Bee Venom Component Inhibits Tumor Cell Growth

Melittin suppresses cathepsin S-induced invasion and angiogenesis via blocking of the VEGF-A/VEGFR-2/MEK1/ERK1/2 pathway in human hepatocellular carcinoma

Oncol Lett. 2016 Jan;11(1):610-618

Melittin, a significant constituent of Apis mellifera (honeybee) venom, is a water-soluble toxic peptide that has traditionally been used as an antitumor agent. However, the underlying mechanisms by which it inhibits tumor cell growth and angiogenesis remain to be elucidated.

In the present study, screening for increased cathepsin S (Cat S) expression levels was performed in MHCC97-H cells and various other hepatocellular carcinoma cell lines by reverse transcription-polymerase chain reaction and western blot analysis. A pcDNA3.1-small hairpin RNA (shRNA)-Cat S vector was stably transfected into MHCC97-H cells (shRNA/MHCC97-H) in order to knockdown the expression of Cat S. The effects resulting from the inhibition of Cat S-induced proliferation, invasion and angiogenesis by melittin were examined using cell proliferation, cell viability, flat plate colony formation, migration, wound healing, Transwell migration and ELISA assays.

In order to substantiate the evidence for melittin-mediated inhibition of Cat S-induced angiogenesis, Cat S RNA was transfected into primary human umbilical vein endothelial cells (Cat S-HUVECs) to induce overexpression of the Cat S gene. The effects of melittin on HUVECs were examined using Transwell migration and tube formation assays.

The findings demonstrated that melittin was able to significantly suppress MHCC97-H cell (Mock/MHCC97-H) proliferation, invasion and angiogenesis, as well as capillary tube formation of Cat S-HUVECs, in a dose-dependent manner. However, proliferation, invasion and angiogenesis in shRNA/MHCC97-H and in native HUVECs (Mock-HUVECs) were unaffected. In addition, melittin specifically decreased the expression of phosphorylated (activated) Cat S, and components of the vascular endothelial growth factor (VEGF)-A/VEGF receptor 2 (VEGFR-2)/mitogen-activated protein kinase kinase 1 (MEK1)/extracellular signal-regulated kinase (ERK)1/2 signaling pathway in Mock/MHCC97-H cells.

In conclusion, the inhibition of tumor cell growth and anti-angiogenic activity exerted by melittin may be associated with anti-Cat S actions, via the inhibition of VEGF-A/VEGFR-2/MEK1/ERK1/2 signaling.

Stingless Bee Honeys Effective Against Multidrug-Resistant Bacteria

Antibacterial synergic effect of honey from two stingless bees: Scaptotrigona bipunctata Lepeletier, 1836, and S. postica Latreille, 1807

Sci Rep. 2016 Feb 12;6:21641

Several studies have tested antimicrobial activity of combinations of honey and various substances.

In this study, we tested a combination of two stingless bee honeys against various bacterial strains. In particular: the antibacterial activity of honeys produced by Scaptotrigona bipunctata (SB) and Scaptotrigona postica (SP) was evaluated against Gram-positive and Gram-negative bacterial strains by agar well diffusion assays, minimum inhibitory concentration (MIC) assessment, construction of growth and viability curves and scanning electron microscopy (SEM).

The interaction of the two honeys was also evaluated by the checkerboard assay. Inhibition zones ranged from 8 to 22 mm. The MIC values of the individual honeys ranged from 0.62 to 10% (v v(-1)) and decreased to 1/4 to 1/32 when the honeys were combined. SEM images showed division inhibition and cell wall disruption for the SB and SP honeys, respectively, and these alterations were observed in same field when the SB and SP honeys were combined.

This study demonstrated that the natural honeys possess in vitro antimicrobial activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. Combination of the SB and SP honeys could lead to the development of new broad-spectrum antimicrobials that have the potential to prevent the emergence of resistant bacterial strains.

Royal Jelly Enhances Brain Levels of Dopamine

Nutrition and dopamine: An intake of tyrosine in royal jelly can affect the brain levels of dopamine in male honeybees (Apis mellifera L.)

Journal of Insect Physiology
Volume 87, April 2016, Pages 45–52

Precursors of neuroactive substances can be obtained from dietary sources, which can affect the resulting production of such substances in the brain. In social species, an intake of the precursor in food could be controlled by social interactions. To test the effects of dietary tyrosine on the brain dopamine levels in social insect colonies, male and worker honeybees were fed tyrosine or royal jelly under experimental conditions and the brain levels of dopamine and its metabolite were then measured. The results showed that the levels of dopamine and its metabolite in the brains of 4- and 8-day-old workers and 8-day-old males were significantly higher in tyrosine-fed bees than in control bees, but the levels in 4-day-old males were not. The brain levels of dopamine and its metabolite in 4- and 8-day-old males and workers were significantly higher in royal jelly-fed bees than in control bees, except for one group of 4-day-old workers. Food exchanges with workers were observed in males during 1–3 days, but self-feedings were also during 5–7 days. These results suggest that the brain levels of dopamine in males can be controlled by an intake of tyrosine in food via exchanging food with nestmates and by self-feeding.

Audio: Manuka Honey Kills Germs

Manuka kills germs, Korean barbershop, backpacker taxes and First Dog on RN Afternoons

ABC, 2/7/2016

We happily trust the food we eat until someone tells us not to - honey in just a moment, and lettuce as part of our coverage of rural news including farmer reaction to cuts in climate change reserach jobs inside the CSIRO.

Manuka: the Healing Honey

Manuka honey’s powerful properties can help combat infections, heal wounds, clear up skin conditions and give a daily energy boost.

Women's Weekly

The manuka is a small tree with aromatic leaves and is native to New Zealand and Tasmania. The honey is produced when bees pollinate the flowers of the bush.

Not all honey collected from the manuka tree (Leptospermum scoparium) has antibacterial properties. It is laboratory tested first to determine whether it is active.

The higher the activity, the higher the rating – and the price.

In Australia, the tree used to make manuka honey is called the jelly bush. Australian jelly bush honey has been found to share the same properties as manuka honey, according to researchers from the University of Waikato in New Zealand, with both possessing the high level of additional non-peroxide, antibacterial components, which are stronger than other hydrogen peroxide types of honey.

Honey an Effective and Economical in Managing Large and Complicated Wounds

Biological properties and therapeutic activities of honey in wound healing: A narrative review and meta-analysis

J Tissue Viability. 2016 Jan 23. pii: S0965-206X(15)00097-2

For thousands of years, honey has been used for medicinal applications. The beneficial effects of honey, particularly its anti-microbial activity represent it as a useful option for management of various wounds. Honey contains major amounts of carbohydrates, lipids, amino acids, proteins, vitamin and minerals that have important roles in wound healing with minimum trauma during redressing.

Because bees have different nutritional behavior and collect the nourishments from different and various plants, the produced honeys have different compositions. Thus different types of honey have different medicinal value leading to different effects on wound healing.

This review clarifies the mechanisms and therapeutic properties of honey on wound healing.

The mechanisms of action of honey in wound healing are majorly due to its hydrogen peroxide, high osmolality, acidity, non-peroxide factors, nitric oxide and phenols. Laboratory studies and clinical trials have shown that honey promotes autolytic debridement, stimulates growth of wound tissues and stimulates anti-inflammatory activities thus accelerates the wound healing processes. Compared with topical agents such as hydrofiber silver or silver sulfadiazine, honey is more effective in elimination of microbial contamination, reduction of wound area, promotion of re-epithelialization. In addition, honey improves the outcome of the wound healing by reducing the incidence and excessive scar formation.

Therefore, application of honey can be an effective and economical approach in managing large and complicated wounds.

Video Report on Medicinal Use of Australian Jellybush (Manuka) Honey

ABC

PIP COURTNEY, PRESENTER: We recently did a story on the manuka honey industry in New Zealand and now it seems it's Australia's turn. Here it was once fed to cattle because of its bitter taste. But jellybush, or manuka honey, could be the saviour of Australia's honey industry. After years of decline, the industry could have access to a billion-dollar market, with new research identifying the trees which produce manuka honey in every Australian state. Sean Murphy reports.


SEAN MURPHY, REPORTER: In the Northern Rivers region of New South Wales, they're searching for one of nature's miracles. It's a special tree with the nectar that helps produce manuka honey.

WOMAN: This honey has literally saved lives.

MAN: We don't end up with resistant infections that are much harder to treat with antibiotics.

AUDIO: Manuka Honey Replaces Antibiotics in Hospitals

ABC

Three Australian universities have teamed up to explore the eighty species of Manuka that could transform the local honey industry from just food to medical saviours.

Primarily produced in New Zealand, Manuka is so effective at preventing infection it's now in high demand in hospitals where anti-biotic resistant bacteria like staphylococcus plays havoc with patient health.

Australian Producers Set to Tap Global Market for Medicinal Honey

Liquid gold rush beckons for Australian honey producers as research identifies best antimicrobial nectar

ABC, 2/5/2016

Australian honey producers are set to tap into a potential billion-dollar global market for medicinal honey, with new research confirming powerful antimicrobial properties in the flowering nectar of trees found across Australia.

The joint study by three Australian universities is testing up to 86 different species of Leptospermum, 10 times more than are found across the Tasman, where the trees are the basis of New Zealand's burgeoning manuka honey industry.

Therapeutic Potential of Brazilian Red Propolis

A pharmacological perspective on the use of Brazilian Red Propolis and its isolated compounds against human diseases

Eur J Med Chem. 2016 Jan 20;110:267-279

Propolis is a complex resinous mixture collected by bees, with high medicinal, historical and economic value. The nutraceutical and pharmacological benefits of propolis have been extensively explored in several fields of medicine as an important resource for prevention and treatment of oral and systemic diseases.

A relatively new type of propolis, named red propolis (in Brazil, Brazilian Red Propolis - BRP), has been arousing attention for the promising pharmacological properties of some of its isolated compounds (vestitol, neovestitol, quercetin, medicarpin, formononetin, etc). Due to a distinct chemical composition, BRP and its isolated compounds (mainly isoflavones) affect a wide range of biological targets and could have an impact against numerous diseases as an antimicrobial, anti-inflammatory and immunomodulatory, antioxidant and antiproliferative agent.

In this review, we comprehensively address the main aspects related to BRP bioprospection, chemistry and therapeutic potential. Further information is provided on mechanisms of action discovered thus far as well as clinical use in humans and regulatory aspects. As of now, BRP and its isolated molecules remain a fascinating topic for further research and application in biomedical areas and dentistry.

Korean Bee Pollen Shows Neuraminidase Inhibitory Activity

Characterization of Neuraminidase Inhibitors in Korean Papaver rhoeas Bee Pollen Contributing to Anti-Influenza Activities In Vitro

Planta Med. 2016 Feb 5

The active constituents of Korean Papaver rhoeas bee pollen conferring neuraminidase inhibitory activities (H1N1, H3N2, and H5N1) were investigated. Six flavonoids and one alkaloid were isolated and characterized by nuclear magnetic resonance and mass spectrometry data. These included kaempferol-3-sophoroside (1), kaempferol-3-neohesperidoside (2), kaempferol-3-sambubioside (3), kaempferol-3-glucoside (4), quercetin-3-sophoroside (5), luteolin (6), and chelianthifoline (7).

All compounds showed neuraminidase inhibitory activities with IC50 values ranging from 10.7 to 151.1 µM. The most potent neuraminidase inhibitor was luteolin, which was the dominant content in the ethyl acetate fraction. All tested compounds displayed noncompetitive inhibition of H3N2 neuraminidase. Furthermore, compounds 1-7 all reduced the severity of virally induced cytopathic effects as determined by the Madin-Darby canine kidney cell-based assay showing antiviral activity with IC50 values ranging from 10.7 to 33.4 µM (zanamivir: 58.3 µM).

The active compounds were quantified by high-performance liquid chromatography, and the total amount of compounds 1-7 made up about 0.592 g/100 g bee pollen, contributing a rich resource of a natural antiviral product.

Flavonoid Present in Honey and Propolis Improves Glycemic Control

Role of chrysin on expression of insulin signaling molecules

J Ayurveda Integr Med. 2015 Oct-Dec;6(4):248-58

BACKGROUND:

Currently available drugs are unsuccessful for the treatment of tye-2 diabetes due to their adverseside-effects. Hence, a search for novel drugs, especially ofplant origin, continues. Chrysin (5,7-dihydroxyflavone) is a flavonoid, natural component of traditional medicinal herbs, present in honey, propolis and many plant extracts that hasbeen used in traditional medicine around the world to treat numerous ailments.

OBJECTIVE:

The present study was aimed to identify the protective role of chrysin on the expression of insulin-signaling molecules in the skeletal muscle of high fat and sucrose-induced type-2 diabetic adult male rats.

MATERIALS AND METHODS:

The oral effective dose of chrysin (100 mg/kg body weight) was given once a day until the end of the study (30 days post-induction of diabetes) to high fat diet-induced diabetic rats. At the end of the experimental period, fasting blood glucose, oral glucose tolerance, serum lipid profile, lipid peroxidation (LPO) and free radical generation, as well as the levels of insulin signaling molecules and tissue glycogen in the gastrocnemius muscle were assessed.

RESULTS:

Diabetic rats showed impaired glucose tolerance and impairment in insulin signaling molecules (IR, IRS-1, p-IRS-1Tyr(632), p- Akt(Thr308)), glucose transporter subtype 4 [GLUT4] proteins and glycogen concentration. Serum insulin, lipid profile, LPO and free radical generation were found to be increased in diabetic control rats. The treatment with chrysin normalized the altered levels of blood glucose, serum insulin, lipid profile, LPO and insulin signaling molecules as well as GLUT4 proteins.

CONCLUSION:

Our present findings indicate that chrysin improves glycemic control through activation of insulin signal transduction in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic male rats.

Water-Soluble Royal Jelly May Help Treat Skin Pigmentation

Whitening Effect of Watersoluble Royal Jelly from South Korea

Korean J Food Sci Anim Resour. 2015;35(5):707-13

Royal jelly has been widely used as a health supplement worldwide. However, royal jelly has been implicated in allergic reactions, and we developed a water-soluble royal jelly (WSRJ) without the allergy inducing protein.

In this study, we aimed to identify the anti-melanogenic efficacy of WSRJ. B16F1 melanoma cells were first treated with 10 nM α-melanocyte stimulating hormone (α-MSH) and then with various doses of WSRJ. In addition, we investigated the mRNA and protein expression of melanogenesis-related genes such as tyrosinase, tyrosinase related protein-1 (TRP-1) and TRP-2 by reverse transcription-polymerase chain reaction and western blotting.

WSRJ directly inhibited tyrosinase and cellular tyrosinase activity, which decreased melanin synthesis in α-MSH stimulated B16F1 melanoma cells a level comparable to that observed with arbutin. WSRJ decreased the mRNA and protein expressions of tyrosinase, TRP-1, and TRP-2, which was comparable to that observed with arbutin. WSRJ has strong anti-melanogenic activity, which invoice direct inhibition of tyrosinase enzyme activity and suppression of expression of melanogenesis related genes.

Results from this study suggests that WSRJ is a potential candidate for the treatment of skin pigmentation.

Propolis had Significant Antifungal Activity

Antifungal Activity of Propolis Against Yeasts Isolated From Blood Culture: In Vitro Evaluation

J Clin Lab Anal. 2016 Jan 20

BACKGROUND:

Due to the failure of available antifungal agents in the treatment of candidemia and the toxic activities of these drugs, a lot of researches are being conducted to develop new nontoxic and effective antifungal agents for optimal control of fungal pathogens. The aim of this study is to evaluate the in vitro antifungal activity of propolis against yeasts isolated from the blood cultures of intensive care unit patients.

METHODS:

Seventy-six strains were included in this study. The in vitro antifungal activity of propolis, fluconazole (FLU), and itraconazole (ITR) was investigated by the microdilution broth methods (CLSI guidelines M27-A3 for yeast). The propolis sample was collected from Kayseri, Turkey.

RESULTS:

Of the 76 isolates, 33 were identified as Candida albicans while 37 were C. parapsilosis, three were C. tropicalis, and three were identified as C. glabrata. The geometric mean range for MIC (μg/ml) with regard to all isolates was 0.077 to 3 μg/ml for FLU and ITR, and 0.375 to 0.70 μg/ml for propolis. It was shown that propolis had significant antifungal activity against all Candida strains and the MIC range of propolis was determined as 0185 to 3 μg/ml.

CONCLUSION:

This study demonstrated that propolis had significant antifungal activity against yeasts isolated from blood culture compared with FLU and ITR. The propolis MIC in azole-resistant strains such as C. glabrata was found lower than the FLU MIC.

Bee Venom Boosts Wound Healing

Bee Venom Accelerates Wound Healing in Diabetic Mice by Suppressing Activating Transcription Factor-3 (ATF-3) and Inducible Nitric Oxide Synthase (iNOS)-Mediated Oxidative Stress and Recruiting Bone Marrow-Derived Endothelial Progenitor Cells

J Cell Physiol. 2016 Jan 30

Multiple mechanisms contribute to impaired diabetic wound healing including impaired neovascularization and deficient endothelial progenitor cell (EPC) recruitment. Bee venom (BV) has been used as an anti-inflammatory agent for the treatment of several diseases. Nevertheless, the effect of BV on the healing of diabetic wounds has not been studied.

Therefore, in this study, we investigated the impact of BV on diabetic wound closure in a type I diabetic mouse model. Three experimental groups were used: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated with BV. We found that the diabetic mice exhibited delayed wound closure characterized by a significant decrease in collagen production and prolonged elevation of inflammatory cytokines levels in wounded tissue compared to control non-diabetic mice. Additionally, wounded tissue in diabetic mice revealed aberrantly up-regulated expression of ATF-3 and iNOS followed by a marked elevation in free radical levels. Impaired diabetic wound healing was also characterized by a significant elevation in caspase-3, -8 and -9 activity and a marked reduction in the expression of TGF-β and VEGF, which led to decreased neovascularization and angiogenesis of the injured tissue by impairing EPC mobilization. Interestingly,

BV treatment significantly enhanced wound closure in diabetic mice by increasing collagen production and restoring the levels of inflammatory cytokines, free radical, TGF-β and VEGF. Most importantly, BV-treated diabetic mice exhibited mobilized long-lived EPCs by inhibiting caspase activity in the wounded tissue. Our findings reveal the molecular mechanisms underlying improved diabetic wound healing and closure following BV treatment.