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Effect of Royal Jelly on spatial learning and memory in rat model of streptozotocin-induced sporadic Alzheimer's disease


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It has been recently demonstrated that Royal jelly (RJ) has a beneficial role on neural functions. Alzheimer's disease (AD) is associated with impairments of learning and memory. Therefore, the present study was designed to examine the effect of RJ on spatial learning and memory in rats after intracerebroventricular injection of streptozotocin (icv-STZ). Rats were infused bilaterally with an icv injection of STZ, while sham rats received vehicle only. The rats were feed with RJ-contained food (3% w/w) (lyophilized RJ mixed with powdered regular food) or regular food for 10 days. Then spatial learning and memory was tested in the rats by Morris water maze test. Results showed that in icv-STZ group latency and path length were increased as compared to sham group, also icv-STZ rats less remembered the target quadrant that previously the platform was located; however, these were protected significantly in STZ group that received RJ-containing food. Our findings support the potential neuroprotective role of RJ and its helpful effects in AD.
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Advanced Biomedical Research | April - June 2012 | Vol 1 | Issue 2 1
Background: It has been recently demonstrated that Royal jelly (RJ) has a beneficial role on neural functions.
Alzheimer’s disease (AD) is associated with impairments of learning and memory. Therefore, the present study
was designed to examine the effect of RJ on spatial learning and memory in rats after intracerebroventricular
injection of streptozotocin (icv-STZ).
Materials and Methods: Rats were infused bilaterally with an icv injection of STZ, while sham rats received
vehicle only. The rats were feed with RJ-contained food (3% w/w) (lyophilized RJ mixed with powdered
regular food) or regular food for 10 days. Then spatial learning and memory was tested in the rats by
Morris water maze test.
Results: Results showed that in icv-STZ group latency and path length were increased as compared to
sham group, also icv-STZ rats less remembered the target quadrant that previously the platform was
located; however, these were protected significantly in STZ group that received RJ-containing food.
Conclusions: Our findings support the potential neuroprotective role of RJ and its helpful effects in AD.
Key words: Alzheimer’s disease, rat, Royal jelly, spatial learning and memory, streptozotocin
Address for correspondence:
Dr. Parham Reisi, Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. E‑mail:
Received: 18‑01‑2012, Accepted: 13‑03‑2012
Effect of Royal Jelly on spatial learning and memory in
rat model of streptozotocin‑induced sporadic Alzheimer’s
Zohre Zamani, Parham Reisi1, Hojjatallah Alaei2, Ali Asghar Pilehvarian3
Applied Physiology Research Center, 1Department of Physiology, School of Medicine and Biosensor Research Center, 2Department of
Physiology, School of Medicine Isfahan University of Medical Sciences, 3Department of Basic Sciences,
Isfahan Payame Noor University, Isfahan, Iran
Original Article
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Alzheimer’s disease (AD) is a disorder with a deadly
outcome and unknown etiology in human that aficted
many people worldwide.[1] This disease is characterized
Copyright: © 2012 Zamani. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction
in any medium, provided the original author and source are credited.
How to cite this article: Zamani Z, Reisi P, Alaei H, Pilehvarian AA. Effect of Royal Jelly on spatial learning and memory in rat model of streptozotocin-induced
sporadic Alzheimer's disease. Adv Biomed Res 2012;1:26.
by a progressive and irreversible neurodegeneration in
various brain regions, especially in the hippocampus,
which is an important area for memory and cognition.[2,3]
The increased production and accumulation of amyloid‑β
peptide (Aβ) contribute to progressive neuronal
degeneration.[4,5] Therefore, Alzheimer’s is associated
with decits in cognitive abilities such as learning
and memory in human beings.[5] Currently, there isn’t
any conclusive treatment for AD and the common
treatments just slow the progression of the disease and
manage some of the symptoms.[3]
Royal jelly (RJ) is an essential food for the honey
bee young larva and the queen herself, it thought to
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2 Advanced Biomedical Research | April - June 2012 | Vol 1 | Issue 2
play important nutritional roles in the queen.[6] It is
a viscous substance secreted by the hypopharyngeal
and mandibular glands of the worker honey bee of the
species, Apis mellifera. It has been reported to have a
variety of biological activities toward various types of
cells and tissues of animal models.[6]
RJ is composed of proteins, carbohydrates, lipids
(including sterols and fatty acids), and traces of
mineral salts and vitamins.[7] This material has been
determined to exhibit a variety of pharmacological
activities including antitumor, antimicrobial,
vasodilative, and hypotensive activities, as well
as growth stimulating and infection preventing,
antihypercholesterolemic and anti‑inflammatory
activities. Several studies have been shown the
antioxidant activity of RJ.[8] For these reasons, for
more than 30 years, RJ has been used commercially
in medical products, healthy foods, and cosmetics, to
a wide extent.[8]
In addition, RJ facilitates the differentiation of all
types of brain cells including neurons from cultured
neural stem/progenitorcells (NS/NPCs).[6] RJ or its
components would facilitate in vivo neurogenesis
in the hippocampal dentate gyrus (DG).[9] However,
there are no reports so far showing the effects of RJ
on cognition behaviorally, especially when there is a
background of neurodegenerative disease.
One of the relevant animal models of Alzheimer’s
disease is intracerebroventricular streptozotocin
(icv‑STZ) injection.[1,10] Streptozotocin is a diabetogenic
drug that used to induce diabetes mellitus,[11] and recent
evidence suggests that the intracerebroventricular
(icv) injection of streptozotocin (STZ) to rats in a
subdiabetogenic dose causes prolonged impairment
of memory and brain metabolic process, as a sporadic
dementia of the Alzheimer’s type (SDAT) that
comprises more than 90% of Alzheimer’s patients in
the world.[1,10] Therefore, the aim of this study was
to evaluate the effect of RJ on learning and memory
in rats after intracerebroventricular injection of
streptozotocin (icv ‑STZ).
Male Wistar rats (320 ± 20 g) were housed four per
cage and maintained on a 12 h light–dark cycle in an
air‑conditioned constant temperature (23 ± 1°C) room,
with food and water made available ad libitum. The
Ethic Committee for Animal Experiments at Isfahan
University approved the study and all experiments were
conducted in accordance with the National Institute
of Health Guide for the Care and Use of Laboratory
Animals (NIH Publications No. 80‑23) revised 1996.
Animals were divided into four groups (n = 9). The
rst group was the sham control (sham group), the
second group consisted of sham animals receiving
RJ‑contained food (sham‑RJ group), the third group
was the ICV‑STZ control (lesion group), and the
fourth group consisted of ICV‑STZ animals receiving
RJ‑contained food (lesion‑RJ). Rats in the control
groups received regular food.
Five days after surgical procedure, for recovery, rats
received RJ‑contained food for 10 days and then spatial
learning and memory was tested in the rats by Morris
water maze test.
RJ was administrated in the form of a mixed food
prepared by adding freeze‑dried RJ at 3% (w/w) in
regular food powder. The mixture and pure regular
food were made into pellets with a small amount of
water and desiccated under vacuum overnight.[9,12]
Surgical procedure
The rats were anesthetized with chloral hydrates
(400 mg/kg, i.p.) and their heads were fixed in
a stereotaxic frame. A heating pad was used
to maintain body temperature at 36.5 ± 0.5°C.
The skull was exposed and two small holes were
drilled and injection canula was lowered into the
lateral ventricles (anterior‑posterior = ‑0.8 mm;
medial‑lateral = ±1.6 mm; and dorsal‑ventral =
‑4.2 mm with reference to bregma).[13] Injection
canula was connected to a Hamilton syringe attached
to a microinjector unit. The lesion group received
a bilateral ICV injection of STZ (1.5 mg/kg in 4 µl
per site) as in previous studies.[10] The sham group
underwent the same surgical procedures, but the same
volume of saline was injected instead of STZ.
Morris water maze test
The circular tank (180 cm in diameter) was lled with
water (22 ± 2°C) made opaque and was surrounded by
a variety of extra‑maze cues. The tank was divided into
four quadrants and four start positions were located at
the interactions of the quadrants. Data were recorded
using custom software (Radiab 1). Twenty‑four hours
before water maze testing, all rats were habituated to
the water and apparatus.
In the spatial acquisition phase, the rats learned to
nd a submerged platform using extra‑maze cues.
A transparent Lucite platform (10 × 10 cm) was
submerged 2 cm underneath the water in north‑east
quadrant of the tank, where it remained for all spatial
trials [Figure 1a]. Each rat participated in 16 trials,
which were organized into daily block of four trials
(1 trial/start position within a block) for 4 consecutive
days. For each trial, the rat was given a maximum time
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Advanced Biomedical Research | April - June 2012 | Vol 1 | Issue 2 3
of 60 s to locate the platform, after which it remained
there for 30 s. If the rat did not locate the platform
within 60 s, it was guided to it by the experimenter.
The next trial started immediately after removal from
the platform. Escape latencies (s), swim distance (cm),
and swim speed (cm/s) were recorded.
In the retention phase, 1 day and 1 week after
the spatial acquisition phase, 60‑s probe trial was
conducted to examine how well the rats had learned
the exact location of the platform. During this trial, the
platform was removed from the tank. The quadrant
time (percent time spent in the training quadrant)
was recorded during the probe trial.[14] To test possible
decits in sensory–motor processes, rats were tested
in the water maze with a visible platform on a new
location on the nal day of training.[15]
Statistical analysis
Data were analyzed using the SPSS 16 for Windows.
Results are given as mean ± S.E.M. The escape
latencies, path length, and swim speed were analyzed
with three‑factor mixed ANOVA for between‑subjects
differences between sham and lesion (“ICV‑STZ”
effect), between non‑RJ and RJ (“RJ” effect), and
ICV‑STZ*RJ effect interaction and repeated measures
(within subjects) effects across block interval 1 to 4
(“BLOCK” effect). The probe trial data for percentage
of time spent in each of the four zones were analyzed
by multivariate ANOVA.
All rats except lesion group showed a reduction in
escape latencies (BLOCK effect, F(3,96) = 46.157,
P < 0.001) and a reduction in the distance swam to
locate the platform (BLOCK effect, F(3,96)=25.259,
P < 0.001) across blocks of trials, indicating spatial
acquisition. Sham groups found the platform more
quickly than lesion groups [28.9 ±1.8 s and 43.54 ± 1.6 s,
respectively; ICV‑STZ effect, F(1,32) = 36.265,
P < 0.001] and took shorter paths to the platform
[637.7 ± 48.1 cm and 958.6 ± 43.6 cm, respectively;
ICV‑STZ effect, F(1,32) = 24.46, P < 0.001]. The rats
that received RJ contained food, found the platform
more quickly than the rats that received regular food
[30.48 ± 1.85 s and 41.94 ± 1.58 s, respectively; RJ
effect, F(1,32) = 22.2, P < 0.001] and took shorter paths
to the platform [687.4 ± 49.4 cm and 908.86 ± 42.9 cm,
respectively; RJ effect, F(1,32) = 11.65, P <0.01]. Also,
RJ contained food maintained both the escape latencies
[ICV‑STZ*RJ effect interaction, F(1,32) = 0.22,
P = 0.64] and the pathlengths [ICV‑STZ*RJ effect
interaction, F(1,32) = 0.06, P = 8] in lesion rats
[Figures 1b and 1c].
Swim speed did not show any change during
continuous day [BLOCK effect, F(3,96) = 2.01,
P = 0.118] and there wasn’t any difference between
the groups [Figure 1d].
Results from the probe trial as measured by the
mean percentage (%) time spent in each of the four
zones indicated that 1 day after acquisition phase the
sham groups spent more time in zone 1, where the
platform was previously located, than the ICV‑STZ
groups [38.14 ± 2.58% and 23.41 ± 2.33%, respectively;
ICV‑STZ effect, F(1,32) = 31.02, P < 0.001]. The
mean percentage (%) time spent in zone 1 was not
signicantly different between the rats that received
RJ‑contained food and the rats that received regular
food [36.71 ± 2.65% and 24.83 ± 2.26%, respectively;
RJ effect, F(1,32) = 3.564, P = 0.068]; however,
RJ‑contained food maintained that in lesion rats
[ICV‑STZ*RJ effect interaction, F(1,32) = 0.85,
P = 0.36] [Figure 2a].
One week after acquisition phase, the sham groups
spent more time in zone 1 than the ICV‑STZ groups
[38.19 ± 2.05% and 22.78 ± 1.86%, respectively;
ICV‑STZ effect, F(1,32) = 17.94, P < 0.001]. The rats
that received RJ‑contained food spent more time
in zone 1 than the rats that received regular food
[33.1 ± 2.1% and 27.87 ± 1.8%, respectively; RJ effect,
F(1,32) = 11.67, P < 0.01]; also, RJ‑contained food
maintained that in lesion rats [ICV‑STZ*RJ effect
interaction, F(1,32) = 0, P = 0.99) [Figure 2b].
The present results showed that use of RJ is effective
in signicant improvement of learning and memory
defects that induced with icv‑STZ in rats.
Like previous studies, our results demonstrated that
ICV‑STZ causes impairment of learning and memory in
rats.[16] The study has been shown that the application
of STZ in a subdiabetogenic dose in rats brain leads to
damage to glucose’s metabolism and causes reduction in
adenosine triphosphate (ATP/ADP ratio). This may be
calculated by the imbalance between intake and output
of energy.[17] It has been shown that acetylcholine is
necessary to formation and improvement of memory;
its synthesis needs to glucose metabolism and insulin
in order to control choline acetyltransferase (ChAT)
activity.[1] Previous researches have demonstrated that
icv‑STZ causes reduced energy metabolism/oxidative
stress leading to cognitive dysfunction by inhibiting the
synthesis of acetyl‑CoA and therefore acetyl‑choline
synthesis. Also, streptozotocin causes reduced ChAT
activity in hippocampus and increased cholinesterase
(ChE) activity in the rat’s brains.[1]
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4 Advanced Biomedical Research | April - June 2012 | Vol 1 | Issue 2
In addition, like in AD, icv‑STZ through prolonged
impairment of brain energy metabolism and oxidative
damage increases the inammatory cytokines, such
as interleukin‑8 (IL‑8) and interleukin‑1 (IL‑1). This
inammatory cytokines and severe oxidative stress
lead to mitochondrial dysfunction and increase the
risk of cell apoptosis in the brain, particularly in the
As a secondary observation, our results demonstrated
that use of RJ in rats enhanced learning and
memory performance. Previous studies showed that
RJ stimulates production of neurotrophic factors,
such as glial cell line‑derived neurotrophic factor
(GDNF), and has neuroprotective effects in the adult
brain, especially in hippocampus.[6] These studies
are compatible with the results from our behavioral
One of unique components in RJ is 10‑hydroxy‑
trans‑2decanoic acid (HDEA), an unsaturated fatty
acid. Because HDEA is a small unsaturated fatty
Figure 1: Effects of Royal jelly (RJ) contained food on performance during the spatial acquisition of Morris water maze test in rats with
intracerebroventricular injection of streptozotocin. Schematic diagram of tank and site of the platform (a). The escape latencies (b), the path length
(c), and the swim speed (d) at different days to reach the platform. Each point represents the day mean ± SEM of 4 swims. For latency and path
length, lower numbers indicate better performance (*P < 0.05 and **P < 0.01 with respect to the sham group, †P < 0.05 signicant difference
between the lesion and the lesion-RJ groups; n = 9).
Figure 2: Effects of Royal jelly (RJ) contained food on performance during the probe trial in rats with intracerebroventricular injection of
streptozotocin, quadrant time, as measured by mean percentage (%) time spent in each of the four zones, 1 day (a) and 1 week (b) after spatial
acquisition phase. Zone 1 was the training quadrant that previously platform was located (*P < 0.05 and **P < 0.01 with respect to the sham
group, †P < 0.05 signicantly difference between the lesion and the lesion-RJ groups; n = 9).
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Advanced Biomedical Research | April - June 2012 | Vol 1 | Issue 2 5
acid, it can pass through blood–brain barrier. It has
been demonstrated that HDEA mimics the effects
of brain‑derived neurotrophic factor (BDNF) and
probably stimulate neurogenesis in the mature
brain.[20] Other active component in RJ is adenosine
monophosphate (AMP) N1‑oxide that is effective in
neuronal differentiation of PC12 cells.[7,20]
One of the factors which play an effective role in
pathogenesis of ageing and neurodegenerative
diseases is oxidative stress, which is an imbalance
between free radicals and antioxidant system.[21,22]
Oxygenate radicals can attack to proteins, nucleic
acids, and lipid membranes and accordingly interrupt
the integrity and performance of the cell.[23] The
brain tissue contains a lot of unsaturated fatty acids
which are especially vulnerable for free‑radical
attacks.[24] Therefore, antioxidant substances can
play an important role in prevention and cure of
neurodegenerative diseases.[10,16] Recently, studies
have suggested that RJ has free‑radical scavenging
capacity and is a highly efcient antioxidant.[25,26] RJ
has been shown that inhibits lipid proxidation both
in vitro and in vivo.[27]
RJ has a potent ability to improve insulin resistance
and this is a valuable effect in AD.[28] Same to AD or
ageing brain, ICV‑STZ in rats causes desensitization
of insulin receptors[29] and it has demonstrated
that ICV‑STZ through damage of the neuronal
insulin receptor induces progressive deteriorations
in the mental capacities of learning, memory, and
In conclusion, our ndings show that RJ protects
spatial learning and memory performance in AD and it
has positive effects on neural functions and cognition.
This research was supported by the Applied Physiology
Research Center of Isfahan University of Medical Sciences,
Isfahan, Iran. Also, the authors wish to thank Isfahanhoney.
com Corporation for preparation and standardization of
royal jelly.
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... Therefore, it is commonly used as a supplement for diseases such as cancer, diabetes, and cardiovascular dementia, and royal jelly has shown significant neuroprotective actions [6]. It has been demonstrated that royal jelly has a beneficial role in neural functions and was investigated on spatial learning and memory in a rat model of streptozotocininduced sporadic Alzheimer's disease [7]. Moreover, royal jelly long-term administration can affect the brain neurotransmitters in naturally aged rats [8]. ...
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Vascular dementia (VaD) is the second most common type of dementia following Alzheimer’s disease, but the therapeutic efficacy is still not effective. This makes the searching for novel neuroprotective agents important. Therefore, we hypothesized that royal jelly, a well-known traditional medicine, could attenuate memory impairment and brain damage in vascular dementia. This study determined the effects of royal jelly hydrolysate (RJH) and possible mechanism of cell damage and cognitive-enhancing effect in animal study. An in vitro study assessed the effects of RJH on acetylcholinesterase inhibitor, cell viability, and cell damage in SH-SY5Y neuroblastoma cells. Then, an in vivo study examined vascular dementia by the occlusion of the right middle cerebral artery (Rt.MCAO); adult male Wistar rats had been orally given RJH at doses ranging from 10, 50, to 100 mg/kg for 14 days before and 14 days after the occlusion of Rt.MCAO to mimic the VaD condition. Rats’ spatial memory was evaluated using Morris water maze and radial arm maze every 7 days after Rt.MCAO throughout a 14-day experimental period, and then, they were sacrificed and the acetylcholinesterase (AChE) activity in the hippocampus was determined. The results showed that RJH has no cytotoxic effect with the final concentration up to 500 μg protein/ml and reduces cell death from the H2O2- and glutamate-induced cell damage in in vitro neuroblastoma cells. Importantly, RJH significantly improved memory performance in Morris water maze test and radial arm maze and decreased the level of acetyl cholinesterase activity. In conclusion, RJH is the potential neuroprotective agent and cognitive enhancer for VaD.
... Alzheimer disease (AD) has complex causes, including nerve fiber tangles, amyloid beta deposition, inflammatory response, and oxidative stress response. In many animal experiments at home and abroad and in vitro cell experiments, it has been proved that royal jelly can improve the spatial learning and memory ability of AD model rats [30] by effectively alleviating the toxicity of β-amyloid in AD and significantly reducing β-amyloid species [31]. However, whether royal jelly and its functional components have a positive effect on the prevention and delaying of human AD and their possible mechanism of action remain to be further studied. ...
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Background Beekeeping and honey gathering are traditional forms of agricultural farming in China. However, only few studies have focused on the nutritional status and health level of this special occupational group. Objective By comparing the health status of apiculturists (beekeepers) and vegetable farmers in plain areas of Hubei Province, and analyzing the influence of dietary structure and intake on their nutritional level, this paper provides a scientific theoretical basis for the further development of health education and disease prevention for beekeepers. Methods From February to April 2016, 191/236 beekeepers (80.9% of the total beekeepers) with large-scale breeding (300-500 colonies) and 182 vegetable farmers in the same area were sampled by the cluster sampling method. Their nutrient composition was analyzed using a human body composition analyzer, dietary structure information was collected using the dietary frequency query method, and cognitive function was investigated. In addition, blood samples of both groups were collected. ResultsA total of 362 valid questionnaires (beekeepers/vegetable farmers: 185/177) were collected, with an effective response rate of 97.1% (362/373). Both beekeepers and vegetable farmers were overweight, and the beekeepers’ grip strength was much stronger than that of the vegetable farmers’ regardless of gender. The dietary structure of beekeepers is very unique: 29.7% (55/185) of beekeepers indicated consuming royal jelly regularly for more than 10 years. Their main foods are grain, cereals, and fresh vegetables; 68.1% (126/185) of the beekeepers never drank milk and other dairy products, and their overall nutrient intake is unbalanced. The average intake of cellulose in this group was also significantly higher than that in the epidemiological survey in the same sex and age group. The intake of vitamin A and selenium in the beekeepers group was significantly higher than that in the vegetable-farmers group (all P
... Previous studies have shown that RJ consumption increased memory, learning and neurotrophins as well as decreased beta amyloid depletion in mouse (8); RJ consumption modulated serotonin and dopamine in the cortex tissue of the elderly rats, however, this effect was dose dependent, so that 100 mg/kg RJ had favorable effects than 50 mg/kg RJ (9). Also, RJ increased neuronal function, memory, and learning in an animal model of AD (10). Given the role of serotonin and dopamine as important neurotransmitters in the central nervous system and their role in the plasticity of hippocampal neurons, it seems that the use of noninvasive and non-pharmacological approaches may be an appropriate strategy to improve cognitive function in patients with AD. ...
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Background Studies have shown that exercises and the use of natural foods have favorable effects on Alzheimer's disease (AD). The purpose of this study was to investigate the effects of resistance training (RT) with royal jelly (RJ) on serotonin and dopamine receptors expression in hippocampal tissue of rats with AD. Methods In this experimental study, 56 rats with AD were randomly divided into (1) control, (2) RT, (3) RT + 100 mg/kg RJ, 4) RT + 200 mg/kg RJ, 5) 100 mg/kg RJ, 6) 200 mg/kg RJ2 and 7) sham. Also in order to review the effects of AD induction on serotonin and dopamine, 8 healthy rats selected as healthy control group. During 8 weeks the groups 3, 4, 5 and 6 received daily RJ with specific doses peritoneally and groups 2, 3 and 4 performed RT three sessions per week with 30–100 percentage of body weight. Independent sample t- test, One way ANOVA and two-way ANOVA was used to investigate the effect of RT, RJ and interaction of RT and RJ also Bonferroni’s post- hoc test was used to evaluate the difference between the doses of RJ using SPSS software (P ≤ 0.05). Results RT had a significant effect on the increase of dopamine (p = 0.001) and serotonin receptors (p = 0.001); RJ had a significant effect on the increase of dopamine receptor(p = 0.01) and serotonin (p = 0.001) also RT simultaneously with RJ consumption had a significant interactive effect on the increase of serotonin receptor (p = 0.001). Conclusion It appears that RT and RJ can enhance serotonergic and dopaminergic function in hippocampal tissue of rats with AD, however, the effects of RJ seems to be dose dependent.
This chapter emphasizes the profile and characteristics of bee products relevant to diabetes mellitus (DM) and their use in DM management. The chapter summarizes and analyses recent scientific data from both preclinical and clinical trials indicating the bee products’ potential in treating DM. Bee products have hypoglycemic, antihyperglycemic, antihyperlipidemic, antioxidant, and antiinflammatory properties, which are favorable factors for diabetics and their control. Bee products reduce oxidative stress, advanced glycation end products (AGE) build-up and adipose tissue inflammation, all of which contribute to insulin resistance and secretion abnormalities, which ameliorate diabetic complications, including nephropathy, retinopathy foot ulcers and nonalcoholic fatty liver disease.
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Background and Aim: Although exercise training and antioxidants improve brain health, interactive effect of resistance training and Royal jelly has not yet been well established. Therefore, the aim of the current study was to investigate the effect of resistance training along with Royal jelly supplementation on hippocampal gene expression of nerve growth factor (NGF) and tyrosine kinase A (TrkA) receptor in rat model of Alzheimer's disease. Materials and Methods: In this experimental study, 42 male Sprague-Dawley rats were injected by Trimethyltin (8 mg/kg/body weight). Then, the rats were randomly divided into 7 equal groups including control, resistance training, resistance training+100 mg/kg Royal jelly supplementation, resistance training+200 mg/kg Royal jelly supplementation, 100 mg/kg Royal jelly supplementation, 200 mg/kg Royal jelly supplementation and sham groups. The resistance training protocol was performed for 8 weeks, three sessions per week at intensity to 30-100% of their body weight. Gene expression was assessed using Real-Time PCR and all primers were designed by Allele IDv7.8 software. Data were analyzed using two-way analysis of variance and Bonferroni post hoc tests at the p<0.05. Results: The resistance training induced a significant increase in NGF expression (p= 0.001). Moreover, 100 and 200 mg/kg Royal jelly supplementation, resistance training+100 and 200 mg/kg Royal jelly supplementation resulted in a significant increases in expression of NGF and TrkA receptor (p=0.001). In addition, the effect of royal jelly supplementation on NGF and TrkA receptor expression was dependent on its dosage, where the dose of 200 mg/kg was significantly higher than the dose of 100 mg/kg (p=0.001). Conclusion: Both resistance training and Royal jelly supplementation, alone and synergistically, can increase neurotrophins expression in the hippocampus of Alzheimer's rats; however higher dose of Royal jelly supplementation may induce more improvement.
Background Alzheimer's disease (AD) is a neurological disorder characterized by loss of memory and cognitive functions caused by oxidative stress, neuroinflammation, change in neuro- transmitter levels, and excessive deposition of Aβ(1–42) plaques. Fucoxanthin is a carotenoid with potential antioxidant, anti-inflammatory, and neuroprotective actions. Objective In the present study, fucoxanthin was employed as a protective strategy in Intracere- broventricular Streptozotocin (ICV-STZ) induced experimental model of cognitive impairment. Methods STZ was injected twice ICV (3 mg/kg) on alternate days 1 and 3, and Wistar rats were evaluated for the memory analysis using Morris water maze and elevated plus-maze. Fucoxanthin at low 50 mg/kg, p.o. and high dose 100 mg/kg, p.o. was administered for 14 days. All animals were sacrificed on day 29, and brain hippocampus tissue after isolation was used for biochemical (MDA, nitrite, GSH, SOD and Catalase), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotrans- mitters (ACh, GABA Glutamate), Aβ(1–42) and Tau protein measurements. Results STZ-infused rats showed significant impairment in learning and memory, increased oxida- tive stress (MDA, nitrite), reduced antioxidant defense (GSH, SOD and Catalase), promoted cy- tokine release, and change in neurotransmitter levels. However, fucoxanthin improved cognitive functions, restored antioxidant levels, reduced inflammatory markers dose-dependently, and res- tored neurotransmitters concentration. Conclusion The finding of the current study suggests that fucoxanthin could be the promising compound for improving cognitive functions through antioxidant, anti-inflammatory, and neuropro- tective mechanisms, and inhibition of acetylcholinesterase (AChE) enzyme activities, Aβ(1–42) accu- mulation, and tau protein.
Royal jelly (RJ) is a kind of bee product widely used in cosmetics, medicine and other fields. Not only can RJ regulate the physiological function of bee population, but also play a specific biological role in many diseases. This paper overviews the main active ingredients in the functional food RJ, including major royal jelly protein, fatty acids, phenols, flavonoids, etc, and summarizes the active role of RJ in the maintenance of human health, such as the regulation of immunity, lifespan, memory, digestive system, blood glucose, obesity, antibacterial and anti-cancer effect, among which the regulation of memory can be used in the treatment of Alzheimer's disease. These findings will benefit for comprehensive understanding and use of RJ, hence making it more effective in maintaining health.
The semi‐organized insect industry of India primarily includes apiculture, sericulture and lac culture. In the last two decades the production of raw silk, including mulberry and “vanya silk”, has doubled. An increasing trend for the country has also been observed with regard to honey and beeswax production. India, moreover, stands in the frontline for lac production, but there is immense scope to expand insect‐based ventures. For example, sericultural products other than silk come to mind and with regard to apiculture honey, and beeswax need not be the only bee‐based commercial items. Insects other than honey bees can be used as food and feed or in the decomposition of waste; some species can be reared and even domesticated as pollinators. In this paper we discuss these unexplored sections, which could open up promising possibilities for the insect‐based industry in India as well as other countries.
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Royal jelly (RJ), a natural honeybee product, has a wide range of antibacterial activities. N-glycosylated major royal jelly protein 2 (N-MRJP2), purified from RJ, can inhibit the growth of Paenibacillus larvae (P. larvae, Gram-positive), a contagious etiological agent of the American foulbrood disease of honeybees. However, the inhibitory mechanism is largely unknown. Antibacterial assay and membrane proteome were conducted to investigate the inhibition capacity of RJ from different instar larvae and P. larvae treated by N-MRJP2, respectively. The similar antibacterial efficiency of RJ from different larval instar indicates that RJ is vital for the adaptive immune defense of small larvae. The killing of P. larvae by N-MRJP2 is achieved by disturbing the cell wall biosynthesis, increasing the permeability of cell membrane, hindering aerobic respiration, restraining cell division and inducing cell death. This demonstrates that RJ is critical for the passive immunity of immature larvae and N-MRJP2 can be used as natural antibiotic substance to resist P. larvae, even for other gram-positive bacteria. This constitutes solid evidence that RJ and N-MRJP2 have potentials as novel antibacterial agents.
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The astronomical increase of the world's aged population is associated with the increased prevalence of neurodegenerative diseases, heightened disability, and extremely high costs of care. Alzheimer's Disease (AD) is a widespread, age-related, multifactorial neurodegenerative disease that has enormous social and financial drawbacks worldwide. The unsatisfactory outcomes of available AD pharmacotherapy necessitate the search for alternative natural resources that can target the various underlying mechanisms of AD pathology and reduce disease occurrence and/or progression. Royal jelly (RJ) is the main food of bee queens; it contributes to their fertility, long lifespan, and memory performance. It represents a potent nutraceutical with various pharmacological properties, and has been used in a number of preclinical studies to target AD and age-related cognitive deterioration. To understand the mechanisms through which RJ affects cognitive performance both in natural aging and AD, we reviewed the literature, elaborating on the metabolic, molecular, and cellular mechanisms that mediate its anti-AD effects. Preclinical findings revealed that RJ acts as a multidomain cognitive enhancer that can restore cognitive performance in aged and AD models. It promotes brain cell survival and function by targeting multiple adversities in the neuronal microenvironment such as inflammation, oxidative stress, mitochondrial alterations, impaired proteostasis, amyloid-β toxicity, Ca excitotoxicity, and bioenergetic challenges. Human trials using RJ in AD are limited in quantity and quality. Here, the limitations of RJ-based treatment strategies are discussed, and directions for future studies examining the effect of RJ in cognitively impaired subjects are noted.
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An inflammatory process has been involved in numerous neurodegenerative disorders such as Parkinson's disease, stroke and Alzheimer's disease (AD). In AD, the inflammatory response is mainly located in the vicinity of amyloid plaques. Cytokines, such as interleukin-8 (IL-8) and interleukin-1α (IL-1α), have been clearly involved in this inflammatory process. Polymorphisms of several interleukin genes have been correlated to the risk of developing AD. The present study investigated the association of AD with polymorphisms IL-8 -251T > A (rs4073) and IL-1α-889C > T (rs1800587) and the interactive effect of both, adjusted by the Apolipoprotein E genotype. 199 blood samples from patients with AD, 146 healthy elderly controls and 95 healthy young controls were obtained. DNA samples were isolated from blood cells, and the PCR-RFLP method was used for genotyping. The genotype distributions of polymorphisms IL-8, IL-1α and APOE were as expected under Hardy-Weinberg equilibrium. The allele frequencies did not differ significantly among the three groups tested. As expected, the APOE4 allele was strongly associated with AD (p < 0.001). No association of AD with either the IL-1α or the IL-8 polymorphism was observed, nor was any interactive effect between both polymorphisms. These results confirm previous studies in other populations, in which polymorphisms IL-8 -251T > A and IL-1α-889C > T were not found to be risk factors for AD.
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Trimethyltin (TMT) is a toxic organotin compound that induces acute neuronal death selectively in the hippocampal dentate gyrus (DG) followed by cognition impairment; however the TMT-injured hippocampal DG itself is reported to regenerate the neuronal cell layer through rapid enhancement of neurogenesis. Neural stem/progenitor cells (NS/NPCs) are present in the adult hippocampal DG, and generate neurons that can function for the cognition ability. Therefore, we investigated whether royal jelly (RJ) stimulates the regenerating processes of the TMT-injured hippocampal DG, and found that orally administered RJ significantly increased the number of DG granule cells and simultaneously improved the cognitive impairment. Furthermore, we have already shown that RJ facilitates neurogenesis of cultured NS/NPCs. These present results, taken together with previous observations, suggest that the orally administered RJ may be a promising avenue for ameliorating neuronal function by regenerating hippocampal granule cells that function in the cognition process.
Forty eight male Balb/c mice, each weighing 30–35 g, were used in the present study. The animals were divided into four equal groups. The first group served as the control group, and the second group was administered royal jelly at a dose of 50 mg/kg bw by gavage for a period of 7 days. The third group received 200 ppm fluoride, as sodium fluoride, for a period of 7 days, in drinking water. Lastly, the fourth group was given 200 ppm fluoride in drinking water, in association with royal jelly at a dose of 50 mg/kg bw by gavage, for a period of 7 days. At the end of the seventh day, blood samples were collected from all groups into heparinised and dry tubes, and liver samples were taken concurrently. Erythrocyte and liver tissue malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were evaluated in the blood and tissue samples obtained. Furthermore, serum cholesterol, triglyceride, glucose, total protein and albumin levels, and aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alcaline phosphatase (ALP) activities were evaluated. In conclusion, fluoride was determined to cause adverse effects in mice, and the administration of royal jelly to these animals alleviated the adverse effects of fluoride.
Royal jelly peptides (RJPx) isolated from hydrolysates of water-soluble royal jelly proteins prepared with protease P exhibited significantly stronger hydroxyl radical-scavenging activity (p<0.001), and antioxidant activity against lipid peroxidation (LPO, p<0.001), than did water-soluble royal jelly protein (WSRJP) in vitro. We also investigated the in vivo antioxidant activity of RJPx against ferric nitrilotriacetate (Fe-NTA)-induced LPO. Male Wistar rats were divided into a control group (Group C), an Fe-NTA group (Group Fe), and an Fe-NTA with RJPx group (Group Fe+R). Rats in Group Fe+R were fed RJPx (2 g/kg body weight) daily for 5 wk. Fe-NTA (8 mg Fe/kg body weight) was then intraperitoneally injected, and serum lipid levels were examined 2 h later. Serum total cholesterol (TC) levels were lower (p<0.05) while low-density lipoprotein (LDL) and LPO were significantly higher (p<0.01) in Group Fe than in Group C. TC (p<0.05) and LPO levels (p<0.01) were lower in Group Fe+R than in Group Fe. Our data suggest that RJPx may inhibit LPO both in vitro and in vivo.
The aim of this study was to investigate if preadministration with Ganoderma lucidum spore (GLS) could (1) alleviate oxidative stress and mitochondrial dysfunction in rat hippocampus of intracerebroventricular (ICV) injection of streptozotocin (STZ), (2) protect neurons from apoptosis, and (3) improve cognitive dysfunction. Three groups of Sprague-Dawley rats were preadministrated with GLS at doses of 2.0, 4.0 and 8.0g/kg, respectively, for 3 weeks before the ICV STZ injury. Thereafter the rats were operated with ICV STZ (1.5mg/kg) bilaterally on days 1 and 3. The behavioral alterations, oxidative stress indexes, ATP, cytochrome oxidase (CytOx), and histopathology of hippocampal neurons were studied. The results showed that ICV STZ model rats exhibited a significant increase of malondialdehyde (MDA), a significant decrease of glutathione reductase (GR), reduced glutathione (GSH), ATP and CytOx, accompanied with marked impairments in spatial learning and memory, and severe damage of hippocampal neuron. In conclusion, preadministration with GLS at dose of 8.0g/kg in ICV STZ rats significantly reversed these abnormalities. In conclusion, preadministration with GLS might protect hippocampus from oxidative impairment and energy metabolism disturbance of ICV STZ. This may also provide useful information for future research on the pathogenesis and prevention of Alzheimer's disease (AD).
Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by a decline in cognitive function and severe neuronal loss in the cerebral cortex and certain subcortical regions of the brain including nucleus basalis magnocellularis (NBM) that play an important role in learning and memory. There are few therapeutic regimens that influence the underlying pathogenic phenotypes of AD, however, of the currently available therapies, exercise training is considered to be one of the best strategies for attenuating the pathological phenotypes of AD for people with AD. Here, we sought to investigate the effect of treadmill running on spatial memory in Alzheimer-induced rats. Male Wistar rats were split into two groups namely shams (n=7) and lesions with the lesion group subdivided further into the lesion-rest (n=7) and lesion-exercise (n=7). The lesion-exercise and shams were subjected to treadmill running at 17 meters per minute (m/min) for 60 min per day (min/day), 7 days per week (days/wk), for 60 days. Spatial memory was investigated using the Morris Water Maze test in the rats after 60 days of Alzheimer induction and the exercise. Our data demonstrated that spatial memory was indeed impaired in the lesion group compared with the shams. However, exercise notably improved spatial memory in the lesion-exercised rats compared to lesion-rested group. The present results suggest that spatial memory is affected under Alzheimer conditions and that treadmill running improves these effects. Our data suggested that treadmill running contributes to the alleviation of the cognitive decline in AD.
The present study was undertaken to investigate possible mechanism of pioglitazone-induced beneficial effect in memory deficits associated with experimental dementia. Dementia was induced in Swiss albino mice by administration of streptozotocin (STZ; 3 mg/kg administered intracerebroventricularly on 1st & 3rd day). Morris Water-Maze test was employed to assess learning and memory of the animals. Brain acetylcholinesterase (AChE) activity was measured by Ell Mann's method. Brain thiobarbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively to assess total oxidative stress. Blood glucose level was also measured. Streptozotocin (STZ) produced a significant decrease in water-maze performance of mice hence reflecting loss of learning and memory. Pioglitazone (20 mg/kg p.o. daily for 14 days) successfully attenuated STZ-induced memory deficits, without any significant per se effect on blood glucose levels. Higher levels of brain AChE activity, TBARS and lower levels of GSH were observed in STZ treated animals, which were significantly attenuated by pioglitazone. Further, the noted beneficial effect of pioglitazone on STZ-induced dementia was significantly abolished by pre-treatment of nitric oxide (NO) synthase inhibitor L-NAME (3 mg/kg i.p.) manifested in the terms of decrease in water-maze performance and increase in brain AChE activity as well as oxidative stress. It is concluded that anti-dementic effect of pioglitazone may involve central cholinergic, oxidative and NO pathways.
It has been demonstrated that exercise has neuroprotective effects in the central nervous system (CNS), especially in hippocampus. Previous studies have indicated that diabetes mellitus affects synaptic plasticity in the hippocampus leading to impairments in learning and memory. The aim of this study was to evaluate the effects of treadmill running on synaptic plasticity at dentate gyrus (DG) of streptozotocin-induced diabetic rats. Experimental groups were the control, the diabetes and the diabetes-exercise groups. Long-term potentiation (LTP) in perforant path-DG synapses was assessed (by 400Hz tetanization) in order to investigate the effect of exercise on synaptic plasticity. Field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude were measured. With respect to the control group, fEPSP were significantly decreased in the diabetes group. However, there were no differences between responses of the diabetes-exercise group and the control. The present results suggest that LTP induction in the dentate gyrus is affected under diabetic conditions and that treadmill running prevents these effects. The data suggest that treadmill running protect against diabetes-induced decrease of learning ability and memory function of the hippocampus.