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.