Apitherapy in Post-Ischemic Brain Neurodegeneration of Alzheimer's Disease Proteinopathy: Focus on Honey and Its Flavonoids and Phenolic Acids.

Neurodegeneration of the brain after ischemia is a major cause of severe, long-term disability, dementia, and mortality, which is a global problem. These phenomena are attributed to excitotoxicity, changes in the blood-brain barrier, neuroinflammation, oxidative stress, vasoconstriction, cerebral amyloid angiopathy, amyloid plaques, neurofibrillary tangles, and ultimately neuronal death. In addition, genetic factors such as post-ischemic changes in genetic programming in the expression of amyloid protein precursor, ß-secretase, presenilin-1 and -2, and tau protein play an important role in the irreversible progression of post-ischemic neurodegeneration. Since current treatment is aimed at preventing symptoms such as dementia and disability, the search for causative therapy that would be helpful in preventing and treating post-ischemic neurodegeneration of Alzheimer's disease proteinopathy is ongoing. Numerous studies have shown that the high contents of flavonoids and phenolic acids in honey have antioxidant, anti-inflammatory, anti-apoptotic, anti-amyloid, anti-tau protein, anticholinesterase, serotonergic, and AMPAK activities, influencing signal transmission and neuroprotective effects. Notably, in many preclinical studies, flavonoids and phenolic acids, the main components of honey, were also effective when administered after ischemia, suggesting their possible use in promoting recovery in stroke patients. This review provides new insight into honey's potential to prevent brain ischemia as well as to ameliorate damage in advanced post-ischemic brain neurodegeneration.

Natural remedies for acute post-viral cough in children.

The post-viral acute cough is the most common symptom in childhood. Consequently, the use of cough relievers is frequent. Many products for treating cough contain natural components. An ancient tradition has always established herbal medicine and honey as effective and safe means to relieve cough. Nevertheless, very few studies adequately investigated the real effectiveness and safety of natural products in treating acute cough. There is some evidence, provided by pediatric randomized controlled trials, about honey, one multicomponent product (containing Plantagolanceolata, Grindelia robusta, Helichrysum italicum, and honey), and Pelargonium sidoides. Other group of substances, including glycerol and isolated natural compounds, can help manage cough but robust evidence still lacks in children. There is an urgent need to perform rigorous studies that confirm the natural products' efficacy and safety for relieving post-viral acute cough.Key points: Acute post-viral cough is prevalent in childhood and adolescence. There is a growing interest concerning the use of natural remedies for post-viral cough. Many herbal medicines could be used satisfactorily for this issue.

Acute cough in children and adolescents: A systematic review and a practical algorithm by the Italian Society of Pediatric Allergy and Immunology.

The current systematic review presented and discussed the most recent studies on acute cough in pediatric age. After that, the Italian Society of Pediatric Allergy and Immunology elaborated a comprehensive algorithm to guide the primary care approach to pediatric patients, such as infants, children, and adolescents, with acute cough. An acute cough is usually consequent to upper respiratory tract infections and is self-resolving within a few weeks. However, an acute cough may be bothersome, and therefore remedies are requested, mainly by the parents. An acute cough may significantly affect the quality of life of patients and their family.Several algorithms for the management of acute cough have been adopted and validated in clinical practice; however, unlike the latter, we developed an algorithm focused on pediatric age, and, also, in accordance to the Italian National Health System, which regularly follows the child from birth to all lifelong. Based on our findings, infants from 6 months, children, and adolescents with acute cough without cough pointers can be safely managed using well-known medications, preferably non-sedative agents, such as levodropropizine and/or natural compounds, including honey, glycerol, and herb-derived components.

Bee products as a source of promising therapeutic and chemoprophylaxis strategies against COVID-19 (SARS-CoV-2).

The emergence of novel coronavirus (SARS-CoV-2) in 2019 in China marked the third outbreak of a highly pathogenic coronavirus infecting humans. The novel coronavirus disease (COVID-19) spread worldwide, becoming an emergency of major international concern. However, even after a decade of coronavirus research, there are still no licensed vaccines or therapeutic agents to treat the coronavirus infection. In this context, apitherapy presents as a promising source of pharmacological and nutraceutical agents for the treatment and/or prophylaxis of COVID-19. For instance, several honeybee products, such as honey, pollen, propolis, royal jelly, beeswax, and bee venom, have shown potent antiviral activity against pathogens that cause severe respiratory syndromes, including those caused by human coronaviruses. In addition, the benefits of these natural products to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells, and stimulation of the innate and adaptive immune responses. Thus, in the absence of specific antivirals against SARS-CoV-2, apitherapy could offer one hope toward mitigating some of the risks associated with COVID-19.

Biodirected Synthesis of Silver Nanoparticles Using Aqueous Honey Solutions and Evaluation of Their Antifungal Activity against Pathogenic Candida Spp.

Silver nanoparticles (AgNPs) were synthesized using aqueous honey solutions with a concentration of 2%, 10%, and 20%-AgNPs-H2, AgNPs-H10, and AgNPs-H20. The reaction was conducted at 35 °C and 70 °C. Additionally, nanoparticles obtained with the citrate method (AgNPs-C), while amphotericin B (AmB) and fluconazole were used as controls. The presence and physicochemical properties of AgNPs was affirmed by analyzing the sample with ultraviolet-visible (UV-Vis) and fluorescence spectroscopy, scanning electron microscopy (SEM), and dynamic light scattering (DLS). The 20% honey solution caused an inhibition of the synthesis of nanoparticles at 35 °C. The antifungal activity of the AgNPs was evaluated using opportunistic human fungal pathogens Candida albicans and Candida parapsilosis. The antifungal effect was determined by the minimum inhibitory concentration (MIC) and disc diffusion assay. The highest activity in the MIC tests was observed in the AgNPs-H2 variant. AgNPs-H10 and AgNPs-H20 showed no activity or even stimulated fungal growth. The results of the Kirby-Bauer disc diffusion susceptibility test for C. parapsilosis strains indicated stronger antifungal activity of AgNPs-H than fluconazole. The study demonstrated that the antifungal activity of AgNPs is closely related to the concentration of honey used for the synthesis thereof.

Manuka honey versus saline sinus irrigation in the treatment of cystic fibrosis-associated chronic rhinosinusitis: A randomised pilot trial.

OBJECTIVES: Manuka honey attacks biofilms, which contribute to bacterial persistence in cystic fibrosis sinusitis. The primary objective was to determine feasibility of investigating manuka honey as an irrigation treatment for cystic fibrosis sinusitis and secondarily to assess the treatment's preliminary effectiveness. DESIGN: Prospective, single-blinded (clinician only), randomised, parallel two-arm pilot trial. SETTING: Tertiary rhinology clinic. PARTICIPANTS: Subjects had recalcitrant cystic fibrosis sinusitis and previous sinus surgery. They received manuka honey or saline sinus irrigations twice daily for 30 days. MAIN OUTCOME MEASURES: Main outcomes were recruitment/retention rates and tolerability. Preliminary effectiveness was assessed based on quality-of-life Sinonasal Outcome Test-22 and Lund-Kennedy endoscopic change scores and post-treatment culture negativity. RESULTS: Over 10 months, 13 subjects were enrolled, and 77% (10/13) were included in the analysis. Manuka honey irrigations were well-tolerated. The quality-of-life change score was clinically significant for manuka honey (-9 [-14,-6]) but not saline (-5 [-9,-1]), although the difference was not statistically significant (P = .29). Lund-Kennedy endoscopic change score was significantly better for manuka honey (-3 [-5,-3]) versus saline (0 [0,0]) (P = .006). There was no difference in post-treatment culture negativity between manuka honey (1/5, 20%) and saline (0/5, 0%) (P = 1.00). CONCLUSIONS: Manuka honey irrigations were well tolerated, and retention rates were high. Preliminary data showed that manuka honey achieved a clinically important difference in quality-of-life score and a significantly better endoscopic outcome. Microbiological control was difficult to achieve. A future definitive trial would require multi-institutional recruitment.

[APITHERAPY - THE GOOD AND THE MYTH].

INTRODUCTION: Apitherapy - applying the Bee venom to treat medical condition is ancient. According to analysis of google searches, over the past decade there was a steady increase in interest regarding apitherapy. There are some controlled studies alluding to its beneficial effects. There are several anti-inflammatory peptides in the venom, i.e. Melittin, Apamin and more. There are efforts to synthesize them and apply them for therapy. Caution is needed to avoid allergy to bee venom as well as to an anaphylactic shock.

Regulation of microRNAs by rape bee pollen on benign prostate hyperplasia in rats.

The miRNAs are dysregulated in BPH. Rape bee pollen (RBP) is used to improve benign prostatic hyperplasia (BPH). Whether RBP treats BPH by regulating the dysregulated miRNAs remains unclear. Here, we identified miRNAs regulated along with the improvement of BPH by RBP in posterior lobes of prostate in rats. Firstly, to screened miRNAs might relate to improvement of BPH by RBP, we compared differentially expressed miRNAs between BPH model group and RBP group by high-throughput sequencing. As a result, 10 known miRNAs and 17 novel miRNA were up-regulated in RBP group, and 6 known and 13 novel miRNAs were down-regulated. Secondly, among the known miRNAs, we identified those that might relate to BPH by RT-qPCR, while only rno-miR-184 was screened, so we compared it among normal control group, BPH model group and RBP group. The results showed that rno-miR-184 was significantly lower expressed in BPH group, but up-regulated along with the improvement of BPH by RBP. Moreover, expression level of rno-miR-184 was no difference between RBP group and normal control level. Therefore, we considered that RBP might improve BPH through regulating expression of miRNAs like rno-miR-184 in prostate in rats.

The role of propolis against paclitaxel-induced oligospermia, sperm abnormality, oxidative stress and DNA damage in testes of male rats.

Paclitaxel (taxol) is one of the most powerful anticancer drugs but it possesses toxic effects on male reproductive system. Propolis, from folkloric remedy, have antioxidant, anti-inflammatory and anticancer effects. The present study established to examine the protective impact of Propolis against malformation of semen induced by taxol. Twenty-four male rats equally divided into four groups. Group I (normal control); group II, administrated Propolis alone; group III, taxol-treated group received taxol; group IV, co-administered of taxol and Propolis extract. After 4 weeks of treatment, the semen were collected and testis 24 hr after the last treatment. Sperm count, motility, viability and sperm morphology were assayed. Tissue supernatants were isolated for oxidative stress, cell energy parameters and 8-OHdG. DNA damage was evaluated using Comet assay in testes. Our results confirmed that taxol-induced significant reduction in sperm count, motility, viability and recorded marked elevation in sperm abnormalities. Also, taxol caused increased in 8-OHdG and DNA damage versus that recorded in control group. Treatment with Propolis improving semen quality and protected testis from detrimental effects of taxol and minimises its toxicity. In conclusions, Oral administration of Propolis modulates the toxic impact of taxol by amelioration semen quality, diminishing oxidation state, DNA damage and preserving cell energy.

Seasonal allergic rhinitis and the role of apitherapy.

BACKGROUND: Apitherapy represents a certain form of complementary and alternative medicine that uses bee products in combination with other methods from this field. One of the basic concepts of this type of medicine is that all diseases can be treated using apitherapy. This study was performed to assess the recommendations from authors of books on apitherapy regarding the treatment of seasonal allergic rhinitis and compare them to findings from the scientific literature. METHODS: One hundred and twenty-nine books on apitherapy were analysed regarding recommendations for allergic seasonal rhinitis. Scientific evidence regarding the efficacy of using various bee products was searched via PubMed and JUSTfind. RESULTS: Only 38.8% of the apitherapy books mentioned seasonal allergic rhinitis. Among these books, we found 29 different recommendations in favour of bee products and one against the use of honey. The most reasonable recommendation according to clinical studies on the subject, namely the use of a mix of honey and pollen, was only found once (0.8%). CONCLUSIONS: The large discrepancies and number of different recommendations demonstrate that apitherapy is not a consistent type of medicine. The recommendations regarding seasonal allergic rhinitis in the vast majority of apitherapy books cannot be considered adequate when compared to the scientific findings.

Apitherapy for menopausal problems.

PURPOSE: Apitherapy, a method from the field of complementary and alternative medicine, claims that all health problems including menopausal problems can be cured using bee products, especially honey, bee-collected pollen, propolis, and royal jelly. This study was to investigate the recommendations of protagonists of holistic apitherapy and compare these to the current evidence. METHODS: Since holistic apitherapy is only promoted in books and apitherapeutical congresses, we identified books on the topic in English, French, and German language via bookseller platforms and the JUSTfind system of the Justus-Liebig-University Gießen, Germany, which comprises 337 databases from the EBSCO Discovery Service. RESULTS: Only 29.5% (n = 38) of the apitherapy books mentioned the topic of menopausal problems. Among these, there were 24 different recommendations. Royal jelly is the number one recommended therapy, followed by pollen, the combination of pollen and royal jelly, and propolis. All other recommendations are mentioned just once. The recommendation regarding royal jelly must be regarded as correct. Strictly speaking, evidence regarding bee-collected pollen is poor, since all studies on pollen did not investigate pollen directly, but pollen extracts and these pollens came from pollen that was anemophilous but not entomophilous. CONCLUSION: Royal jelly and pollen could be interesting treatment options in cases of menopausal symptoms. In order to promote bee products for menopausal symptoms with a good conscience trials, comparing bee products against other options, such as selective serotonin reuptake inhibitors, C. racemosa extracts, and/or yoga should be initiated, since these methods have already proven their value.

Medical grade honey for the treatment of paediatric abdominal wounds: a case series.

OBJECTIVE: Children are at high risk of injuries and wounds. The application of medical grade honey is a promising approach to improving the healing of wounds of various origin and severity. However, the use of medical grade honey in young paediatric patients remains limited. The aim of this study is to show the safety, efficacy and usefulness of medical grade honey in abdominal wounds, of different causes, in paediatric patients. METHOD: This was a prospective, observational case series evaluating five young infants with abdominal wounds at the General Hospital in Thessaloniki. All wounds were treated in the same manner with daily medical grade honey applied to the wound area and closely monitored. RESULTS: All treated wounds rapidly presented granulation tissue formation and underwent re-epithelialisation. Peripheral oedema and inflammation decreased upon initial application. Necrotic tissue was effectively debrided when present. Slough was removed and no signs of infection were detected, irrespective of initial wound presentations. Scar formation was minimal and the full range of motion was preserved in all cases. CONCLUSION: Based on this case study, medical grade honey is safe and effective in treating different abdominal wounds, including infected or dehisced wounds as well as burns. The easy application and broad applicability make medical grade honey recommendable as a first-line treatment in paediatric patients.

Anti-inflammatory effect of bee venom in phthalic anhydride-induced atopic dermatitis animal model.

Globally, many people have been affected with atopic dermatitis (AD), a chronic inflammatory skin disease. AD is associated with multiple factors such as genetic, inflammatory, and immune factors. Bee venom (BV) is now widely used for the treatment of several inflammatory diseases. However, its effect on 5% phthalic anhydride (PA)-induced AD has not been reported yet. We investigated the anti-inflammatory and anti-AD effects of BV in a PA-induced animal model of AD. Balb/c mice were treated with topical application of 5% PA to the dorsal skin and ears for induction of AD. After 24 h, BV was applied on the back and ear skin of the mice three times a week for 4 weeks. BV treatment significantly reduced the PA-induced AD clinical score, back and ear epidermal thickness, as well as IgE level and infiltration of immune cells in the skin tissues compared to those of control mice. The levels of inflammatory cytokines in the serum were significantly decreased in BV-treated group compared to PA-treated group. In addition, BV inhibited the expression of iNOS and COX-2 as well as the activation of mitogen-activated protein kinase (MAPK) and NF-Ò¡B induced by PA in the skin tissues. We also found that BV abrogated the lipopolysaccharide or TNF-α/IFN-γ-induced NO production, expression of iNOS and COX-2, as well as MAPK and NF-Ò¡B signaling pathway in RAW 264.7 and HaCaT cells. These results suggest that BV may be a potential therapeutic macromolecule for the treatment of AD.

Honey dressings for diabetic foot ulcers: overview of evidence-based practice for novice researchers.

This article explores how nurses can use evidence-based practice to appraise the rationale and evidence for specific nursing procedures or practices. A literature review of published evidence on honey dressings for diabetic foot ulcers was conducted by a novice researcher (lead author) under the supervision of a lecturer (second author). A methodology was followed to construct an answerable research question and to guide the search and retrieval of evidence. The strengths and limitations of a selected study were appraised, and its implications for practice considered. This article highlights an area of practice that warrants further attention and demonstrates the use of evidence-based practice to consider the quality and utility of clinical research.

Time to perforation for button batteries lodged in the esophagus.

INTRODUCTION: New strategies recently proposed to mitigate injury caused by lithium coin cell batteries lodged in the esophagus include prehospital administration of honey to coat the battery and prevent local hydroxide generation and in-hospital administration of sucralfate suspension (or honey). This study was undertaken to define the safe interval for administering coating agents by identifying the timing of onset of esophageal perforations. METHODS: A retrospective study of 290 fatal or severe battery ingestions with esophageal lodgment was undertaken to identify cases with esophageal perforations. RESULTS: Esophageal perforations were identified in 189 cases (53 fatal, 136 severe; 95.2% in children ≤4 years). Implicated batteries were predominantly lithium (91.0%) and 92.0% were ≥20 mm diameter. Only 2% of perforations occurred in <24 h following ingestion, including 3 severe cases with perforations evident at 11-17 h, 12 h, and 18 h. Another 7.4% of perforations (11 cases) became evident 24 to 47 h post ingestion and 10.1% of perforations (15 cases) became evident 48 to 71 h post ingestion. By 3 days post ingestion, 26.8% of perforations were evident, 36.9% by 4 days, 46.3% by 5 days, and 66.4% by 9 days. CONCLUSION: Esophageal perforation is unlikely in the 12 h after battery ingestion, therefore the administration of honey or sucralfate carries a low risk of extravasation from the esophagus. This first 12 h includes the period of peak electrolysis activity and battery damage, thus the risk of honey or sucralfate is low while the benefit is likely high.

Alterations in the Transcriptional Profile of the Liver Tissue and the Therapeutic Effects of Propolis Extracts in Alcohol-induced Steatosis in Rats.

The hepatoprotective effects of the ethanolic extracts of propolis (EEP) on alcohol-induced liver steatosis were investigated in Wistar rats. Chronic alcoholic fatty liver was induced by administration of 52% alcohol to male Wistar rats at the dose of 1% body weight for 7 weeks. Then animals were simultaneously treated with 50% ethanol solutions of EEP or normal saline at the dose of 0.1% body weight for 4 further weeks. Serological analyses and liver histopathology studies were performed to investigate the development of steatosis. Microarray analysis was conducted to investigate the alterations of hepatic gene expression profiling. Our results showed that 4-week treatment of EEP helped to restore the levels of various blood indices, liver function enzymes and the histopathology of liver tissue to normal levels. Results from the microarray analysis revealed that the hepatic expressions of genes involved in lipogenesis were significantly down-regulated by EEP treatment, while the transcriptional expressions of functional genes participating in fatty acids oxidation were markedly increased. The ability of EEP to reduce the negative effects of alcohol on liver makes propolis a potential natural product for the alternative treatment of alcoholic fatty liver.

Successful treatment of a diabetic foot ulcer with exposed bone using Trigona honey: a case study.

Many studies have shown that honey might improve wound healing. However, its efficacy for large wounds which may be followed by a systemic effect remains unclear. The effectiveness of honey-based dressings in treating large diabetic foot ulcers (DFU) is still unknown. This study presents the case of a 38-year-old female patient presenting with an extensive infected DFU with exposed bone. The DFU was treated with propolis-enriched Trigona honey, used as a single treatment, in a home visit setting. After two months' follow-up, the wound exhibited complete re-epithelialisation despite the patient's initial poor condition.

Lip creams with propolis special extract GH 2002 0.5% versus aciclovir 5.0% for herpes labialis (vesicular stage) : Randomized, controlled double-blind study.

A lip cream with special propolis extract GH 2002 at a concentration of 0.5% (199 patients) was tested against aciclovir 5% (198 patients) in the treatment of episodes of herpes labialis under double-blind conditions. Upon inclusion, all patients were in the vesicular phase. Application was five times daily of approximately 0.2 g of cream to the entire upper and lower lip. The primary parameter was the difference in time between groups to complete encrustation or epithelization of the lesions. Secondary endpoints were the course of typical herpes symptoms (pain, burning and itching, tension and swelling), the global assessment of efficacy and the safety of application. The predefined clinical situation was reached after a (median) 3 days with propolis and 4 days with aciclovir (p < 0.0001). Significant differences in favor of propolis were also found for all secondary parameters. No allergic reactions, local irritations or other adverse events occurred.

A review of interventions to reduce pain in chronic wounds.

Reduction of chronic wound pain has the potential to improve patients' quality of life, expedite the healing process and, ultimately, relieve pressure on community services. Despite this, education on pain assessment in the management of chronic wounds is lacking. This literature review seeks to provide evidence-based recommendations to reduce chronic wound pain and inform the practice of community nurses. The results of a thematic analysis indicate that a honey dressing or native collagen matrix dressing and conditioning exercises for the lower leg can reduce pain, and nitroglycerin ointment is especially effective. The review also highlights the need for an individualised approach to the assessment and treatment of pain in patients with chronic wounds.

Evaluation of the effect of honey on the healing of tooth extraction wounds in 4- to 9-year-old children.

OBJECTIVE: The aim of the this study was to evaluate the effect of honey on the healing of tooth extraction wounds in children 4‒9 years of age. SUBJECTS AND METHODS: In the present randomized clinical trial, 51 patients, 4‒9 years of age were selected randomly. All the subjects required extraction of one deciduous molar tooth. The subjects were randomly assigned to two groups. In group 1, after extraction of the tooth, the dentist used a cotton swab applicator to place a layer of honey on a piece of gauze moistened with normal saline solution (NSS) and placed it on the socket. In group 2, honey was not used; rather, NSS was applied. On days 3 and 7 after tooth extraction, the wound sizes were measured. RESULTS: In both groups, the wound sizes decreased significantly on the third day compared with baseline and on the seventh day compared with the third day (P < 0.05). On the third and seventh days after tooth extraction, wound sizes in the honey group were significantly lower than those in the NSS group (P < 0.05). CONCLUSION: Honey resulted in a decrease in wound sizes and faster healing after extraction of teeth in children. Therefore, use of honey can be recommended after minor surgeries in the oral cavity.