces oxidative damage by creating free radicals and lipid
peroxidation [
49
], as part of its pathophysiological pathways. Propoxur was found to cause
negative variations in most of the body’s biological markers such as urine metabolites
and oxidative stress [
27
,
50
]. Twenty-eight female Wistar rats were divided into 4 equal
groups. Group 1 served as the control group, whereas groups 2–4 received bee pollen
extracts of 100 mg/kg/bw/day, propoxur of 20 mg/kg/bw/day, and bee pollen extracts
of 100 mg/kg/bw/day plus propoxur extracts of 20 mg/kg/bw/day, respectively, for
14 days. Significant improvements were observed in oxidative stress parameters (SOD,
CAT, and GP
X
) for groups receiving bee pollen combined with propoxur and similar to the
control group [
27
]. Bee pollen could ameliorate the harmful effects because of the presence
of antioxidant compounds (phenolic compounds and non-phenolic antioxidants (amino
acids), which have been considered free radical quenchers [51].
Fluoride (F) anion has harmful effects when consumed repeatedly. Fluorosis is a
condition where people have utilized contaminated water, food, and dental materials
to a degree at which fluorine intake has exceeded safe doses [
52
]. Supplementation of
bee pollen to male albino rats reduced the fluorine toxicity and enhanced antioxidant
functions as MDA level was decreased. Furthermore, SOD activity and GSH levels in the
brain and blood were significantly increased. Alkaline phosphatase activity (ALP), urea,
sodium, potassium, and Cr levels were decreased. Bee pollen increased serum levels of
total protein, magnesium, calcium, and phosphorous compared to groups that were treated
with sole fluoride [
53
]. Studies have shown that bee pollen could significantly reduce
fluorine toxicity.
6. Effects of Bee Pollen on Bone Metabolism
Bee pollen has been shown to have an anabolic effect on bone components. When
bone tissues were grown for 48 h in a medium containing water, vehicle, or ethanol
solubilized extracts (10, 100, and 1000 g/mL medium) from Cistus ladaniferus bee pollen,
this was readily apparent. The content of calcium was increased in femoral diaphyseal
and metaphyseal tissues in the presence of water (100 and 1000
µ
g/mL) and ethanol
(
1000 µg/mL
) bee pollen extracts. An increase in ALP (one of the enzymes participating
in the mineralization of bone) and DNA content was observed
in vitro
in the presence of
water solubilized extracts (100 and 1000
µ
g/mL). Orally administrated water solubilized
bee pollen extracts (5 and 10 mg/100 g body weight) once daily for seven days can also
increase calcium content in diaphyseal or metaphyseal tissues [
54
]. DNA and alkaline
phosphatase could be increased significantly after oral administration of water solubilized
extracts
in vivo
and in streptozotocin-diabetic rats [
54
,
55
]. Additionally, it is healthy to
administer diets with vitamin D to maintain calcium homeostasis, as the primary function

Nutrients 2021,13, 1876 9 of 15
of vitamin D is to improve intestinal calcium absorption. Interestingly enough, one of the
bee pollen’s active metabolites is vitamin D [56].
7. Bee Pollen Regulates the Ovarian Functions
Bee pollen contributed to both secretion and apoptotic activities of ovarian functions
of clinically healthy 40-day-old female Wistar rats. The animals were divided randomly
into three groups of 5 animals each. The groups either received commercial granular feed
mixture (FM) alone (control, group 1) or were supplemented with unifloral rapeseed bee
pollen in doses of 3 kg/1000 kg mixture for group 2 and 5 kg/1000 kg mixture for group 3
for 90 days. A significant decrease in insulin-like growth factor 1 (IGF-1) release and an
increase in progesterone and estradiol secretion in group 3 but not in group 2 was observed.
An increase in BCl-2 was also detected in group 2 but not in group 3. Ovarian BAX was
observed at higher levels in groups 2 and 3. The up-regulation of caspase-3 was detected
in group 3 but not in group 2. Medium and high doses of bee pollen can regulate ovarian
secretions and promote BAX (pro-apoptotic) and BCL-2 (blocker of BAX, anti-apoptotic)
molecules. From these results, bee pollen supplementation was recognized as an effective
regulator of animal ovarian functions [57].
In an
in vitro
model, adding 10 ng/mL bee pollen to porcine ovarian granulosa cells
significantly reduced IGF-I release. Progesterone release, proliferating cell nuclear antigen
(PCNA) expression (proliferation markers), and apoptosis (caspase-3) were not affected by
bee pollen doses of 100 and 1000 ng/mL [
58
]. It can be seen that both
in vivo
and
in vitro
studies of bee pollen have shown a regulatory effect on ovarian functions.
8. Bee Pollen Affects Intestinal Morphology and Function
Forty Wistar albino rats were divided randomly into 4 groups of 10 rats each. The
pollen-free control group (C) received a basic diet; group L received a diet with an additional
0.2% (w/w); group M an additional 0.5% (w/w) and group H an additional 0.75% (w/w)
bee pollen Brassica napus L. for 90 days. The relative volume of the structures of the
intestinal mucosa (relative volume of epithelium and lamina propria), length of villi,
and development of Lieberkühn crypts were assessed. Quantitative morphological and
histological measures showed a significant increase in the relative epithelium volume and
a decrease in the volume of jejunum connective tissue in groups M and H compared to
the control. The length of the intestinal villi increased significantly in all study groups.
The depth of Lieberkühn increased significantly only for groups L and M but decreased
in group H. Longer and more compact jejunum villi enable more surface area to digest
and absorb the nutrients at an expanded mucosal surface. Therefore, bee pollen has
a concentration-dependent effect on the development of the small intestine and seems
beneficial to its function [59].
In another study, 144 commercial broilers chickens were divided into two groups. One
served as a control group that received a basic diet, and the second received a basic diet
supplemented with additional 1.5% bee pollen for six weeks. The digestive organs from 12
randomly selected broilers were collected each week. In the early developmental stages in
broilers, especially for the first two weeks, the duodenum, jejunum, and ileum villi of the
small intestine were longer and thickener in the bee pollen group. Additionally, the density
and depth of glands in the small intestine increased in the bee pollen supplemented group.
From these results, we can conclude that medium supplementation (0.5% and 1.5%) of bee
pollen to the diet can enhance the early development of the small intestine and facilitate
absorption and digestion functions [
60
]. The supplementation of bee pollen (20 g/kg)
to broiler Chickens impacted their intestinal morphology and absorption. A significant
difference in the villus height to crypt depth ratio was observed by the 42
nd
day of the
feeding [61].

Nutrients 2021,13, 1876 10 of 15
9. Bee Pollen Acts as an Immunostimulant and Anti-Allergic Agent
The immunoprotective effect of bee pollen has been confirmed by many studies. De
Oliveira with his group conducted a study to determine the effects of dietary inclusion
of bee pollen on IgG (immunoglobulin G) and IgM (immunoglobulin M) titers and the
weight of lymph organs (bursa, thymus, and spleen) in broilers aged 21 and 42 days. Four
hundred birds were used with 4 treatments (0, 0.5, 1, and 1.5% of bee pollen feed inclusion)
and five replicates in a fully randomized model. With bee pollen dietary inclusion, IgM
titers increased linearly at 21 days, and thymus weight increased at 42 days, indicating that
up to 1.5 percent bee pollen could be included in broiler feeds until the age of 21 days to
improve bird immunity [62].
To assess the immunoprotective effects of bee pollen against food-borne mycotoxins
(aflatoxins), the Elbialy group used rat models (32 male Wistar rats (120–150 g) where the
animals were fed a diet containing aflatoxins in the presence or absence of bee pollen for
30 days. Rats were divided into 4 groups, Group 1; control group, Group 2; aflatoxins
(3 mg/kg basal diet), Group 3; bee pollen (20 g/kg basal diet), and Group 4; aflatoxins
plus bee pollen in a basal diet. Bee pollen ingestion here led to significant increases
in the proliferation of lymphocytes ex vivo. Such findings could be attributed simply
to the presence of amino acids, vitamins, and essential minerals in bee pollen that can
enhance immune cell proliferation [
63
]. Polysaccharides are also another essential bee
pollen component that can stimulate the formation of T-lymphocytes [
64
]. The use of
bee pollen decreased spleen H
2
O
2
levels, increased GSH output, and maintained normal
NO formation levels. The presence of phenolics and flavonoids in bee pollen showed an
antioxidant effect that can maintain normal NO levels [
28
]. Bee pollen’s immunoprotective
effect was also reported in terms of increased total serum protein and globulin levels,
restored healthy neutrophil polymorphonuclear leukocyte (PMN)/lymphocyte ratio, and
increased phagocytic activity of PMN [65].
Bee pollen also has an anti-allergy action. Bee pollen inhibited degranulation of mast
cells
in vitro
when added to cells at the time of IgE (immunoglobulin E) sensitization.
Varying concentrations of bee pollen inhibited the binding of IgE to mast cells without
influencing the expression of Fc
ε
RI (the high-affinity receptor for the Fc region of IgE).
In line with this, bee pollen at small doses (0.1–1
µ
g/mL) inhibited TNF (tumor necrosis
factor) production from mast cells. Another mechanism of action was that bee pollen
inhibited the signal transduction pathways as observed in bone marrow-derived mast cells
(BMMC)
in vitro
[
66
]. In the murine model of OVA-induced allergy, bee pollen phenolic
extract reduced immunological parameters. Bee pollen phenolic extract inhibits paw edema
caused by OVA. This was explained by the bee pollen inhibition of inflammatory mediators’
production after mast cell activation by allergens. The findings also showed a decrease
in IgE and IgG1 production. Both cell migration to the lung and eosinophil activation
was inhibited by bee pollen phenolic extract, which slightly shielded the mice against
anaphylactic shock. These observations were explained by the presence of myricetin (one
of the flavonoids in bee pollen phenolic extract) as myricetin was studied in the murine
model and showed a specific decrease of IgE and IgG1
,
and OVA production. It also inhibits
cell migration to the pulmonary cavity [67].
Healthcare practitioners should be aware of the danger of allergic reactions to bee
pollen consumption, particularly in patients who are allergic to weed pollens. In the
case study; the patient who had allergic rhinitis and sensitivity to weed pollens from the
Compositae family, such as mugwort, ragweed, chrysanthemum, and dandelion, tested
positive for bee pollen using Enzyme-linked immunosorbent assay (ELISA) inhibition.
These results revealed that the bee pollen extracts had considerable cross-reactivity with
chrysanthemum and dandelion pollen, which could imply a significant anaphylactic
reaction [
68
,
69
]. Fungi like Aspergillus and Cladosporium identified in bee pollen may
have also contributed to the allergic reactions [70].

Nutrients 2021,13, 1876 11 of 15
10. Bee Pollen as a Useful Agent for Cognitive Dysfunction
Liao and his colleagues looked into the impact of bee pollen on scopolamine-induced
cognitive impairment. They used the Morris water maze test, the passive avoidance test,
and the Y-maze test. In the passive avoidance test, bee pollen extract (100 or 300 mg/kg
per os (p.o.)) appeared to reverse scopolamine-induced cognitive impairment, improve
spontaneous alternation in the Y-maze test, and increase swimming time in the target area
in the Morris water maze test. The effects of bee pollen on hippocampus memory-related
signaling molecules were assessed using Western blotting. The phosphorylation levels of
the extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate (cAMP),
response element-binding protein (CREB), protein kinase B (Akt), glycogen synthase
kinase-3
β
(GSK-3
β
), the expression levels of brain-derived neurotrophic factor (BDNF),
and the tissue plasminogen activator (tPA) in the hippocampus were increased in response
to the treatment with bee pollen extract (100 or 300 mg/kg, p.o.). They revealed that
cognitive function was improved due to conversion of pro-BDNF to mature BDNF by
tPA, possibly via the ERK-CREB pathway or AKT-GSK-3
β
signaling pathway. Since bee
pollen extracts contain many flavonoids or phenolic acids, lipids, minerals, vitamins, and
amino acids, the presence of active metabolites was responsible for improving cognitive
function. The antioxidants quercetin, luteolin, and apigenin have been shown to improve
cognitive function. The exact active metabolite (s) or mechanism of action, however, is
unknown. [71].
11. Bee Pollen as a Functional Food
The expression of ‘functional food’ can describe a food that has an additional role
in terms of health promotion or disease prevention by incorporating one or more of the
existing components or even by illustrating the synergistic activity between similar or new
biomolecules that can be produced. The functional food industry, food supplements, and
other beverages have experienced rapid growth in the last few years. Functional foods
are designed to have physiological benefits and/or minimize the risk of chronic disease
beyond nutritional functions and serve as a part of the daily diet [72].
The demands of consumers in the field of food production have shifted dramatically.
Food today is used to not only satisfy hunger and provide essential nutrients for humans
but also to prevent nutrition-related diseases and increase physical and mental activity
among consumers. Functional foods are extremely effective at improving body functions
and lowering the risk of certain diseases, such as cholesterol-lowering agents, and curing
certain diseases [73].
Bee pollen is an alternative natural product that is at the forefront of research and
can act as a functional food. Bee pollen has a great potential in nutritional and biomedical
applications (Figure 4), which has allowed it to be one of the main functional food products.
For instance, adding grounded bee pollen (0.5, 1.0, 2.5 and 3.0%, w/v) to yogurts from
cow, goat, and sheep milk resulted in a food matrix with a higher antioxidant capacity
and total phenolic content
in vitro
, in addition to improving the taste, smell, appearance,
and cohesion of yogurt. It also improved surface and interface material because of the
formation of active lipid-linked protein [74].
The addition of multiflora bee pollen to gluten-free bread improved the physical and
chemical properties of the loaves produced. The results of the study showed that adding bee
pollen (1–5%) to the dough system resulted in a well-leavened dough system with no major
issues with dough machinability or gassing capability during fermentation. As compared
to the control, the pollen-fortified breads had higher length, smoother, homogeneous
qualities, finer crumb grain, desirable crust color, and lower staling kinetics. Sensory
acceptability was observed in all pollen-enriched bread [75].

Nutrients 2021,13, 1876 12 of 15
Nutrients 2021, 13, x FOR PEER REVIEW 12 of 15
mogeneous qualities, finer crumb grain, desirable crust color, and lower staling kinetics.
Sensory acceptability was observed in all pollen-enriched bread [75].
Figure 4. Bee pollen improves different functions of the human body.
12. Conclusions
Global interest and the increase of consumer awareness, especially regarding the
nutritional and medicinal value of what they eat or drink, awaken the concept of re-
turning to natural products, especially bee products. Bee pollen has had attracted a big
deal of focus from the food supplement and food processing industries due to its high
health value. The involvement of bee pollen in various formulations i.e., pills, tablets,
capsules, and powders, helped to cover many customers’ needs. Bee pollen has served to
prevent and treat many chronic diseases, especially metabolic disorders. It has a preven-
tive role in various ailments such as diabetes, obesity, hyper-dyslipidemia, and heart
complications. Bee pollen was recommended as a daily supplement to maintain a healthy
weight. Additionally, bee pollen as a functional food can be used daily to protect against
heart muscle diseases and the harmful impacts of food toxins. Long-term bee pollen
consumption can improve health, foster blood circulation, delay aging, enhance immun-
ity and increase physical and mental activities. More studies on metabolic pathways and
biomedical interactions are required to establish bee pollen’s bioactivity in controlling
body functions and preventing diseases. Boosting clinical practice and encouraging the
search for bee pollen products play a significant role in fostering future innovations and
possible applications.
Author Contributions: Conceptualization, S.A.M.K. and H.R.E.-S., writing of the original draft,
M.H.E., N.Y., Z.G., A.A.A.E.-W. and S.G.M.; revision and editing of the final version, S.A.M.K.,
H.R.E.-S., M.D., L.N., S.D.S., W.C., X.Z., J.X., H.A.O. and M.-E.F.H.; supervision, S.A.M.K. and
H.R.E.-S. All authors have read and agreed to the published version of the manuscript.
Funding: This work was supported by Swedish Research links Grant VR 2016–05885.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: No new data were created or analyzed in this study. Data sharing is
not applicable to this article.
Figure 4. Bee pollen improves different functions of the human body.
12. Conclusions
Global interest and the increase of consumer awareness, especially regarding the
nutritional and medicinal value of what they eat or drink, awaken the concept of returning
to natural products, especially bee products. Bee pollen has had attracted a big deal of focus
from the food supplement and food processing industries due to its high health value. The
involvement of bee pollen in various formulations i.e., pills, tablets, capsules, and powders,
helped to cover many customers’ needs. Bee pollen has served to prevent and treat many
chronic diseases, especially metabolic disorders. It has a preventive role in various ailments
such as diabetes, obesity, hyper-dyslipidemia, and heart complications. Bee pollen was
recommended as a daily supplement to maintain a healthy weight. Additionally, bee
pollen as a functional food can be used daily to protect against heart muscle diseases
and the harmful impacts of food toxins. Long-term bee pollen consumption can improve
health, foster blood circulation, delay aging, enhance immunity and increase physical and
mental activities. More studies on metabolic pathways and biomedical interactions are
required to establish bee pollen’s bioactivity in controlling body functions and preventing
diseases. Boosting clinical practice and encouraging the search for bee pollen products play
a significant role in fostering future innovations and possible applications.
Author Contributions:
Conceptualization, S.A.M.K. and H.R.E.-S., writing of the original draft,
M.H.E., N.Y., Z.G., A.A.A.E.-W. and S.G.M.; revision and editing of the final version, S.A.M.K.,
H.R.E.-S., M.D., L.N., S.D.S., W.C., X.Z., J.X., H.A.O. and M.-E.F.H.; supervision, S.A.M.K. and
H.R.E.-S. All authors have read and agreed to the published version of the manuscript.
Funding: This work was supported by Swedish Research links Grant VR 2016–05885.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement:
No new data were created or analyzed in this study. Data sharing is
not applicable to this article.
Acknowledgments:
Authors are very grateful to the Swedish Research links Grant VR 2016–05885
and the Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, Sweden,
for the financial support.
Conflicts of Interest: The authors declare no conflict of interest.

Nutrients 2021,13, 1876 13 of 15
References
1.
Abdelnour, S.A.; Abd El-Hack, M.E.; Alagawany, M.; Farag, M.R.; Elnesr, S.S. Beneficial impacts of bee pollen in animal
production, reproduction and health. J. Anim. Physiol. Anim. Nutr. 2019,103, 477–484. [CrossRef]
2.
Mauriello, G.; De Prisco, A.; Di Prisco, G.; La Storia, A.; Caprio, E. Microbial characterization of bee pollen from the Vesuvius area
collected by using three different traps. PLoS ONE 2017,12, e0183208. [CrossRef] [PubMed]
3.
Li, Q.Q.; Wang, K.; Marcucci, M.C.; Sawaya, A.C.H.F.; Hu, L.; Xue, X.F.; Wu, L.M.; Hu, F.L. Nutrient-rich bee pollen: A treasure
trove of active natural metabolites. J. Funct. Foods 2018,49, 472–484. [CrossRef]
4.
Mayda, N.; Özkök, A.; Ecem Bayram, N.; Gerçek, Y.C.; Sorkun, K. Bee bread and bee pollen of different plant sources: Deter-
mination of phenolic content, antioxidant activity, fatty acid and element profiles. J. Food Meas. Charact.
2020
,14, 1795–1809.
[CrossRef]
5.
Liolios, V.; Tananaki, C.; Papaioannou, A.; Kanelis, D.; Rodopoulou, M.A.; Argena, N. Mineral content in monofloral bee pollen:
Investigation of the effect of the botanical and geographical origin. J. Food Meas. Charact. 2019,13, 1674–1682. [CrossRef]
6.
Thakur, M.; Nanda, V. Composition and functionality of bee pollen: A review. Trends Food Sci. Technol.
2020
,98, 82–106. [CrossRef]
7.
Hou, Y.; Yin, Y.; Wu, G. Dietary essentiality of “nutritionally non-essential amino acids” for animals and humans. Exp. Biol. Med.
2015,240, 997–1007. [CrossRef] [PubMed]
8.
Almeida-Muradian, L.B.; Pamplona, L.C.; Coimbra, S.; Barth, O.M. Chemical composition and botanical evaluation of dried bee
pollen pellets. J. Food Compos. Anal. 2005,18, 105–111. [CrossRef]
9. Szczesna, T. Long-chain fatty acids composition of honeybee-collected pollen. J. Apic. Sci. 2006,50, 65–79.
10.
Komosinska-Vassev, K.; Olczyk, P.; Ka´zmierczak, J.; Mencner, L.; Olczyk, K. Bee pollen: Chemical composition and therapeutic
application. Evid. Based Complement. Altern. Med. 2015,2015. [CrossRef]
11.
Campos, M.G.R.; Bogdanov, S.; de Almeida-Muradian, L.B.; Szczesna, T.; Mancebo, Y.; Frigerio, C.; Ferreira, F. Pollen composition
and standardisation of analytical methods. J. Apic. Res. 2008,47, 154–161. [CrossRef]
12.
Campos, M.G.R.; Frigerio, C.; Lopes, J.; Bogdanov, S. What is the future of bee-pollen? J. ApiProduct ApiMedical Sci.
2010
,2,
131–144. [CrossRef]
13.
Dong, J.; Gao, K.; Wang, K.; Xu, X.; Zhang, H. Cell wall disruption of rape bee pollen treated with combination of protamex
hydrolysis and ultrasonication. Food Res. Int. 2015,75, 123–130. [CrossRef] [PubMed]
14.
Uddin, M.J.; Liyanage, S.; Abidi, N.; Gill, H.S. Physical and biochemical characterization of chemically treated pollen shells for
potential use in oral delivery of therapeutics. J. Pharm. Sci. 2018,107, 3047–3059. [CrossRef] [PubMed]
15. Wu, W.; Qiao, J.; Xiao, X.; Kong, L.; Dong, J.; Zhang, H. In vitro and In vivo digestion comparison of bee pollen with or without
wall-disruption. J. Sci. Food Agric. 2021,101, 2744–2755. [CrossRef]
16.
Xu, X.; Sun, L.; Dong, J.; Zhang, H. Breaking the cells of rape bee pollen and consecutive extraction of functional oil with
supercritical carbon dioxide. Innov. Food Sci. Emerg. Technol. 2009,10, 42–46. [CrossRef]
17.
Wu, W.; Wang, K.; Qiao, J.; Dong, J.; Li, Z.; Zhang, H. Improving nutrient release of wall-disrupted bee pollen with a combination
of ultrasonication and high shear technique. J. Sci. Food Agric. 2019,99, 564–575. [CrossRef]
18.
Filannino, P.; Di Cagno, R.; Vincentini, O.; Pinto, D.; Polo, A.; Maialetti, F.; Porrelli, A.; Gobbetti, M. Nutrients bioaccessibility and
anti-inflammatory features of fermented bee pollen: A comprehensive investigation. Front. Microbiol.
2021
,12, 622091–622101.
[CrossRef]
19.
Filannino, P.; Di Cagno, R.; Gambacorta, G.; Tlais, A.Z.A.; Cantatore, V.; Gobbetti, M. Volatilome and bioaccessible phenolics
profiles in lab-scale fermented bee pollen. Foods 2021,10, 286. [CrossRef]
20.
U
t
,
oiu, E.; Matei, F.; Toma, A.; Digu
t
,
ă, C.F.;
S
,
tefan, L.M.; Mănoiu, S.; Vrăjma
s
,
u, V.V.; Moraru, I.; Oancea, A.; Israel-Roming, F.; et al.
Bee collected pollen with enhanced health benefits, produced by fermentation with a Kombucha Consortium. Nutrients
2018
,10,
1365. [CrossRef]
21.
Zuluaga-Domínguez, C.; Castro-Mercado, L.; Cecilia Quicazán, M. Effect of enzymatic hydrolysis on structural characteristics
and bioactive composition of bee-pollen. J. Food Process. Preserv. 2019,43, e13983. [CrossRef]
22. Llnskens, H.F.; Jorde, W. Pollen as food and medicine—A review. Econ. Bot. 1997,51, 78–87. [CrossRef]
23. Grundy, S.M. Metabolic syndrome pandemic. Arterioscler. Thromb. Vasc. Biol. 2008,28, 629–636. [CrossRef]
24.
Feldeisen, S.E.; Tucker, K.L. Nutritional strategies in the prevention and treatment of metabolic syndrome. Appl. Physiol. Nutr.
Metab. 2007,32, 46–60. [CrossRef]
25.
Kosti´c, A.; Milinˇci´c, D.D.; Bara´c, M.B.; Shariati, M.A.; Teši´c, Ž.L.; Peši´c, M.B. The application of pollen as a functional food and
feed ingredient—the present and perspectives. Biomolecules 2020,10, 84. [CrossRef]
26.
Shen, Z.; Geng, Q.; Huang, H.; Yao, H.; Du, T.; Chen, L.; Wu, Z.; Miao, X.; Shi, P. Antioxidative and cardioprotective effects of
Schisandra chinensis bee pollen extract on isoprenaline-induced myocardial infarction in rats. Molecules
2019
,24, 1090. [CrossRef]
27.
Eraslan, G.; Kanbur, M.; Silici, S.; Liman, B.C.; Altınordulu, ¸S.; Sarıca, Z.S. Evaluation of protective effect of bee pollen against
propoxur toxicity in rat. Ecotoxicol. Environ. Saf. 2009,72, 931–937. [CrossRef] [PubMed]
28.
Daudu, O.M. Bee pollen extracts as potential antioxidants and inhibitors of
α
-amylase and
α
-glucosidase enzymes-
in vitro
assessment. J. Apic. Sci. 2019,63, 315–325. [CrossRef]
29.
Mohamed, N.A.; Ahmed, O.M.; Hozayen, W.G.; Ahmed, M.A. Ameliorative effects of bee pollen and date palm pollen on the
glycemic state and male sexual dysfunctions in streptozotocin-Induced diabetic wistar rats. Biomed. Pharmacother.
2018
,97, 9–18.
[CrossRef] [PubMed]

Nutrients 2021,13, 1876 14 of 15
30.
Rzepecka-Stojko, A.; Kabała-Dzik, A.; Kubina, R.; Jasik, K.; Kajor, M.; Wrze´sniok, D.; Stojko, J. Protective effect of polyphenol-rich
extract from bee pollen in a high-fat diet. Molecules 2018,23, 805. [CrossRef]
31.
Shobana, S.; Sreerama, Y.N.; Malleshi, N.G. Composition and enzyme inhibitory properties of finger millet (Eleusine coracana L.)
seed coat phenolics: Mode of inhibition of α-glucosidase and pancreatic amylase. Food Chem. 2009,115, 1268–1273. [CrossRef]
32.
Matsui, T.; Ueda, T.; Oki, T.; Sugita, K.; Terahara, N.; Matsumoto, K.
α
-Glucosidase inhibitory action of natural acylated
anthocyanins. 1. Survey of natural pigments with potent inhibitory activity. J. Agric. Food Chem.
2001
,49, 1948–1951. [CrossRef]
[PubMed]
33.
La Vignera, S.; Condorelli, R.; Vicari, E.; D’Agata, R.; Calogero, A.E. Diabetes mellitus and sperm parameters. J. Androl.
2012
,33,
145–153. [CrossRef] [PubMed]
34.
Shrilatha, B. Early oxidative stress in testis and epididymal sperm in streptozotocin-induced diabetic mice: Its progression and
genotoxic consequences. Reprod. Toxicol. 2007,23, 578–587. [CrossRef]
35.
Chauhan, N.S.; Sharma, V.; Dixit, V.K.; Thakur, M. A review on plants used for improvement of sexual performance and virility.
Biomed Res. Int. 2014,2014. [CrossRef]
36.
Luo, Y.; Lin, H. Inflammation initiates a vicious cycle between obesity and nonalcoholic fatty liver disease. Immunity Inflamm. Dis.
2021,9, 59–73. [CrossRef]
37.
Chen, G.; Xie, M.; Dai, Z.; Wan, P.; Ye, H.; Zeng, X.; Sun, Y. Kudingcha and fuzhuan brick tea prevent obesity and modulate gut
microbiota in high-fat diet fed mice. Mol. Nutr. Food Res. 2018,62, 1700485–1700495. [CrossRef]
38. Cheng, N.; Chen, S.; Liu, X.; Zhao, H.; Cao, W. Impact of schisandrachinensis bee pollen on nonalcoholic fatty liver disease and
gut microbiota in highfat diet induced obese mice. Nutrients 2019,11, 346. [CrossRef]
39.
Li, X.; Gong, H.; Yang, S.; Yang, L.; Fan, Y.; Zhou, Y. Pectic bee pollen polysaccharide from Rosa rugosa alleviates diet-induced
hepatic steatosis and insulin resistance via induction of AMPK/mTOR-mediated autophagy. Molecules
2017
,22, 699. [CrossRef]
40.
Yildiz, O.; Can, Z.; Saral, Ö.; Yulu
ˇ
g, E.; Öztürk, F.; Aliyazicio
ˇ
glu, R.; Canpolat, S.; Kolayli, S. Hepatoprotective potential of chestnut
bee pollen on carbon tetrachloride-induced hepatic damages in rats. Evid. Based Complement. Altern. Med.
2013
,2013. [CrossRef]
41.
Huang, H.; Shen, Z.; Geng, Q.; Wu, Z.; Shi, P.; Miao, X. Protective effect of Schisandra chinensis bee pollen extract on liver and
kidney injury induced by cisplatin in rats. Biomed. Pharmacother. 2017,95, 1765–1776. [CrossRef]
42.
Bagatini, M.D.; Martins, C.C.; Battisti, V.; Gasparetto, D.; Da Rosa, C.S.; Spanevello, R.M.; Ahmed, M.; Schmatz, R.; Schetinger,
M.R.C.; Morsch, V.M. Oxidative stress versus antioxidant defenses in patients with acute myocardial infarction. Heart Vessel.
2011,26, 55–63. [CrossRef]
43.
Rzepecka-Stojko, A.; Stojko, J.; Jasik, K.; Buszman, E. Anti-atherogenic activity of polyphenol-rich extract from bee pollen.
Nutrients 2017,9, 1369. [CrossRef]
44.
Pignatelli, P.; Di Santo, S.; Buchetti, B.; Sanguigni, V.; Brunelli, A.; Violi, F. Polyphenols enhance platelet nitric oxide by inhibiting
protein kinase C-dependent NADPH oxidase activation: Effect on platelet recruitment. FASEB J.
2006
,20, 1082–1089. [CrossRef]
[PubMed]
45.
Norata, G.D.; Marchesi, P.; Passamonti, S.; Pirillo, A.; Violi, F.; Catapano, A.L. Anti-inflammatory and anti-atherogenic effects of
cathechin, caffeic acid and trans-resveratrol in apolipoprotein E deficient mice. Atherosclerosis 2007,191, 265–271. [CrossRef]
46.
Wang, R.; Su, G.; Wang, L.; Xia, Q.; Liu, R.; Lu, Q.; Zhang, J. Identification and mechanism of effective components from rape
(Brassica napus L.) bee pollen on serum uric acid level and xanthine oxidase activity. J. Funct. Foods
2018
,47, 241–251. [CrossRef]
47.
Juárez-Gómez, J.; Ramírez-Silva, M.T.; Guzmán-Hernández, D.; Romero-Romo, M.; Palomar-Pardavé, M. Construction and
optimization of a novel acetylcholine ion-selective electrode and its application for trace level determination of propoxur pesticide.
J. Electrochem. Soc. 2020,167, 087501–087507. [CrossRef]
48.
Shields, J.N.; Hales, E.C.; Ranspach, L.E.; Luo, X.; Orr, S.; Runft, D.; Dombkowski, A.; Neely, M.N.; Matherly, L.H.;
Taub, J.W.; et al.
Exposure of larval zebrafish to the insecticide propoxur induced developmental delays that correlate with behavioral abnormali-
ties and altered expression of hspb9 and hspb11. Toxics 2019,7, 50. [CrossRef]
49.
El-Demerdash, F.M. Lipid peroxidation, oxidative stress and acetylcholinesterase in rat brain exposed to organophosphate and
pyrethroid insecticides. Food Chem. Toxicol. 2011,49, 1346–1352. [CrossRef]
50.
Tsitsimpikou, C.; Tzatzarakis, M.; Fragkiadaki, P.; Kovatsi, L.; Stivaktakis, P.; Kalogeraki, A.; Kouretas, D.; Tsatsakis, A.M.
Histopathological lesions, oxidative stress and genotoxic effects in liver and kidneys following long term exposure of rabbits to
diazinon and propoxur. Toxicology 2013,307, 109–114. [CrossRef]
51. Campos, M.G.; Webby, R.F.; Markham, K.R.; Mitchell, K.A.; Da Cunha, A.P. Age-induced diminution of free radical scavenging
capacity in bee pollens and the contribution of constituent flavonoids. J. Agric. Food Chem. 2003,51, 742–745. [CrossRef]
52. Ozsvath, D.L. Fluoride and environmental health: A review. Rev. Environ. Sci. Bio/Technol. 2009,8, 59–79. [CrossRef]
53.
Khalil, F.A.; El-Sheikh, N.M. The effects of dietary Egyptian propolis and bee pollen supplementation against toxicity if sodium
fluoride in rats. J. Am. Sci. 2010,11, 310–316.
54.
Yamaguchi, M.; Hamamoto, R.; Uchiyama, S.; Ishiyama, K.; Hashimoto, K. Anabolic effects of bee pollen Cistus ladaniferus extract
on bone components in the femoral-diaphyseal and-metaphyseal tissues of rats
in vitro
and
in vivo
.J. Health Sci.
2006
,52, 43–49.
[CrossRef]
55.
Yamaguchi, M.; Hamamoto, R.; Uchiyama, S.; Ishiyama, K.; Hashimoto, K. Preventive effects of bee pollen Cistus ladaniferus
extract on bone loss in streptozotocin-diabetic rats in vivo. J. Health Sci. 2007,53, 190–195. [CrossRef]

Nutrients 2021,13, 1876 15 of 15
56.
Christakos, S.; Dhawan, P.; Porta, A.; Mady, L.J.; Seth, T. Vitamin D and intestinal calcium absorption. Mol. Cell. Endocrinol.
2011
,
347, 25–29. [CrossRef]
57.
Kolesarova, A.; Bakova, Z.; Capcarova, M.; Galik, B.; Juracek, M.; Simko, M.; Toman, R.; Sirotkin, A.V. Consumption of bee pollen
affects rat ovarian functions. J. Anim. Physiol. Anim. Nutr. 2013,97, 1059–1065. [CrossRef]
58.
Adriana, K.; Capcarova, M.; Bakova, Z.; Branislav, G.; Miroslav, J.; Milan, S.; Sirotkin, A.V. The effect of bee pollen on secretion
activity, markers of proliferation and apoptosis of porcine ovarian granulosa cells
in vitro
.J. Environ. Sci. Health Part B Pestic.
Food Contam. Agric. Wastes 2011,46, 207–212. [CrossRef]
59.
Toman, R.; Hajkova, Z.; Hluchy, S. Changes in intestinal morphology of rats fed with different levels of bee pollen. Pharmacogn.
Commun. 2015,5, 261–264. [CrossRef]
60.
Wang, J.; Li, S.; Wang, Q.; Xin, B.; Wang, H. Trophic effect of bee pollen on small intestine in broiler chickens. J. Med. Food
2007
,10,
276–280. [CrossRef]
61.
Prakatur, I.; Miskulin, M.; Pavic, M.; Marjanovic, K.; Blazicevic, V.; Miskulin, I.; Domacinovic, M. Intestinal morphology in broiler
chickens. Animals 2019,9, 301. [CrossRef]
62.
De Oliveira, M.C.; Da Silva, D.M.; Loch, F.C.; Martins, P.C.; Dias, D.M.B.; Simon, G.A. Effect of bee pollen on the immunity and
tibia characteristics in broilers. Braz. J. Poult. Sci. 2013,15, 323–327. [CrossRef]
63. Calder, P.C. Branched-chain amino acids and immunity. J. Nutr. 2006,136, 288S–293S. [CrossRef] [PubMed]
64.
Stingele, F.; Corthésy, B.; Kusy, N.; Porcelli, S.A.; Kasper, D.L.; Tzianabos, A.O. Zwitterionic polysaccharides stimulate T cells
with no preferential V
β
usage and promote anergy, resulting in protection against experimental abscess formation. J. Immunol.
2004,172, 1483–1490. [CrossRef] [PubMed]
65.
El-Bialy, B.E.; Abdeen, E.E.; El-Borai, N.B.; El-Diasty, E.M. Experimental studies on some immunotoxicological aspects of
aflatoxins containing diet and protective effect of bee pollen dietary supplement. Pak. J. Biol. Sci.
2016
,19, 26–35. [CrossRef]
[PubMed]
66.
Ishikawa, Y.; Tokura, T.; Nakano, N.; Hara, M.; Niyonsaba, F.; Ushio, H.; Yamamoto, Y.; Tadokoro, T.; Okumura, K.; Ogawa,
H. Inhibitory effect of honeybee-collected pollen on mast cell degranulation
in vivo
and
in vitro
.J. Med. Food
2008
,11, 14–20.
[CrossRef] [PubMed]
67.
Medeiros, K.C.P.; Figueiredo, C.A.V.; Figueredo, T.B.; Freire, K.R.L.; Santos, F.A.R.; Alcântara-Neves, N.M.; Silva, T.M.S.;
Piuvezam, M.R. Anti-allergic effect of bee pollen phenolic extract and myricetin in ovalbumin-sensitized mice. J. Ethnopharmacol.
2008,119, 41–46. [CrossRef] [PubMed]
68. Jagdis, A.; Sussman, G. Anaphylaxis from bee pollen supplement. Cmaj 2012,184, 1167–1169. [CrossRef]
69.
Choi, J.H.; Jang, Y.S.; Oh, J.W.; Kim, C.H.; Hyun, I.G. Bee pollen-induced anaphylaxis: A case report and literature review. Allergy
Asthma Immunol. Res. 2015,7, 513–517. [CrossRef]
70.
Greenberger, P.A.; Flais, M.J. Bee pollen-induced anaphylactic reaction in an unknowingly sensitized subject. Ann. Allergy, Asthma
Immunol. 2001,86, 239–242. [CrossRef]
71.
Liao, Y.; Bae, H.J.; Zhang, J.; Kwon, Y.; Koo, B.; Jung, I.H.; Kim, H.M.; Park, J.H.; Lew, J.H.; Ryu, J.H. The ameliorating effects of
bee pollen on scopolamine-induced cognitive impairment in mice. Biol. Pharm. Bull. 2019,42, 379–388. [CrossRef]
72.
Martirosyan, D.M.; Singh, J. A new definition of functional food by FFC: What makes a new definition unique? Funct. Foods
Health Dis. 2015,5, 209–223. [CrossRef]
73. Mark-Herbert, C. Innovation of a new product category—functional foods. Technovation 2004,24, 713–719. [CrossRef]
74.
Karabagias, I.; Karabagias, V.; Gatzias, I.; Riganakos, K. Bio-functional properties of bee pollen: The case of “bee pollen yoghur.
Coatings 2018,8, 423. [CrossRef]
75.
Conte, P.; Del Caro, A.; Balestra, F.; Piga, A.; Fadda, C. Bee pollen as a functional ingredient in gluten-free bread: A physical-
chemical, technological and sensory approach. LWT 2018,90, 1–7. [CrossRef]