Propolis Component Protects Kidneys

Caffeic Acid Phenethyl Ester Protects Against Oxidative Stress-Related Renal Dysfunction in Rats Treated with Cyclosporin A
Fundamental & Clinical Pharmacology, Early View (Articles online in advance of print)

The therapeutic index of cyclosporin A (CsA), an immunosuppressive drug, is limited by its nephrotoxic effect. Oxidative stress is suggested to play a crucial role as pathogenic factors.

The present study aimed at investigating the effects of caffeic acid phenethyl ester (CAPE), a phenolic antioxidant, on renal function, morphology, and oxidative stress following CsA treatment.

Rats were treated with vehicle, CsA (50 mg/kg), and CsA plus CAPE (10 and 30 μmol/kg) for 10 days. Renal function, histopathology, and tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels were evaluated 24 h after the last treatment.

CsA produced nephrotoxicity as indicated by a significant increase in serum creatinine and blood urea nitrogen, but decrease creatinine and urea clearance compared to those treated with vehicle. Severe vacuolations and tubular necrosis were evident in the kidney of CsA-treated rats. CsA also increased renal MDA and decreased GSH content significantly. Administration of CAPE along with CsA restored all the changes caused by CsA.

These results clearly demonstrate the pivotal role of oxidative stress and its relation to renal dysfunction and also point to the protective potential of CAPE against CsA nephrotoxicity. The protection afforded by CAPE is mediated, at least in part, through inhibiting renal lipid peroxidation and enhancing or maintaining the antioxidant glutathione content.

Royal Jelly Fatty Acids Studied

The Absolute Configurations of Hydroxy Fatty Acids from the Royal Jelly of Honeybees (Apis mellifera)
Lipids, 2010 Nov 17

9-Hydroxy-2E-decenoic acid (9-HDA) is a precursor of the queen-produced substance, 9-oxo-2E-decenoic acid (9-ODA), which has various important functions and roles for caste maintenance in honeybee colonies (Apis mellifera).

9-HDA in royal jelly is considered to be a metabolite of 9-ODA produced by worker bees, and it is fed back to the queen who then transforms it into 9-ODA.

Recently we found that 9-HDA is present in royal jelly as a mixture of optical isomers (R:S, 2:1). The finding leads us to suspect that chiral fatty acids in royal jelly are precursors of semiochemicals.

Rather than looking for semiochemicals in the mandibular glands of the queen bee, this study involves the search for precursors of pheromones from large quantities of royal jelly.

Seven chiral hydroxy fatty acids, 9,10-dihydroxy-2E-decenoic, 4,10-dihydroxy-2E-decenoic, 4,9-dihydroxy-2E-decenoic, 3-hydroxydecanoic, 3,9-dihydroxydecanoic, 3,11-dihydroxydodecanoic, and 3,10-dihydroxydecanoic acids were isolated.

The absolute configurations of these acids were determined using the modified Mosher's method, and it was revealed that, similar to 9-HDA, five acids are present in royal jelly as mixtures of optical isomers.

Study Examines Anti-Inflammatory Action of Chinese Propolis

Inhibitory Effect of Chinese Propolis on Phosphatidylcholine-Specific Phospholipase C Activity in Vascular Endothelial Cells
Evidence-Based Complementary and Alternative Medicine, Volume 2011 (2011)

To understand the mechanisms underlying the anti-inflammatory action of Chinese propolis, we investigated its effect on the activity of phosphatidylcholine-specific phospholipase C (PC-PLC) that plays critical roles in control of vascular endothelial cell (VEC) function and inflammatory responses. Furthermore, p53 and reactive oxygen species (ROS) levels and mitochondrial membrane potential (Δψm) were investigated.

Our data indicated that treatment of Chinese propolis 6.25 and 12.5 μg/ml for 12 hours increased VEC viability obviously. Exposure to Chinese propolis 6.25, 12.5, and 25 μg/ml for 6 and 12 hours significantly decreased PC-PLC activity and p53 level, and ROS levels were depressed by Chinese propolis 12.5 μg/ml and 25 μg/ml dramatically.

The Δψm of VECs was not affected by Chinese propolis at low concentration but disrupted by the propolis at 25 μg/ml significantly, which indicated that Chinese propolis depressed PC-PLC activity and the levels of p53 and ROS in VECs but disrupted Δψm at a high concentration.

New Purification Method Creates Water-Soluble Propolis

New Method to Purify Propolis for Mouth Ulcer Gel Source: University of Bradford

The healing properties of propolis - a mixture of resin and wax made by honey bees to seal and sterilise their hives - have been known for many years. But its use in medicine and food supplements has been limited because the sticky substance is not water soluble and has a strong, off-putting smell.

Now researchers at the University of Bradford's Centre for Pharmaceutical Engineering Science have developed a way of purifying propolis that retains its medicinal properties, but makes it dissolve in water and eliminates its pungent smell. The technique has already led to the development of a new mouth ulcer gel and opens the door to a huge range of other pharmaceutical and nutraceutical applications for the substance.

"Propolis is a complex chemical mix and a very useful natural product," explains Centre Director, Professor Anant Paradkar, who led the research. "Propolis has been shown to be anti-microbial, anti-fungal, a strong anti-oxidant, non-allergenic and can boost the immune system. It also promotes wound healing and has anaesthetic properties…

Honey Can Help Manage Wound Odor

Managing Wound Odor #218
Journal of Palliative Medicine, October 2010: 1286-1287

Honey can be bacteriocidal, and has been increasingly studied for wound healing.

There is some evidence that it decreases odor.

Honey Bees Show That Diet May Alter DNA

Bees Prove a Good Diet Can Set Our Path in Life
By Bridie Smith, Sydney Morning Herald, 11/16/2010

YOU are what you eat. Grow up eating a nutrition-rich diet of royal jelly and you will become, well, royalty. Stick to honey and you are destined for life as a worker.

That is the way it is for honey bees, research published in the journal PLoS Biology shows.

But the research, led by Ryszard Maleszka, of the Australian National University's college of medicine, biology and environment, has implications for humans, too. The findings suggest environmental factors such as diet could modify the ''genetic hardware'' of the human brain, as was the case with the research that found diet not only influenced bee behaviour but its DNA.

Advertisement: Story continues below Two groups of genetically identical female bees developed from differentially fed larvae were studied at the ANU and the German Cancer Institute researchers. One group was fed highly nutritious royal jelly; the others honey. The results showed the honey-fed bees became the workers while those fed royal jelly became queen bees. But most significantly, a difference emerged in the two groups' DNA.

The implications for human health emerge because the enzymes that mark the DNA in the bee are the same ones that mark DNA in human brains...

Propolis Component Blocks Tumor Growth

Antitumor Progression Potential of Caffeic Acid Phenethyl Ester Involving p75(NTR) in C6 Glioma Cells
Chem Biol Interact, 2010 Dec 5;188(3):607-15

The previous data showed that caffeic acid phenethyl ester (CAPE), a component of propolis, possesses inducing cell cycle arrest and antiproliferation effect on C6 glioma cells in vitro and in vivo.

In the present study, C6 glioma cells treated with CAPE resulted in morphological changes to an astrocytic phenotype and increased the expression of glial differentiation marker proteins including glial fibrillary acidic protein (GFAP) and S-100β.

In addition, with scratch assay and Boyden chamber assay, CAPE exhibited inhibitory effects on the motility and invasion of C6 glioma cells. Furthermore, CAPE induced the expression of nerve growth factor (NGF) and p75 neurotrophin receptor (p75(NTR)), which were involved in neural cell differentiation.

CAPE could also inhibit the activity of matrix metalloproteinases (MMPs) and induce the expression of RhoB, a tumor suppressor. To examine the involvement of p75(NTR) in the anti-invasive property of CAPE, Western blotting and Boyden Chamber assay were performed by addition of an anti-p75(NTR) antibody in C6 cells.

The results showed that blocking p75(NTR) could decrease the CAPE-induced expression of RhoB and the inactivation of MMP-2, -9 as well as the anti-invasion effect in C6 glioma cells. Furthermore, CAPE suppressed IκB-α phosphorylation which was down stream of p75(NTR).

Finally, the effect of CAPE on metastasis by lung colonization of the tumor cell in nude mice was also evaluated. It was found that the groups of nude mice injected with CAPE-pretreated cells could decrease both lung size and weight as compared to the positive control group which did not receive CAPE treatment. In addition, histological examination of the mouse lung sections showed that the CAPE-treated group inhibited the metastasis of C6 glioma cells.

These data suggest CAPE possesses antitumor progression potential.

Trace Mineral Content Helps Determine Propolis Origin

Trace Mineral Content of Argentinean Raw Propolis by Neutron Activation Analysis (NAA): Assessment of Geographical Provenance by Chemometrics
LWT - Food Science and Technology, Volume 44, Issue 1, January 2011, Pages 256-260

Multielement analysis of raw propolis samples, collected from different central Argentinean regions, was carried out by Neutron Activation Analysis (NAA) aiming at developing a reliable method in their traceability.

This work presents a characterization of 96 raw propolis samples selected from three different geographical origins in middle region of Argentina.

Multivariate chemometric techniques, such as Principal Component Analysis (PCA), were applied to perform a preliminary study of the data structure. Two supervised pattern recognition procedures including stepwise linear discriminant analysis (LDA) and K-nearest neighbors (kNN) were used to classify samples into the three categories considered on the basis of the chemical data.

Eight trace elements (Br, Co, Cr, Fe, Rb, Sb, Sm and Zn) were selected by stepwise-LDA explaining the classification of propolis according to their geographical origin. Application of k-nearest neighbor classification procedure to these eight selected variables produced a good correlation (98% correct classification ratio) of propolis with its provenance.

The trace element profiles provided sufficient information to develop classification rules for propolis identification according to their provenance.

Bee Venom May Help Reduce Fatty Deposits in Arteries

Bee Venom Reduces Atherosclerotic Lesion Formation via Anti-Inflammatory Mechanism
Am J Chin Med, 2010;38(6):1077-92

The components of bee venom (BV) utilized in the current study were carefully scrutinized with chromatography. Despite its well documented anti-inflammatory property, there are no reports regarding the influence of BV on the expression of cellular adhesion molecules in the vascular endothelium.

A great amount of information exists concerning the effects of an atherogenic diet on atherosclerotic changes in the aorta, but little is known about the molecular mechanisms and the levels of gene regulation involved in the anti-inflammatory process induced by BV.

The experimental atherosclerosis was induced in mice by a lipopolysaccharide (LPS) injection and an atherogenic diet. The animals were divided into three groups, the NC groups of animals that were fed with a normal diet, the LPS/fat group was fed with the atherogenic diet and received intraperitoneal injections of LPS, and the LPS/fat + BV group was given LPS, an atherogenic diet and intraperitoneal BV injections. At the end of each treatment period, the LPS/fat + BV group had decreased levels of total cholesterol (TC) and triglyceride (TG) in their serum, compared to the LPS/fat group.

The LPS/fat group had significant expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the serum, compared with the NC group (p < 0.05). The amount of cytokines reduced consistently in the BV treatment groups compared with those in LPS/fat group.

BV significantly reduced the amount of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), transforming growth factor-β1 (TGF-β1) and fibronectin in the aorta, compared with the LPS/fat group (p < 0.05). A similar pattern was also observed in the heart.

In conclusion, BV has anti-atherogenic properties via its lipid-lowering and anti-inflammatory mechanisms.

Melittin is Effective Anti-Arthritis Component of Bee Venom

The Anti-Arthritic Effects of Synthetic Melittin on the Complete Freund's Adjuvant-Induced Rheumatoid Arthritis Model in Rats
Am J Chin Med, 2010;38(6):1039-49

Bee venom (BV) has been used for millennia in Chinese traditional medicine to treat rheumatoid arthritis (RA). However, its components and mechanism remain unclear, which has hampered its development and application for the treatment of RA.

In this study, we examined the anti-arthritis effects of melittin, which composes nearly 50% of the dry weight of whole BV, on the complete Freund's adjuvant-induced (CFA-induced) RA model in rats.

The RA animal models were treated with solutions of BV, melittin, and saline by injection into a specific acupoint (Zusanli).

The BV and melittin treatments statistically diminished the thickness of the arthroses in the injected side of the paw, compared to the saline treatment. Melittin therapy also significantly reduced arthritis-induced nociceptive behaviors, as assessed by the thermal hyperalgesia test. In addition, CFA-induced Fos expression in the superficial layer of the lumbar spinal cord was significantly suppressed by the BV and melittin treatments, compared to the saline treatment.

These results indicate that melittin is an effective anti-arthritis component of whole bee venom, making it a promising candidate as an anti-arthritis drug.

Bee Venom Gel Offers Contraception, HIV Protection

Unconventional Idea for Antiviral Contraceptive Gel Wins Gates Foundation Grant
EurekAlert

A vaginal gel that affords both contraception and HIV protection using nanoparticles that carry bee venom is one of the bold, unconventional ideas that won a 2010 Grand Challenges Explorations grant from the Bill & Melinda Gates Foundation.

Grand Challenges Explorations is a Gates Foundation initiative to foster innovative projects in areas where unorthodox thinking is most urgently needed. Recipients receive grants to explore creative solutions to global health issues.

Sam Wickline, MD, professor of medicine, of cell biology and physiology, of physics and of biomedical engineering at Washington University School of Medicine in St. Louis is one of 65 scientists selected in November to participate in the grant program.

Wickline proposes to develop a contraceptive, antiviral gel containing trillions of nanoparticles that will target both HIV and sperm and deliver a bee venom toxin that will incapacitate them.

"Sperm and HIV (the human immunodeficiency virus that can lead to acquired immune deficiency syndrome, or AIDS) are remarkably similar in their natural mechanism of genetic transmission," Wickline says. "Both need to fuse with their target cell in order to deliver their genetic payloads ? DNA in the case of sperm, and RNA in the case of HIV."

Wickline's plan is to use the very means by which sperm and HIV operate to destroy them...

A toxin derived from the substance bees insert into their victims when they sting is the agent that will destroy the sperm and HIV. The toxin, called melittin, comprises more than half of the dry weight of the venom of the honeybee Apis mellifera.

The nanoparticles will carry a synthetic version of the toxin melittin to the targets.

"Cells readily take in melittin," Wickline says. "But once it gets in, it pokes holes in cell membranes destroy the cells."

A local biotech startup company, Kereos Inc., is testing melittin as an anti-cancer agent.

Since melittin can annihilate almost any cell, the trick is to target the melittin to the specific cells intended for destruction (cancer, sperm, HIV) without causing collateral damage to other cells in the body.

Wickline and colleague Paul Schlesinger, MD, PhD, associate professor of cell biology and physiology, attacked that problem two years ago when they developed "nanobees," the name coined for nanoparticles that sequester melittin so that it neither harms healthy tissue nor is degraded before it reaches the intended target.

Wickline and his colleagues have also developed the ability to add agents to the nanobees to cause them to home in on specific target cells. Although nanoparticles are a few thousand times smaller than the dot above an "i," each can carry hundreds of thousands of molecules on its surface...

Canadian Honey Antioxidant, Antibacterial Activity Examined

The Relationship Between the Content of Maillard Reaction-Like Products and bioaCtivity of Canadian Honeys
Food Chemistry, Volume 124, Issue 3, 1 February 2011, Pages 869-874

Honey possesses antioxidant and antibacterial activities; however the compounds that are responsible for these activities are still under investigation.

To determine whether there are common features/compounds that underlie the antioxidant and antibacterial activities, 20 Canadian honeys were analysed using the oxygen radical absorbance capacity (ORAC) and the broth micro-dilutions assay, respectively.

Principal component analysis revealed the highest correlation between ORAC and Maillard reaction-like products (MRLP). In addition, the extremely significant correlations between ORAC, MRLPs, phenolic content and honey colour may suggest that these compounds represent the same chemical entity and exert their antioxidant activity while being part of a higher molecular weight structure. Moreover, the antioxidant activity and MRLPs were also the dominant variables contributing to the antibacterial activity against Escherichia coli however no such correlation against Bacillus subtilis.

In conclusion, MRLPs in honey appear to underlie the antioxidant and partially the antibacterial activity against E. coli.

Brazilian Propolis Effective Against Bacteria That Cause Tooth Decay

A New Type of Brazilian Propolis: Prenylated Benzophenones in Propolis from Amazon and Effects Against Cariogenic Bacteria
Food Chemistry, Volume 125, Issue 3, 1 April 2011, Pages 966-972

Ethanol extracts of four propolis samples (E1–E4) from Manaus (Brazilian Amazon) were analysed by HPLC/DAD/ESI–MS/MS and GC/EIMS. The major constituents of E2 and E4 were analysed by NMR (1H and 13C) and ESI/MS/MS.

The main constituents of E2 and E4 are polyprenylated benzophenones: 7-epi-nemorosone, 7-epi-clusianone (major E4 constituents), xanthochymol and gambogenone (major E2 constituents), making up a chemical profile so far unreported for Brazilian propolis. Aristhophenone, methyl insigninone, 18-ethyloxy-17-hydroxy-17,18-dihydroscrobiculatone B, and derivatives of dimethyl weddellianone A and B, propolones, and a scrobiculatone derivative, were detected as minor constituents. Triterpenoids (β-amyrins, β-amyrenone, lupeol and lupenone) were ubiquitous and predominant in E1 and E3.

The extracts E2 and E4 were highly active against the cariogenic bacteria Streptococcus mitis, Streptococcus mutans and Streptococcus salivarius. E2 was more active than E4, probably due to a higher content of 2-epi-nemorosone, while the latter was richer in di-hydroxylated compounds.

Honey Boosts Healing of Infected Burn Wounds

Effect of Honey on Healing of Pseudomonas aeruginosa Infected Burn Wounds in Rat
Journal of Applied Animal Research, 2010, Volume : 37, Issue : 2

To determine the effect of honey on healing of burn wounds infected with Pseudomonas aeruginosa, 57 male Sprague-Dawley 180–220 g rats were randomly divided into 3 equal groups (A-C).

Group A (control) did not receive any treatment, group B was treated with honey and group C with silver sulfadiazine.

After 24 h of burn production, 108 colony forming units (CFU) of toxigenic strains of P. aeruginosa (PA 103) were inoculated subcutaneously into the burnt area. Samples were obtained from the infected areas for the presence of P. aeruginosa on the 2nd, 7th, 14th and 21st d post burns. After 1, 2 and 3 weeks, the animals were sacrificed and burn areas were examined histologically.

Bacterial count on the d 2 was 105P. aeruginosa. On d 7, 14 and 21, there was a significant decrease in the number of bacteria in groups B and C. Re-epithelization was significantly more in honey group on d 14 in comparison to silver sulfadiazine and the control.

Based on this experiment, application of honey for treatment of burn site even infected with P. aeruoginosa could be safe. However, to clinically use this natural product more supportive trials are needed.

Propolis Flavonoid Has Neuroprotective Properties

Astaxanthin Upregulates Heme Oxygenase-1 Expression Through ERK1/2 Pathway and Its Protective Effect Against Beta-Amyloid-Induced Cytotoxicity in SH-SY5Y Cells
Brain Res, 2010 Nov 11;1360:159-67

Astaxanthin (ATX), the most abundant flavonoids in propolis, has been proven to exert neuroprotective property against glutamate-induced neurotoxicity and ischemia-reperfusion-induced apoptosis.

Previous study have revealed that ATX can rescue PC12 cells from Aβ(25-35)-induced apoptotic death. However, the mechanisms by which ATX mediates its therapeutic effects in vitro are unclear.

In the present study, we explored the underlying mechanisms involved in the protective effects of ATX on the Aβ(25-35)-induced cytotoxicity in SH-SY5Y cells.

Pre-treatment with ATX for 4h significantly reduced the Aβ(25-35)-induced viability loss, apoptotic rate and attenuated Aβ-mediated ROS production. In addition, ATX inhibited Aβ(25-35)-induced lowered membrane potential, decreased Bcl-2/Bax ratio. We also demonstrated that ATX could prevent the activation of p38MAPK kinase pathways induced by Aβ. Moreover, we for the first time have revealed the ATX increased antioxidant enzyme heme oxygenase-1 (HO-1) expression in concentration-dependent and time-dependent manners, which were correlated with its protective effect against Aβ(25-35)-induced injury. Because the inhibitor of HO-1 activity, ZnPP reversed the protective effect of ATX against Aβ(25-35)-induced cell death.

We also demonstrated that the specific ERK inhibitor, PD98059, concentration-dependently blocked on ATX-induced HO-1 expression, and meanwhile PD98059 reversed the protective effect of ATX against Aβ25-35-induced cell death.

Taken together, these findings suggest that astaxanthin can induce HO-1 expression through activation of ERK signal pathways, thereby protecting the SH-SY5Y cells from Aβ(25-35)-induced oxidative cell death.