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Honey is rich in phenolic compounds, which act as natural antioxidants and are becoming increasingly popular because of their potential role in contributing to human health. A wide range of phenolic constituents is present in honey like quercetin, caffeic acid phenethyl ester (CAPE), acacetin, kaempferol, galangin which have promising effect in the treatment of cardiovascular diseases. Many epidemiological studies have shown that regular intake of phenolic compounds is associated with reduced risk of heart diseases. In coronary heart disease, the protective effects of phenolic compounds include mainly antithrombotic, anti-ischemic, anti-oxidant, and vasorelaxant. It is suggested that flavonoids decrease the risk of coronary heart disease by three major actions: improving coronary vasodilatation, decreasing the ability of platelets in the blood to clot, and preventing low-density lipoproteins (LDLs) from oxidizing. In this review paper, we discussed the preventive role of polyphenols of honey against cardiovascular diseases.
Khalil and Sulaiman Afr J Tradit Complement Altern Med. (2010) 7(4):315-321 315
Khalil M. I.*a,, Sulaiman S. A.**b
Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus,
16150 Kubang Kerian, Kelantan, Malaysia.
E-mail: **Corresponding author:, *
Honey is rich in phenolic compounds, which act as natural antioxidants and are becoming increasingly popular because
of their potential role in contributing to human health. A wide range of phenolic constituents is present in honey like quercetin,
caffeic acid phenethyl ester (CAPE), acacetin, kaempferol, galangin which have promising effect in the treatment of
cardiovascular diseases. Many epidemiological studies have shown that regular intake of phenolic compounds is associated with
reduced risk of heart diseases. In coronary heart disease, the protective effects of phenolic compounds include mainly
antithrombotic, anti-ischemic, anti-oxidant, and vasorelaxant. It is suggested that flavonoids decrease the risk of coronary heart
disease by three major actions: improving coronary vasodilatation, decreasing the ability of platelets in the blood to clot, and
preventing low-density lipoproteins (LDLs) from oxidizing. In this review paper, we discussed the preventive role of polyphenols
of honey against cardiovascular diseases.
Key words: Honey; Antioxidant; Polyphenols; Cardiovascular diseases
Antioxidant substances in produce and other foods may actually represent a modern-day "fountain of youth." Evidences
suggest that vitamins C and E, and beta-carotene, a precursor to vitamin A, may reduce the risk of some forms of cancer, heart
disease, strokes, and cataracts and may slow the aging process (National Honey Board, 2007). Honey is a remarkably complex
natural liquid that is reported to contain at least 181 substances (White, 1975). The composition of honey is variable and primarily
depends on the floral source; however, certain external factors may play a role also, such as seasonal and environmental factors
and processing. Honey is a supersaturated solution of sugars, of which fructose (38%) and glucose (31%) are the main
contributors. A wide range of minor constituents is also present in honey, many of which are known to have antioxidant properties
(Ferreres et al., 1992; Andrade et al., 1997; Tan et al., 1989; Cherchi et al., 1994; White and Rudyj, 1978). The antioxidant
activity of phenolic compounds might significantly contribute to the human health benefits of plant foods and beverages such as
red wine and tea (Hertog et al., 1993; Bravo, 1998; Renaud and Lorgeril, 1992; Serafini et al., 1994).
Epidemiological data and studies with animal model point to a possible protective effect of flavonoids against
cardiovascular diseases. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their
biological actions are still not completely known (Depeint et al., 2002). Many of the pharmacological properties of flavonoids can
be linked to the abilities of these compounds to inhibit enzymes involved in cell activation. In vitro experiments demonstrated the
capacity of flavonoids to modify the activity of enzymatic systems in mammals (kinases, phospholipases, ATPase,
lipooxygenases, cyclooxygenases, phosphodiesterases etc.). A correlation has also been observed in some cases between the
flavonoid structure and its enzymatic activity (Benavente-Garcı´a et al., 1997; Marchend, 2002; Yanez et al., 2004; Bravo, 1998;
Rodriguez et al., 2002; Martinez et al., 2003). Much of these effects can be attributed to the abilities of flavonoids to interact with
the nucleotide-binding sites of regulatory enzymes. Research has also shown that flavonoids are potent radical scavengers and,
thus, able to reduce many aging and degenerative events including reactive oxygen species (Benavente-Garcı´a et al., 1997).
There is more information regarding the health benefits of honey but less information is available about the antioxidant properties
of honey and its role against cardiovascular diseases. In this review, the discussion focuses on the antioxidant properties of honey
and their ability to protect cardiovascular diseases.
Antioxidant properties of honey
"Gram for gram, antioxidants in buckwheat honey equals those of fruits and vegetables," said Dr. May Berenbaum,
head of the University of Illinois' entomology department. "It packs the antioxidant power of Vitamin C in a tomato." Researchers
at the University of Illinois-Champaign/Urbana have identified the antioxidant values of 14 unifloral honeys. The antioxidative
components of honey were compared to an ascorbic acid standard. The water-soluble antioxidant content of the honey samples
varied more than 20-fold, from a high value of 4.32×10-3 eq for Illinois buckwheat honey to a low value of 21.3×10-5 eq for
Khalil and Sulaiman Afr J Tradit Complement Altern Med. (2010) 7(4):315-321 316
California button sage honey. Research showed a correlation between color and antioxidant capacity, with the darker honeys
providing the highest levels of antioxidants. With antioxidant levels reaching 4.32×10-3 meq., honey rivals those levels found in
tomatoes (2.83×10-3 meq) and sweet corn (1.36×10-3 meq). Although honey by itself may not serve as a major source of dietary
antioxidants, it demonstrates the potential for honey to play a role in providing antioxidants in a highly palatable form. Due to
honey's pleasing taste, it may be more readily consumed by individuals reluctant to ingest plant-derived antioxidants. Certainly,
compared to sucrose, which has no antioxidant value, honey can be a flavorful, supplementary source of antioxidants (National
Honey Board: Food Technology Program, cited 2009).
Honey has been found to contain several antioxidant enzymes including glucose oxidase, catalase and other antioxidant
components like ascorbic acid, flavonoids, phenolic acids, carotenoid derivatives, organic acids, Maillard reaction products,
amino acids and proteins (Beretta et al., 2005; D'Arcy, 2005; Frankel et al., 1998; Aljadi and Kamaruddin, 2004; Inoue et al.,
2005; Fahey and Stephenson, 2002; Blasa et al., 2006; Nagai et al., 2006 and Perez et al., 2007). Various polyphenols are reported
in honey. Some of the polyphenols of honey like caffeic acid, caffeic acid phenyl ester, chrysin, galangin, quercetin, acacetin,
kaempferol, pinocembrin, Pinobanksin and apigenin have evolved as promising pharmacological agents (Jaganathan and Mandal,
2009). Gheldof and Engeseth (2002) measured the antioxidative activity of honey polyphenols in vitro by comparing the oxygen
radical absorbance capacity (ORAC) with the total phenolics concentration and showed that out of 14 honey samples Buckwheat
Illinois honey have the highest value of ORAC and total phenolic content (16.95 μmol trolox equivalent/g and 796 gallic acid
equivalent/kg respectively). A significant correlation between the antioxidant activity, the phenolic content of honey and the
inhibition of the in vitro lipoprotein oxidation of human serum was found by Gheldof et al. (2003). Furthermore, in a lipid
peroxidation model system buckwheat honey showed a similar antioxidant activity as 1 mM α-tocopherol. The influence of honey
ingestion on the antioxidative capacity of plasma was tested in two studies (Schramm et al., 2003; Al-Waili, 2003). In the first
one, the subjects were given maize syrup or buckwheat honeys with a different antioxidant capacity in a dose of 1.5 g/kg body
weight. In comparison to the sugar control, honey caused an increase of both the antioxidant and the reducing serum capacity. In
the second study, humans received a diet supplemented with a daily honey of 1.2 g/kg body weight. Honey increased the body
antioxidant agents: blood vitamin C concentration by 47%, β-carotene by 3%, uric acid by 12%, and glutathione reductase by 7%.
The antioxidant activity depends on the botanical origin of honey and varies to a great extent in honeys from different botanical
sources (Baltrusaityte et al., 2007; Kücük et al., 2007 and Vela et al., 2007).
Polyphenols and heart diseases
Reactive oxygen species (ROS) are highly reactive molecules that are constantly produced by enzymatic reactions in
cells. In normal physiological conditions, ROS are produced at low levels, which are necessary for maintaining normal cell
functions, and the endogenous anti-oxidant defense systems of the body have the capacity to avert any harmful effects. However,
several established risk factors for cardiovascular disease have been linked to excessive generation of ROS, known as a state of
oxidative stress. For instance, in animal models of hiperlipidemia (Miller et al., 1998; Mugge et al., 1994), hypertension
(Morawietz et al., 2001; Zalba et al., 2000; Suzuki et al., 1995), and diabetes (Hink et al., 2001; Sano et al., 1998), elevated levels
of vascular superoxide anion production. Moreover, clinical studies have demonstrated that hypercholesterolemia and diabetes in
humans are also associated with increased vascular superoxide anion generation (Guzik et al., 2000). All these data strongly
suggest that increased oxidative stress is involved in the pathophysiology of cardiovascular disease.
Many epidemiological studies have shown that regular flavonoid intake is associated with a reduced risk of
cardiovascular diseases (Middleton et al., 2000). In the coronary heart disease, the protective effects of flavonoids include mainly
antithrombotic, antiischemic, anti-oxidant, and vasorelaxant (Jendekova et al., 2006). It is suggested that flavonoids decrease the
risk of coronary heart disease by three major actions: (A) improving coronary vasodilatation, (B) decreasing the ability of platelets
in the blood to clot and (C) preventing LDLs from oxidizing (Garc´ia and Castillo, 2008). Oxidation of low density lipoproteins is
believed to play an important role in the development of atherosclerosis (Witztum and Steinberg, 1991; Parthasarathy et al.,
1992). Oxidized low density lipoprotein cholesterol (LDL cholesterol) is taken up more readily by macrophages, which leads to
the formation of foam cells and atherosclerotic plaques (Palinski et al., 1989). Mechanisms that slow or prevent this chain of
events may decrease the risk of coronary heart disease (CHD) and stroke (Catapano, 1997). Flavonoids are a group of phenolic
compounds and are known to have antioxidant properties (Kandaswani and Middleton, 1994). They have been reported to be
scavengers of free radicals, including superoxide anions (Robak and Gryglewski, 1988), singlet oxygen (Husain et al., 1987), and
lipid peroxy-radicals (Sorata et al., 1982). In addition, flavonoids have been shown to prevent LDL cholesterol oxidation and
cytotoxicity in vitro (De Whalley et al., 1990).
According to Beretta et al. (2007), the experiments with endothelial cells fortified with the isolated fraction from native
honey enriched in antioxidants, exposed to peroxyl radicals from 1,1-diphenyl-2-picrylhydrazyl (AAPH, 10 mM) and to hydrogen
peroxide (H2O2, 50-100 microM), indicated that phenolic acids and flavonoids were the main causes of the protective effect. They
suggested that, through the synergistic action of its antioxidants, honey by reducing and removing ROS, may lower the risks and
effects of acute and chronic free radical induced pathologies in vivo.
Rakha et al. (2008) showed that natural wild honey may exert its cardioprotective and therapeutic effects against
epinephrine-induced cardiac disorders and vasomotor dysfunction directly, via its very pronounced total antioxidant capacity and
its great wealth of both enzymatic and nonenzymatic antioxidants involved in cardiovascular defense mechanisms.
Nagyova et al. (2004) also demonstrated that short-term and modest supplementation with a mixture of antioxidant
nutrients improves antioxidative capacity and reduces products of lipid peroxidation in plasma. Since a more pronounced effect
Khalil and Sulaiman Afr J Tradit Complement Altern Med. (2010) 7(4):315-321 317
was observed within the group of survivors of myocardial infarction, a recommendation of antioxidant supplements seems
appropriate for patients with a history of cardiovascular disease.
Yochum et al. (1999) demonstrated that Flavonoids, a group of phenolic compounds, are known to have antioxidant
properties. They prevent low density lipoprotein oxidation in vitro and thus may play a role in the prevention of coronary heart
disease (CHD). In 1986, in a prospective study of 34,492 postmenopausal women in Iowa, the authors examined the association
of flavonoid intake with CHD and stroke mortality. The data of this study suggested that flavonoid intake may reduce risk of
death from CHD in postmenopausal women.
Another study by Xia et al. (2003) showed that the endothelium-derived vasoconstrictor endothelin-1 was increased
after cardiopulmonary bypass in children with congenital heart defects. The study determined whether antioxidant therapy with
Salvia miltiorrhiza injection, an herb extract containing phenolic compounds, prevents the postoperative increase of endothelin-1.
They concluded that antioxidant therapy reduces myocardial damage and attenuates postoperative vasoactive mediator imbalance.
Honey polyphenols for cardiovascular diseases
Some of the polyphenols like quercetin, acacetin, caffeic acid phenethyl ester (CAPE), kaempferol, and galangin present
in honey have been reported as promising pharmaceutical drugs in the treatment of cardiovascular diseases.
In a study (Yoshizumi et al., 2001) it has been proposed that daily intake of bioflavonoids belonging to polyphenols
reduces the incidence of ischemic heart diseases (known as "French paradox"). It was hypothesized that bioflavonoids may affect
Ang II-induced MAP kinase activation in cultured rat aortic smooth muscle cells (RASMC). The findings showed that Ang II
stimulated rapid and significant activation of extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and
p38 in RASMC. Ang II-induced JNK activation was inhibited by 3,3',4',5,7-pentahydroxyflavone (quercetin), a major
bioflavonoid in foods of plant origin, whereas ERK1/2 and p38 activation by Ang II were not affected by quercetin. Ang II caused
a rapid tyrosine phosphorylation of Src homology and collagen (Shc), which was inhibited by quercetin. Quercetin also inhibited
Ang II-induced Shc.p85 association and subsequent activation of phosphatidylinositol 3-kinase (PI3-K)/Akt pathway in RASMC.
Furthermore, LY294002, a PI3-K inhibitor and a quercetin derivative, inhibited Ang II-induced JNK activation as well as Akt
phosphorylation. Finally, Ang II-induced [(3)H] leucine incorporation was abolished by both quercetin and LY294002. These
findings suggested that the preventive effect of quercetin on Ang II-induced VSMC hypertrophy are attributable, in part, to its
inhibitory effect on Shc- and PI3-K-dependent JNK activation in VSMC. Thus, inhibition of JNK by quercetin may imply its
usefulness for the treatment of cardiovascular diseases relevant to VSMC growth.
Several studies have found that chronic treatment with the dietary flavonoid quercetin lowers blood pressure and
restores endothelial dysfunction in hypertensive animal models. Spontaneously hypertensive (male) rats (SHR) and Wistar-Kyoto
(WKY) rats (5 weeks old) were treated with quercetin (10 mg/kg) or vehicle for 13 weeks. Changes in vascular expression of
eNOS, caveolin-1 and p47 were analysed by Western blot, eNOS activity by conversion of [H]arginine to L-[H]citrulline, and
NADPH oxidase activity by NADPH-enhanced chemoluminescence of lucigenin. In SHR, quercetin reduced the increase in blood
pressure and heart rate and enhanced the endothelium-dependent aortic vasodilation induced by acetylcholine, but had no effect
on the endothelium-independent response induced by nitroprusside. However, quercetin had no effect on endothelium-dependent
vasoconstriction and aortic thromboxane B2 production. Compared to WKY, SHR showed upregulated eNOS and p47 protein
expression, downregulated caveolin-1 expression, increased NADPH-induced superoxide production but, paradoxically, eNOS
activity was reduced. Chronic quercetin treatment prevented all these changes in SHR. In WKY, quercetin had no effect on blood
pressure, endothelial function or the expression or activity of the proteins analysed. Enhanced eNOS activity and decreased
NADPH oxidase-mediated superoxide anion (O2) generation associated with reduced p47 expression appear to be essential
mechanisms for the improvement of endothelial function and the antihypertensive effects of chronic quercetin (Sánchez et al.,
In another study, Carlstrom et al. (2007) showed that diets high in quercetin may decrease the risk of developing
cardiovascular disease. They tested whether quercetin delays or reduces the severity of hypertension, vascular dysfunction, or
cardiac hypertrophy in the spontaneously hypertensive rat (SHR). Normotensive, 5-wk–old SHR consumed standard (n ¼ 18) or
quercetin-supplemented diet (1.5 g quercetin/kg diet, n ¼ 22, SHR-Q) for 5 or 11 wks. Wistar Kyoto rats (WKY, n ¼ 19), fed a
standard diet, served as controls. At 16 wk, plasma quercetin, measured by HPLC, was 2.09 6 0.33 mmol/L in SHR-Q and below
assay detection limits in SHR and WKY rats. At 10 and 16 wk of age, arterial blood pressure and heart weight:body weight were
not different between SHR and SHR-Q. At 16 wk, cardiac function (echocardiography), vascular morphology (hematoxylin and
eosin staining of aortae), and resistance and conductance vessel reactivity (wire myography) were unchanged in SHR vs. SHR-Q.
Thus, a quercetin supplemented diet does not delay the onset or lessen the severity of cardiovascular complications that develop in
SHR. The efficacy of quercetin depends on its method of delivery, 15-wk–old SHR were given quercetin (10 mg/kg) once daily
via oral gavages for 4 consecutive days. Arterial blood pressure (mm Hg) was lower in gavaged SHR (148 6 5) than in SHR-Q
(162 6 2, P, 0.02) and SHR (168 6 3, P, 0.001) These data suggested that mode of delivery is a critical determinant in whether
quercetin provides cardiovascular benefits.
In another study, the effects of an oral daily dose (10 mg kg71) of the avonoid quercetin for 5 weeks in spontaneously
hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) were analysed. Quercetin induced a significant reduction in
Khalil and Sulaiman Afr J Tradit Complement Altern Med. (2010) 7(4):315-321 318
systolic (718%), diastolic (723%) and mean (721%) arterial blood pressure and heart rate (712%) in SHR but not in WKY rats.
The left ventricular weight index and the kidney weight index in vehicle-treated SHR were significantly greater than in control
WKY and these parameters were significantly reduced in quercetin-treated SHR in parallel with the reduction in systolic blood
pressure. Quercetin had no effect on the vasodilator responses to sodium nitroprusside or to the vasoconstrictor responses to
noradrenaline or KCl but enhanced the endothelium-dependent relaxation to acetylcholine (Emax=58+5% vs 78+5%, in isolated
aortae. The 24 h urinary isoprostane F2a excretion and the plasma malonyldialdehyde (MDA) levels in SHR rats were increased
as compared to WKY rats. In quercetin-treated SHR rats, both parameters were similar to those of vehicle-treated WKY. These
data demonstrated that quercetin reduces the elevated blood pressure, the cardiac and renal hypertrophy and the functional
vascular changes in SHR rats without effect on WKY. These effects were associated with a reduced oxidant status due to the
antioxidant properties of the drug (Duarte et al., 2001).
Epidemiological studies reported that quercetin, an antioxidant flavonol is associated with reduced risk of coronary
heart disease and stroke. Quercetin supplementation also reduces blood pressure in hypertensive rodents. The efficacy of
quercetin supplementation to lower blood pressure in hypertensive humans has never been evaluated. This study tested the
hypothesis that quercetin supplementation reduces blood pressure in hypertensive patients and then it has been determined
whether the antihypertensive effect of quercetin is associated with reductions in systemic oxidant stress. Men and women with
prehypertension (n ¼ 19) and stage 1 hypertension (n ¼ 22) were enrolled in a randomized, double-blind, placebo-controlled,
crossover study to test the efficacy of 730 mg quercetin/d for 28 d vs. placebo. Blood pressure (mm Hg, systolic/diastolic) at
enrollment was 137 6 2/86 6 1 in prehypertensives and 148 6 2/96 6 1 in stage 1 hypertensive subjects. Blood pressure was not
altered in prehypertensive patients after quercetin supplementation. In contrast, reductions in (P, 0.01) systolic (27 62mmHg),
diastolic (25 6 2mmHg), and mean arterial pressures (25 6 2 mm Hg) were observed in stage 1 hypertensive patients after
quercetin treatment. However, indices of oxidant stress measured in the plasma and urine were not affected by quercetin. These
data showed that quercetin supplementation reduces blood pressure in hypertensive subjects. Contrary to animal-based studies,
there was no quercetin-evoked reduction in systemic markers of oxidative stress (Randi et al., 2007)
Gui-Rong et al. (2008) investigated whether the natural flavone acacetin would be an atrium-selective anti-atrial
fibrillation agent. The effects of acacetin on human atrial ultrarapid delayed rectifier K+ current (IKur) and other cardiac ionic
currents were studied with a whole-cell patch technique. Acacetin suppressed IKur and the transient outward K+ current (IC50 3.2
and 9.2 µmol/L, respectively) and prolonged action potential duration in human atrial myocytes. The compound blocked the
acetylcholine-activated K+ current; it had no effect on the Na+current, L-type Ca2+ current, or inward-rectifier K+ current in
guinea pig cardiac myocytes. Although acacetin caused a weak reduction in the hERG and hKCNQ1/hKCNE1 channels stably
expressed in HEK 293 cells, it did not prolong the corrected QT interval in rabbit hearts. In anesthetized dogs, acacetin (5 mg/kg)
prolonged the atrial effective refractory period in both the right and left atria 1 to 4 hrs after intraduodenal administration without
prolongation of the corrected QT interval, whereas sotalol at 5 mg/kg prolonged both the atrial effective refractory period and the
corrected QT interval. Acacetin prevented atrial fibrillation (AF) induction at doses of 2.5 mg/kg (50%), 5 mg/kg (85.7%), and 10
mg/kg (85.7%). Sotalol 5 mg/kg also prevented AF induction (60%). The study demonstrated that the natural compound acacetin
is an atrium-selective agent that prolongs the atrial effective refractory period without prolonging the corrected QT interval and
effectively prevents AF in anesthetized dogs after intraduodenal administration. These results have indicated that oral acacetin is a
promising atrium-selective agent for the treatment of AF.
Caffeic acid
Caffeic acid phenethyl ester (CAPE) is a phenolic active component of propolis of honeybee hives and reduces heart
rate and blood pressure in rats. Iraz et al. (2005) have investigated the role of vagal activity and atropine blockage on the
bradycardic and hypotensive effects of CAPE in rats. The rats were divided into five groups (n = 8). Saline and vehicle (10%
ethanol) of CAPE were given to the first and second groups, respectively. Group 3 was treated with 5 mg/kg CAPE. Group 4
bivagotomized and treated with 5 mg/kg CAPE. Group 5 treated with atropine (5 microg/microL/min) continuously and treated
with CAPE. The electrophysiological monitoring was done for each experiment under urethane anesthetia. As a result, CAPE
caused intense and transient bradycardia and hypotension. Vagotomy completely abolished bradycardia which occurred via CAPE
injection; however atropine attenuated bradycardic effects of CAPE. On the other hand, hypotensive effect of CAPE was affected
from neither bilateral vagotomy nor atropine treatment. It was thought that CAPE may exert its effects on heart rate via a central
parasympathetic control mechanism, but not on central parasympathetic blood pressure control system.
Xu et al. (2006) investigated the vascular effects of kaempferol in isolated porcine coronary artery rings. U46619 (9,11-
dideoxy-9α, 11α-methanoepoxy prostaglandin F2α, 30 nM) was used to contract porcine coronary arterial rings. Concentration
relaxation curve of kaempferol (1nM – 100μM) was constructed and kaempferol demonstrated significant relaxation at high
concentrations. However, at low concentration, kaemferol has no significant effect on relaxation. Kaempferol (10μM) enhanced
relaxation produced by bradykinin, the calcium ionophore A23187, isoproterenol and sodium nitroprusside in endothelium-intact
porcine coronaryarteries.
Khalil and Sulaiman Afr J Tradit Complement Altern Med. (2010) 7(4):315-321 319
In endothelium-disrupt rings, kaempferol (10μM) also enhanced the relaxation caused by isoproterenol, sodium
nitroprusside, levcromakalim and nifedipine. On the other hand, antioxidant agents did not affect bradykinin-induced relaxation or
the enhancement effect of kaempferol. It was concluded that a low concentration of kaempferol (10μM), devoid of significant
vascular effect, has the ability to enhance endothelium-dependent and endothelium-independent relaxations. This action of
kaempferol is unrelated to its antioxidant property.
Another study examined whether or not the ER stress and Bcl-2 proteins are linked to the protective effect of
kaempferol, a phytoestrogen, on ischemia-reperfusion (I/R)-induced cardiac damage. In order to determine if kaempferol modifies
the I/R-induced response in H9c2 cardiac muscle cells, the cells were exposed to kaempferol followed by ischemia
12h/reperfusion 4h. kaempferol had a protective effect on the apoptosis induced by I/R in the cardiac muscle cells. The
kaempferol treatment significantly increased the expression level of the anti-apoptotic protein, Bcl-2, but decreased the level of
the pro-apoptotic protein, bax. Kaempferol down-regulated the expressions of the endoplasmic reticulum (ER) stress proteins,
GRP78, ATF-6alpha, XBP-2, IRE1-alpha, phosphor-eIF-2alpha and CHOP. In ex vivo-Langendorff experiment, the kaempferol
treatment regulated the expression of ER stress proteins-CHOP and GRP78. The kaempferol also improved the post-ischemic
LVEDP and LVDP significantly after 20, 30, 40 and 50 min of reperfusion compared with the untreated control hearts, which
showed that kaempferol offers protection against I/R-associated cardiac dysfunction (Kim et al., 2008).
Galangin has anti-oxidative effect on endothelial tissues, thus affects lipid peroxidation and can prevent heart
disease)Therefore, it helps to preserve other protective antioxidants such as vitamin E, vitamin C, and other flavonoids, and also
can prevent lipid peroxidation (Lysias-Derrida, 2006).
Antioxidants present in honey come from a variety of sources, and include Vitamin C, monophenolics, flavonoids, and
polyphenolics. Regular flavonoid intake is associated with a reduced risk of cardiovascular diseases. In the coronary heart disease,
the protective effects of flavonoids include mainly antithrombotic, antiischemic, antioxidant, and vasorelaxant and flavonoids
decrease the risk of coronary heart disease by three major actions: (a) improving coronary vasodilatation, (b) decreasing the
ability of platelets in the blood to clot, and (c) preventing LDLs from oxidizing. Although there is a wide spectrum of polyphenols
types, quercetin, caffeic acid phenethyl ester, acacetin, kaempferol, galangin, predominate in many honeys. This review has
clearly demonstrated that certain honey polyphenols have a promising pharmacological role in preventing cardiovascular diseases.
After generating more in-depth and exhaustive information of these compounds jointly in vitro and in vivo studies, clinical trials
should be initiated to further validate these compounds in medical applications.
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... Sci. 2022, 12, x FOR PEER REVIEW 3 of 27 caffeic acid, quercetin, and chlorogenic acid, which prevent the formation of free radicals through chelation [20][21][22]. The current research on honey is intensively focused on its powerful antibacterial activity, highlighting its use in modern medicine as an attractive alternative treatment for combating multi-resistant pathogens. ...
... The composition of honey is extremely complex; flavonoids and polyphenols have strong antioxidant effects through their ability to donate hydrogen groups to eliminate free radicals, thus reducing oxidative stress. Among the most well-known compounds are caffeic acid, quercetin, and chlorogenic acid, which prevent the formation of free radicals through chelation [20][21][22]. ...
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Citation: Ionit ,ȃ-Mîndrican, C.-B.; Mititelu, M.; Musuc, A.M.; Oprea, E.; Ziani, K.; Neacs , u, S.M.; Grigore, N.D.; Negrei, C.; Dumitrescu, D.-E.; Mires , an, H.; et al. Honey and Other Beekeeping Products Intake among the Romanian Population and Their Therapeutic Use. Appl. Sci. 2022, 12, 9649. https://doi.
... Sci. 2022, 12, x FOR PEER REVIEW 3 of 27 caffeic acid, quercetin, and chlorogenic acid, which prevent the formation of free radicals through chelation [20][21][22]. The current research on honey is intensively focused on its powerful antibacterial activity, highlighting its use in modern medicine as an attractive alternative treatment for combating multi-resistant pathogens. ...
... The composition of honey is extremely complex; flavonoids and polyphenols have strong antioxidant effects through their ability to donate hydrogen groups to eliminate free radicals, thus reducing oxidative stress. Among the most well-known compounds are caffeic acid, quercetin, and chlorogenic acid, which prevent the formation of free radicals through chelation [20][21][22]. ...
Full-text available
Honey and other bee products have been used for food and therapeutic purposes since ancient times. There are many varieties of honey with time-proven therapeutic properties, used in both traditional and modern medicine, along with various beekeeping products. In this study, conducted based on the dissemination of a questionnaire with 43 questions, an evaluation of the consumption of different types of honey for both food and therapeutic purposes was carried out. Hence, the frequency of the consumption of honey for food purposes was evaluated, as well as the pharmaceutical forms of honey and bee products utilized for therapeutic purposes, the population’s trust in their therapeutic potential, and their trust in the quality of bee products among the Romanian population. After processing the data, 917 responses were recorded, and it was found that the preferred types of honey were black locust (83.5%), multi-floral (81.9%), and linden (74.9%), and among the other bee products, the most consumed were propolis (44.2%) and bee pollen (29.2%). Regarding the use of honey as a sweetener, the majority of the respondents considered honey to be the healthiest option (81.7%), and regarding the use of honey for therapeutic purposes, most of the respondents stated that they used honey to strengthen the immune system (65.4%), as well as for skin treatment, laxative action, or energizing. The centralization and processing of the collected responses indicated a considerable level of readiness related to the increase in honey consumption in particular, but there is a need for the dissemination of effective information related to the nutritional and therapeutic value of beekeeping products to the population.
... Concerning a study that assessed 105 different types of raw honey, produced by 3 countries, the honey-based gel used in the present study exhibited higher polyphenolic content from all honey samples except for the buckwheat honey (69). It is plausible that the high level of TPC, determined in the product used in the present study, may be due to substances such as caffeic acid, quercetin and kaempferol which are also found in honey and contribute to its antioxidant activity (70,71). In fact, the honey-based gel used is a mix of 87% fir honey and pollen. ...
... It displays cardioprotective actions like vasodilation, balancing vascular homeostasis and enhancements in lipid profile Bogdanov et al. [11] . Flavonoids in honey diminishes the danger of Coronary Heart Disease and improves coronary vasodilation, diminishes the capacity of platelets to form clots, forestall oxidation of lowdensity lipoproteins and increases high density lipoproteins and improves endothelial functions (Khalil et al [37]. ...
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Apitherapy is the use of bee products such as honey, pollen, propolis, bee wax, royal jelly and venom to prevent or to treat illness and promote healing. Apitherapy dates back to 460 BC, where Hippocrates utilized bee stings on his patients for the treatment of diseases. Its importance was highlighted with the publication of the First scientific paper by Desjardins, on the successful treatment and curative properties of bee venom for rheumatic disease. Filip Terc, who treated many of his patients with bee venom was considered as the "Father of Apitherapy". Christopher Kim, patented the first standardized and federal regulated injectable form of honey bee venom known as Apitoxin. Bee products have been used for treatment of varieties of ailments. Honey is used for wound management, pediatric care, gastrointestinal disorder, pharyngitis, cough etc. Pollen that results from agglutination of honey is widely used for burn wounds, allergies and cosmetics. Propolis is used for gastrointestinal disorder and oncological treatment. Royal jelly is used for enhancing reproductive health and treating neurodegenerative disorders. Bee wax is effectively used as coating for slow drug release. Venom is used for treatment of Parkinson's disease, neuralgia and cancer. "APILARNIL" and Bee hive airare also used for their beneficial effects on humans.
... Compared to conventional honey, abbamele features a richer flavor and more micronutrients. Polyphenols in honey products are known to prevent heart diseases [28], while pollens collected by honeybee are known to have antimutagenic, antioxidant, and anti-inflammatory effects that are attributable to its phenolic compounds, particularly to the flavonoids [29]. A similar production method is also performed by natives from southern Portugal to produce the nutrient-rich Água-mel [30]. ...
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Sardinia is one of the five Longevity Blue Zones (LBZs) in the world. Compared to other LBZs, the percentage of male centenarians in Sardinia is much higher. Due to the island’s isolation, the genetic traits of Sardinian people have shown that they are direct descendants of their Nuragic ancestors from the Neolithic era. To survive during times of food scarcity, many “famine foods” are created; acorn bread containing clay, cheese ripened in goat abomasum, and soft cheese with worms are examples of these uncommon foods. Although considered food taboo by the outside world, they are cherished as cultural heritage and local delicacy. Studies have shown that Sardinian longevity is closely related to their special famine foods. They are not only nutritious; the production of these foods resulted in low stress and increased lifespan. Moreover, local food production practices have resulted in a strong cultural bond and helped the Sardinian people to survive cultural erosion from industrialization and modernization.
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Alzheimer’s disease (AD), a leading cause of dementia, has been a global concern. AD is associated with the involvement of the central nervous system that causes the characteristic impaired memory, cognitive deficits, and behavioral abnormalities. These abnormalities caused by AD is known to be attributed by extracellular aggregates of amyloid beta plaques and intracellular neurofibrillary tangles. Additionally, genetic factors such as abnormality in the expression of APOE, APP, BACE1, PSEN-1, and PSEN-2 play a role in the disease. As the current treatment aims to treat the symptoms and to slow the disease progression, there has been a continuous search for new nutraceutical agent or medicine to help prevent and cure AD pathology. In this quest, honey has emerged as a powerful nootropic agent. Numerous studies have demonstrated that the high flavonoids and phenolic acids content in honey exerts its antioxidant, anti-inflammatory, and neuroprotective properties. This review summarizes the effect of main flavonoid compounds found in honey on the physiological functioning of the central nervous system, and the effect of honey intake on memory and cognition in various animal model. This review provides a new insight on the potential of honey to prevent AD pathology, as well as to ameliorate the damage in the developed AD.
Chinese cabbage is a nutrients-rich vegetable with diverse leaf colors. Here, we used widely-targeted metabolomics technology to study the metabolic responses of three Chinese cabbage varieties with representative leaf colors after blue light treatment. The inner leaf color of orange varieties 20S530 and 15S1094 changed from yellow to golden yellow, while no visible color change occurred in the common variety 14S23 after the treatment. A total of 844 metabolites were measured from the leaf samples of these three varieties in a time course study after short term blue light treatment, with kaempferol-4'-O-glucoside, isoquercitrin, hyperin, arbutin, sulforaphane as enriched nutritional metabolites. Orange Chinese cabbage varieties showed additional nutrition enhancement after the treatment. This study is the first to explore the global metabolic responses of Chinese cabbage after blue light treatment, and our findings provided valuable insights on how to effectively use lighting conditions to enhance specific groups of nutrients in vegetables.
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Apitherapy is a form of alternative therapy that relies on the use of bee products, i.e., honey, royal jelly, propolis, pollen, and bee venom (known as apitoxin), for the prevention and treatment of various diseases. Various in vitro and in vivo studies suggest that these products may be effective in the prophylaxis and treatment of cardiovascular diseases (CVDs). This mini-review of papers identified in various electronic databases describes new aspects of the bioactivity of certain bee products, viz. bee pollen, royal jelly, bee venom, propolis, and bee bread, as natural interesting products for the prevention and treatment of common CVDs.
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Honey is the principal premier product of beekeeping familiar to Homo for centuries. In every geological era and culture, evidence can be traced to the potential usefulness of honey in several ailments. With the advent of recent scientific approaches, honey has been proclaimed as a potent complementary and alternative medicine for the management and treatment of several maladies including various neurological disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis, etc. In the literature archive, oxidative stress and the deprivation of antioxidants are believed to be the paramount cause of many of these neuropathies. Since different types of honey are abundant with certain antioxidants, primarily in the form of diverse polyphenols, honey is undoubtedly a strong pharmaceutic candidate against multiple neurological diseases. In this review, we have indexed and comprehended the involved mechanisms of various constituent polyphenols including different phenolic acids, flavonoids, and other phytochemicals that manifest multiple antioxidant effects in various neurological disorders. All these mechanistic interpretations of the nutritious components of honey explain and justify the potential recommendation of sweet nectar in ameliorating the burden of neurological disorders that have significantly increased across the world in the last few decades.
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Induction of hyperadrenergic activity was experimentally achieved in urethane-anesthetized rats using epinephrine (adrenaline). Acute administration of epinephrine (100 microg/kg) for 2 hours induced several cardiac disorders and vasomotor dysfunction. Pretreatment with natural wild honey (5 g/kg) for 1 hour prior to the injection with epinephrine (100 mug/kg) protected the anesthetized normal rats from the incidence of epinephrine-induced cardiac disorders and vasomotor dysfunction. Moreover, posttreatment with natural wild honey (5 g/kg) following the injection with epinephrine (100 microg/kg) for 1 hour showed several ameliorative outcomes to the electrocardiographic parameters and vasomotor dysfunction of anesthetized stressed rats. Furthermore, natural wild honey preserved the positive inotropic effect of epinephrine in both cases. Also, the total antioxidant capacity (AOC) of natural wild honey was found to be very pronounced. Levels of both reduced glutathione and ascorbic acid (vitamin C) were considered relatively high in natural wild honey. Activity of superoxide dismutase (SOD) was also high, whereas catalase activity was relatively low, especially when compared to the value of SOD activity. It would appear from the results of the present study that natural wild honey may exert its cardioprotective and therapeutic effects against epinephrine-induced cardiac disorders and vasomotor dysfunction directly, via its very pronounced total AOC and its great wealth of both enzymatic and nonenzymatic antioxidants involved in cardiovascular defense mechanisms, besides its substantial quantities of mineral elements such as magnesium, sodium, and chlorine, and/or indirectly, via the enhancement of the endothelium-derived relaxing factor nitric oxide release through the influence of ascorbic acid (vitamin C).
Seven flavonoids and three non-flavonoid antioxidants, i.e. butylated hydroxyanisole, chlorpromazine and BW 755 C, were studied as potential scavengers of oxygen free radicals. Superoxide anions were generated enzymatically in a xanthine-xanthine oxidase system and non-enzymatically in a phenazine methosulphate-NADH system, and assayed by reduction of nitro blue tetrazolium. The generation of malonaldehyde (MDA) by the ascorbate-stimulated air-oxidised boiled rat liver microsomes was considered as an index of the non-enzymatic formation of hydroxyl radicals. Flavonoids but not non-flavonoid antioxidants lowered the concentration of detectable superoxide anions in both enzymic and non-enzymic systems which generated these SOD-sensitive radicals. The most effective inhibitors of superoxide anions were quercetin, myricetin and rutin. Four out of seven investigated flavonoids seemed also to suppress the activity of xanthine oxidase as measured by a decrease in uric acid biosynthesis. All ten investigated compounds inhibited the MDA formation by rat liver microsomes. Non-flavonoid antioxidants were more potent MDA inhibitors than flavonoids. It is concluded that antioxidant properties of flavonoids are effected mainly via scavenging of superoxide anions whereas non-flavonoid antioxidants act on further links of free radical chain reactions, most likely by scavenging of hydroxyl radicals.
Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.
A method is described for determining protein in honey. Removal of interfering materials of low molecular weight by dialysis allows the use of the Lowry photometric analysis for protein. For 740 samples of honey, a mean value of 169 mg/100 g was found, with a standard deviation of 71 mg/100 g and a range of 58–786. From 40% to 80% of the nitrogen in most honeys is in the protein fraction.
In most countries, high intake of saturated fat is positively related to high mortality from coronary heart disease (CHD). However, the situation in France is paradoxical in that there is high intake of saturated fat but low mortality from CHD. This paradox may be attributable in part to high wine consumption. Epidemiological studies indicate that consumption of alcohol at the level of intake in France (20-30 g per day) can reduce risk of CHD by at least 40%. Alcohol is believed to protect from CHD by preventing atherosclerosis through the action of high-density-lipoprotein cholesterol, but serum concentrations of this factor are no higher in France than in other countries. Re-examination of previous results suggests that, in the main, moderate alcohol intake does not prevent CHD through an effect on atherosclerosis, but rather through a haemostatic mechanism. Data from Caerphilly, Wales, show that platelet aggregation, which is related to CHD, is inhibited significantly by alcohol at levels of intake associated with reduced risk of CHD. Inhibition of platelet reactivity by wine (alcohol) may be one explanation for protection from CHD in France, since pilot studies have shown that platelet reactivity is lower in France than in Scotland.
The water-soluble antioxidant capacity of 19 samples of honey from 14 different floral sources was determined by a spectrophotometric assay. The highest concentration of antioxidants measured was 20.3 times that of the lowest, showing that great variation exists in the chemical nature of honey from different floral sources. Antioxidant content was positively correlated with both water content and honey colour. Because of the health benefits of dietary antioxidants, floral source should be a factor in evaluating the potential of honey as an antioxidant-containing food supplement.
The antioxidative effects of honey species and their related products were evaluated using a lipid peroxidation model system. The antioxidant activities of honey species gradually decreased with passage of time. Buckwheat honey was as effective as 1 mM α-tocopherol. Superoxide-scavenging activities of propolis and royal jelly were strongest among the honey species tested. 1,1-Diphenyl-2-picrylhydrazyl radical scavenging ability of sample species were lower than those of 1 mM ascorbic acid and α-tocopherol. Hydroxyl radical scavenging activity was very high in all honeys (over 77% inhibition). From the results of the bacterial test on storage of meat and muscle, each honey exhibited the inhibition of bacterial growth. In particular, propolis and royal jelly exhibited the strongest inhibitory effects against bacterial growth. This suggests that honey species from different floral sources possess strong antioxidative and antibacterial activities and are scavengers of active oxygen species.