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Effect of natural honey on human platelets and blood coagulation proteins

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Present study was conducted to determine the effects of honey on blood hemostasis, in-vitro effect of honey was observed on platelet aggregation and blood coagulation employing, activated partial prothrombin time (aPTT), prothrombin time (PT), thrombin time (TT) and fibrinogen levels in blood. Honey samples showed moderate inhibition of platelet aggregation with IC(50) 5-7.5%. The coagulation assays showed that at higher concentrations (>15%) honey samples increased whole blood clotting time. When assayed in platelet poor plasma (PPP), honey samples significantly (P>0.005) prolonged aPTT, PT, and TT. The honey samples (at 3.75% and 7.5% concentrations) cause mean increment of aPTT = 19±10% and 62±10%; PT 6±5% and 40±5%; TT 35±15% and 112±30% respectively. Moreover, PPP isolated from whole blood pre-incubated with honey samples (9.0% for 10 minutes) showed mean prolongation of aPTT, PT and TT of 45±21%, 26±9% and 105±24% respectively. Interestingly, incubation of honey at 6.25% and 11.75% concentrations in PPP considerably (P≥0.005) reduced fibrinogen levels i.e. 13±4% and 86±30% respectively. The present study outlines the inhibitory effect of natural honey on platelet aggregation and blood coagulation. These observations provide first line data for modulatory role(s) of honey on process of hemostasis.
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Pak. J. Pharm. Sci., Vol.24, No.3, July 2011, pp.389-397 389
REPORT
EFFECT OF NATURAL HONEY ON HUMAN PLATELETS
AND BLOOD COAGULATION PROTEINS
ASIF AHMED1, RAFEEQ ALAM KHAN2*, M. KAMRAN AZIM3, S. ARSHAD SAEED3,
M. AHMED MESAIK3, SHAKIL AHMED4 AND IMRAN IMRAN3
1Department of Pharmacology, Baqai Medical University, Karachi, Pakistan
2Department of Pharmacology, Faculty of Pharmacy, University of Karachi, Karachi, Pakistan
3Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS,
University of Karachi, Karachi, Pakistan
4Industrial Analytical Centre, International Center for Chemical and Biological Sciences
University of Karachi, Karachi, Pakistan
ABSTRACT
Present study was conducted to determine the effects of honey on blood hemostasis, in-vitro effect of honey was
observed on platelet aggregation and blood coagulation employing, activated partial prothrombin time (aPTT),
prothrombin time (PT), thrombin time (TT) and fibrinogen levels in blood.
Honey samples showed moderate inhibition of platelet aggregation with IC50 5-7.5%. The coagulation assays
showed that at higher concentrations (15%) honey samples increased whole blood clotting time. When assayed
in platelet poor plasma (PPP), honey samples significantly (P0.005) prolonged aPTT, PT, and TT. The honey
samples (at 3.75% and 7.5% concentrations) cause mean increment of aPTT = 19±10% and 62±10%; PT 6±5%
and 40±5%; TT 35±15% and 112±30% respectively. Moreover, PPP isolated from whole blood pre-incubated
with honey samples (9.0% for 10 minutes) showed mean prolongation of aPTT, PT and TT of 45±21%, 26±9%
and 105±24% respectively. Interestingly, incubation of honey at 6.25% and 11.75% concentrations in PPP
considerably (P0.005) reduced fibrinogen levels i.e. 13±4% and 86±30% respectively.
The present study outlines the inhibitory effect of natural honey on platelet aggregation and blood coagulation.
These observations provide first line data for modulatory role(s) of honey on process of hemostasis.
Keywords: Nutraceuticals; cardiovascular diseases and cerebro-vascular accident; thrombosis; anti-platelet;
anticoagulation.
INTRODUCTION
Vascular diseases contribute a major fraction in human
diseases. All over the world, major vascular diseases such
as cardiovascular diseases (CVD) and cerebro-vascular
accident (CVA) accounts for high mortality and morbidity
(Kumar and Clark, 2005). Atherosclerotic lesion is the
primary pathology found in CVA and CVD (Steinberg,
1992; Wegge et al., 2004).
In the established atherosclerotic disease; disturbed
platelet aggregation and blood coagulation complicates
the silent atherosclerotic lesion, by the formation of
superimposed thrombus (Escandon et al., 1999; Meigs et
al., 2000; Carr, 2001; Sobel, 2002). This thrombus
formation leads to a variety of acute clinical events such
as unstable angina, myocardial infarction or
cerebrovascular accidents (Franco et al., 2000; Libby et
al., 2002; Levi et al., 2004).
Unhealthy diet is a major cause of high mortality and
morbidity of vascular diseases (Pearson, 1999;
Kuulasmaa et al., 2000; Kelly, 2003). Therefore, it could
be prudent to consume a diet that is supplemented with
the food that may interfere physiologically with platelet
aggregation and blood coagulation; thus interrupts the
thrombotic progress of atherosclerotic disease. As part of
normal healthy diet, people around the world use natural
honey as a sweetener as well as due to its medicinal
benefits (Amy and Carlos, 1996). Honey is a
supersaturated sugar solution mainly comprises of D-
fructose, D-glucose, sucrose, maltose and higher sugars
(~80% of solid mass); while other natural products
includes alkaloids, flavonoids / isoflavones, glycosides,
phenolics, peptides/proteins are present in minor amounts
(White et al., 1962). Health benefits of honey have been
reported in a variety of conditions including microbial
infections (Cooper et al., 2002), wound healing (Molan,
2001a,b), anti-inflammation and inhibition of reactive
oxygen species (Mesaik et al., 2008; Ahmad et al., 2009),
glucose tolerance (Ahmad et al., 2008) and analgesia
(Azim et al., 2007).
In continuation of our studies, on medicinal attributes of
honey, we hypothesized that honey might have effects on
blood hemostasis. This effect of honey was assessed in
vitro, on platelet aggregation and blood coagulation.
*Corresponding author: e-mail: rkhan1959@gmail.com
Effect of natural honey on human platelets
Pak. J. Pharm. Sci., Vol.24, No.3, July 2011, pp.389-397
390
MATERIALS AND METHODS
Honey Samples
Six commercially available unifloral and multifloral
honey samples were used in this study. Pakistani honey
samples were collected from colonies of Apis mellifera
bees foraged on Acacia modesta (Sha), Plectranthus spp.
(Swa) and Ziziphus spp. (Sid). For comparison, Clover
honey (Clo), Eucalyptus honey (Cap) and LangneseTM
honey (Lan) from USA, Australia and Germany
respectively were included in the study. Information
regarding the floral origin of these commercial honeys
was obtained as detailed on the packing labels. The honey
samples were diluted with sterile phosphate buffered
saline pH 7.4.
Estimation of predominant sugars, water content, pH,
ash, viscosity and specific gravity of honey samples
In the present study, determination of amount of simple
sugars present in honey samples were done by using high
performance liquid chromatography. Simple sugars in
honey samples were separated isocratically by reversed
phase HPLC on a Prevail Carbohydrate ES, 5µm, 250 x
4.6mm column with acetonitrile/water. Karl Fischer
titration method was used to estimate the water content in
honey samples (Cedergren, 1974; Hoffmann, 1998),
where as estimation of pH in honey samples were carried
out by using pH meter. Ash content of honey samples
was determined by dry ashing, through Furnace method
(Milne et al., 1992). Viscosity was measured using a
Brookfield Viscometer (Cheng, 1990) and specific gravity
of honey samples was determined by Pycnometer -
density bottle method (Wattiaux et al., 1991; Wattiaux et
al., 1992; Bailoni and Bittante, 1994).
Determination of anti platelet activity of honey
Human platelets were isolated from blood samples
collected from healthy subjects (n=6), aged 35-48, who
did not consumed any medication in the last two weeks.
Blood was taken by clean vein puncture and immediately
mixed with 3.8% (w/v) sodium citrate solution (9:1) and
centrifuged at 260×g for 15 minutes at 20°C to obtain
platelet rich plasma (PRP).
Platelet count was determined by phase contrast
microscopy and all aggregation studies were carried out at
37°C with PRP having counts between 2.5-3.0×108/ml of
plasma (Shah and Saeed, 1995). All experiments were
performed within 2 h of PRP preparation. Platelet
aggregation was monitored using Dual-channel lumi-
aggregometer (Model 400 Chronolog Corporation,
Chicago, USA) using 0.425-0.49 ml aliquots of PRP
(Shah and Saeed, 1995, Shah et al., 1996). The final
volume was made up to 0.5 ml with the honey samples,
dissolved in sterile phosphate buffer saline pH 7.4.
Aggregation was induced with 10 µl of adenosine 5’-
diphosphate (ADP) solution (4 µM). The time of addition
of inducer was defined as 0 time. Various concentrations
(2.5, 5, 6 and 7.5%) of honey samples were added
following addition of the aggregation agent. Percentage of
aggregation inhibition was calculated comparing with the
control (no honey).
Determination of effects of honey on blood coagulation
Blood was taken by clean vein puncture from normal
human healthy volunteers; who did not consumed any
medication in the last two weeks. Platelet poor Plasma
(PPP) was obtained by centrifugation at 1500×g for 10
min at 4°C. Effects of honey samples on blood
coagulation were carried out by using HemoStat-aPTT-
EL, HemoStat Thromboplastin-SI, HemoStat-Thrombin
time and HemoStat-Fibrinogen. All reagents were
prepared, maintained and performed as directed by the
manufacturer (Human Diagonista-Germany GmbH) with
some modifications (Posta et al., 2002; Nilsson et al.,
1997; Berry et al., 2002; Valeria et al., 2000). Clotting
time for all coagulation assays was measured by taking
the average of 2-5 measurements using Coagulometer
(Human Diagonista-Germany GmbH).
Effect of honey on whole blood coagulation
The extracted blood from the healthy human volunteer
(male) was equally distributed (0.3ml) into glass tubes
(without anticoagulant) containing diluted honey samples
(Lan and Swa) at the final concentrations of 15, 24 and
30%. Upon addition of blood into tubes, whole blood
clotting time was noted by optical method. Whole blood
(no honey) was taken as control. For the validity of
coagulation test results, sterile phosphate buffer saline
was also tested.
Effect of honey on coagulation parameters tested in
platelet poor plasma
Blood was collected from 30 healthy human volunteers
(20 males, 10 females; aged 32±6). Whole blood was
mixed with anticoagulant (sodium citrate) and platelet
poor plasma (PPP) was removed by using plastic pipette
and kept in covered plastic tube to avoid pH changes.
Diluted honey samples were mixed with PPP in pre-
warmed tubes and clotting was timed, after addition of
reagents for aPTT, PT, TT and Fibrinogen level. For
aPTT, PT, TT assays the final concentrations of honey
samples were 3.75 and 7.5%; whereas for fibrinogen
assays, final concentrations were 6.25 and 11.76%.
Platelet free plasma (no honey) was taken as control. For
the validity of coagulation test results, sterile phosphate
buffer saline and Dextran solution (Clinical grade, M.W.
=200,000-300,000) were also tested.
Effect of honey mixed in whole blood and coagulation
parameters tested on extracted platelet poor plasma
Blood samples collected from 7 healthy male human
volunteers (aged, 25.8±8.2) were taken and placed into
two tubes in equal amounts (containing sodium citrate as
Asif Ahmed et al.
Pak. J. Pharm. Sci., Vol.24, No.3, July 2011, pp.389-397 391
anticoagulant). Diluted honey samples (9.0%) were added
to one of the tube (T1) and incubated for 10 minutes.
After incubation, PPP was removed and aPTT, PT and TT
assays were carried out. Platelet free plasma (tube-T2,
with no honey) was taken as control. For the validity of
coagulation test results, sterile phosphate buffer saline and
dextran solution (Clinical grade, M.W. =200,000-
300,000) were also tested.
Statistical analysis
Results are mentioned as mean with standard deviation.
The mean values were calculated from 2-5 observations.
One-way analysis of variance (ANOVA), two-way
analysis of variance (ANOVA), test for homogeneity of
variance, and post-hoc tests (Tukey HSD and Games-
Howell) were all performed wherever applied. All
analyses were carried out using Excel (Microsoft Corp.,
Redmond, Wash., U.S.A.) and SPSS version 12 (Aspire
Software Intl., Ashburn, Va., U.S.A.).
RESULTS
Estimation of predominant sugars, water content, pH,
ash, viscosity and specific gravity of honey samples
Table 1 shows percentage composition of honey sugars
analyzed by HPLC (see methods). During the study, first
glucose, fructose, maltose and sucrose separately and then
a mixture of four sugars were standardized and considered
as control. Later all honey samples were analyzed against
the control. Table 2 shows the results of Ash content (%),
Viscosity (Poise), pH, Sp. Gravity (20oC) and Water
content (% w/w basis) of honey samples.
Effect of honey on blood hemostasis
The results of present study show honey-mediated (a)
inhibition of platelet aggregation, (b) prolongation of
aPTT, PT, and TT and (c) reduction in Fibrinogen levels.
Platelet aggregation activity of honey
In this study, effect of different honey samples on platelet
aggregation assay was carried out. Fig. 1 shows, that
addition of honey in the reaction mixture, inhibited ADP-
induced platelet aggregation. Table 3 shows IC50 dose of
honey samples that remained between 5.0-6.5 %. Among
the honey samples studied in this experiment,
Plectranthus (Swa) and Euclayptus honeys (Cap) showed
maximum inhibition of platelet aggregation with IC50~5.0
%. PRP without honey was taken as control. In order to
eliminate the false positive effect due to the viscosity of
honey, Dextran (9.0 %) was also tested. However, no
significant effect was observed supporting the inhibitory
activity of honey.
Effect of honey on blood clotting time
Fig. 2 shows, effect of honey on whole blood coagulation.
In this study, Lan and Swa honey samples were tested in
15, 24 and 30% concentrations. Honey at less than 15%
concentration (results not shown) did not show any effect
on clotting time. However, after addition of 15% honey in
whole blood resulted 2.5 and 5% increase in clotting time.
With 24% honey, mean clotting time was increased to 18
and 27% and finally honey at dose of 30% increased the
mean clotting time by 38%. Whole blood (no honey) was
taken as control.
Table 1: Percentage composition of honey sugars (in %).
Honey Samples Glucose Fructose Sucrose Maltose Total sugar %
Reference Ranges
28-36% 36-50% 0.8-5.0% 1.7-11.8% *
Cap 30.09 38.45 5.17 2.1 75.84
Clo 33.33 37.33 3.03 1.83 75.52
Lan 26.78 33.91 6.4 2.59 69.73
Swa 25.09 23.54 4.38 3.67 56.69
Sid 24.3 31.66 9.4 3.79 69.15
Sha 33.63 36.9 2.59 1.87 74.99
Table 2: Composition of honey samples
Ash
( % )
Viscosity
(Poise) pH Sp. Gravity
(20o C)
Water content
(% w/w basis)
Reference Ranges
Honey Samples
0.04-0.93% 150 3.3-5.6 1.423 15-18
Cap 0.06 130 4.098 1.4335 20.412
Clo 0.07 140 3.859 1.4277 20.364
Lan 0.07 114 4.09 1.4203 21.237
Swa 0.06 140 3.701 1.429 21.814
Sid 0.05 145 5.057 1.422 23.931
Sha 0.06 130 5.216 1.4293 22.798
Effect of natural honey on human platelets
Pak. J. Pharm. Sci., Vol.24, No.3, July 2011, pp.389-397
392
Table 3: Effect of honey on platelet aggregation
No. Honey Samples IC50 (%)
1. Plectranthus honey (Swa) 5.0±0.1
2. Ziziphus honey (Sid) 5.5±0.15
3. Acacia modesta honey (Sha) 5.5±0.09
4. Euclayptus honey (Cap) 5.0±0.2
5. Clover honey (Clo) 6.5±0.1
6. LangneseTM honey (Lan) 6.0±0.17
Effect of honey on coagulation parameters tested in
platelet poor plasma
In this study, six honey samples were tested in platelet
poor plasma using aPTT, PT, TT and Fibrinogen level
assays. Results clearly indicate that addition of honey
significantly increased measured aPTT, PT, TT and
decreased the Fibrinogen levels.
Fig. 2: Effect of honey samples on whole blood clotting
time.
Fig. 1: Effect of honey samples on human platelet aggregation
Asif Ahmed et al.
Pak. J. Pharm. Sci., Vol.24, No.3, July 2011, pp.389-397 393
Effect of honey on aPTT tested in platelet poor plasma
Fig. 3 shows effect of different honey samples on aPTT.
Incubation of natural honey at different concentrations
i.e., 3.75 and 7.5% showed progressive prolongation in
aPTT. Results shows, the mean increase in aPTT by
incubation of 3.75 and 7.5% honey in PPP determined as
19±10% (Swa honey response not included) and 62±10%
respectively. PPP (without honey) was taken as control.
Effect of honey on pt tested in platelet poor plasma
Fig. 3 shows, effect of different honey samples on PT.
Incubation of natural honey at concentration 3.75 and
7.5% caused progressive prolongation in PT and
determined as 6.0±5.0% and 40±5.0% respectively. PPP
(no honey) was taken as control.
Fig. 3: Effect of honey on activated partial prothrombin
time in platelet poor plasma.
Effect of honey on TT tested in platelet poor plasma
Similar to above results, fig. 4, show that incubation of
natural honey at concentration 3.75 and 7.5% caused
progressive prolongation in TT and determined as
35±15% and 112±30% respectively. PPP (no honey) was
taken as control.
Fig. 4: Effect of honey on prothrombin time in platelet
poor plasma.
Effect of honey on fibrinogen level tested in platelet
poor plasma
Fig. 5 shows results of honey samples with natural honey
at concentrations 6.25 and 11.75% that shows decrease in
Fibrinogen level and determined as, as 13±4% (Sha honey
response not included) and 86±30% respectively. PPP (no
honey) was taken as control.
Fig. 5: Effect of honey on thrombin time in platelet poor
plasma.
Effect of honey mixed in whole blood and coagulation
parameters tested on extracted platelet poor plasma
Fig. 6 shows the results of different honey samples at 9%
concentration that were initially incubated in whole
blood; later PPP was isolated and assayed for aPTT, TT,
PT. This experiment showed that honey treatment of
whole blood caused significant prolongation of tested
assays. The mean increase in aPTT, PT and TT in
extracted PPP determined as 45±21%, 26±9% (Sid honey
response not included) and 105±24%, respectively. PPP
(no honey) was taken as control.
Fig. 6: Effect of honey on fibrinogen level in platelet poor
plasma.
Effect of natural honey on human platelets
Pak. J. Pharm. Sci., Vol.24, No.3, July 2011, pp.389-397
394
DISCUSSION
The present study is the first report about the effect of
honey on blood hemostasis. Previously, only
anticoagulant properties of honey bee venom were known
(Ouyang et al., 1979; Kini et al., 1994; Gowlik et al.,
2004; Franco et al., 1994). During the pathogenesis of the
vascular disorder, the formation of unwanted thrombus on
the pre-existing atherosclerotic plaques can cause partial
or complete occlusion of the blood vessel, which leads to
sinister clinical events such as acute myocardial infarction
or cerebrovascular accidents (Victor et al., 2002; Thomas,
2008). More over independent, abnormal and
uncontrolled coagulation termed as hypercoagulability
leads to serious clinical events such as deep vein
thrombosis (Libby, 2002; Kannel, 2005). The formation
of thrombus is initiated by the platelet aggregation
(platelet plug); that follows the activation of blood
coagulation proteins to further reinforcement platelet plug
by forming a mesh work of insoluble fibrin (Kannel,
2005; Rauch et al., 2001; Furie and Furie, 2005).
Platelets play a key role in primary hemostasis,
thrombosis and inflammation (Ahmad, 2003). Therefore,
the importance of anti-platelet therapy in the prevention
of vascular disorder is unquestionable. The results of the
present study indicate that addition of natural honey into
the reaction mixture; causes the inhibition of platelet
aggregation.
The mechanism by which honey inhibits the platelet
aggregation can be explained by many factors such as,
honey contains hydrogen peroxide (Molan, 2001a, b);
studies shows that exogenous exposure to hydrogen
peroxide result in platelet inhibition (Ferroni et al.,
2004a), therefore it can be assumed that the presence of
hydrogen peroxide might be the underlying basis of honey
induced inhibition of platelet aggregation. Moreover, it
can be suggested that honey is competitively antagonizing
ADP receptor mediated aggregation. Natural honey is
known to have suppressive effects on reactive oxygen
species (Ahmad et al., 2009). Here it would be
meaningful to mention, that activated platelets during and
after the platelet aggregation release different cytokines
which in turn activates phagocytes. Thus platelet activated
phagocytes results in increase production of free oxygen
radicals (Pervushina et al., 2004; Kazemi et al., 2008).
Since honey inhibits the aggregation of platelets therefore
it can be assumed that it indirectly inhibits the production
of free oxygen radicals. Interestingly free oxygen radicals
indirectly act on platelet function via oxidative
modification of low-density lipoproteins or oxidation of
lipids and their derivatives (Ferroni et al., 2004a). Hence
it can be assumed that honey can influence the platelet
function by inhibition of LDL oxidation (Hegazi and El-
Hady, 2007) that indirectly affects platelets function.
Natural honey causes physiological euglycemia (Ahmad
et al., 2008) and it has been reported that hyperglycemia
causes redox activation of platelets (Ferroni et al., 2004b).
The honey induced physiological euglycemia might be
additional factor, affecting the functions of platelets.
After the process of primary hemostasis induced by
platelets; secondary hemostasis is achieved by the
activation of blood coagulation that resulted in the
formation of fibrin mesh work. Therefore, the importance
of anti-coagulant therapy in the prevention of vascular
disorder is also without a shred of doubt.
Results of present study demonstrate that honey inhibited
the coagulation proteins of all three coagulation pathways
i.e., intrinsic pathway (assayed by aPTT); extrinsic
pathway (assayed by PT) and final common pathway
(assayed by TT). Moreover, during this study honey-
induced decrease in fibrinogen levels that is in agreement
with the prolongation of aPTT, PT and TT observed.
There could be several reasons for natural honey to have
anticoagulant attributes such as, honey contains variety of
flavonoids that may affect the activity of coagulation
factors like fibrinogen and factor VII (Cazenave, 1988;
Middleton and Kandaswami, 1992; Beretz and Cazenave
1991). Similarly different types of sugars affect the
process of blood coagulation. Honey contains glucose
(28-36%) and it has been suggested that high level of
glucose interferes with coagulation through different
mechanisms such as, non-enzymatic glycation, the
development of increased oxidative stress, and a decrease
in the levels of subendothelial heparin sulphate (Carr,
1996; Bakaltcheva and Reid, 2003). Moreover, honey
contains maltose (1.7-11.8%) that also reported to
interfere with blood coagulation (Carr and Carr 1995;
Carr et al., 1996; Bakaltcheva and Reid, 2003).
The results of present study, provides clear evidence for
multi-dimensional anti-haemostatic properties of honey;
that encompasses interference with the intrinsic, extrinsic,
common coagulation cascades as well as platelet
aggregation. It can be assumed that observation of median
levels of efficacy in honeys originated from different
floral sources and geographical regions indicated that
anti-platelets / anticoagulant activity might be a general
property of honey. These observations provide first line
evidence for modulatory role(s) of honey on process of
hemostasis.
Medicinal properties of honey, encompass various
mechanisms that might play a role in the prevention of
atherosclerotic vascular disorders e.g., cardiovascular and
cerebrovascular disorders. Honey has reported to inhibit
thrombin (main enzyme of blood coagulation) induce
formation of reactive oxygen species from phagocytes; as
Asif Ahmed et al.
Pak. J. Pharm. Sci., Vol.24, No.3, July 2011, pp.389-397 395
free oxygen radicals particularly superoxide and
hypochlorous acid provides the nidus for the development
of atherosclerotic plaque, thus honey might interrupts the
nidus formation of atherosclerotic plaque (Ahmad et al.,
2009). Honey independently inhibits LDL oxidation that
also prevents the development of primary atherosclerotic
lesion (Hegazi and El-Hady 2004). It is reported that
fasting blood sugar is an independent predictor of platelet
dependent thrombosis in patients with coronary artery
(Shechter et al., 2000). Honey has reported to have
physiological euglycemia in fasted human subjects
(Ahmad et al., 2008). This effect also possibly interferes
with the process of thrombosis.
On the basis of present and previous results, it can
assumed that honey might interferes at several steps in the
formation of atherosclerotic disease this effect finally
translates into the prevention of vascular disorders such as
cardiovascular and cerebrovascular disorders.
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... Macrophages and neutrophils are known to produce a significant amount of ROS. The increased oxidative stress level has a role to play in pulmonary injuries including acute lung injury (ALI) and acute Rats Tuscany honey -Reduced formation of fats and proteins in diabetic rat -Inhibition of alpha-glucosidase activities [69] Rats (liver cells) Tuscany honey Suppressing PTP1B while encouraging alteration in serum lipid profiles and expression of insulin receptor [69] Rat MGO -Reduced wound size -Increase urine osmolarity, osmolar clearance, creatinine clearance, and free water clearance [101] Human Natural honey Prevention of platelet aggregation, extend APPT, PT, and TT while decreasing amount of fibrinogen in platelet-poor plasma [78] Human (peripheral blood) ...
... Both of these present in honey which makes it a potential therapeutic against cardiovascular disease [68,74,75,76,77]. Another study showed that honey can prevent platelet aggregation, extend partial prothrombin time (APTT), prothrombin time (PT), thrombin time (TT) while it may decrease the amount of fibrinogen in platelet-poor plasma [78]. ...
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... Its most common application is for healing wounds and skin infections [27][28][29]. Honey possesses significant antibacterial [30][31][32], antiviral [33,34], antifungal [27,[35][36][37], antioxidant [27,[38][39][40], anti-inflammatory [41][42][43], antineoplastic [28,44], antimicrobial [45][46][47], anticarcinogen [48][49][50], antiarrhythmic [51,52], antileishmanial [53,54], antithrombotic, antiplatelet [55,56], antimutagenic [57,58], antinociceptive [59,60], antimycobacterial [7,61], antiproliferative [62,63], and immune-boosting [64][65][66] properties. It is also shown to have hypocholesterolemic [67,68], cardioprotective [69,70], antihypertensive [71], hepatoprotective [72,73], gastroprotective [41,74], neuroprotective [75,76], nephroprotective [77,78], and hypoglycemic [79,80] effects. ...
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... A study by Ahmed et al., (2011) showed that presence of high amount of sugar (~80%), acidic pH (3.2-6), minerals and vitamins, hydrogen peroxide, antioxidant contents, stimulation of immunity neutrophils and osmotic effects are responsible for the antimicrobial characteristics of honey. Different studies have proved that in addition to antibiofilm and antibacterial properties, honey has many other properties like stimulating epithelialization and tissue growth, reducing inflammation, B and T lymphocytes and proliferation of phagocytes A study by Verrases et al., (2013) showed that N-Acyl-Lhomoserine lactone (AHL) production in biofilm could be lessened by using honey and another study by Wahjudi et al., (2013) also explained that QS of Chromobacterium violaceum can be inhibited by using ...
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... [9] In Charakachikitsa 4 th adhyaya, Madhu is said to be use with paravatshakutachurna in case of "grathitRaktadushti". [10] Natural honey contains phospholipase and melittin.Madhu shows Antithrombotic action. It means Madhu helps to increase blood clotting time and showed the inhibitory effect on platelet aggregation & blood coagulation [11] . Raktadhatu [12] . ...
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... 98 In this context, in vitro and in vivo assays confirmed the inhibitory effects of honey and its main components on platelet aggregation and blood coagulation. [99][100][101][102][103][104][105][106] For example, the in vitro, in vivo, and ex vivo models showed the anti-thrombotic and anti-coagulant effect of quercetin. 103 Indeed, several studies have reported that quercetin decreased, similar to other natural polyphenols (resveratrol, curcumin, ginkgo biloba and bilberry) diastolic pressure by potentiating eNOS activation, nitric oxide production 107,108 and the activity of thrombin, formation of fibrin clots and blood clotting through modulating the coagulation cascade. ...
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... Moreover, it has been suggested to have a role against COVID-19 epidemic [174,175], it has six compounds related to the receptor active site of COVID-19's main protease according to a in silico approach [176] and is currently being tested in a clinical trial (clinical trial NCT04323345) [176]. It is noted that honey displays anti-thrombotic activity [177] and it especially acts as a PAF inhibitor [178]. In total, the antibacterial, the anti-thrombotic and anti-PAF effects of honey render it a potentially useful food against the COVID epidemic. ...
Preprint
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The new coronavirus disease 2019 (COVID-19) pandemic is an emerging situation with high rates of morbidity and mortality, in the pathophysiology of which inflammation and thrombosis are implicated. The disease is directly connected to the nutritional status of patients and a well-balanced diet is recommended by official sources. Recently, the role of platelet activating factor (PAF) was suggested in the pathogenesis of COVID-19. In the present review several micronutrients (vitamin A, vitamin C, vitamin E, vitamin D, selenium, omega-3 fatty acids, minerals), phytonutrients and Mediterranean diet compounds (olive oil, fish, honey, plant foods) with potential anti-COVID activity are presented. We further underline that the well-known anti-inflammatory and anti-thrombotic actions of the investigated nutrients and/ or holistic dietary schemes, such as the Mediterranean diet, are also mediated through PAF. In conclusion, although there is no single food to prevent coronavirus, the aim is to follow a healthy diet containing PAF inhibitors in order to target both inflammation and thrombosis and try to avoid or/and reduce the deleterious effects of the COVID-19 epidemic.
... 12,26 Furthermore, anti-platelet and anti-coagulant effects of HNS may also shield COVID-19 patients from thromboembolic complications, which are among the leading complications and causes of mortality. 27 The hepato-and reno-protective . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. ...
Preprint
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BACKGROUND No definitive treatment exists for Coronavirus Disease 2019 (COVID-19). Honey and Nigella sativa (HNS) have established antiviral, antibacterial, anti-inflammatory and immunomodulatory properties. Hence, we investigated efficacy of HNS against COVID-19. wide METHODS We conducted a multicenter, placebo-controlled, randomized clinical trial at 4 centers in Pakistan. RT-PCR confirmed COVID-19 adults showing moderate or severe disease were enrolled in the study. Patients presenting with multi-organ failure, ventilator support, and chronic diseases (except diabetes mellitus and hypertension) were excluded. Patients were randomly assigned in 1:1 ratio to receive either honey (1 gm/Kg/day) and Nigella sativa seeds (80 mg/Kg/day) or placebo up-to 13 days along with standard care. The outcomes included symptom alleviation, viral clearance, and a 30-day mortality in intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT04347382 . RESULTS Three hundred and thirteen patients - 210 moderate and 103 severe - underwent randomization from April 30 to July 29, 2020. Among these, 107 were assigned to HNS whereas 103 to placebo for moderate cases. For severe cases, 50 were given HNS and 53 were given placebos. HNS resulted in ∼50% reduction in time taken to alleviate symptoms as compared to placebo (Moderate (4 versus 7 days), Hazard Ratio [HR]: 6.11; 95% Confidence Interval [CI]: 4.23-8.84, P<0.0001 and severe (6 versus 13 days) HR: 4.04; 95% CI, 2.46-6.64, P<0.0001). HNS also cleared the virus 4 days earlier than placebo group in moderate (6 versus 10 days, HR: 5.53; 95% CI: 3.76-8.14, P<0.0001) and severe cases (8.5 versus 12 days, HR: 4.32; 95% CI: 2.62-7.13, P<0.0001). HNS further led to a better clinical score on day 6 with normal activity resumption in 63.6% versus 10.9% among moderate cases (OR: 0.07; 95% CI: 0.03-0.13, P<0.0001) and hospital discharge in 50% versus 2.8% in severe cases (OR: 0.03; 95% CI: 0.01-0.09, P<0.0001). In severe cases, mortality rate was four-fold lower in HNS group than placebo (4% versus 18.87%, OR: 0.18; 95% CI: 0.02-0.92, P=0.029). No HNS-related adverse effects were observed. CONCLUSION HNS significantly improved symptoms, viral clearance and mortality in COVID-19 patients. Thus, HNS represents an affordable over the counter therapy and can either be used alone or in combination with other treatments to achieve potentiating effects against COVID-19. FUNDING Funded by Smile Welfare Organization, Shaikh Zayed Medical Complex, and Services Institute of Medical Sciences.
Chapter
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The new coronavirus disease 2019 (COVID-19) pandemic is an emerging situation with high rates of morbidity and mortality, in the pathophysiology of which inflammation and thrombosis are implicated. The disease is directly connected to the nutritional status of patients and a well-balanced diet is recommended by official sources. Recently, the role of platelet activating factor (PAF) was suggested in the pathogenesis of COVID-19. In the present review several micronutrients (vitamin A, vitamin C, vitamin E, vitamin D, selenium, omega-3 fatty acids, and minerals), phytochemicals and Mediterranean diet compounds with potential anti-COVID activity are presented. We further underline that the well-known anti-inflammatory and anti-thrombotic actions of the investigated nutrients and/or holistic dietary schemes, such as the Mediterranean diet, are also mediated through PAF. In conclusion, there is no single food to prevent coronavirus Although the relationship between PAF and COVID-19 is not robust, a healthy diet containing PAF inhibitors may target both inflammation and thrombosis and prevent the deleterious effects of COVID-19. The next step is the experimental confirmation or not of the PAF-COVID-19 hypothesis.
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The effects of solubility and water-holding capacity on functional and unit specific gravity were evaluated in samples of fish, soybean, linseed, corn gluten, corn gluten feed, corn, barley, and dehydrated alfalfa meals and in wheat bran, raw flaked soybeans, cottonseeds, and dried sugar beet pulp. Solubility was estimated by washing the samples in nylon bags in a washing machine. Functional specific gravity was estimated in a pycnometer for unwashed and washed samples after 0 and 15 h of soaking in distilled water. Water-holding capacity was measured by a centrifugation method and by a filtration method. Unit specific gravity was estimated as the weighted mean of the functional specific gravity of insoluble DM and the specific gravity of water held by the particles. Solubility and functional specific gravity of insoluble DM varied significantly among feedstuffs from 5.0 to 53.2% of DM and from 1.31 to 1.62, respectively. The increase in functional specific gravity from soaking was small. Water-holding capacity was lower with filtration than with centrifugation methods and varied from .94 to 6.44 g of H2O/g of DM. Unit specific gravity varied significantly from 1.07 to 1.24. Soluble fractions and water-holding capacity can markedly influence the functional and unit specific gravity of concentrate particles.
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This article reviews reports on the use of honey in the treatment of human disorders which are supported by clinical tests and published in medical journals. Firstly, the composition of honey is described, followed by a revision of its effect on the growth of several strains of pathogenic bacteria in laboratory tests. Finally, the influence of honey on gastroenteritis, gastric ulcers, wounds and other disorders is reviewed.
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When Ancil Keys demonstrated many years ago that saturated fat intake was related to elevated cholesterol levels and coronary artery disease death rates around the world [1], he ignited a debate which has not yet been fully settled. There is a direct linear relationship between saturated fat intake, cholesterol levels, and coronary artery disease. It is less clear whether changing saturated fat intake changes blood cholesterol levels in adults to a sufficient degree to significantly reduce coronary disease. The implications of these relationships are of great economic as well as health importance in those countries in which saturated fat intake is high. The outcome of this debate is not only of significance to physicians and their patients, but also to farmers, livestock producers, food distributors, and the governments which represent and oversee them.
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This document is the methodological appendix to the paper titled "Estimating the contribution of changes in classical risk factors to trends in coronary-event rates across the WHO MONICA Project populations" published in Lancet, 2000;355:675-687. It covers three topics: - brief description of the regression analysis and the output statistics used in the paper; - justification for the age-standardization used for calculating risk factor trends for the regression analysis; and - derivation of the quality score which was used to weight the populations in the regression analysis.
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The ever-increasing demand for blood products challenges scientists to develop new and more effective techniques for their preservation. The progress of these novel preservation technologies uses a wide variety of cryoprotectant, lyoprotectant, and other preservatives, which will need to be explored and assessed for their biological effects during blood product formulation. The leading factor in protectant selection is for their ability to provide superior preservation for a particular blood product. We believe that such protectants used in blood product development should also be evaluated for their ability to preserve normal hemostasic mechanisms. In this review, high-molecular-weight cryoprotectants, lyoprotectants, polyols, amino acids, antioxidants, and surfactants, used because of their protective properties, were evaluated for their possible role in relation to their effect on normal hemostatic mechanisms.