Review of Anti-Cancer Effect of Bee Venom

Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy

Cancer Lett. 2017 May 20. pii: S0304-3835(17)30332-4

Melittin (MEL), a major peptide component of bee venom, is an attractive candidate for cancer therapy. This agent has shown a variety of anti-cancer effects in preclinical cell culture and animal model systems. Despite a convincing efficacy data against variety of cancers, its applicability to humans has met with challenges due to several issues including its non-specific cytotoxicity, degradation and hemolytic activity. Several optimization approaches including utilization of nanoparticle based delivery of MEL have been utilized to circumvent the issues.

Here, we summarize the current understanding of the anticancer effects of bee venom and MEL on different kinds of cancers. Further, we also present the available information for the possible mechanism of action of bee venom and/or MEL.

Stingless Bee Propolis May Help Treat Head and Neck Cancer

Cytotoxic Activity of Propolis Extracts from the Stingless Bee Trigona Sirindhornae Against Primary and Metastatic Head and Neck Cancer Cell Lines

Asian Pac J Cancer Prev. 2017 Apr 1;18(4):1051-1055

Background: Propolis, a resinous substance produced by the honeybee, has a wide spectrum of potent biological activities. However, anti-cancer activity of propolis obtained from Trigona sirindhornae, a new species of stingless bee, has not yet been reported. This study concerned cytotoxicity of propolis extracts from T. sirindhornae against two head and neck squamous cell carcinoma (HNSCC) cell lines.

Materials and Methods: A dichloromethane extract of propolis (DMEP) was prepared generating 3 fractions: DMEP-A, DMEP-B, and DMEP-C. Genetically-matched HNSCC cell lines derived from primary (HN30) and metastatic sites (HN31) in the same patient were used to study cytotoxic effects of the DMEPs by MTT assays. The active compounds in the DMEPs were analyzed by reversephase high performance liquid chromatography.

Results: DMEP-A exhibited cytotoxic activity on HN30 cells with significantly decreased viability at 200 μg/ml compared with the control (p < 0.05). However, no significant cytotoxic effect was evident in HN31 cells. DMEP-B and DMEP-C significantly decreased the viability of both cell lines from 100–200 μg/ml and 50–200 μg/ml, respectively (p < 0.05). Interestingly, HN31 cells were more toxically sensitive compared with the HN30 cells when treated with DMEP-B and DMEP-C. IC50 values for DMEP-B with HN30 and HN31 cells were more than 200 μg/ml and 199.8±1.05 μg/ml, respectively. The IC50 of DMEP-C to HN30 and HN31 cells was found to be 114.3±1.29 and 76.33±1.24 μg/ml, respectively. Notably, apigenin, pinocembrin, p-coumaric acid, and caffeic acid were not detected in our propolis extracts.

Conclusion: T. sirindhornae produced propolis displays cytotoxic effects against HNSCC cells s. Moreover, DMEP-B and DMEP-C differentially inhibited the proliferation of a metastatic HNSCC cell line.

Honey and Royal Jelly Protect Against Kidney Damage

Effect of Honey and Royal Jelly against Cisplatin-Induced Nephrotoxicity in Patients with Cancer

J Am Coll Nutr. 2017 May 26:1-5

OBJECTIVES:

Cisplatin constitutes one of the most potent antineoplastic drugs; however, nephrotoxicity limited its eligibility for optimal clinical use. This study was designed to evaluate the role of honey and royal jelly with antioxidant properties in the protection of cisplatin-induced acute kidney injury in patients with cancer.

METHODS:

Patients with cancer assigned for cisplatin chemotherapy were randomly divided into bee honey and royal jelly groups pretreated before the initiation and during cisplatin chemotherapeutic regimen and control group on cisplatin only. Serum creatinine and urea levels were measured before and after the chemotherapeutic cycle and over 2 cycles.

RESULTS:

Patients on crude bee honey and royal jelly capsules showed lower serum levels of renal injury products (creatinine and urea) compared to those in the control group. The changes in kidney parameters were significantly (p < 0.05) lower when compared within the bee honey group before and after cisplatin treatment. Royal jelly was found to be effective; however, the difference in creatinine and urea levels before and after chemotherapy was not statistically significant.

CONCLUSIONS:

The use of bee honey and royal jelly as natural compounds is effective in reducing cisplatin nephrotoxicity and may offer a promising chance for clinically meaningful prevention. This study has potentially important implications for the treatment of cisplatin kidney side effects and is considered to be the first to investigate this effect of honey and royal jelly in human subjects. However, due to its small sample size, we recommend further investigation using a larger sample size.

Thyme Honey Boosts Wound Healing

Evaluation of the Effects of Local Application of Thyme Honey in Open Cutaneous Wound Healing

Iran J Public Health. 2017 Apr;46(4):545-551.

BACKGROUND:

Clinicians have been searching for ways to obtain "super normal" wound healing. Honey is a traditional remedy for the treatment of infected wounds. We aimed to evaluate the wound contraction and antibacterial properties of locally produced Thyme honey on managing full-thickness wounds in vivo.

METHODS:

This experimental study was conducted in 2015, in Department of Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran on 54 adult male Wistar rats weighing 200-250 gr, and ages of 3-4 months. A square 1.5*1.5 wound was made on the back of the neck. The rats were divided into control and two experimental groups. Additionally, the control and experimental groups were separated into three subgroups corresponding to 4, 7, and 14 d of study. The control group did not receive any treatment. For histological studies, samples were taken from the wound and adjacent skin. This tissue was examined using histological staining (H&E). Wound surface and wound healing were evaluated. Data were analyzed by using one-way ANOVA with post hoc Tukey test and (P < 0.05) was significant.

RESULTS:

The macroscopic and microscopic evaluations showed that the percentage of wound healing on different days in the control and experimental groups were significant (P < 0.05).

CONCLUSION:

Using honey twice a day on open wounds will accelerate the healing process.

Acacia Honey Component Has Therapeutic Effects on Many Cancers

Sulfonation Disposition of Acacetin: In Vitro and In Vivo

J Agric Food Chem. 2017 May 25

Acacetin, an important component of acacia honey, exerts extensive therapeutic effects on many cancers. However, sulfonation disposition of acacetin has rarely been reported. Therefore, this study aims to investigate the sulfonation disposition of acacetin systematically. Results showed that acacetin-7-sulfate was the main metabolite mediated primarily by sulfotransferases (SULT) 1A1.

Dog liver S9 presented the highest formation rate of acacetin-7-sulfate. Compared with that in wild-type Friend Virus B (FVB) mice, plasma exposure of acacetin-7-sulfate decreased significantly in multiple drug resistance protein 1 knockout (Mrp1-/-) mice, while increased evidently in breast cancer resistance protein knockout (Bcrp-/-) mice. In Caco-2 monolayers, efflux and clearance of acacetin-7-sulfate reduced distinctly by the BCRP inhibitor Ko143 in apical side and by the MRP1 inhibitor MK571 in basolateral side.

In conclusion, acacetin sulfonation was mediated mostly by SULT1A1. Acacetin-7-sulfate was transported mainly by BCRP and MRP1. Hence, SULT1A1, BCRP and MRP1 were responsible for acacetin-7-sulfate exposure in vivo.

Bee Pollen Protects the Brain From Injury

Glutamate excitotoxicity induced by orally administered propionic acid, a short chain fatty acid can be ameliorated by bee pollen

Lipids Health Dis. 2017 May 22;16(1):96

BACKGROUND:

Rodent models may guide investigations towards identifying either environmental neuro-toxicants or drugs with neuro-therapeutic effects. This work aims to study the therapeutic effects of bee pollen on brain glutamate excitotoxicity and the impaired glutamine-glutamate- gamma amino butyric acid (GABA) circuit induced by propionic acid (PPA), a short chain fatty acid, in rat pups.

METHODS:

Twenty-four young male Western Albino rats 3-4 weeks of age, and 45-60 g body weight were enrolled in the present study. They were grouped into four equal groups: Group 1, the control received phosphate buffered saline at the same time of PPA adminstration; Group 2, received 750 mg/kg body weight divided into 3 equal daily doses and served as acute neurotoxic dose of PPA; Group 3, received 750 mg/kg body weight divided in 10 equal doses of 75 mg/kg body weight/day, and served as the sub-acute group; and Group 4, the therapeutic group, was treated with bee pollen (50 mg/kg body weight) for 30 days after acute PPA intoxication. GABA, glutamate and glutamine were measured in the brain homogenates of the four groups.

RESULTS:

The results showed that PPA caused multiple signs of excitotoxicity, as measured by the elevation of glutamate and the glutamate/glutamine ratio and the decrease of GABA, glutamine and the GABA/glutamate ratio. Bee pollen was effective in counteracting the neurotoxic effects of PPA to a certain extent.

CONCLUSION:

In conclusion, bee pollen demonstrates ameliorating effects on glutamate excitotoxicity and the impaired glutamine-glutamate-GABA circuit as two etiological mechanisms in PPA-induced neurotoxicity.

Royal Jelly Can Help Reduce Cholesterol

Effects of Royal Jelly on Cholesterol Levels

May 24, 2017

Scientists have revealed that a 3-month treatment with Royal Jelly can reduce triglyceride, LDL-cholesterol and subsequently the risk of cardiovascular diseases.

Cholesterol is found in all cells and serves many functions throughout the body. Our bodies need cholesterol but too much can be harmful. Elevated levels of low-density lipoprotein (LDL) cholesterol, known as the bad cholesterol, accumulates in the walls of blood vessels leading to formation of atherosclerotic plaques that narrow the vessels and inhibit blood flow. This process leads to cardiovascular disease.

Various classes of medication such as Statins, Niacin and Fibrates are administered to lower blood LDL cholesterol.

A recently published Pharmaceutical Biology article evaluated the hypocholesterolemic effects of Royal Jelly, a secretion produced by worker honey bees, on healthy subjects.

Indian Karanj Honey Shows Anti-Cancer Activity

Natural Predominance of Abscisic Acid in Pongammia pinnata ('Karanj') Honey Contributed to its Strong Antimutagenicity

J Agric Food Chem. 2017 May 23

Various samples of raw (unprocessed) floral honey collected from different geographical locations of India were assayed for its antimutagenicity against ethyl methanesulfonate in E. coli MG1655 cells through rifampicin resistance assay.

A monofloral honey ('Pongammia pinnata', local name 'Karanj') displayed maximum antimutagenicity (78.0 ± 1.7; P ≤ 0.05). Solid phase extraction (using amberlite XAD-2 resin) followed by HPLC resulted into different peaks displaying varying antimutagenicity. Peak at retention time (Rt) 27.9 min (henceforth called as P28) displayed maximum antimutagenicity and was further characterized to be abscisic acid (ABA) using ESI-MS and NMR. Its antimutagenicity was reconfirmed through human lymphoblast cell line (TK6) mutation assay using thymidine kinase (tk+/-) cell line.

Although ABA from this honey displayed strong antimutagenicity, it lacked any in-vitro antioxidant capacity indicating non-involvement of any radical scavenging in the observed antimutagenicity.

Propolis Component Protects Against Ulcerative Colitis

Caffeic acid phenethyl ester is protective in experimental ulcerative colitis via reduction in levels of pro-inflammatory mediators and enhancement of epithelial barrier function

Inflammopharmacology. 2017 May 20

BACKGROUND:

Inhibition of the nuclear factor kappa beta (NF-κβ) pathway has been proposed as a therapeutic target due to its key role in the expression of pro-inflammatory genes, including pro-inflammatory cytokines, chemokines, and adhesion molecules. Caffeic acid phenethyl ester (CAPE) is a naturally occurring anti-inflammatory agent, found in propolis, and has been reported as a specific inhibitor of NF-κβ. However, the impact of CAPE on levels of myeloperoxidases (MPO) and pro-inflammatory cytokines during inflammation is not clear. The aims of this study were to investigate the protective efficacy of CAPE in the mouse model of colitis and determine its effect on MPO activity, pro-inflammatory cytokines levels, and intestinal permeability.

METHOD:

Dextran sulphate sodium was administered in drinking water to induce colitis in C57/BL6 mice before treatment with intraperitoneal administration of CAPE (30 mg kg-1 day-1). Disease activity index (DAI) score, colon length and tissue histology levels of MPO, pro-inflammatory cytokines, and intestinal permeability were observed.

RESULTS:

CAPE-treated mice had lower DAI and tissue inflammation scores, with improved epithelial barrier protection and significant reduction in the level of MPO and pro-inflammatory cytokines.

CONCLUSION:

Our results show that CAPE is effective in suppressing inflammation-triggered MPO activity and pro-inflammatory cytokines production while enhancing epithelial barrier function in experimental colitis. Thus, we conclude that CAPE could be a potential therapeutic agent for further clinical investigations for treatment of inflammatory bowel diseases in humans.

Polyphenols as Possible Markers of Botanical Origin of Honey

J AOAC Int. 2017 May 19

In recent years, the botanical and geographical origin of food has become an important topic in the context of food quality and safety, as well as consumer protection, in accordance with international standards.

Finding chemical markers, especially phytochemicals, characteristic for some kind of food is the subject of interest of a significant number of researchers in the world. This paper is focused on the use of polyphenols as potential markers for the determination of botanical origin of honey. It includes a review of the polyphenols present in various honey samples and the methods for their separation and identification. Special emphasis in this paper is placed on the identification of honey polyphenols using advanced LC-MS techniques in order to find specific markers of botanical origin of honey.

In this regard, this study gives an overview of the literature that describes the use of LC-MS techniques for the isolation and determination of honey polyphenols. This review focuses on the research performed in the past two decades.

Propolis Interacts with Warfarin

Effects of propolis on warfarin efficacy

Kardiochir Torakochirurgia Pol. 2017 Mar;14(1):43-46

INTRODUCTION:

Warfarin is commonly used to avoid thromboembolism, predominantly for cardiovascular pathologies. However, the consumption of several herbal products is not permitted during its use due to the associated interactions. Propolis is a popular phytotherapy product made by honey bees. The use of propolis has been dramatically increasing in recent times.

AIM:

To evaluate the possible interactions between propolis and warfarin in a mouse model with determination of the international normalized ratio (INR) values.

MATERIAL AND METHODS:

CD-1 mice were employed in the experimental model. The mice were warfarinized, and propolis was administered simultaneously. The INR values were obtained. All animals were sacrificed at the end of the study.

RESULTS:

The baseline INR value was 0.8 ±0.1. After 72 h, the INR value increased as expected. The INR value was 7.28 ± 1.08 in the control group and 5.8 ± 2.88 in the propolis group. At the end of the study, the INR value was 1.3 ± 0.37. Propolis interacted with warfarin and caused a decrease in the INR value.

CONCLUSIONS:

Propolis interactions, especially with warfarin, should be kept in mind and further studied. Healthcare specialists should be aware of this possible interaction between warfarin and propolis and inform patients about it.

Leptospermum Honey-Impregnated Dressings Help Treat Diabetic Charcot Deformity

Novel Use of Active Leptospermum Honey for Ringed Fixator Pin Site Care in Diabetic Charcot Deformity Patients

Foot Ankle Spec. 2017 May 1:1938640017709907

INTRODUCTION:

Open reduction with external fixation (OREF) utilizing fine wire ringed fixators for correction of Charcot deformity has gained popularity over the past decade. Pin site infections are a well-documented complication of external fixation as well as a driver of escalating health care costs. We aimed to demonstrate the safety and efficacy of a novel method of pin site care utilizing active Leptospermum honey-impregnated dressings (MediHoney) in diabetic patients undergoing deformity correction with OREF.

METHODS:

Twenty-one diabetic patients with Charcot deformities of the lower extremity were prospectively enrolled and followed for pin site complications following OREF for deformity correction. Active Leptospermum honey dressings were applied at metal-cutaneous interfaces at the end of the OREF procedure and replaced weekly for a total of 8 weeks. Patients were monitored for pin site infections from the time of surgery until external fixator removal. Sixteen consecutive patients receiving standard OREF for Charcot deformities were evaluated retrospectively to serve as a control group.

RESULTS:

Of the 21 enrolled patients, 19 underwent OREF and followed up throughout the study period. Treated patients had a mean age of 58.5 years and mean body mass index measuring 33.3 kg/m2 as documented prior to surgery. The 15 patients with hemoglobin A1c labs drawn in the 3 months preceding surgery averaged 7.5. Fixators were removed at an average of 12.1 weeks after adequate bony healing. Of the 244 pin sites in 19 patients, 3 pin sites (1.2% of pins) in 2 patients (10.5% of patients) showed evidence of superficial infection. All infections resolved with oral antibiotics. Infection rates were significantly reduced when compared to the standard care control group.

CONCLUSIONS:

Pilot data in a prospectively collected case series demonstrate safety and efficacy of active Leptospermum honey-impregnated dressings when used for fine wire ringed fixator pin site care in diabetic Charcot deformity patients. Further investigation in the form of a prospective randomized controlled study is warranted to demonstrate the potential value of this novel intervention.

Iranian Propolis May Help Treat Malaria

Anti-Plasmodial Assessment of Four Different Iranian Propolis Extracts

Arch Iran Med. 2017 May;20(5):270-281

BACKGROUND:

Eradication of malaria will depend on discovery of new intervention tools such as anti-malarial drugs. Due to the increasing interest in the application of propolis against significant clinical pathogenic agents, the aim of the present investigation was to evaluate the anti-plasmodial effect of Iranian propolis extracts against chloroquine (CQ)-sensitive Plasmodium falciparum 3D7 and Plasmodium berghei (ANKA strain).

METHODS:

Crude samples of honeybee (Apis mellifera) propolis were collected from four provinces in northern (Kalaleh, Golestan), northeastern (Chenaran, Razavi Khorasan), central (Taleghan, Alborz) and western (Morad Beyg, Hamedan) areas of Iran with different types of flora. The dried propolis samples were extracted with three different solvents, including ethanol 70% (EtOH), ethyl acetate (EA) and dichloromethane (DCM).

RESULTS:

All extracts were shown to have in vitro anti-plasmodial activity with IC50 ranging from 16.263 to 80.012 µg/mL using parasite lactate dehydrogenase (pLDH) assay. The DCM extract of Morad Beyg propolis indicated the highest anti-plasmodial activity (IC50: 16.263 ± 2.910 μg/mL; P = 0.027, Kruskal-Wallis H-test). The samples were also evaluated in mice for their in vivo anti-plasmodial effect. The curative effect against established infection (Rane test) showed that both extracts at all doses (50, 100, and 200 mg/kgBW) produced anti-plasmodial activity against the parasite. Furthermore, using gas chromatography-mass spectrometry (GC-MS), the quantity of flavonoids in DCM and EtOH 70% extracts were found to be 7.42% and 3.10%, respectively.

CONCLUSION:

The potent anti-plasmodial activity of both EtOH 70% and DCM extracts of the propolis of Morad Beyg, Hamedan suggests further analyses of individual components to assess its utilization as anti-malarial drugs.

Easy-to-Make Pectin-Honey Hydrogel Enhances Wound Healing

A new, easy-to-make pectin-honey hydrogel enhances wound healing in rats

BMC Complement Altern Med. 2017 May 16;17(1):266

BACKGROUND:

Honey, alone or in combination, has been used for wound healing since ancient times and has reemerged as a topic of interest in the last decade. Pectin has recently been investigated for its use in various biomedical applications such as drug delivery, skin protection, and scaffolding for cells. The aim of the present study was to develop and evaluate a pectin-honey hydrogel (PHH) as a wound healing membrane and to compare this dressing to liquid honey.

METHODS:

Thirty-six adult male Sprague-Dawley rats were anesthetized and a 2 × 2 cm excisional wound was created on the dorsum. Animals were randomly assigned to four groups (PHH, LH, Pec, and C): in the PHH group, the pectin-honey hydrogel was applied under a bandage on the wound; in the LH group, liquid Manuka honey was applied; in the Pec group, pectin hydrogel was applied (Pec); and in the C group, only bandage was applied to the wound. Images of the wound were taken at defined time points, and the wound area reduction rate was calculated and compared between groups.

RESULTS:

The wound area reduction rate was faster in the PHH, LH, and Pec groups compared to the control group and was significantly faster in the PHH group. Surprisingly, the Pec group exhibited faster wound healing than the LH group, but this effect was not statistically significant.

CONCLUSION:

This is the first study using pectin in combination with honey to produce biomedical hydrogels for wound treatment. The results indicate that the use of PHH is effective for promoting and accelerating wound healing.

Bee Venom Has Potential for Topical Uses

Evaluation of the skin phototoxicity and photosensitivity of honeybee venom

Journal of Cosmetic Dermatology

Objective

Bee (Apis mellifera L.) venom (BV) has been used as a cosmetic ingredient owing to its anti-aging, anti-inflammatory, and antibacterial effects. The aim of this study was to assess the skin safety of BV.

Methods

For this purpose, skin phototoxicity and sensitization tests were conducted in healthy male Hartley guinea pigs. The animals were divided into three groups (n=5) for the phototoxicity test: G1 (negative control), G2 (BV gel treatment), and G3 (positive control). After specified treatments, the animals were irradiated with ultraviolet A (15 J/cm2). The photosensitivity test was also performed in three groups: G4 (negative control, n=5), G5 (BV gel treatment, n=10), and G6 (positive control, n=5).

Results

Erythema and edema were observed after 24, 48, and 72 hours in the positive control group, but not in the negative control and BV gel groups. Application of BV to the guinea pig skin had no toxic effects on any clinical signs, body weight, or mortality. In addition, it did not evoke a skin reaction in both either the skin phototoxicity and skin photosensitization tests.

Conclusion

Therefore, it can be concluded that BV has the potential to be developed as a drug ingredient for topical uses.

Bee Stings Help Treat Lyme Disease

Lyme disease sufferer claims bee stings help control her symptoms

BBC, May 8, 2017

A woman with Lyme disease has claimed being stung by bees helps ease her symptoms.

Ingrid Watt, 36, who grew up in Orkney and now lives in Inverness, believes she has had the disease, which be transmitted to humans by tick bites, since she was 18.

Underlying health problems became worse five years ago and included reoccurring shingles and neurological issues.

She believes properties in the bee venom help control her Lyme disease.

Mrs Watt, who has tried mainstream GP-prescribed medicine, came across the alternative treatment while on a discussion forum used by other sufferers.

After further reading on the treatment, she began buying bees online. She says the insects involved are at the end of their lives and not endangered.

Using tweezers, her husband Darren puts bees on her back to sting her.

Mr Watt has this done 30 times every week.

She told BBC Radio Orkney: "At first we thought 'this is so crazy, what are we doing'.

"But within two weeks of having the bee therapy I feel I have more energy and less pain."...

Propolis Best for Preserving Knocked-Out Tooth

In vitro comparative evaluation of different storage media (hank's balanced salt solution, propolis, Aloe vera, and pomegranate juice) for preservation of avulsed tooth

Eur J Dent. 2017 Jan-Mar;11(1):71-75

OBJECTIVES:

Prognosis of the avulsed teeth is mostly affected by extraoral dry period and storage medium used to store teeth before reimplantation. However, ability of storage media can affect cell viability and success of treatment. Various storage media were tried with some success. The present study was undertaken to comparatively evaluate the efficacy of hank's balanced salt solution (HBSS), propolis, Aloe vera, and pomegranate juice (PJ) in preserving the vitality of periodontal ligament (PDL) cells of avulsed teeth.

MATERIALS AND METHODS:

Fifty orthodontically extracted sound teeth with healthy PDL were selected for the present study. Selected teeth were randomly divided into study groups (10 in each) and 5 each as positive and negative control groups. All the teeth were immersed immediately after extraction into respective storage media. Data were statistically analyzed using IBM SPSS software for Windows, Version 19.0., IBM Corp., Armonk, NY, USA. Analysis of variance and multiple range were done using Tukey's honestly significant difference with level of significance at 5% (P > 0.05).

RESULTS:

Propolis (285,000 viable cells with standard deviation 4.11028 and standard error of 1.38097) showed more viable PDL cells followed by HBSS, A. vera, and PJ.

Manuka, Strawberry Tree Honey May Help Treat Cancer

Manuka and strawberry tree honey helps decrease colon cancer cell viability: In vitro study

By Gary Scattergood+, 11-May-2017

Strawberry tree honey and Manuka honey can induce cell death in colon cancer cells, an in vitro study has found.

Honeydew Honey Boosts Wound Healing

Honeydew honey: biological effects on skin cells

Mol Cell Biochem. 2017 May 11 [Epub ahead of print]

Honey is a natural product well known by humankind and now reconsidered for its use as topical agent for wound and burn treatments. Floral honey is made by honeybees from the nectar of blossoms, while honeydew honey is prepared from secretions of plants or excretions of plant-sucking insects.

Chemical composition is different between blossom and honeydew honeys and there is very few information about the biological properties of honeydew honey. So, this study was specifically designed to explore the potential wound healing effects of the honeydew honey. We used in vitro scratch wound healing model consisting of fibroblasts and keratinocytes.

Data showed that honeydew honeys is able to increase wound closure by acting both on fibroblasts and keratinocytes. Based on our findings, honeydew honey has the potential to be useful for clinical settings.

Brazilian Green Propolis Extract Boosts Anti-Cancer Drug

Brazilian Green Propolis Extract Synergizes with Protoporphyrin IX-mediated Photodynamic Therapy via Enhancement of Intracellular Accumulation of Protoporphyrin IX and Attenuation of NF-κB and COX-2

Molecules. 2017 May 4;22(5). pii: E732

Brazilian green propolis (BGP) is noted for its impressive antitumor effects and has been used as a folk medicine in various cultures for many years. It has been demonstrated that BGP could enhance the cytotoxic effect of cytostatic drugs on tumor cells. Photodynamic therapy (PDT) is a therapeutic approach used against malignant cells.

To assess the synergistic effect of BGP extract on protoporphyrin IX (PpIX)-mediated photocytotoxicity, MTT assays were performed using A431 and HeLa cells. TUNEL assay and Annexin V-FITC/PI staining were performed to confirm the induction of apoptosis. Western blotting analysis was performed to examine the pro-apoptotic proteins, anti-apoptotic proteins and inflammation related proteins in A431 cells. Intracellular accumulation of PpIX was examined by flow cytometry. The synergistic effect of BGP extract in PpIX-PDT was also evaluated with a xenograft model.

Our findings reveal that BGP extract increased PpIX-mediated photocytotoxicity in A431 and HeLa cells. PpIX-PDT with BGP extract treatment resulted in a decrease in Bcl-xL and an increase in NOXA, Bax and caspase-3 cleavage. The protein expression levels of p-IKKα/β, NF-κB and COX-2 were upregulated by PpIX-PDT but significantly attenuated when in combination with BGP extract. BGP extract was also found to significantly enhance the intracellular accumulation of PpIX in A431 cells. BGP extract increased PpIX-mediated photocytotoxicity in a xenograft model as well.

Our findings provide evidence for a synergistic effect of BGP extract in PpIX-PDT both in vitro and in vivo.

Review of Use of Bee Venom to Treat Parkinson's Disease

Bee venom for the treatment of Parkinson's disease: How far is it possible?

Biomed Pharmacother. 2017 May 3;91:295-302

Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta leading to depletion of striatal dopamine and motor symptoms as bradykinesia, resting tremors, rigidity, and postural instability.

Current therapeutic strategies for PD are mainly symptomatic and may cause motor complications, such as motor fluctuations and dyskinesia. Therefore, alternative medicine may offer an effective adjuvant treatment for PD. Bee venom therapy (BVT) has long been used as a traditional therapy for several conditions, such as rheumatoid arthritis, asthma, and skin diseases.

Experimental and clinical studies showed that BVT could be an effective adjuvant treatment for PD. Several mechanisms were suggested for these findings including the ability of BVT to attenuate neuroinflammation, inhibit apoptosis of dopaminergic neurons, protect against glutamate-induced neurotoxicity, and restore normal dopamine levels in the nigrostriatal pathway.

In this article, we reviewed and summarized the literature regarding the potential of BVT for the treatment of PD.

Malaysian Tualang and New Zealand Manuka Honeys May Help Treat Breast Cancer

Oral Administration of Tualang and Manuka Honeys Modulates Breast Cancer Progression in Sprague-Dawley Rats Model

Evid Based Complement Alternat Med. 2017;2017:5904361

Breast cancer has been recognized as the leading cause of death in women worldwide. Research has shown the importance of complementary and alternative therapies in cancer.

In this study, we investigated the antitumoural therapeutic effects of Malaysian Tualang honey (TH) and Australian/New Zealand Manuka honey (MH) against breast cancer in rats.

Thirty syngeneic virgin female Sprague-Dawley (SD) rats were induced by the carcinogen 1-methyl-1-nitrosourea (MNU) 80 mg/kg. The treatment started when first palpable tumour reached 10-12 mm in size by dividing rats into following groups: Group 0 (negative control); Group 1 (positive control); and Groups 2 and 3 which received 1.0 g/kg body weight/day of TH and MH, respectively, for 120 days.

The data demonstrate that cancer masses in TH and MH treated groups showed a lower median tumour size, weight, and multiplicity compared with the nontreated positive control (p < 0.05). Treatment also showed a dramatic slower growth rate (up to 70.82%) compared with the nontreated control (0%) (p < 0.05). The antitumoural effect was mediated through modulation of tumour growth, tumour grading, estrogenic activity, and haematological parameters.

Our findings demonstrate that systemic administration of TH and MH increases the susceptibility of expression of proapoptotic proteins (Apaf-1, Caspase-9, IFN-γ, IFNGR1, and p53) and decreases the expression of antiapoptotic proteins (TNF-α, COX-2, and Bcl-xL 1) in its mechanism of action. This highlights a potential novel role for TH and MH in alleviating breast cancer.

Honey May Help Treat Dermatitis

Honey is potentially effective in the treatment of atopic dermatitis: Clinical and mechanistic studies

Immun Inflamm Dis. 2017 Jun;5(2):190-199

INTRODUCTION:

As manuka honey (MH) exhibits immunoregulatory and anti-staphylococcal activities, we aimed to investigate if it could be effective in the treatment of atopic dermatitis (AD).

METHODS:

Adult volunteers with bilateral AD lesions were asked to apply MH on one site overnight for seven consecutive days and leave the contralateral site untreated as possible. Three Item Severity score was used to evaluate the response. Skin swabs were obtained from both sites before and after treatment to investigate the presence of staphylococci and enterotoxin production. In addition, the ability of MH and its methanolic and hexane extracts to down regulate IL4-induced CCL26 protein release from HaCaT cells was evaluated by enzyme linked immunosorbent assay. Also, the ability of MH to modulate calcium ionophore-induced mast cell degranulation was assessed by enzyme immunoassay.

RESULTS:

In 14 patients, AD lesions significantly improved post MH treatment versus pre-treatment as compared to control lesions. No significant changes in the skin staphylococci were observed after day 7, irrespective of honey treatment. Consistent with the clinical observation, MH significantly down regulated IL4-induced CCL26 release from HaCaT cells in a dose-dependent manner. This effect was partially lost, though remained significant, when methanolic and hexane extracts of MH were utilized. In addition, mast cell degranulation was significantly inhibited following treatment with MH.

CONCLUSIONS:

MH is potentially effective in the treatment of AD lesions based on both clinical and cellular studies through different mechanisms. This needs to be confirmed by randomized and controlled clinical trials.

Possible Use of Propolis in Dentistry

Cytotoxic Effect of Chitosan-H, Resveratrol, β-Carotene and Propolis and their Chitosan Hydrogels on Balb/C Mouse 3T3 Fibroblast Cells

Background/purposes: The beneficial effect (bond strength and longevity) of the addition of different chitosan/antioxidant hydrogels to dental restoratives was reported. However, it still needs to be verified whether their presence would not damage the pulp cells. Therefore, the purpose of this study was to determine the relative cytotoxic effect of resveratrol, propolis and β-carotene in relation to their respective chitosan/antioxidant hydrogels on mouse Balb/c mouse 3T3 fibroblast cells.

Materials and Methods: The mentioned hydrogels were prepared by the dispersion of the corresponding components in glycerol and acetic acid with the addition of the chitosan polymer. The cell survival rate was determined over a 24hour period according to the standard MTT assay.

Results and Conclusion: The Kruskal-Wallis Multiple-Comparison Test and Bonferroni test showed significant differences in the cell survival rates (p < 0.05) amongst resveratrol (31%), propolis (64%) and β-carotene (95%):Also amongst chitosan (114%), chitosan/resveratrol (87%) and resveratrol (31%); chitosan (114%), chitosan/β-carotene(100%) and β-carotene (95%); chitosan (114%), chitosan/propolis (95%) and propolis (64%).

To conclude, this study showed: 1) that chitosan-H has a positive effect on the cell survival rate of Balb/c mouse 3T3 fibroblast cells and therefore most probably also on human pulp fibroblast cells, 2) these chitosan hydrogels are safe to be used to improve the bond strength and longevity of a tooth dental material, and 3) it further proved that chitosan in itself improved the cell survival rate of various antioxidants. The mean cell survival rate was found to be: resveratrol (31%); propolis (64%); β-carotene (95%), chitosan+resveratrol (87%), chitosan+propolis (95%), chitosan+ β-carotene (100%) and chitosan (114%).

Brazilian Propolis May Help Treat Diabetes

Strong Antihyperglycemic Effects of Water-Soluble Fraction of Brazilian Propolis and Its Bioactive Constituent, 3,4,5-Tri-O-caffeoylquinic Acid

Biological and Pharmaceutical Bulletin
Vol. 27 (2004) No. 11 P 1797-1803

To clarify the suppression of postprandial blood glucose rise via α-glucosidase (AGH) inhibitory action by natural compounds, propolis was examined in this study. A single oral administration of propolis extract (50% methanol fraction on XAD-2 column chromatography) in Sprague–Dawley rats demonstrated a potent antihyperglycemic effect with the significant AUC0—120 min reduction of 38% at a dose of 20 mg/kg compared to that of controls. Among the active compounds isolated from the fraction, 3,4,5-tri-caffeoylquinic acid was found to be a prominent candidate that exerts the effect and shows a strong maltase-specific inhibition with an IC50 value of 24 μM. In addition, the noncompetitive inhibition power apparently increased with the number of caffeoyl groups bound to quinic acid.

Honey as a Complementary Medicine

Integr Med Insights. 2017 Apr 24;12:1178633717702869

The beneficial effects of honey on human health have long been recognized. Today, many of those positive effects have been studied to elucidate its mode of action. This review briefly summarizes the best studied features of honey, highlighting it as an appealing alternative medicine.

In these reports, the health benefits of honey range from antioxidant, immunomodulatory, and anti-inflammatory activity to anticancer action, metabolic and cardiovascular benefits, prebiotic properties, human pathogen control, and antiviral activity. These studies also support that the honey's biological activity is mainly dependent on its floral or geographic origin. In addition, some promising synergies between honey and antibiotics have been found, as well as some antiviral properties that require further investigation.

Altogether, these studies show that honey is effectively a nutraceutical foodstuff.

Stingless Bee 'Geopropolis' Shows High Antioxidant, Antimicrobial Activity

Chemical Profile and Antioxidant, Anti-Inflammatory, Antimutagenic and Antimicrobial Activities of Geopropolis from the Stingless Bee Melipona orbignyi

Int J Mol Sci. 2017 May 3;18(5)

Geopropolis is a resin mixed with mud, produced only by stingless bees. Despite being popularly known for its medicinal properties, few scientific studies have proven its biological activities.

In this context, the objective of this study was to determine the chemical composition and antioxidant, anti-inflammatory, antimutagenic and antimicrobial activities of the Melipona orbignyi geopropolis. The hydroalcoholic extract of geopropolis (HEGP) was prepared and its chemical composition determined by high performance liquid chromatography coupled to diode array detector and mass spectrometry (HPLC-DAD-MS). The antioxidant activity was determined by the capture of free radicals and inhibition of lipid peroxidation in human erythrocytes. The anti-inflammatory activity was evaluated by the inhibition of the hyaluronidase enzyme and the antimutagenic action was investigated in Saccharomyces cerevisiae colonies. The antimicrobial activities were determined against bacteria and yeasts, isolated from reference strains and hospital origin.

The chemical composition of HEGP included flavonoids, derivatives of glycosylated phenolic acids and terpenoids. HEGP showed high antioxidant activity, it inhibited the activity of the inflammatory enzyme hyaluronidase and reduced the mutagenic effects in S. cerevisiae.

In relation to the antimicrobial activity, it promoted the death of all microorganisms evaluated. In conclusion, this study reveals for the first time the chemical composition of the HEGP of M. orbignyi and demonstrates its pharmacological properties.

Mono and Multifloral Bee Pollen Extracts Show Antioxidant Activity

Chemical Composition and Biological Activities of Mono- and Heterofloral Bee Pollen of Different Geographical Origins

Int J Mol Sci. 2017 Apr 27;18(5)

Recent research shows variations in pollen chemical constituents and, consequently, in their therapeutic properties. Mono and multifloral bee pollen extracts were investigated for antioxidant and enzyme inhibitory activity properties, phenolic compounds and fatty acid composition.

Generally, Eucalyptus spp. and multifloral extracts exhibited potent inhibitory activity against α-amylase, acetylcholinesterase, tyrosinase, lipoxygenase, lipase and hyaluronidase. On the other hand, Miconia spp. demonstrated higher antihemolytic activity. Cocos nucifera and Miconia spp. extracts exhibited important antioxidant properties in the different assays (ABTS, DPPH, β-carotene/linoleic acid and reducing power). Moreover, these extracts had greater amounts of total phenols and flavonoids in comparison to others.

The increase in antioxidant activity (decrease in EC50 values) was accompanied by an increase in the amount of total phenols in the extracts.

The pollen extracts contained linoleic acid and α-linolenic acid as major fatty acids, followed by palmitic acid, and oleic acid. In this study, differences were observed in both chemical constituents and biological activities of the samples related to the geographical and botanical origin of bee pollen.

Bee Pollen May Help Treat Obesity, Dabetes

Pectic Bee Pollen Polysaccharide from Rosa rugosa Alleviates Diet-Induced Hepatic Steatosis and Insulin Resistance via Induction of AMPK/mTOR-Mediated Autophagy

Molecules. 2017 Apr 28;22(5)

Despite it is used as a nutraceutical against diabetes and obesity, the mechanism of action of bee pollen is still unclear.

Pectic bee pollen polysaccharide (RBPP-P) was isolated from Rosa rugosa, and its structure was characterized by 13C-NMR and Fourier transform-infrared spectroscopy (FT-IR). Using high glucose and fatty acids-treated HepG2 cells and high fat diet (HFD)-induced obesity mice, we detected its effect on insulin function and lipid metabolism based on autophagy.

RBPP-P contained arabinogalactan, rhamnogalacturonan I, and homogalacturonan domains. In vivo studies demonstrated that RBPP-P markedly ameliorated insulin resistance, glucose intolerance, and liver steatosis in obese mice. The suppressive effects of RBPP-P on liver steatosis and triglyceride content were mediated by increased autophagy and lipase expression in liver. In AMPK knockdown cells (prkaa 1/2-/- MEF) and HFD-fed mice tissues (liver, gonadal white adipose, and inguinal white adipose), RBPP-P enhanced autophagy in AMPK/mTOR-dependent way in liver, but not in adipose tissue.

These findings demonstrated that bee pollen polysaccharide alleviated liver steatosis and insulin resistance by promoting autophagy via an AMPK/mTOR-mediated signaling pathway, suggesting that RBPP-P could be a novel therapeutic agent used for the treatment of obesity and diabetes.

Propolis Counteracts Some Threats to Honey Bee Health

Insects 2017, 8(2), 46

Honey bees (Apis mellifera) are constantly dealing with threats from pathogens, pests, pesticides and poor nutrition. It is critically important to understand how honey bees’ natural immune responses (individual immunity) and collective behavioral defenses (social immunity) can improve bee health and productivity.

One form of social immunity in honey bee colonies is the collection of antimicrobial plant resins and their use in the nest architecture as propolis. We review research on the constitutive benefits of propolis on the honey bee immune system, and its known therapeutic, colony-level effects against the pathogens Paenibacillus larvae and Ascosphaera apis. We also review the limited research on the effects of propolis against other pathogens, parasites and pests (Nosema, viruses, Varroa destructor, and hive beetles) and how propolis may enhance bee products such as royal jelly and honey. Although propolis may be a source of pesticide contamination, it also has the potential to be a detoxifying agent or primer of detoxification pathways, as well as increasing bee longevity via antioxidant-related pathways.

Throughout this paper, we discuss opportunities for future research goals and present ways in which the beekeeping community can promote propolis use in standard colonies, as one way to improve and maintain colony health and resiliency.