In vitro activity of Western Australian honeys and Manuka honey against clinically important yeasts.

With the steady rise in antifungal resistance amongst clinically important yeasts, antifungal drug discovery remains of the utmost importance. To determine the potential of some honeys as alternative antifungal agents, we quantified the antifungal activity of 12 Western Australian honey samples, two Manuka honey samples and an artificial honey against 10 yeast isolates including clinical and reference strains. Results showed that the tested honeys varied in activity, and yeasts species also differed in susceptibility, with minimum inhibitory concentrations (MICs) determined by broth microdilution ranging from 8% to >44% w/v honey. Honeys with the highest overall activity were derived from Blackbutt (Eucalyptus patens), Jarrah (E. marginata), and Karri (E. diversicolor). The optical density of each MIC microtitre plate was determined after incubation and showed that at relatively low concentrations of honey the growth of all yeasts was enhanced compared to the untreated control, whereas at and above approximately 12% w/v, honeys exerted a dose-dependent growth inhibitory effect, the extent of which varied by honey type. Time-kill studies with 64% w/v honey showed that all eight of the natural honeys tested had greater fungicidal activity than the comparator artificial honey. Our findings suggest that the specific nectar-derived phytochemicals present within each honey play an important role in antifungal activity, and support the notion that activity is due to a combination of factors including osmotic activity, hydrogen peroxide and phytochemical compounds. These data indicate that honey is worthy of further investigation as a potential therapeutic agent for superficial yeast infections.

Bee venom as a promising therapeutic strategy in central nervous system diseases.

Central nervous system (CNS) disorders are one of the leading health problems today, accounting for a large proportion of global morbidity and mortality. Most these disorders are characterized by high levels of oxidative stress and intense inflammatory responses in degenerated neuronal tissues. While extensive research has been conducted on CNS diseases, but few breakthroughs have been made in treatment methods. To date, there are no disease-modifying drugs available for CNS treatment, underscoring the urgent need for finding effective medications. Bee venom (BV), which is produced by honeybee workers' stingers, has been a subject of interest and study across various cultures. Over the past few decades, extensive research has focused on BV and its therapeutic potentials. BV consists a variety of substances, mainly proteins and peptides like melittin and phospholipase A2 (PLA2). Research has proven that BV is effective in various medical conditions, including pain, arthritis and inflammation and CNS disorders such as Multiple sclerosis, Alzheimer's disease and Parkinson's disease. This review provides a comprehensive overview of the existing knowledge concerning the therapeutic effects of BV and its primary compounds on various CNS diseases. Additionally, we aim to shed light on the potential cellular and molecular mechanisms underlying these effects.

Hive Products: Composition, Pharmacological Properties, and Therapeutic Applications.

Beekeeping provides products with nutraceutical and pharmaceutical characteristics. These products are characterized by abundance of bioactive compounds. For different reasons, honey, royal jelly, propolis, venom, and pollen are beneficial to humans and animals and could be used as therapeutics. The pharmacological action of these products is related to many of their constituents. The main bioactive components of honey include oligosaccharides, methylglyoxal, royal jelly proteins (MRJPs), and phenolics compounds. Royal jelly contains jelleins, royalisin peptides, MRJPs, and derivatives of hydroxy-decenoic acid, particularly 10-hydroxy-2-decenoic acid (10-HDA), which possess antibacterial, anti-inflammatory, immunomodulatory, neuromodulatory, metabolic syndrome-preventing, and anti-aging properties. Propolis has a plethora of activities that are referable to compounds such as caffeic acid phenethyl ester. Peptides found in bee venom include phospholipase A2, apamin, and melittin. In addition to being vitamin-rich, bee pollen also includes unsaturated fatty acids, sterols, and phenolics compounds that express antiatherosclerotic, antidiabetic, and anti-inflammatory properties. Therefore, the constituents of hive products are particular and different. All of these constituents have been investigated for their properties in numerous research studies. This review aims to provide a thorough screening of the bioactive chemicals found in honeybee products and their beneficial biological effects. The manuscript may provide impetus to the branch of unconventional medicine that goes by the name of apitherapy.

Bee Sting Venom as a Viable Therapy for Breast Cancer: A Review Article.

Breast cancer is a kind of aggressive cancer that significantly affects women worldwide, thus making research on alternative and new therapies necessary. The potential impact of bee venom on breast cancer is the main subject of this analysis of this research article. Bee venom has drawn the attention of the world with the help of its constituent ingredients, namely the bioactive compounds, enzymes, and complex blend of proteins. They have a particularly varied chemical makeup and proven anti-cancer capabilities. This is a detailed review demonstrating the components of bee venom and their individual functions in fighting cancer, as well as the results of previously conducted in-vitro and in-vivo research. As described later, bee venom has given positive results in triggering apoptosis, preventing cell migration, inhibiting metastasis and invasion, and suppressing the existing breast cancer cells. It is found to have worked better along with the already existing chemotherapy treatments. These results were also proved with the help of various animal studies that showed reduced tumor development, reduced metastasis, and improved therapeutic effectiveness. Furthermore, certain studies and case reports from all over the world have exhibited consistent results in females affected by breast cancer. This study found that people receiving chemotherapy experienced improved health outcomes and reduced discomfort, with fewer negative side effects. It is important to conduct extensive research on the safety and effectiveness of this treatment because it is yet to be approved. The ideal dosage and administration methods must be explored in clinical trials. Moreover, it is imperative to evaluate the results of any combined treatments with current medications. There should be constant monitoring to prevent any potential side effects. Other important things like allergic reactions and hidden concerns should also be considered.

Bee Venom: Composition and Anticancer Properties.

Among the various natural compounds used in alternative and Oriental medicine, toxins isolated from different organisms have had their application for many years, and Apis mellifera venom has been studied the most extensively. Numerous studies dealing with the positive assets of bee venom (BV) indicated its beneficial properties. The usage of bee products to prevent the occurrence of diseases and for their treatment is often referred to as apitherapy and is based mainly on the experience of the traditional system of medical practice in diverse ethnic communities. Today, a large number of studies are focused on the antitumor effects of BV, which are mainly attributed to its basic polypeptide melittin (MEL). Previous studies have indicated that BV and its major constituent MEL cause a strong toxic effect on different cancer cells, such as liver, lung, bladder, kidney, prostate, breast, and leukemia cells, while a less pronounced effect was observed in normal non-target cells. Their proposed mechanisms of action, such as the effect on proliferation and growth inhibition, cell cycle alterations, and induction of cell death through several cancer cell death mechanisms, are associated with the activation of phospholipase A2 (PLA2), caspases, and matrix metalloproteinases that destroy cancer cells. Numerous cellular effects of BV and MEL need to be elucidated on the molecular level, while the key issue has to do with the trigger of the apoptotic cascade. Apoptosis could be either a consequence of the plasmatic membrane fenestration or the result of the direct interaction of the BV components with pro-apoptotic and anti-apoptotic factors. The interaction of BV peptides and enzymes with the plasma membrane is a crucial step in the whole process. However, before its possible application as a remedy, it is crucial to identify the correct route of exposure and dosage of BV and MEL for potential therapeutic use as well as potential side effects on normal cells and tissues to avoid any possible adverse event.

Impact of apitherapy on canine, equine, and chicken lymphocytes, in vitro.

Apitherapy is a form of alternative medicine that utilizes products from the western honeybee (Apis mellifera), including honey, propolis, and honeybee venom, to improve the health status of human patients by altering host immunity. An added benefit of these products is that they are nutraceuticals and relatively inexpensive to aquire. Currently, little is known about the use of honeybee products in veterinary species, as well as their impact on host immunity. In the present in vitro study, honey, propolis, and honeybee venom were co-cultured with enriched canine, equine, and chicken peripheral blood lymphocytes (PBLs) with cell proliferation, cell viability/apoptosis, and cellular morphology evaluated. Concanavalin A (Con A) and dexamethasone were used as stimulatory and suppressive controls, respectively. Honeybee products' effects on the three veterinary species varied by product and the species. Honey stimulated the PBLs proliferation in all three species but also displayed some increased cytotoxicity. Propolis stimulated proliferation in canine and equine PBLs, however, it suppressed proliferation in the chicken PBLs. Honeybee venom was the strongest PBL stimulant for all three species and in the equine, surpassed the stimulant response of Con A and yet, enhanced PBL cell viability post culture. In summary, the results of this preliminary in vitro study show that these three honeybee products do impact lymphocyte proliferation and viability in dogs, horses, and chickens, and that more research both in vitro and in vivo will be necessary to draw conclusions regarding their future use as immune stimulants or inhibitors.

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.

Recent advances and opportunities related to the use of bee products in food processing.

Nowadays, natural foods that can provide positive health effects are gaining more and more popularity. Bees and the products they produce are our common natural heritage that should be developed. In the article, we presented the characteristics of bee products and their use in industry. We described the development and importance of beekeeping in the modern world. Due to their high nutritional value and therapeutic properties, bee products are of great interest and their consumption is constantly growing. The basis for the use of bee products in human nutrition is their properties and unique chemical composition. The conducted research and opinions confirm the beneficial effect of bee products on health. The current consumer awareness of the positive impact of food having a pro-health effect on health and well-being affects the increase in interest and demand for this type of food among various social groups. Enriching the daily diet with bee products may support the functioning of the organism. New technologies have appeared on the market to improve the process of obtaining bee products. The use of bee products plays a large role in many industries; moreover, the consumption of bee products and promotion of their medicinal properties are very important in shaping proper eating habits.

An Updated Review Summarizing the Anticancer Efficacy of Melittin from Bee Venom in Several Models of Human Cancers.

Apitherapy (using bee products) has gained broad recognition in cancer therapeutics globally. Honeybee venom has a broad range of biological potential, and its utilization is rapidly emerging in apitherapy. Bee products have significant potential to strengthen the immune system and improve human health. Thus, this review is targeted toward recapitulating the chemo-preventive potential of melittin (MEL), which constitutes a substantial portion of honeybee venom. Honeybee venom (apitoxin) is produced in the venom gland of the honeybee abdomen, and adult bees utilize it as a primary colony defense mechanism. Apitoxin comprises numerous biologically active compounds, including peptides, enzymes, amines, amino acids, phospholipids, minerals, carbohydrates, and volatile components. We are mainly focused on exploring the potential of melittin (a peptide component) of bee venom that has shown promising potential in the treatment of several human cancers, including breast, stomach, lung, prostate, ovary, kidney, colon, gastric, esophageal, cervical cancers, melanoma, osteosarcoma, and hepatocellular carcinoma. This review has summarized all potential studies related to the anticancerous efficacy of melittin (apitoxin), its formulations, conjugates, and nano-formulations against several human carcinomas, which would further pave the way for future researchers in developing potent drugs for cancer management.

Effects of apitherapy against salivary gland disorder after radioactive iodine therapy for differentiated thyroid cancer.

OBJECTIVE: Sialadenitis and salivary gland disorders are complications of radioactive iodine therapy (RAIT) that affect the quality of life of patients with differentiated thyroid cancer (DTC). The current study aimed to provide evidence on the protective effect of apitherapy on salivary gland function during RAIT in patients with DTC. METHODS: In total, 120 patients with DTC who underwent total thyroidectomy were divided into the apitherapy group (group A, n = 60) and the control group (group B, n = 60). Group A received 2.5 g of acacia honey three times daily after each meal during admission for RAIT. Statistical analyses were performed using the Saxon test (which is used to evaluate saliva volume) and salivary gland scintigraphy (which is applied to assess maximum uptake ratio and washout ratio). RESULTS: Compared with group B, group A presented with a more significantly positive change in the rate of amount of saliva before and after treatment (P < 0.01). Group B presented a significant decrease in the maximum uptake ratio of the bilateral parotid and submandibular glands on salivary gland scintigraphy (P < 0.05) and washout ratio of all salivary glands (P < 0.05). Group A did not present significant differences in the maximum uptake ratio and washout ratio. CONCLUSIONS: Apitherapy can have protective effects against salivary gland disorder associated with RAIT in patients with DTC.

Mellitin peptide quantification in seasonally collected crude bee venom and its anticancer effects on myelogenous K562 human leukaemia cell line.

BACKGROUND: Apitherapy is an emerging field in cancer research, particularly in developing communities. The potency of Melittin (MEL), a major constituent in bee venom is accounted for the cytotoxic capacity against cancer cells. It is postulated that the genotype of bees and the time of venom collection influences its specific activity against certain types of cancer. METHOD: Hereby, Jordanian crude bee venom (JCBV) was collected during different seasons of the year, specifically spring, summer and autumn and investigated for in vitro antitumour effects. Venom collected during springtime comprised the highest quantity of MEL in comparison to venom collected some other time. Springtime-collected JCBV extract and MEL were tested on an immortal myelogenous leukaemia cell line, namely K562 leukemic cells. Treated cells were examined for cell modality via flow cytometry analysis and cell death mediating gene expressions. RESULTS: Springtime-collected JCBV extract and MEL showed an IC50 of 3.7 ± 0.37 µg/ml and 1.84 ± 0.75 µg/ml, respectively. In comparison to JCBV and positive control, MEL-treated cells exhibited late apoptotic death with a moderate cellular arrest at G0/G1 and an increase of cell number at G2/M phase. Expression of NF-κB/MAPK14 axis was inhibited in MEL and JCBV-treated cells, as well as expression of c-MYC and CDK4. Moreover, marked upregulation in ABL1, JUN and TNF was observed. In conclusion, springtime-collected JCBV showed the highest content of MEL while both JCBV and pure MEL showed apoptotic, necrotic, and cell cycle arrest efficiency against K562 leukemic cells. CONCLUSION: Integration of bee venom in chemotherapy needs more investigation and should be carefully translated into clinical use. During such translation, the correlation of bee genotype, collection time and concentration of MEL in CBV should be profiled.

Therapeutic Use of Bee Venom and Potential Applications in Veterinary Medicine.

Apitherapy is a branch of alternative medicine that consists of the treatment of diseases through products collected, processed, and secreted by bees, specifically pollen, propolis, honey, royal jelly, and bee venom. In traditional medicine, the virtues of honey and propolis have been well-known for centuries. The same, however, cannot be said for venom. The use of bee venom is particularly relevant for many therapeutic aspects. In recent decades, scientific studies have confirmed and enabled us to understand its properties. Bee venom has anti-inflammatory, antioxidant, central nervous system inhibiting, radioprotective, antibacterial, antiviral, and antifungal properties, among others. Numerous studies have often been summarised in reviews of the scientific literature that have focused on the results obtained with mouse models and their subsequent transposition to the human patient. In contrast, few reviews of scientific work on the use of bee venom in veterinary medicine exist. This review aims to take stock of the research achievements in this particular discipline, with a view to a recapitulation and stabilisation in the different research fields.

Current Status of the Bioactive Properties of Royal Jelly: A Comprehensive Review with a Focus on Its Anticancer, Anti-Inflammatory, and Antioxidant Effects.

Royal jelly (RJ) has been one of the most widely used natural products in alternative medicine for centuries. Being produced by both hypopharyngeal and mandibular glands, RJ exhibits an extraordinary complexity in terms of its composition, including proteins, lipids, carbohydrates, polyphenols, vitamins, and hormones. Due to its heterogeneous structure, RJ displays various functional roles for honeybees, including being involved in nutrition, learning, memory, and social behavior. Furthermore, a wide range of studies reported its therapeutic properties, including anticancer, anti-inflammatory, and antioxidant activities, to name a few. In this direction, there is a wide range of health-related problems for which the medical area specialists and researchers are continuously trying to find a cure, such as cancer, atherosclerosis, or infertility. For the mentioned diseases and more, it has been proven that RJ is a key player in finding a valuable treatment. In this review, the great impact of RJ as an alternative medicine agent is highlighted, with a focus on its anticancer, anti-inflammatory, and antioxidant activities. Moreover, we link it to its apitherapeutic potential by discussing its composition. Herein, we discuss a wide range of novel studies and present the latest research work.

The benefits of propolis in periodontal therapy. A scoping review of preclinical and clinical studies.

ETHNOPHARMACOLOGICAL RELEVANCE: The treatment of periodontal disease (PD) is aimed at adequate control of bacterial plaque. In many patients mechanical methods are unable to eliminate this plaque leading to the need for adjuvant chemical products. Propolis is a natural product that has demonstrated therapeutic properties and has shown to be effective as an anti-inflammatory and antibacterial agent in dentistry. AIM OF THE STUDY: Considering the beneficial effects of propolis on various oral conditions, this study aimed to review, update and summarize the available evidence on the benefits of propolis in in vitro studies, animal models, and human clinical trials on non-surgical periodontal therapy. MATERIALS AND METHODS: An electronic search in three databases was performed up to December 2021. The search strategy included the terms "propolis" and "periodontal disease" to identify relevant studies on the potential advantages of propolis in periodontal therapy in in vitro studies, animal models, and human clinical trials. RESULTS: The search yielded 538 results, discarding 459 studies that did not clearly meet the inclusion criteria. A total of 42 studies were included: 18 in vitro, one animal, and 23 randomized clinical trials. In vitro studies have demonstrated that propolis has antimicrobial activity against periodontal pathogens and clinical studies have reported its use as an adjunct to non-surgical periodontal therapy. The clinical effects of propolis have been reported in conjunction with prophylaxis, polishing, and scaling and root planing (SRP). It has shown to have anti-plaque activity and improve gingival health. Propolis was found to be more effective in improving clinical parameters than conventional treatment (SRP alone) and demonstrated similar efficacy in treating chronic periodontitis compared to positive controls. Only one study reported an allergic reaction. CONCLUSION: The evidence available on the benefits of propolis in in vitro studies, animal models, and clinical trials suggests that propolis could be a promising adjunct to conventional therapy of gingivitis and periodontitis. However, further studies are needed to determine its superiority to other therapies in the treatment of PD.

Antibacterial interactions between two monofloral honeys and several topical antiseptics, including essential oils.

BACKGROUND: Honey has broad spectrum antibacterial activity against clinically important organisms and may be suitable for treating superficial bacterial infections. However, very little data are available describing potential interactions between honey and other topically applied agents such as antiseptics or essential oils. METHODS: Interactions between pairs of antibacterial agents were investigated by performing checkerboard assays and determining the fractional inhibitory concentration indices (FICIs). Interactions between the two monofloral honeys marri (from Corymbia calophylla) and manuka, and the antiseptic agents benzalkonium chloride, chlorhexidine digluconate, silver (I) nitrate, tea tree oil, and Eucalyptus polybractea oil were investigated against Staphylococcus aureus ATCC® 43300 and Pseudomonas aeruginosa ATCC® 27853. RESULTS: Additive or indifferent interactions (FICI 0.5-2) were observed for all combinations against both organisms tested, with the exception of chlorhexidine and honey. Chlorhexidine and marri honey showed an antagonistic relationship against S. aureus (median FICI 2.00, range 1.25-4.83). Similarly, chlorhexidine and manuka honey showed antagonism against S. aureus (median FICI 2.33, range 2.00-2.67). CONCLUSIONS: With the exception of chlorhexidine, these data indicate that honey does not interfere with the antimicrobial activity of the tested agents, and that honey may be suitable for combination therapy with other topically applied antibacterial agents for treating superficial bacterial infections.

Calluna vulgaris as a Valuable Source of Bioactive Compounds: Exploring Its Phytochemical Profile, Biological Activities and Apitherapeutic Potential.

Calluna vulgaris, belonging to the Ericaceae family, is an invasive plant that has widely spread from Europe all across Asia, North America, Australia and New Zealand. Being able to survive in rigid soil and environmental conditions, it is nowadays considered to be of high nature-conservation value. Known for its nutritional and medicinal properties, C. vulgaris stands out for its varied physiochemical composition, spotlighting a wide range of biological activity. Among the most important bioactive compounds identified in C. vulgaris, the phenolic components found in different parts of this herbaceous plant are the main source of its diverse pro-health properties (antioxidant, anti-inflammatory, antimicrobial, chemoprotective, etc.). Nonetheless, this plant exhibits an excellent nectariferous potential for social insects such as honeybees; therefore, comparing the bioactive compounds observed in the plant and in the final product of the beehive, namely honey, will help us understand and find new insights into the health benefits provided by the consumption of C. vulgaris-related products. Thus, the main interest of this work is to review the nutritional profile, chemical composition and biological activities of the C. vulgaris plant and its related honey in order to encourage the future exploration and use of this health-promoting plant in novel foods, pharmacological products and apitherapy.

A Review of Commonly Used Methodologies for Assessing the Antibacterial Activity of Honey and Honey Products.

Honey, a naturally sweet and viscous substance is mainly produced by honeybees (Apis mellifera) from flower nectar. Honey exerts a plethora of biological and pharmacological activities, namely, antioxidant, antimicrobial and anti-inflammatory activity, because of the presence of an extensive variety of bioactive compounds. The antibacterial activity is one of the most reported biological properties, with many studies demonstrating that honey is active against clinically important pathogens. As a result, beside honey's widespread utilization as a common food and flavouring agent, honey is an attractive natural antimicrobial agent. However, the use of neat honey for therapeutic purposes poses some problems, for instance, its stickiness may hamper its appeal to consumers and health care professionals, and the maintenance of an adequate therapeutic concentration over a sufficient timeframe may be challenging due to honey liquidity and leakage. It has motivated researchers to integrate honey into diverse formulations, for example, hydrogels, dressings, ointments, pastes and lozenges. The antibacterial activity of these formulations should be scientifically determined to underscore claims of effectiveness. Some researchers have made efforts to adapt the disc carrier and suspension test to assess the antimicrobial activity of topical products (e.g., silver-based wound dressings). However, there is currently no established and validated method for determining the in vitro antimicrobial potential of natural product-based formulations, including those containing honey as the active principle. Against the backdrop of a brief discussion of the parameters that contribute to its antibacterial activity, this review provides an outline of the methods currently used for investigating the antibacterial activity of neat honey and discusses their limitations for application to honey-based formulations.

In vitro antibacterial activity of Western Australian honeys, and manuka honey, against bacteria implicated in impetigo.

Impetigo is a contagious skin disease caused by Staphylococcus aureus and Streptococcus pyogenes. Without treatment, impetigo may be recurrent, develop into severe disease, or have serious, life-threatening sequelae. Standard treatment consists of topical or systemic antibiotic therapy (depending on severity), however, due to antibiotic resistance some therapies are increasingly ineffective. In this study we evaluated the potential for honey as an alternative treatment for impetigo. A broth microdilution assay in 96-well microtitre trays was used to determine the minimum inhibitory concentrations (MICs) of six monofloral honeys (jarrah, marri, red bell, banksia, wandoo, and manuka), a multifloral honey and artificial honey against S. aureus (n = 10), S. pyogenes (n = 10), and coagulase-negative staphylococci (CoNS) (n = 10). The optical density (OD) of all microtitre tray wells was also determined before and after assay incubation to analyse whether sub-MIC growth inhibition occurred. Jarrah, marri, red bell, banksia, and manuka honeys were highly effective at inhibiting S. aureus and CoNS, with MIC50 values ranging from 4 to 8% w/v honey. S. pyogenes was also inhibited by these same honeys, albeit at higher concentrations (8-29% w/v). Wandoo and multifloral honeys had the least antibacterial activity with MICs of >30% (w/v) for all isolates. However, OD data indicated that sub-MIC concentrations of honey were still partially restricting bacterial growth. Our pre-clinical data indicate that honey may be a potential therapeutic agent for the routine treatment of mild impetigo, and we suggest that clinical trials would be appropriate to further investigate this.

Apitherapy and Periodontal Disease: Insights into In Vitro, In Vivo, and Clinical Studies.

Periodontal diseases are caused mainly by inflammation of the gums and bones surrounding the teeth or by dysbiosis of the oral microbiome, and the Global Burden of Disease study (2019) reported that periodontal disease affects 20-50% of the global population. In recent years, more preference has been given to natural therapies compared to synthetic drugs in the treatment of periodontal disease, and several oral care products, such as toothpaste, mouthwash, and dentifrices, have been developed comprising honeybee products, such as propolis, honey, royal jelly, and purified bee venom. In this study, we systematically reviewed the literature on the treatment of periodontitis using honeybee products. A literature search was performed using various databases, including PubMed, Web of Science, ScienceDirect, Scopus, clinicaltrials.gov, and Google Scholar. A total of 31 studies were reviewed using eligibility criteria published between January 2016 and December 2021. In vitro, in vivo, and clinical studies (randomized clinical trials) were included. Based on the results of these studies, honeybee products, such as propolis and purified bee venom, were concluded to be effective and safe for use in the treatment of periodontitis mainly due to their antimicrobial and anti-inflammatory activities. However, to obtain reliable results from randomized clinical trials assessing the effectiveness of honeybee products in periodontal treatment with long-term follow-up, a broader sample size and assessment of various clinical parameters are needed.

Royal-jelly-based apitherapy can attenuate damages to male reproductive parameter following nicotine administration.

BACKGROUND: Nicotine administration can generate severe oxidative stress and lipid peroxidation. Royal jelly, with its antioxidant properties, acts as a scavenger of reactive oxygen species. This study describes the apitherapy effects of royal jelly on testicular damage following nicotine administration. METHODS: Forty-eight male BALB/c mice were divided into 8 groups (n = 6): saline, 3 different doses of royal jelly (100, 150, and 200 mg/kg body weight (BW) per day), nicotine (1.5 mg/kg), and 3 different groups of Nic + Roy (1.5 mg/kg of Nic + 100, 150, and 200 mg/kg BW per day of royal jelly). Nicotine was administrated intraperitoneally, and royal jelly was prescribed orally for 10 consecutive days. Serum levels of hormones (testosterone, luteinizing hormone, and follicle-stimulating hormone), total antioxidant capacity, nitric oxide (NO) status, malondialdehyde levels, sperm DNA fragmentation, sperm parameters, histopathological changes (H&E staining), immunohistochemistry against apoptotic proteins, and gene expression of Bcl-2, p53, Caspase-3, and Nrf2 (real-time PCR) were assessed to evaluate the molecular and histological changes. RESULTS: Hormone levels, sperm parameters, and status of antioxidants were decreased significantly (p < .05) following nicotine administration. Moreover, royal jelly treatment normalized hormonal and antioxidant characteristics, decreased apoptotic gene expression, increased Nfr2 gene expression, and restored histopathological alteration to the physiological status significantly (p < .05). CONCLUSION: Royal jelly upregulates the antioxidant status, inhibits the mitochondrial-dependent apoptosis pathway, and increases the rate of proliferation. This therapeutic agent effectively protected the testis against nicotine-associated damages by antioxidant and anti-apoptotic effects.