Bee Venom May Help Treat Fatty Liver

The therapeutic effects of bee venom on some metabolic and antioxidant parameters associated with HFD-induced non-alcoholic fatty liver in rats

Exp Ther Med. 2018 Jun;15(6):5091-5099

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The present study was designed to investigate the therapeutic effects of bee venom (BV) on high-fat diet (HFD)-induced non-alcoholic fatty liver (NAFL) in rats at different levels.

Histological manifestations, hepatic lipid content, liver function tests, glucose homeostasis, lipid abnormalities, adipocytokines, lipid peroxidation, disturbed glutathione and antioxidant enzymes systems and dysregulation of Nrf2 transcription factor were assessed. In the present study, the NAFL rats were subcutaneously treated with BV with different doses (0.01, 0.05, 0.1 mg/kg). The results indicated that BV treatment completely normalized the lipid profile values of NAFL rats. Fasting blood sugar, insulin level and homeostatic model assessment of insulin resistance significantly decreased.

BV treated rats showed a significantly lower level of all liver enzymes and bilirubin. Moreover, BV treatment significantly increased the levels of active nuclear erythroid factor 2 like 2, glutathione (GSH) (total and reduced), GSH/glutathione disulphide ratio and activities of glutathione reductase, glutathione-S-transferase and glutathione peroxidase (total and Se-dependent). The level of tumor necrosis factor-α was reduced. Treatment showed correction of adiponectin level, and significant downregulation of hepatic triglycerides and cholesterol. At the histological level, BV improved the architecture of liver cells showing normal sinusoids.

It may be concluded that BV may represent an interesting therapeutic alternative for the treatment of NAFL disease.

Propolis Component May Help Treat Nose and Throat Cancer

Caffeic Acid Phenethyl Ester Induces N-myc Downstream Regulated Gene 1 to Inhibit Cell Proliferation and Invasion of Human Nasopharyngeal Cancer Cells

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Int J Mol Sci. 2018 May 8;19(5). pii: E1397

Caffeic acid phenethyl ester (CAPE), a bioactive component extracted from propolis, is widely studied due to its anti-cancer effect. Nasopharyngeal carcinoma (NPC) is distinct from other head and neck carcinomas and has a high risk of distant metastases. N-myc downstream regulated gene 1 (NDRG1) is demonstrated as a tumor suppressor gene in several cancers. Our result showed that CAPE treatment could repress NPC cell growth, through induction of S phase cell cycle arrest, and invasion.

CAPE treatment stimulated NDRG1 expression in NPC cells. NDRG1 knockdown increased NPC cell proliferation and invasion and rendered NPC cells less responsive to CAPE growth-inhibiting effect, indicating CAPE repressed NPC cell growth partly through NDRG1indcution. CAPE treatment increased phosphorylation of ERK, JNK, and p38 in a dose- and time-dependent manner. Pre-treatments by inhibitors of ERK (PD0325901), JNK (SP600125), or p38 (SB201290), respectively, all could partly inhibit the CAPE effect on NDRG1 induction in NPC cells. Further, STAT3 activity was also repressed by CAPE in NPC cells.

In summary, CAPE attenuates NPC cell proliferation and invasion by upregulating NDRG1 expression via MAPK pathway and by inhibiting phosphorylation of STAT3. Considering the poor prognosis of NPC patients with metastasis, CAPE could be a promising agent against NPC.

Honey-Based Gel May Help Treat Skin, Ear Infections in Dogs

In vitro efficacy of a honey‐based gel against canine clinical isolates of Staphylococcus pseudintermedius and Malassezia pachydermatis

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Veterinary Dermatology
Volume 29, Issue 3, June 2018, Pages 180-e65

Background

Staphylococcus pseudintermedius and Malassezia pachydermatis are important agents in canine pyoderma and otitis.

Hypothesis/Objectives

Determine the in vitro efficacy of a honey‐based gel (HBO) against meticillin‐susceptible S. pseudintermedius (MSSP), meticillin‐resistant S. pseudintermedius (MRSP) and M. pachydermatis, by minimum bactericidal concentration (MBC), minimum fungicidal concentration (MFC) and time‐kill assay (TKA). Efficacy of the product's honey component (HO) also was evaluated.

Methods

Sixty S. pseudintermedius and 10 M. pachydermatis canine isolates were selected. All isolates were tested against serial dilutions of an HBO containing 40% HO (40%, 20%, 10%, 5% and 2.5% w/v) and HO alone (undiluted, 40%, 20%, 10%, 5% and 2.5% w/v). Microbroth assay followed by subculture was used to determine MBC and MFC. The same protocol was applied after product exposure to catalase. A well‐diffusion assay for S. pseudintermedius was used to generate inhibition zones. A TKA for 10 isolates of S. pseudintermedius and 10 isolates of M. pachydermatis was performed.

Results

MBC was 20% w/v (5–20% w/v) for HBO and HO. HBO had lower MBC values when compared to HO (P = 0.003). No statistical difference was observed between MSSP/MRSP isolates (HBO P = 0.757, HO P = 0.743). Only HO was affected by catalase (P = 0.015). MFC for HBO was 10% w/v (5–10% w/v) and 40% w/v for HO (20–≥40% w/v). All isolates were killed after 4 h of exposure.

Conclusions and clinical importance

Staphylococcus pseudintermedius and M. pachydermatis are susceptible to the HBO and these results can be used for future clinical trials.

Bee Venom May Help Treat Stomach Cancer

Effect of dimerized melittin on gastric cancer cells and antibacterial activity

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Amino Acids. 2018 May 16

Melittin is the peptide toxin found in bee venom and is effective against cancer cells. To enhance its activity, a branched dimeric form of melittin was designed.

The monomeric form of the peptide was more cytotoxic against gastric cancer cells at low concentrations (1-5 μM) than the dimer form, while the cytotoxic effect was comparable at higher concentrations (10 μM). Confocal microscopy showed that both the monomer and dimer forms of melittin with fluorescent label at the C terminus penetrated the cytoplasm and localized at the cell nucleus and disrupted the cell membrane.

The results indicated that both peptides localized in the nucleus and no significant difference in penetration was observed between monomer and dimer of melittin. Although the C and N termini are important for melittin activity, using C terminus for dimerization of the peptide resulted in similar activity for the monomer and dimer against bacteria and gastric cancer cells.

Propolis Helps Treat Inflammation of the Eye

Propolis modulates NOS2/arginase-1 pathway in tropomyosin-induced experimental autoimmune uveitis

Inflammopharmacology

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In this study, we evaluated the preventive and curative effects of ethanolic extract of Propolis (EEP) during α-Tropomyosin-induced uveitis in an experimental model using Wistar rats, through the regulation of inducible nitric oxide synthase (NOS2) and arginase-1.

In this context, rats received daily injection of EEP (100 mg/kg) for 5 days prior to immunization or for 9 days commencing 5 days post immunization with α-Tropomyosin extract, then were sacrificed at day 14. Histological examination, NOS2, arginase-1, and nuclear factor-κB (NF-κB) expression were evaluated in the retinas. Plasmatic production of nitric oxide (NO), urea, IL-4, and TNF-α was assessed.

We have found that treatment with EEP substantially reduced the retinal histological damages induced by α-Tropomyosin. In the same context, a significant decrease of NO and TNF-α levels was noticed. Interestingly, EEP down-modulated NOS2 and NF-κB expression in retina. Also, an increase in urea and IL-4 levels was concomitant to an up-modulation of arginase-1 expression.

Hence, it appears that EEP attenuated retinal damages through the induction of Th2 response and the inhibition of NF-κB/NOS2 pathway.

Brazilian Stingless Bee Propolis Disturbs Bacterial Cell Membrane

Chemical characterization, antioxidant and antimicrobial activity of propolis obtained from Melipona quadrifasciata quadrifasciata and Tetragonisca angustula stingless bees

Braz J Med Biol Res. 2018;51(6):e7118

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In this study, we investigated the chemical composition, and antioxidant and antibacterial properties of ethanolic extracts of propolis (EEP) from Melipona quadrifasciata quadrifasciata and Tetragonisca angustula.

Chemical composition of EEP was determined by colorimetry and chromatographic (HPLC-DAD and UPLC-Q/TOF-MS/MS) analysis. Antimicrobial activity of EEP was evaluated against gram-positive (S. aureus, methicillin-resistant S. aureus, E. faecalis) and gram-negative (E. coli and K. pneumoniae) bacteria by the minimal inhibitory concentration (MIC) test using the microdilution method. Furthermore, the growth curve and integrity of cell membrane of S. aureus and E. coli were investigated using standard microbiological methods.

HPLC-DAD analysis showed that the EEP of M. quadrifasciata quadrifasciata has a more complex chemical composition than the EEP of T. angustula. Moreover, UPLC-MS analyses of M. quadrifasciata quadrifascita indicated flavonoids and terpenes as major constituents. The bactericidal activity of both EEPs was higher against gram-positive bacteria than for gram-negative bacteria. The EEP from M. quadrifasciata quadrifasciata presented MIC values lower than the EEP from T. angustula for all tested bacteria.

The EEP from M. quadrifasciata quadrifasciata caused lysis of the bacterial wall and release of intracellular components from both E. coli and S. aureus.

Our findings indicate that the chemical composition of propolis from stingless bees is complex and depends on the species. The extract from M. quadrifasciata quadrifascita was more effective against gram-positive than gram-negative strains, especially against S. aureus and methicillin-resistant S. aureus compared to T. angustula extract, by a mechanism that involves disturbance of the bacterial cell membrane integrity.

Honey Can Boost Testosterone, Decrease Side Effects of Chemotherapy on Reproductive Systems and Prevent Sterility (Cancer, Iran, Testicular)

Protective effects of Persian honey, Apis Mellifera Meda Skorikov on side effects of chemotherapy and ischemia/reperfusion induced testicular injury

J Complement Integr Med. 2018 May 23

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Introduction 

The aim of the present study was to survey the protective effect of pretreatment with Persian honey on amelioration of side effects of chemotherapy and ischemia/reperfusion induced testicular injury.

Materials and methods 

Forty adult's male wistar rats were divided into four groups of ischemia-reperfusion (IR), honey + ischemia-reperfusion (HIR), Busulfan (B) and Busulfan intraperitoneally+ honey (BH). The seminiferous tubules were rated for their modified spermatogenesis index (SI) by Johnsons score. Detection of single- and double-stranded DNA breaks at the early stages of apoptosis was performed using the in-situ cell death detection kit. Total serum concentration of Follicle-stimulating hormone (FSH) , Luteinizing hormone (LH) and testosterone was measured using ELISA. All data were expressed as mean ± SD and significance was set at p ≤ 0.05.

Results 

Honey improved SI in the HIR and BH groups and serum levels of FSH and LH in the BH and HIR groups (p < 0.001). Also, serum levels of testosterone were significantly higher in BH and HIR groups. But, apoptotic cells in IR and B groups significantly increased (p < 0.001), while in HIR and BH groups, the number of apoptotic cells decreased and the positive cells of TUNEL (TdT-mediated dUTP-X nick end labelling) staining were detected in spermatocytes and spermatid.

Discussion 

Pretreatment with honey protect testis against chemotherapy and testicular IR injury, increase FSH and LH and testosterone and decrease the cellular damage and apoptosis. Honey can decrease the side effects of chemotherapy on reproductive system and prevent sterility.

Thyme Honey Helps Treat Radiation-Induced Oral Mucositis, Improve Quality of Life in Head and Neck Cancer Patients

The effect of the use of thyme honey in minimizing radiation - induced oral mucositis in head and neck cancer patients: A randomized controlled trial.

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Eur J Oncol Nurs. 2018 Jun;34:89-97

PURPOSE:

Radiation-induced oral mucositis is one of the main side effects during and after the treatment of head and neck cancer patients. The study was designed to provide evidence on the effectiveness of thyme honey on oral mucositis management.

METHODS:

This was a randomised controlled trial (RCT) with 72 head and neck cancer patients who were divided either to the intervention group (thyme honey rinses) or to the control group (saline rinses). Oral mucositis was assessed according to the Radiation Therapy Oncology Group (RTOC criteria), and assessments were performed weekly starting at the 4th week of the radiotherapy for seven weeks and repeated once 6 months later. Additionally, the Oral Mucositis Weekly Questionnaire (OMWQ) was given at 4th week of radiotherapy, 1 month after the completion of radiotherapy and 6 months later. The ClinicalTrials.gov Identifier for this study is NCT01465308. This paper reports on the findings regarding thyme honey's effectiveness on oral mucositis.

RESULTS:

Generalized estimating equations revealed that patients in the intervention group were graded lower in the objective assessment of oral mucositis (p < 0,001), maintained their body weight (p < 0,001) and showed an improvement in their global health (p = 0.001) compared to the control group. Quality of life of the patients in the same group was also statistically significantly higher than that of the patients of the control group (p < 0,001).

CONCLUSION:

The study provided evidence on the positive effect of thyme honey on the management of radiation-induced oral mucositis and quality of life in head and neck cancer patients.

7th Apimedica & 6th Apiquality International Symposium Sibiu, Romania, 11 - 15 October 2018 (Bee Venom, Bee Pollen, Beeswax, Honey, Propolis, Royal Jelly)

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The meeting, organised by the Romanian Apitherapy Society (Apimondia member), in collaboration with Apimondia (the International Federation of Beekeepers’ Associations), will address the most relevant issues pertaining to apitherapy and the qualitative aspects of the production/use of bee products and is open to researchers, medical doctors, pharmacists, biochemists, biologists, therapists, students as well as to beekeepers.

The symposium will include: oral presentations, a poster session, keynote speakers, specific sessions (active compounds, properties, pharmacology and clinical applications of hive products; clinical aspects in human and veterinary medicine; best practices; residues in hive products; alkaloids in honey and pollen; standards and frauds) and practical training (practical demonstration and clinical evidence of apitherapy; on-field standard tools; innovative systems for beehives and hive products traceability).

The programme of the symposium will be as follows:

October 10, in the evening: Welcome Cocktail
October 11 (all day) + October 12 (until noon): Apiquality Symposium
October 12 evening: Social Dinner (optional)
October 12 (afternoon)-October 14: Apimedica Symposium
October 14 (afternoon): Technical Tour 1 (optional)
October 15: Workshops (optional)
October 16: Technical Tour 2 (optional)

For more details contact Dr Stefan Stangaciu at: drstangaciu@gmail.com

Bee Venom May Help Prevent Viral Diseases

Nasal delivery of chitosan/alginate nanoparticle encapsulated bee (Apis mellifera) venom promotes antibody production and viral clearance during porcine reproductive and respiratory syndrome virus infection by modulating T cell related responses

Vet Immunol Immunopathol. 2018 Jun;200:40-51

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In this study, we administered specially developed chitosan/alginate nanoparticle encapsulated BV (CH/AL-BV) which has slow-releasing properties and mucosal adhesiveness to pig via nasal route and evaluate whether it can facilitate systemic immune response and improve clearance of porcine reproductive and respiratory syndrome virus (PRRSV).

The CH/AL-BV-administered group with PRRSV vaccination showed significantly enhanced Th1-related responses including a high population of CD4+ T lymphocyte and cytokine mRNA levels including interferon-gamma (IFN-γ) and interleukin (IL)-12 and increased PRRSV-specific IgG levels. In the PRRSV challenge experiment, the CH/AL-BV group showed a significant decrease of viral burden in the sera and tissues (lung and bronchial lymph node) and mild interstitial pneumonia signs on both lung gross examination and microscopic evaluation with high levels of PRRSV-specific IgG and viral neutralizing antibody. CH/AL-BV also effectively induced not only Th1-related immune responses including increase in portion of CD4+ T lymphocyte, cytokines (IFN-γ and IL-12), and transcriptional factors (STAT4 and T-bet), but also stimulated IFN-γ-secreting cell families such as CD4+ T lymphocytes and Th/memory cells. Interestingly, the CH/AL-BV group showed decrease in PRRSV-specific immune-suppressive actions, including the T regulatory cell population and its related cytokines (IL-10 and TGF-β) and transcriptional factors (STAT5 and Foxp3).

Therefore, nasal-delivered CH/AL-BV may effectively induce non-specific immune stimulating actions, particularly those related to Th1 responses and viral clearance activities against PRRSV infection. Based on these results, CH/AL-BV could be a promising strategy for overcoming the disadvantages of classical PRRSV vaccination and can be applied as a preventive agent against PRRSV and other viral diseases, particularly those with immune-suppressive characteristics.

Phenolic Compounds and Flavonoids in Brazilian Geopropolis of Stingless Bees

Characterisation of phenolic compounds by UPLC-QTOF-MS/MS of geopropolis from the stingless bee Melipona subnitida (jandaíra)

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Phytochem Anal. 2018 May 17

INTRODUCTION:

Melipona subnitida Ducke (jandaíra) is a stingless bee native to north-eastern Brazil, which produces geopropolis, a mixture of beeswax, plant resins, pollens and earth that is used for sealing beehives.

OBJECTIVE:

To extend the knowledge on phenolic compounds in fractions obtained by C18-solid phase extraction (SPE) of nine geopropolis samples from Melipona subnitida collected at different times.

METHODOLOGY:

Chromatographic profiles of nine samples of geopropolis from jandaíra were analysed by ultra-performance liquid chromatography coupled with a diode array detector and quadrupole time-of-flight mass spectrometry (UPLC-DAD-QTOF-MS/MS) and combined with the use of data-independent acquisition (MSE) for the profiling and structural characterisation of the phenolic compounds. The isolated compound was identified by nuclear magnetic resonance of hydrogen and carbon (1 H- and 13 C-NMR).

RESULTS:

The present study with geopropolis of jandaíra resulted in the characterisation of 51 phenolics by UPLC-DAD-QTOF-MS/MS: four galloyl glucosides, one ellagic acid, 11 acyl-hexosides, 23 acyl-galloyl-hexosides and 12 flavonoids. The structures of two compounds (1,6-di-O-(E)-coumaroyl-2-O-galloyl-β-d-glucopyranoside and 1-O-cinnamoyl-6-O-(E)-coumaroyl-2-O-galloyl-β-d-glucopyranoside) were established by 1 H and the attached proton test (APT) experiments as well as high-resolution electrospray ionisation mass spectroscopy (HR-ESI-MS) analysis.

CONCLUSION:

The geopropolis of jandaíra showed phenolic compounds galloyl hexosides, ellagic acid, acyl-(cinnamoyl/coumaroyl)-hexosides, acyl-(cinnamoyl/coumaroyl)-galloyl-hexosides and flavonoids (aglycones and acylated-O-glycosides).

Propolis May Help Treat Bone Tumors in Dogs (Cancer, Pets)

Positive effects of antitumor drugs in combination with propolis on canine osteosarcoma cells (spOS-2) and mesenchymal stem cells

Biomed Pharmacother. 2018 May 15;104:268-274

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The combination of lower concentrations of antitumor drugs (carboplatin - CARB, doxorubicin - DOX, and methotrexate - MET) with propolis was investigated against canine osteosarcoma (spOS-2) and mesenchymal stem cells (MSC) in vitro. The mechanism of action in the combinations was analyzed.

spOS-2 cells were incubated up to 72 h with propolis (50 μg/ml) alone or in combination with CARB (10-400 μmol/l), DOX (0.5-2 μmol/l) or MET (50-200 μmol/l). Cell viability was assessed by MTT assay, apoptosis/necrosis by flow cytometry, and MSC was incubated with the optimum combination. Propolis alone exerted no cytotoxic action against spOS-2 cells, whereas CARB (400, 200 and 100 μmol/l) exhibited the highest cytotoxic effects comparing to DOX and MET.

The combination of propolis with the lowest concentrations of CARB led to better results comparing to CARB alone, which was not observed using DOX and MET. Apoptosis was involved in the action of propolis + CARB in spOS-2 cells. MSC were not affected by CARB/propolis, indicating that the cytotoxic action of the combination was specific to tumor cells but not to normal ones. Propolis improved the action of CARB against spOS-2 cells using lower concentrations of this drug, without affecting MSC.

These findings are relevant and indicate a possible application of propolis in OSA treatment.

Propolis Helps Treat Inflammation of the Eye

Propolis modulates NOS2/arginase-1 pathway in tropomyosin-induced experimental autoimmune uveitis

Inflammopharmacology. 2018 May 11

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In this study, we evaluated the preventive and curative effects of ethanolic extract of Propolis (EEP) during α-Tropomyosin-induced uveitis in an experimental model using Wistar rats, through the regulation of inducible nitric oxide synthase (NOS2) and arginase-1.

In this context, rats received daily injection of EEP (100 mg/kg) for 5 days prior to immunization or for 9 days commencing 5 days post immunization with α-Tropomyosin extract, then were sacrificed at day 14. Histological examination, NOS2, arginase-1, and nuclear factor-κB (NF-κB) expression were evaluated in the retinas. Plasmatic production of nitric oxide (NO), urea, IL-4, and TNF-α was assessed. We have found that treatment with EEP substantially reduced the retinal histological damages induced by α-Tropomyosin. In the same context, a significant decrease of NO and TNF-α levels was noticed. Interestingly, EEP down-modulated NOS2 and NF-κB expression in retina. Also, an increase in urea and IL-4 levels was concomitant to an up-modulation of arginase-1 expression.

Hence, it appears that EEP attenuated retinal damages through the induction of Th2 response and the inhibition of NF-κB/NOS2 pathway.

Propolis Extracts Used to Ameliorate Immunogenicity of Pasteurella Bacterin (Fowl Cholera, Poultry, Atrophic Rhinitis, Pigs, Bovine Hemorrhagic Septicemia, Cows)

The Enhancement of the Pasteurella's Bacterin by Propolis Extracts

Rep Biochem Mol Biol. 2018 Apr;6(2):208-218

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Background:

Pasteurella multocida continues to pose a danger to prone farm and wild animals all over the world. Chemotherapeutic treatments are progressively losing their effectiveness, last for long time, and cost a lot of money, as well as being toxic to human consumers. Therefore, clearing the way for immunization as a big-wheel alternative against the economic grain. Yet, the vaccines available in the market do not confer the necessary protection against the pathogen. The integration of the well adjuvanted killed vaccine with the attenuated vaccines proved to offer an effective protection to the host animals. However, the bare use of the killed bacterin to provide protection from the possible harm of the live attenuated vaccine was doubtful.

Methods:

In the present study, propolis extracts were used to ameliorate the immunogenicity of the Pasteurella bacterin. The cellular and humoral activities were assessed for the different bacterin formulations.

Results:

Propolis extracts adjuvants proved to broaden and extend the IgG potency, as well as to induce a unique mucosal protection against the bacterium. Simultaneously it offered an anti-inflammatory effect that increased the tolerability to the bacterin. While the cellular activity was relatively reduced with propolis extracts.

Conclusion:

These results confirm the effectiveness of the formulation of the bacterin with propolis to offer a potent homologous primary protection to the animals against the long-life use of the attenuated Pasteurella vaccines.

Propolis May Help Prevent Heart Attacks

Propolis ethanolic extracts reduce adenosine diphosphate induced platelet aggregation determined on whole blood

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Nutr J. 2018 May 14;17(1):52

BACKGROUND:

Propolis is a well-known bee product containing more than 2000 identified compounds. It has many beneficial effects on human health that include antibacterial, antiviral, anticancer and hepatoprotective justifying its use as a dietary supplement. Platelet aggregation plays crucial role in thrombus formation that can cause stroke or heart attacks. As cardiovascular diseases, including those caused by thrombus formation, are related to 50% of deaths of Western population, the objective of this study was to determine antiaggregatory activity of propolis on platelet aggregation on the whole blood samples.

METHODS:

Twenty one propolis samples from Southeast Europe were characterized by spectrophotometric methods to determine content of the total flavonoids and phenolic acids. High performance liquid chromatography coupled with diode array detection was used to identify and quantify individual polyphenols. Platelet aggregation was tested by impedance aggregometry on the whole blood samples of ten healthy volunteers.

RESULTS:

The mean content of total polyphenols was 136.14 mg/g and ranged from 59.23 to 277.39 mg/g. Content of total flavonoids ranged between 6.83 and 55.44 mg/g with the mean value of 19.28 mg/g. Percentage of total phenolic acids was in the range 8.79 to 45.67% (mean 26.63%). Minimal antiaggregatory concentration, representing the lowest concentration of propolis extract sample that can cause statistically significant reduction of aggregation, ranged from 5 μM to 10.4 mM. Samples of propolis with lower content of luteolin and higher content of pinocembrin-7-methyleter showed better antiplatelet activity i.e. lower values of minimal antiaggregatory concentration.

CONCLUSIONS:

This is the first study that shows antiaggregatory potential of propolis ethanolic extracts on the whole blood samples in the low micromolar concentrations suggesting that propolis supplementation may influence platelet aggregation and consequently thrombus formation. Further in vivo studies are needed to confirm the beneficial effects in prevention of cardiovascular diseases.