Honey, Propolis Component Protects Against Brain, Heart, Liver, Testis, Kidney Toxicity

The antidiabetic and anticholinergic effects of chrysin on cyclophosphamide-induced multiple organ toxicity in rats: Pharmacological evaluation of some metabolic enzyme activities

J Biochem Mol Toxicol. 2019 Feb 22:e22313

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Chrysin (CH) or 5,7-dihydroxyflavone is a flavonoid present in various plants, bee propolis, and honey. Cyclophosphamide (CYP) is a chemotherapeutic drug, which is extensively used in the treatment of multiple human malignancies.

In our study, we aimed to investigate the effects of CYP and CH on some metabolic enzymes including carbonic anhydrase, aldose reductase, paraoxonase-1, α-glycosidase, acetylcholinesterase, and butyrylcholinesterase enzyme activities in the brain, heart, testis, liver, and kidney tissues of rats. Thirty-five adult male Wistar rats were used. The animals were pretreated with CH (25 and 50 mg/kg b.w.) for seven days before administering a single dose of CYP (200 mg/kg b.w.) on the seventh day.

In all the tissues, the treatment of CH significantly regulated these enzyme activities in CYP-induced rats. These results showed that CH exhibited an ameliorative effect against CYP-induced brain, heart, liver, testis, and kidney toxicity.

Honey May Be Healthy Alternative Sweetener for Those with Diabetes

Antioxidants of honey in perspective of blood glycaemic control

Journal of the Pakistan Medical Association, February 2019, Volume 69, Issue 2

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Diabetes is a heterogeneous metabolic disorder that is characterized by an abnormal increase of blood glucose level over the range of 126 mg/dl in fasting condition.

Prolonged stay of glucose in blood leads to hyperglycaemia, which is an established index of diabetes development. Chronically, this high blood sugar predisposes to different types of complications. Hyperglycaemia is a key factor in the pathogenesis of diabetic complications by increasing protein glycation and gradual buildup of advanced glycated end products (AGEs) in body tissues.

...Antioxidant-rich diets have been proposed as attractive candidates for diabetes management. Recently, a study reported the binding mechanism of phytochemicals with two enzymes (-amylase and -glucosidase) to ameliorate their antidiabetic and antiglycation potentials. It is also intrigued that amylose-antioxidants complex formation may modulate starch digestion.

One of the natural products is palatable honey which is a juicy excretion of honeybees and is derived from nectar of plant flowers. In other words it is true to say that bioactive compounds/antioxidants in honey come from plant (floral) origins.However, in comparison with the other plant based natural products, antioxidants in honey are readily available to consume in delicious semi-liquid form due to sugar contents.

Thus, the consumption of floral/plant based antioxidants through honey suppress oxidative stress to prevent vital body organs from free radicals/ROS attacks. It also decreases starch digestibility in gastrointestinal tract, reducing blood glycaemic response.Therefore, due to high antioxidative potential honey seems to be a highly efficacious and effective supplement for many of the pathologies/ailments. But diabetic patients are reluctant to use this natural honeybee produce.

...In light of above described facts, prospective research is warranted to identify different floral origins from which honeys are derived/produced. Hopefully, in futuristic studies low glycaemic indexed honey(s) will be exploited as natural healthy alternative sweetener(s) to refined sugar and antioxidant suppressant by preventing harmful effects of ROS. Furthermore, vital honey(s) along with floral origin(s) can be exploited at commercial scale in the form of honeybee farms for diabetic patients.

Propolis Has Well Documented Germ-Fighting Properties and is Rich in Antioxidants

The Many, Many Wellness Benefits of Bee By-Products

Total Beauty

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"Propolis has well documented germ-fighting properties and is rich in antioxidants as well as hundreds of beneficial plant compounds – bees line every inch of their hives with this sticky stuff to keep things clean and germ-free; it's pretty much their built-in immune system," adds Stein. "They even keep what is essentially a propolis doormat by the hive entrance to ensure no one tracks in any nasties!" And, if they do, Dr. Noah Wilson-Rich, the founding partner and chief scientific officer at The Best Bees Company says that bees can self-medicate by adding more propolis inside their nest after exposure to a disease-causing fungus...

Propolis May Help Treat Glaucoma

Oculohypotensive effects of various acetozolamide nanopreparations for topical treatment of animal model-induced glaucoma and their impact on optic nerve

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PLoS One. 2019 Feb 21;14(2):e0212588

Acetozolamide-ACZ, carbonic anhydrase inhibitor- is still the most effective systemic drug for glaucoma treatment. Due to its limited ocular bioavailability, topical formulations are not available yet.

This study introduces within the framework of nanotechnology three nanopreparations of acetozolamide for topical application, one of them is liposomal phospholipid vehicle and the other two preparations are propolis and Punica granatum (pomegranate).

The hypotensive effect of these different nanopreparations in lowering the increased intraocular pressure that was induced in experimental rabbits is monitored for 130 hrs. Structural characteristics of the optic nerve dissected from all involved groups were studied by Fourier transfrom infrared spectroscopy.

The obtained results indicate the impact of the topically applied acetozolamide nanopreparations in lowering the intraocular pressure to its normotensive control value. On the other hand, the optic nerve characteristics were found to be dependent on the way acetozolamide introduced.

Glaucoma affects structural components that contain OH group and increases β-turns of the protein secondary structure while, reducing the content of both α-helix and Turns. In the same context, liposomal-acetozolamide and propolis nanopreparations protecting the optic nerve protein secondary structure from these changes associated with glaucoma.

Propolis Component May Help Treat Gum (Periodontal) Disease

Caffeic acid phenethyl ester protects against oxidative stress and dampens inflammation via heme oxygenase 1

Int J Oral Sci. 2019 Feb 20;11(1):6

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Periodontal disease is associated with chronic oxidative stress and inflammation.

Caffeic acid phenethyl ester (CAPE), which is a potent inducer of heme oxygenase 1 (HO1), is a central active component of propolis, and the application of propolis improves periodontal status in diabetic patients.

Here, primary murine macrophages were exposed to CAPE. Target gene expression was assessed by whole-genome microarray, RT-PCR and Western blotting. The antioxidative and anti-inflammatory activities of CAPE were examined by exposure of the cells to hydrogen peroxide, saliva and periodontal pathogens. The involvement of HO1 was investigated with the HO1 inhibitor tin protoporphyrin (SnPP) and knockout mice for Nrf2, which is a transcription factor for detoxifying enzymes. CAPE increased HO1 and other heat shock proteins in murine macrophages. A p38 MAPK inhibitor and Nrf2 knockout attenuated CAPE-induced HO1 expression in macrophages.

 CAPE exerted strong antioxidative activity. Additionally, CAPE reduced the inflammatory response to saliva and periodontal pathogens. Blocking HO1 decreased the antioxidative activity and attenuated the anti-inflammatory activity of CAPE.

In conclusion, CAPE exerted its antioxidative effects through the Nrf2-mediated HO1 pathway and its anti-inflammatory effects through NF-κB inhibition. However, preclinical models evaluating the use of CAPE in periodontal inflammation are necessary in future studies.

Propolis in Combination with Boric Acid Protects Against Ischemia/Reperfusion-Induced (I/R) Acute Kidney Injury

Propolis and Its Combination with Boric Acid Protect Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Oxidative Stress, Inflammation, DNA Damage, and Apoptosis in Rats

Biol Trace Elem Res. 2019 Feb 19

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Ischemia reperfusion (I/R) injury which causes kidney dysfunction is one of the most studied diseases directly linked to oxidative stress.

In this regard, it is important to protect cells against damage by inducing antioxidant response.

Herein, we aimed to evaluate the therapeutic roles and possible mechanisms of propolis and boric acid in kidney I/R injury based on relevant basic research and clinical studies. Sprague-Dawley rats were subjected to 50 min of ischemia followed by 3 h of reperfusion.

Animals were randomly divided into a control group (the abdominal wall was just opened and closed), an I/R injury group, the propolis intervention group (200 mg/kg, intragastric administration, 1 h before ischemia), boric acid intervention group (14 mg/kg, intragastric administration 1 h before ischemia), and the propolis + boric acid intervention group (intragastric administration 1 h before ischemia). Kidney function, the antioxidant defensive system, and renal damage were assessed. In addition, the oxidative stress and inflammatory status were estimated in renal tissue.

Furthermore, DNA damageand apoptosis were detected by immunohistochemistry. When compared with I/R group, propolis alone and especially propolis + boric acid groups significantly improved functional parameters. While the antioxidant response was increased, renal injury size and apoptosis were significantly decreased in both groups. Also, the MDA and TNF-α levels besides the 8-OHdG formation were downregulated.

According to these outcomes, it can be said that especially propolis together with boric acid ameliorates kidney injury caused by I/R through acting as an antioxidant, anti-inflammatory, and antiapoptotic agent. In conclusion, propolis alone and its combination with boric acid could be developed as therapeutic agents against serious renal I/R injuries.

Brazilian Red Propolis Effective in Treating Diabetic Foot Wounds

Bacterial cellulose membrane associated with red propolis as phytomodulator: Improved healing effects in experimental models of diabetes mellitus

Biomed Pharmacother. 2019 Feb 19;112:108640

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Since early times, propolis has been used in folk medicine. The red propolis, collected in the northeast region of Brazil has been highlighted due to its popular use as an antimicrobial, with anti-inflammatory and healing properties, which are associated with its chemical composition.

Here, we combine a bacterial membrane with red propolis to treat wounds of diabetic mice. This work aims to evaluate a biocurative from bacterial cellulose associated with red propolis in diabetic mice as wound healing model. Biocuratives from bacterial cellulose membrane and different extracts of red propolis were produced. The qualification and quantification of the presence of propolis chemical compounds in the membrane were investigated through high-resolution mass spectrometry (HRMS). Tests in vivo with biocuratives were performed on Swiss male diabetic mice induced by estroptozotocin.

The animals were submitted to a surgical procedure and a single lesion was produced in the dorsal region, which was treated with the biocuratives. Macroscopic assessments were performed at 2, 7 and 14 postoperative days, and biopsies were collected on days 0, 7 and 14 for histological analysis, myeloperoxidase enzyme activity (MPO) and cytokines (TNF-α, IL-1β, and TGF-β). Altogether, ten compounds were identified in membranes and five were further quantified. The ethyl acetate extract showed more red propolis markers, and the most prevalent compound was Formononetin with 4423.00-2907.00 μg.g-1.

Macroscopic analyses demonstrated that the two groups treated with red propolis (GMEBT and GMEAE) showed significantly greater healing capabilities compared to the control groups (GS and GMS). An increase in leukocyte recruitment was observed, confirmed by the activity of the enzyme myeloperoxidase (MPO) in GMEBT and GMEAE groups. The levels of TNF-α were significantly higher in wounds stimulated with red propolis, as well as in TGF-β (GMEBT and GMEAE) on day 7. This was different from the IL-1β levels that were higher in the control groups (GS and GMS).

In summary, the biocuratives produced in this work were able to accelerate the wound healing process in a diabetic mouse model. In this way, the traditional knowledge of red propolis activity helped to create a biotechnological product, which can be used for diabetic wound healing purpose.

Bee Venom and Royal Jelly Useful in Treating Critical Bone Defects

Effects of chitosan scaffold along with royal jelly or bee venom in regeneration of critical sized radial bone defect in rat

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Iran J Vet Res. 2018 Fall;19(4):246-254.

The aim of this study was to compare the efficacy of honey bee venom (BV) and royal jelly (RJ) alongside chitosan scaffold (CS) in improving radius bone defect in rats.

A total of 60 full thickness radial bone defects with a length of 5 mm were created in 60 male Wistar rats. Six healthy radial bones (3 rats) were also assigned as normal control for biomechanical studies. The defects were left empty (untreated group) or were filled by the autograft (autograft group), CS (CS group), CS alongside the BV solution (CS-BV group), and CS alongside the RJ solution (CS-RJ group). Healing of the bone defects were evaluated clinically and radiologically on days 0, 28, 42 and 56 after operation while the biomechanical testing and histopathological examination were performed on the 56th day after surgery.

The autograft was more radiopaque than the untreated and CS groups at the 28th, 42nd and 56th postoperative days (P < 0.05). The CS-BV and CS-RJ groups showed significantly higher radiographic outcomes than the untreated and CS groups at the 56th post-operative day (P < 0.05). The density of osseous tissue (DOT) and the osteocytes and osteoblasts count of the CS-RJ and CS-BV groups were significantly higher than the CS and autograft groups (P < 0.05). The biomechanical results of the CS-RJ group were significantly superior to the autograft, while the biomechanical properties of CS-BV group were not significantly different with the autograft group (P > 0.05).

The scaffolds in CS group were observable in the surgical site after 56 days. There was no significant difference in radiographs, DOT, cartilage tissue and fibrous tissue, and also biomechanical performances of the CS-BV and CS-RJ groups at the 42nd and 56th day after surgery. The untreated and CS groups showed weakest biomechanical results among all groups.

It could be concluded that both treatment strategies in the CS-BV and CS-RJ groups were appropriate and useful in treating critical bone defects.

Honey Consumption Decreased Waist Circumference of Patients with Type 2 Diabetes

Effect of Natural Honey on Glycemic Control and Anthropometric Measures of Patients with Type 2 Diabetes: A Randomized Controlled Crossover Trial

Int J Prev Med. 2019 Jan 15;10:3

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Background:

Due to high content of fructose, honey has been introduced as a suitable natural sweetener for patients with type 2 diabetes. We investigated the effect of honey consumption on glycemic control and anthropometric measures of patients with type 2 diabetes.

Methods:

This randomized controlled crossover clinical trial was conducted on 53 patients with type 2 diabetes. The participants were randomly divided into groups of control (weight maintenance diet) or treatment (weight maintenance diet +50 g/day honey) for 8 weeks. After a 4-week washout, the second phase began, in which the role of the groups was interchanged. Blood glycated hemoglobin (HbA1c), glucose, insulin, and anthropometric characteristics were measured. Statistical analysis was performed with SPSS. Repeated measures of ANOVA were used to test differences within- and between the two conditions.

Results:

Forty-two patients completed the study. HbA1c significantly decreased in control (-0.22%, P = 0.03) and nonsignificantly increased in honey condition (+0.17%, P = 0.22). There was a significant difference between the two conditions (P = 0.02). Fasting glucose did not significantly change in either honey or control condition but insulin concentrations (-0.85 μU/ml, P = 0.01) and insulin secretion (-10.7%, P = 0.01) decreased significantly in the control condition. There was no significant difference in any of these parameters between the two conditions. Waist circumference decreased by honey treatment with a significant difference between the two conditions (P = 0.02).

Conclusions:

Eight weeks consumption of 50 g/day honey increased HbA1c and decreased waist circumference of patients with type 2 diabetes.

Bee Venom Component May Help Treat Vaginal Yeast Infections (Vulvovaginal Candidiasis)

Antifungal activity of analogues of antimicrobial peptides isolated from bee venoms against vulvovaginal Candida spp.

FEMS Yeast Res. 2019 Feb 11

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Candida albicans is the main causative agent of vulvovaginal candidiasis, a common mycosis in women, relapses of which are difficult to manage due to biofilm formation.

This study aimed to develop novel non-toxic compounds active against Candida spp. biofilms. We synthesized analogues of natural antifungal peptides LL-III (LL-III/43) and HAL-2 (peptide VIII) originally isolated from bee venoms and elucidated their structures by nuclear magnetic resonance spectroscopy.

The haemolytic, cytotoxic, antifungal and anti-biofilm activities of LL-III/43 and peptide VIII were then tested. LL-III/43 and VIII showed moderate cytotoxicity to HUVEC-2 cells and had comparable inhibitory activity against C. albicans and non-albicans spp. The lowest minimum inhibitory concentration (MIC90) of LL-III/43 was observed towards C. tropicalis (0.8 µM). That was 8-fold lower than that of antimycotic amphotericin B. Both peptides can be used to inhibit Candida spp. biofilms formation.

Biofilm inhibitory concentrations (BIC50) ranged from 0.9 to 58.6 µM and biofilm eradication concentrations (BEC50) for almost all tested Candida spp. strains ranged from 12.8 to 200 µM.

Also proven were the peptides' abilities to reduce area colonized by biofilm, inhibit hyphae formation and permeabilize cell membranes in biofilm. LL-III/43 and VIII are promising candidates for further development as therapeutics against vulvovaginal candidiasis.

Honey an Effective Treatment for Mucositis in Children

The effect of oral care with chlorhexidine, vitamin E and honey on mucositis in pediatric intensive care patients: A randomized controlled trial

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J Pediatr Nurs. 2019 Feb 8. pii: S0882-5963(18)30519-0

PURPOSE:

This study was performed to determine the effect of oral care using chlorhexidine, vitamin E and honey on oral mucositis (OM) management in children treated in a pediatric intensive care unit (PICU).

DESIGN AND METHODS:

The study was a randomized controlled trial with a parallel design. The study sample was composed of 150 children who were treated in the PICU of a university hospital in Turkey. Children enrolled in the study were randomly divided into six groups based on the oral care solutions used (n = 25 in each group). The Demographic Information Form and the World Health Organization Oral Mucositis Index were used for data collection.

RESULTS:

The mucositis indices of the children presenting with and without OM upon admission to the PICU were compared on days 1, 3, 6, 9, 12, 15, 18 and 21 and the study found that the mucositis index values of the children treated with vitamin E were significantly lower than in the other groups (p < 0.05 for each), while those of the children given chlorhexidine were significantly higher than in the other groups (p < 0.05 for each).

CONCLUSIONS:

At the end of the study, vitamin E was determined to be the most effective agent in OM management, followed by honey as the second most effective agent. Chlorhexidine was found to be less effective in OM management compared to the other two agents. Based on this, vitamin E is recommended for use in oral mucositis-preventive and therapeutic oral care practices.

PRACTICE IMPLICATIONS:

The results of the present study conducted with PICU patients will be useful in the administration of oral care. These findings are also important for nurses who have the responsibility of oral mucositis management.

Honey-Mediated Wound Healing

H₂O₂ Entry through AQP3 Determines Extracellular Ca2+ Influx

Int J Mol Sci. 2019 Feb 11;20(3). pii: E764

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Since Biblical times, honey has been utilized in "folk medicine", and in recent decades the positive qualities of honey have been re-discovered and are gaining acceptance. Scientific literature states that honey has been successfully utilized on infections not responding to classic antiseptic and antibiotic therapy, because of its intrinsic H₂O₂ production.

In our study, we demonstrated the involvement of H₂O₂ as a main mediator of honey regenerative effects on an immortalized human keratinocyte cell line. We observed that this extracellularly released H₂O₂ could pass across the plasma membrane through a specific aquaporin (i.e., AQP3). Once in the cytoplasm H₂O₂, in turn, induces the entry of extracellular Ca2+ through Melastatin Transient Receptor Potential 2 (TRPM2) and Orai1 channels. Honey-induced extracellular Ca2+ entry results in wound healing, which is consistent with the role played by Ca2+ signaling in tissue regeneration.

This is the first report showing that honey exposure increases intracellular Ca2+ concentration ([Ca2+]i), due to H₂O₂ production and redox regulation of Ca2+-permeable ion channels, opening up a new horizon for the utilization of the honey as a beneficial tool.

Magnolia Berry (Five-Flavor-Fruit) Bee Pollen Extract May Help Treat Obesity, Nonalcoholic Fatty Liver Disease (NAFLD)

Impact of Schisandra Chinensis Bee Pollen on Nonalcoholic Fatty Liver Disease and Gut Microbiota in HighFat Diet Induced Obese Mice

Nutrients. 2019 Feb 6;11(2). pii: E346

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Schisandra chinensis bee pollen has been used as a health food in China for centuries; however, its bioactive constituents and functions are not very clear. In this study, we investigated the phenolic compounds of Schisandra chinensis bee pollen extract (SCPE) by UHPLC-Q-Orbitrap-HRMS/HPLC-DAD-ECD and its prevention from nonalcoholic fatty liver disease (NAFLD) and modulation of gut microbiota in high fat diet induced obese C57BL/6 mice.

The results showed that 12 phenolic compounds were identified in SCPE, and naringenin, rutin and chrysin were the main constituents. The content of naringenin reached 1.89 mg/g, and total phenolic content (TPC) of SCPE were 101.83 mg GA/g. After obese mice were administrated with SCPE at 7.86 and 15.72 g/kg BW for 8 weeks, body weight gains were reduced by 18.23% and 19.37%. SCPE could decrease fasting blood glucose, cut down the lipid accumulation in serum and liver, lessen oxidative injury and inflammation in obesity mice.

Moreover, SCPE could effectively inhibit the formation of NAFLD by inhibition of LXR-α, SREBP-1c and FAS genes expression, and modulate the structural alteration of gut microbiota in obesity mice.

These findings suggested that SCPE could attenuate the features of the metabolism syndrome in obesity mice, which can be used to prevent obesity and NAFLD of human beings.

Rainforest Sialang Honey Helps Treat Diabetic Foot Wounds

Effectiveness of using sialang honey on wound bed preparation in diabetic foot ulcer

Enferm Clin. 2019 Feb 4. pii: S1130-8621(19)30028-2

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OBJECTIVE:

The aim of this study is to determine the effectiveness of sialang honey on wound bed preparation in diabetic foot ulcer.

METHOD:

The study design was quasy experiment with one group pre test post test design approach. The sampling technique used was consecutive sampling, where respondents were selected based on the criteria that had been planned. Instrument used in this study was wound bed score, where the measurement results will be analyzed using Wilcoxon test with 95% confidence level.

RESULT:

Result of this study was average wound bed score before intervention was 2.75 and became 9.25 after the intervention on a scale of 0-16. Wilcoxon test in this study obtained p value 0.011 with the conclusion that sialang honey had a significant effect on wound bed preparation in diabetic foot ulcer.

CONCLUSION:

Statistically, honey can help the occurrence of wound bed preparation in diabetic foot ulcer.

Propolis, Honey Component May Help Treat Neuroinflammation

A20 as a novel target for the anti-neuroinflammatory effect of chrysin via inhibition of NF-κB signaling pathway

Brain Behav Immun. 2019 Feb 7. pii: S0889-1591(18)30634-2

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Neuroinflammation is now recognized to be a feature of many neurological disorders. More accumulated evidences suggested chrysin which was contained in honey, propolis, vegetables, fruits and plants can exert biological activities including anti-neuroinflammatory effects. However, the precise molecular mechanisms of anti-neuroinflammatory effects remain unclear. In the present study, we explored a novel molecular mechanism involved in the anti-neuroinflammatory effect of chrysin. Firstly, we investigated the anti-neuroinflammatory effects of chrysin in LPS-induced BV2, primary microglial cells and mice. Next, we found chrysin can inhibit NF-κB pathway and TRAF6 expression, but upregulate the expression of zinc-finger protein A20. Further studies have revealed upregulation of A20 can regulate the inhibitory effects of chrysin on NF-κB pathways via regulation of TRAF6 polyubiquitination. This present study demonstrates that chrysin exerts an anti-neuroinflammatory effect via a novel mechanism, the upregulation of A20 expression, also validates A20 is a novel effective pharmacological target for developing agents in the treatment of neuroinflammation-related diseases.