The Effects of a Dietary Supplement (PediaFlù) Plus Standard of Care in Children With Acute Tonsillopharyngitis/Rhinopharyngitis: Protocol for a Randomized Controlled Trial.

BACKGROUND: A dietary supplement containing Pelargonium sidoides extract, propolis, zinc, and honey has been recently developed and proven to be an effective adjuvant in clinical practice for seasonal diseases and the treatment of respiratory tract disorders. OBJECTIVE: This trial aims to verify the efficacy of the tested dietary supplement in a pediatric population with acute tonsillopharyngitis/rhinopharyngitis (ATR). METHODS: The trial includes children aged between 3 and 10 years with ATR ≤48 h, a negative rapid test for beta-hemolytic streptococcus or culture identification of nasal and/or pharyngeal exudates, and SARS-CoV-2 infection. The dietary supplement tested is an oral solution already on the market based on Pelagon P-70 (equivalent to Pelargonium sidoides d.e. 133.3 mg/100 ml), propolis, zinc, and honey. The product is administered at 5 ml 3 times a day for 6 days for children younger than 6 years and 10 ml 3 times a day for 6 days for children older than 6 years. The study design is open label, randomized, and controlled, with the tested dietary supplement plus standard of care (SoC) versus SoC alone. Patients are enrolled from 3 sites in Romania. The change in Tonsillitis Severity Score and number of treatment failures (using ibuprofen or high-dose paracetamol as rescue medication) are the primary end points. Based on the Tonsillitis Severity Score and the 2-sample comparison of the means formula with a 5% significance level, 80% power, and a minimally clinically important difference of 2 (SD 3.85) points, 120 patients are required. To account for potential screening failures and dropouts, we need to screen a population of approximately 150 children. RESULTS: Patient enrollment began on June 3, 2021 (first patient's first visit), and ended on August 12, 2021 (last patient's last visit). The data collection period was from June 3, 2021, to September 16, 2021. The study was funded in February 2023. Data analysis is currently ongoing (April 2024). We expect the results to be published in a peer-reviewed clinical journal in the third quarter of 2024 and presented at scientific meetings in the last quarter of 2024. CONCLUSIONS: The data from this trial may help identify new adjuvant treatments for children with ATR when streptococcal infection is excluded by a negative rapid test, thereby avoiding unnecessary antibiotic administration. TRIAL REGISTRATION: ClinicalTrials.gov NCT04899401 https://clinicaltrials.gov/study/NCT04899401. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53703.

Effect of propolis mouthwash on the incidence of ventilator-associated pneumonia in intensive care unit patients: a comparative randomized triple-blind clinical trial.

OBJECTIVES: Ventilator-associated pneumonia (VAP) increases the length of hospitalization and mortality rate. This study aimed to determine the effect of propolis mouthwash on the incidence of VAP in intensive care unit (ICU) patients. MATERIALS AND METHODS: Triple-blind, comparative randomized, controlled clinical trial was conducted over one year, with 110 ICU patients at Imam-Hossein and Bahar hospitals (Shahroud) and Kowsar Hospital (Semnan) in Iran. The intervention group used 15 cc of 0.06% propolis mouthwash solution twice daily at 8 AM and 4 PM for seven days. The control group used 15 cc of 0.2% chlorhexidine mouthwash at the same times and duration. Data were collected using a demographic questionnaire, APACHE II, Beck Oral Assessment Scale, and Modified Clinical Pulmonary Infection Score (MCPIS). RESULTS: There was no significant difference in demographic information, disease severity, and oral health between the two groups before and after intervention (P > 0.05). The incidence of VAP in the intervention group compared to the control group was 10.9% vs. 30.9% on the third day (P = 0.0166, 95% CI: 0.53-0.83 and RR = 0.35), 23.6% vs. 43.6% on the fifth day (P = 0.0325 and 95% CI: 0.31-0.95 and RR = 0.54), and 25.5% vs. 47.3% on the seventh day (P = 0.0224, 95% CI: 0.32-0.92, and RR = 0.54). The Mann-Whitney indicated the incidence of VAP was significantly lower in the intervention group on the third, fifth, and seventh days. CONCLUSION: Propolis mouthwash can be considered as an alternative to chlorhexidine mouthwash for ICU patients. CLINICAL RELEVANCE: Propolis mouthwash serves as a simple, economical intervention to potentially reduce incidence of VAP. TRIAL REGISTRATION: (IRCT20110427006318N12, date 02.04.2019).

Comparison of the effect of propolis and Gluma desensitizer on the management of dentin hypersensitivity: A randomized controlled trial.

OBJECTIVE: To compare the effect of propolis and gluma desensitisers on the management of dentin hypersensitivity. METHODS: The single-blind, randomised controlled trial was conducted at the Department of Operative Dentistry, Dr Ishrat ul Ebad Khan Institute of Oral Health Sciences, Dow University of Health Sciences, Karachi, from October 2020 to September 2021, and comprised patients with dentin hypersensitivity who had pain scores of at least 2 on the visual analogue scale. The teeth were randomised into propolis group A and Gluma group B. Baseline pain scores were assessed using visual analogue scale and Schiff's sensitivity scores and compared with scores immediately after the intervention, and then after one week and one month of the intervention. Data was analysed using SPSS 23. RESULTS: Of the 22 patients, 12(54.5%) were females and 10(45.4%) were males. Of the 80 teeth, there were 40(50%) in each of the 2 groups. Significant reduction was observed in dentin hypersensitivity immediately after the application of the desensitising agents (p<0.05). However, after one month, Gluma was more effective than propolis (p<0.05). CONCLUSIONS: Both Gluma and propolis were found to be effective desensitising agents, but the effectiveness of propolis decreased over one month. Clinical Trial Number: Clinical Trials.gov: NCT04819867.

Comparative effectiveness of Propolis with chlorhexidine mouthwash on gingivitis - a randomized controlled clinical study.

BACKGROUND: To assess and compare the effectiveness of propolis mouthwash with chlorhexidine mouthwash in the reduction of plaque and gingivitis. METHODS: A single centre, latin-square cross-over, double masked, randomized controlled clinical trial was conducted on 45 chronic generalized gingivitis subjects who were chosen from the dental clinic of MAHSA University, Malaysia. A total of 45 subjects were randomly assigned into one of the three different groups (n = 15 each) using a computer-generated random allocation sequence: Group A Propolis mouthwash; Group B Chlorhexidine mouthwash; and Group C Placebo mouthwash. Supragingival plaque and gingival inflammation were assessed by full mouth Plaque index (PI) and gingival index (GI) at baseline and after 21 days. The study was divided into three phases, each phase lasted for 21 days separated by a washout period of 15 days in between them. Groups A, B and C were treated with 0.2% Propolis, Chlorhexidine, and Placebo mouthwash, respectively, in phase I. The study subjects were instructed to use the assigned mouthwash twice daily for 1 min for 21 days. On day 22nd, the subjects were recalled for measurement of PI and GI. After phase I, mouthwash was crossed over as dictated by the Latin square design in phase II and III. RESULTS: At baseline, intergroup comparison revealed no statistically significant difference between Groups A, B and C (p > 0.05). On day 21, one-way ANOVA revealed statistically significant difference between the three groups for PI (p < 0.001) and GI (p < 0.001). Bonferroni post-hoc test showed statistically significant difference between Propolis and Chlorhexidine mouthwash (P < 0.001), with higher reduction in the mean plaque and gingival scores in propolis group compared to chlorhexidine and placebo groups. CONCLUSIONS: Propolis mouthwash demonstrated significant improvement in gingival health and plaque reduction. Thus, it could be used as an effective herbal mouthwash alternative to chlorhexidine mouthwash. TRIAL REGISTRATION: The trial was retrospectively registered on 25/07/2019 at clinicaltrials.gov and its identifier is NCT04032548.

Preventive effect of propolis on cognitive decline in Alzheimer's disease model mice.

Brazilian green propolis (propolis) is a chemically complex resinous substance that is a potentially viable therapeutic agent for Alzheimer's disease. Herein, propolis induced a transient increase in intracellular Ca2+ concentration ([Ca2+]i) in Neuro-2A cells; moreover, propolis-induced [Ca2+]i elevations were suppressed prior to 24-h pretreatment with amyloid-ß. To reveal the effect of [Ca2+]i elevation on impaired cognition, we performed memory-related behavioral tasks in APP-KI mice relative to WT mice at 4 and 12 months of age. Propolis, at 300-1000 mg/kg/d for 8 wk, significantly ameliorated cognitive deficits in APP-KI mice at 4 months, but not at 12 months of age. Consistent with behavioral observations, injured hippocampal long-term potentiation was markedly ameliorated in APP-KI mice at 4 months of age following repeated propolis administration. In addition, repeated administration of propolis significantly activated intracellular calcium signaling pathway in the CA1 region of APP-KI mice. These results suggest a preventive effect of propolis on cognitive decline through the activation of intracellular calcium signaling pathways in CA1 region of AD mice model.

Exploring the Prospective Role of Propolis in Modifying Aging Hallmarks.

Aging populations worldwide are placing age-related diseases at the forefront of the research agenda. The therapeutic potential of natural substances, especially propolis and its components, has led to these products being promising agents for alleviating several cellular and molecular-level changes associated with age-related diseases. With this in mind, scientists have introduced a contextual framework to guide future aging research, called the hallmarks of aging. This framework encompasses various mechanisms including genomic instability, epigenetic changes, mitochondrial dysfunction, inflammation, impaired nutrient sensing, and altered intercellular communication. Propolis, with its rich array of bioactive compounds, functions as a potent functional food, modulating metabolism, gut microbiota, inflammation, and immune response, offering significant health benefits. Studies emphasize propolis' properties, such as antitumor, cardioprotective, and neuroprotective effects, as well as its ability to mitigate inflammation, oxidative stress, DNA damage, and pathogenic gut bacteria growth. This article underscores current scientific evidence supporting propolis' role in controlling molecular and cellular characteristics linked to aging and its hallmarks, hypothesizing its potential in geroscience research. The aim is to discover novel therapeutic strategies to improve health and quality of life in older individuals, addressing existing deficits and perspectives in this research area.

Propolis in the management of cardiovascular disease.

BACKGROUND: Propolis is a resinous compound that is obtained from honey bees. It consists of numerous chemical constituents that impart different therapeutic action. The heart is the core of the body and cardiovascular disease (CVD) is a burden for the human being. This article emphasizes how propolis is fruitful in the management of various CVDs. SCOPE AND APPROACH: This review focuses on how various constituents of the propolis (such as terpenes, flavonoids, phenolics, etc.) impart cardio protective actions. KEY FINDING AND CONCLUSION: With the support of various clinical trials and research outcomes, it was concluded that propolis owns niche cardio protective properties that can be a boon for various cardiac problems (both in preventive and therapeutic action) such as atherosclerosis, excessive angiogenesis, hypertension, and many more.

Effect of Mexican Propolis on Wound Healing in a Murine Model of Diabetes Mellitus.

Diabetes mellitus (DM) affects the wound healing process, resulting in impaired healing or aberrant scarring. DM increases reactive oxygen species (ROS) production, fibroblast senescence and angiogenesis abnormalities, causing exacerbated inflammation accompanied by low levels of TGF-ß and an increase in Matrix metalloproteinases (MMPs). Propolis has been proposed as a healing alternative for diabetic patients because it has antimicrobial, anti-inflammatory, antioxidant and proliferative effects and important properties in the healing process. An ethanolic extract of Chihuahua propolis (ChEEP) was obtained and fractionated, and the fractions were subjected to High-Performance Liquid Chromatography with diode-array (HPLC-DAD), High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) and Gas Chromatography-Mass Spectrometry (GC-MS) analyses and 46 compounds were detected. Deep wounds were made in a murine DM model induced by streptozotocin, and the speed of closure and the wound tensile strength were evaluated by the tensiometric method, which showed that ChEEP had similar activity to Recoveron, improving the speed of healing and increasing the wound tensile strength needed to open the wound again. A histological analysis of the wounds was performed using H&E staining, and when Matrix metalloproteinase 9 (MMP9) and α-actin were quantified by immunohistochemistry, ChEEP was shown to be associated with improved histological healing, as indicated by the reduced MMP9 and α-actin expression. In conclusion, topical ChEEP application enhances wound healing in diabetic mice.

Antineoplastic Activity Evaluation of Brazilian Brown Propolis and Artepillin C in Colorectal Area of Wistar Rats.

OBJECTIVE: The study's aim was to evaluate Brazilian Brown Propolis (BBP) and Artepillin C (ARC) chemopreventive action in Wistar rats' colons. METHODS: Fifty male Wistar rats were divided into ten experimental groups, including control groups, groups with and without 1,2-dimethylhydrazine (DMH) induction, and BBP, ARC, and ARC enriched fraction (EFR) treatments, for sixteen weeks. Aberrant crypt foci (ACF) were classified as hyperplastic or dysplastic, and proliferating cell nuclear antigen (PCNA) expression was quantified. RESULT: ACF amounts in experimental groups (induced or not) decreased in both colon portions, while the isolated Aberrant Crypt (AC) number increased. Experimental groups of animals showed higher hyperplasia and dysplasia amounts compared with control groups. The ACF dysplastic amount present in groups induced and treated, in both colon portions, had similar values to IDMH (DMH induction group without treatment). In addition, DMH was effective in ACF inducing and there was positive staining for PCNA in basal and upper dysplastic foci portions in all experimental groups, in the mitotic index (MI) evaluation. To conclude, considering all the experimental groups, the one treated with EFR (fraction enriched with ARC) had the lowest rates of cell proliferation. CONCLUSION: BBP and its derivatives prevented crypt cell clonal expansion.

Propolis Use in Dentistry: A Narrative Review of Its Preventive and Therapeutic Applications.

Propolis is a resinous substance produced naturally by bees, and it consists of the exudates of plants mixed with enzymes, wax, and pollen. Propolis continues to gain considerable scientific interest due to its potential health benefits. The modern-day use of propolis in pharmaceutical preparations, such as toothpastes, mouthwashes, chewable tablets, mucoadhesive gels, and sprays, is increasing. However, the effectiveness of using propolis-containing pharmaceuticals in dentistry is not clear. The present paper aims to review the literature on the dental applications of propolis in preventive dentistry, periodontics, oral medicine, and restorative dentistry and discuss its clinical effectiveness. A literature search was conducted using Scopus, PubMed, and Web of Science databases. In total, 104 studies were included, of which 46 were laboratory studies, 5 animal studies, and 53 human clinical studies. Overall, the laboratory studies revealed a range of antimicrobial effects of propolis on oral pathogens. Clinical investigations of propolis in biofilm and dental caries control as well as adjuvant periodontal therapies reported positive outcomes in terms of plaque control, pathogenic microbial count reduction, and periodontal tissue inflammation control. Additional investigations included the use of propolis for the management of recurrent aphthous stomatitis, oral mucositis, and cavity disinfection after caries removal as well as the development of a range of restorative dental materials. Based on the reported outcomes of the studies, the clinical usage of propolis has potential. However, the majority of the evidence is derived from studies with flaws in their methodological design, making their results and conclusions questionable. As a consequence, properly designed and well-reported clinical studies are required to affirm the effectiveness of propolis for dental applications. Additionally, the safety of propolis and the optimal concentrations and extraction methods for its clinical use warrant further investigation. Utilisation of standardised propolis extracts will help in quality control of propolis-based products and lead to the achievement of reproducible outcomes in research studies.

Comparative evaluation of propolis mouthwash with 0.2% chlorhexidine mouthwash as an adjunct to mechanical therapy in improving the periodontitis among perimenopausal women: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of Propolis mouthwash compared to chlorhexidine mouthwash as an adjunct to mechanical therapy in improving clinical parameters in perimenopausal women with chronic periodontitis. METHODOLOGY: A double-blind, randomized, controlled clinical trial was conducted by recruiting 144 subjects with mild to moderate chronic periodontitis. After scaling and root planning, subjects were allocated to two treatment groups: 0.2% chlorhexidine mouthwash and 20% propolis mouthwash twice daily for six weeks. Clinical parameters such as pocket probing depth (PPD), clinical attachment loss (CAL) and bleeding on probing (BOP) were analysed at baseline, six weeks, and 12 weeks. RESULT: The mean value of PPD in the propolis group was 4.67 at baseline, reduced to 4.01 at six weeks and 3.59 at 12 weeks. While in the chlorhexidine group, the baseline value of 4.65 reduced to 4.44 and 4.25 at six weeks and 12 weeks, respectively. The baseline value of the mean CAL in the propolis group was 4.45. This value was reduced to 4.15 at six weeks and 3.77 at 12 weeks. For the chlorhexidine group, the baseline value of CAL was 4.80, which was reduced to 4.50 and 4.19 at six weeks and 12 weeks. The mean value of bleeding on probing in the propolis group was 77.20, which decreased to 46.30 at six weeks and 14.60 at the final visit. In the chlorhexidine group, the mean value of 77.30 was reduced to 49.60 and 22.80 at subsequent visits. CONCLUSION: This study concludes that both propolis and chlorhexidine mouthwash positively improve clinical parameters; however, propolis is significantly more effective in improving BOP. TRIAL REGISTRATION: ID: NCT05870059, Date of Registration: 02/02/2022. ( https://beta. CLINICALTRIALS: gov/study/NCT05870059 ).

Effects of Anatolian Propolis and Hypertonic Saline Combination Nasal Spray on Allergic Rhinitis Symptoms: A Prospective, Multicenter Study.

Objectives: This study aimed to evaluate how Rhinapi nasal spray affects symptoms of allergic rhinitis. Methods: In this prospective, multicenter, observational study, 10,000 patients (comprising 5028 males and 4972 females) exhibiting symptoms of allergic rhinitis (namely, nasal discharge, sneezing, nasal itching, and nasal obstruction) from different centers in different regions of Turkey were enrolled in the study between March 2022 and March 2023. All the patients wanted to participate in the study and were administered Rhinapi one puff to each nostril three times a day, for a period of 3 weeks. Total symptom scores, quality of life (QoL) scores, and otolaryngological examination scores were evaluated before and 3 weeks after treatment. Results: The scores for discharge from the nose, sneezing, nasal pruritus, and blockage of the nose all indicated improvement when compared to pre-medication and post-medication. This difference achieved statistical significance (P < .001). The mean total symptom score fell following treatment (P < .001): whilst the score was 11.09 ± 3.41 before administering Rhinapi; after administration, the average score was 6.23 ± 2.41. The mean QoL scores also altered after medication (P < .001), improving from a mean value of 6.44 ± 1.55 to a mean of 7.31 ± 1.24. Significant improvement was also noted in the scores for conchal color and degree of edema after the treatment had been administered (P < .001). Conclusion: The study demonstrates that Rhinapi nasal spray decreases total symptom scores, and results in improved QoL and otolaryngological examination scores. Propolis spray may be recommended for patients with allergic rhinitis alongside other treatments.

Effects of Propolis-Based Herbal Toothpaste on Dentine Hypersensitivity.

INTRODUCTION: The objective of this in vitro study was to compare the effectiveness of a propolis-based herbal toothpaste with 5% sodium fluoride varnishin obstructing human dentinal tubules; Scanning electron microscopy was utilised to obtain quantitative and qulitative data on tubular obstruction. METHODS: Thirty-nine extracted human premolar teeth were collected. The cementum layer was removed using a water-cooled diamond bur and the smear layer using ethylenediaminetetraacetic acid (EDTA) 17%. Then, the samples were randomly divided into 3 groups (n = 13 each), as follows: group 1: dentin discs exposed to the propolis-based herbal toothpaste (Herbex); group 2: dentin discs exposed to 5% sodium fluoride varnish; and group 3: control. Then, all discs were observed and imaged in 4 non-overlapping fields by an electron microscope at 2000× magnification. The topography and number of open, closed, and semi-closed tubules were counted in all images. The data were analysed using Kruskal-Wallis test, Mann-Whitney U test, and Friedman test. The statistical analysis was performed with SPSS statistic 22.0 software, with a significance level of α = 0.05. RESULTS: In pairwise comparisons of the groups considering the percentage of open, closed, and semi-closed tubules, the difference was not statistically significant between the 5% sodium fluoride varnish and propolis groups in the closed and semi-closed tubules, but it was statistically significant with the control group. Additionally, the percentage of open tubules in the propolis-based herbal toothpaste group was significantly lower than in the 5% sodium fluoride varnish and control group. CONCLUSIONS: Both propolis-based herbal toothpaste and 5% sodium fluoride varnish is effective in blocking human dentin tubules to various extents.

Therapeutic potential of propolis in alleviating inflammatory response and promoting wound healing in skin burn.

Burns can cause inflammation and delayed healing, necessitating alternative therapies due to the limitations of conventional treatments. Propolis, a natural bee-produced substance, has shown promise in facilitating burn healing. This literature review provides a comprehensive overview of propolis' mechanisms of action, wound-healing properties, and its application in treating skin burns. Propolis contains bioactive compounds with antimicrobial, antioxidant, and anti-inflammatory properties, making it a promising candidate for managing skin burn injuries. It helps prevent infections, neutralize harmful free radicals, and promote a well-balanced inflammatory response. Moreover, propolis aids in wound closure, tissue regeneration, collagen synthesis, cellular proliferation, and angiogenesis, contributing to tissue regeneration and remodeling. The article discusses various propolis extracts, extraction methods, chemical composition, and optimized formulations like ointments and creams for burn wound treatment. Considerations regarding dosage and safety are addressed. Further research is needed to fully understand propolis' mechanisms, determine optimal formulations, and establish suitable clinical dosages. Nevertheless, propolis' natural origin and demonstrated benefits make it a compelling avenue for burn care exploration, potentially complementing existing therapies and improving burn management outcomes.

Propolis as an adjunctive therapy for treatment of uncomplicated cystitis in women: A randomized double-blind placebo-controlled trial.

The current research is designed to investigate the effect of propolis supplementation on the clinical manifestations in women suffering from uncomplicated cystitis. In this randomized double-blind, placebo-controlled trial, 120 women with uncomplicated cystitis were selected and randomly assigned into two groups to receive two 500 mg capsules of propolis or placebo daily for 7 days along with ciprofloxacin (250 mg). Clinical symptoms including hematuria, urinary frequency, dysuria, suprapubic pain, and urgency, as well as bacteriuria, were assessed before and after the intervention. After supplementation, participants in the intervention group had significantly fewer days of urinary frequency (p < 0.001), dysuria (p = 0.005), and urgency (p = 0.03). However, there was no significant difference between the two groups regarding hematuria and suprapubic pain (p > 0.05). Furthermore, the severity of bacteriuria decreased significantly in both groups. In conclusion, it seems that propolis supplementation in women with uncomplicated cystitis could improve urinary frequency, dysuria, and urgency. However, further clinical trials should be conducted to fully understand the effects of propolis in women suffering from uncomplicated cystitis.

The influence of propolis plus Hyoscyamus niger L. against COVID-19: A phase II, multicenter, placebo-controlled, randomized trial.

The incubation period of COVID-19 symptoms, along with the proliferation and high transmission rate of the SARS-CoV-2 virus, is the cause of an uncontrolled epidemic worldwide. Vaccination is the front line of prevention, and antiinflammatory and antiviral drugs are the treatment of this disease. In addition, some herbal therapy approaches can be a good way to deal with this disease. The aim of this study was to evaluate the effect of propolis syrup with Hyoscyamus niger L. extract in hospitalized patients with COVID-19 with acute disease conditions in a double-blinded approach. The study was performed on 140 patients with COVID-19 in a double-blind, randomized, and multicentral approach. The main inclusion criterion was the presence of a severe type of COVID-19 disease. The duration of treatment with syrup was 6 days and 30 CC per day in the form of three meals. On Days 0, 2, 4, and 6, arterial blood oxygen levels, C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell, as well as the patient's clinical symptoms such as fever and chills, cough and shortness of breath, chest pain, and other symptoms, were recorded and analyzed. Propolis syrup with H. niger L. significantly reduces cough from the second day, relieving shortness of breath on the fourth day, and significantly reduces CRP, weakness, and lethargy, as well as significantly increased arterial blood oxygen pressure on the sixth day compared to the placebo group (p < 0.05). The results in patients are such that in the most severe conditions of the disease 80% < SpO2 (oxygen saturation), the healing process of the syrup on reducing CRP and increasing arterial blood oxygen pressure from the fourth day is significantly different compared with the placebo group (p < 0.05). The use of syrup is associated with a reduction of 3.6 days in the hospitalization period compared with the placebo group. Propolis syrup with H. niger L. has effectiveness in the viral and inflammatory phases on clinical symptoms and blood parameters and arterial blood oxygen levels of patients with COVID-19. Also, it reduces referrals to the intensive care unit and mortality in hospitalized patients with COVID-19. So, this syrup promises to be an effective treatment in the great challenge of COVID-19.

Flavonoid extract from propolis alleviates periodontitis by boosting periodontium regeneration and inflammation resolution via regulating TLR4/MyD88/NF-κB and RANK/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, propolis has been used for treating oral diseases for centuries, widely. Flavonoid extract is the main active ingredient in propolis, which has attracted extensive attention in recent years. AIM OF THE STUDY: The objective and novelty of the current study aims to identify the mechanism of total flavonoid extract of propolis (TFP) for the treatment of periodontitis, and evaluate the therapeutic effect of TFP-loaded liquid crystal hydrogel (TFP-LLC) in rats with periodontitis. METHODS: In this study, we used lipopolysaccharide-stimulated periodontal ligament stem cells (PDLSCs) to construct in vitro inflammation model, and investigated the anti-inflammatory effect of TFP by expression levels of inflammatory factors. Osteogenic differentiation was assessed using alkaline phosphatase activity and alizarin red staining. Meanwhile, the expression of toll like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor-kappa B (NF-κB), receptor activator of NF-κB (RANK) etc, were quantitated to investigate the therapeutic mechanism of TFP. Finally, we constructed TFP-LLC using a self-emulsification method and administered it to rats with periodontitis via periodontal pocket injection to evaluate the therapeutic effects. The therapeutic index, microcomputed tomography (Micro-CT), H&E staining, TRAP staining, and Masson staining were used for this evaluation. RESULTS: TFP reduced the expression of TLR4, MyD88, NF-κB and inflammatory factor in lipopolysaccharide-stimulated PDLSCs. Meanwhile, TFP simultaneously regulating alkaline phosphatase, RANK, runt-associated transcription factor-2 and matrix metalloproteinase production to accelerate osteogenic differentiation and collagen secretion. In addition, TFP-LLC can stably anchor to the periodontal lesion site and sustainably release TFP. After four weeks of treatment with TFP-LLC, we observed a decrease in the levels of NF-κB and interleukin-1ß (IL-1ß) in the periodontal tissues of rats, as well as a significant reduction in inflammation in HE staining. Similarly, Micro CT results showed that TFP-LLC could significantly inhibit alveolar bone resorption, increase bone mineral density (BMD) and reduce trabecular bone space (Tb.Sp) in rats with periodontitis. CONCLUSION: Collectively, we have firstly verified the therapeutic effects and mechanisms of TFP in PDLSCs for periodontitis treatment. Our results indicate that TFP perform anti-inflammatory and tissue repair activities through TLR4/MyD88/NF-κB and RANK/NF-κB pathways in PDLSCs. Meanwhile, for the first time, we employed LLC delivery system to load TFP for periodontitis treatment. The results showed that TFP-LLC could be effectively retained in the periodontal pocket and exerted a crucial role in inflammation resolution and periodontal tissue regeneration.

Applications of propolis-based materials in wound healing.

Due to its excellent antiseptic efficacy and antimicrobial properties, propolis has shown attractive advantages in wound dressings. However, an inclusive review of the propolis-based materials as a wound dressing is still lacking. The current short review summarizes the skin wound healing process, relates evaluation parameters, and then reviews the refined propolis-based materials dressings such as antimicrobial property, adhesion and hemostasis, anti-inflammatory and substance delivery. The approaches implemented to achieve these functions are classified and discussed. Furthermore, applications of propolis wound dressing for treating different types of wounds such as heal wounds, burns, and ulcers are presented. The future directions of propolis-based wound dressings for wound healing are further proposed. This review showed that propolis-based materials might be a promising new dressing for wound occlusion and tissue repairing.

Fluconazole and propolis co-encapsulated in chitosan nanoparticles for the treatment of vulvovaginal candidiasis in a murine model.

Vulvovaginal candidiasis (VVC) is a fungal infection caused mainly by Candida albicans. The treatment of VVC with azoles has been impaired due to the increased cases of resistance presented by this pathogen. The aim of the present study was to investigate the antifungal activity of mucoadhesive chitosan nanoparticles encapsulating both green propolis and fluconazole for topical use in the treatment of VVC. The nanoparticles were prepared by the ionic gelation method, resulting in a size of 316.5 nm containing 22 mg/kg of green propolis and 2.4 mg/kg of fluconazole. The nanoparticles were non-toxic in vitro using red blood cells or in vivo in a Galleria mellonella toxicity model. The treatment of female BALB/c mice infected by C. albicans ATCC 10231 with topical nanoparticles co-encapsulating fluconazole and green propolis was effective even using a fluconazole amount 20 times lower than the amount of miconazole nitrate 2% cream. Considering that the mucoadhesive property of chitosan, which is known to allow a prolonged retention time of the compounds at the mucous epithelia, the antifungal potential of the phenols and flavonoids present in green propolis may have favored the effectiveness of this treatment. These results indicate that this formulation of topical use for fluconazole associated with green propolis can be used as a promising approach to therapy for the treatment of VVC, thus contributing to reducing the development of resistance to azoles.

Vulvovaginal candidiasis is a fungal infection for which we search for alternatives for its treatment. Thus, a nanoparticle formulation based on fluconazole and green propolis was developed. These nanoparticles were tested, and we obtained adequate results in laboratory tests.

Propolis Has an Anticancer Effect on Early Stage Colorectal Cancer by Affecting Epithelial Differentiation and Gut Immunity in the Tumor Microenvironment.

Colorectal cancer (CRC) is one of the most common cancers and is the second leading cause of cancer-related death in the world. Due to the westernization of diets, young patients with CRC are often diagnosed at advanced stages with an associated poor prognosis. Improved lifestyle choices are one way to minimize CRC risk. Among diet choices is the inclusion of bee propolis, long recognized as a health supplement with anticancer activities. Understanding the effect of propolis on the gut environment is worth exploring, and especially its associated intratumoral immune changes and its anticancer effect on the occurrence and development of CRC. In this study, early stage CRC was induced with 1,2-dimethylhydrazine (DMH) and dextran sulfate sodium (DSS) for one month in an animal model, without and with propolis administration. The phenotypes of early stage CRC were evaluated by X-ray microcomputed tomography and histologic examination. The gut immunity of the tumor microenvironment was assessed by immunohistochemical staining for tumor-infiltrating lymphocytes (TILs) and further comparative quantification. We found that the characteristics of the CRC mice, including the body weight, tumor loading, and tumor dimensions, were significantly changed due to propolis administration. With further propolis administration, the CRC tissues of DMH/DSS-treated mice showed decreased cytokeratin 20 levels, a marker for intestinal epithelium differentiation. Additionally, the signal intensity and density of CD3+ and CD4+ TILs were significantly increased and fewer forkhead box protein P3 (FOXP3) lymphocytes were observed in the lamina propria. In conclusion, we found that propolis, a natural supplement, potentially prevented CRC progression by increasing CD3+ and CD4+ TILs and reducing FOXP3 lymphocytes in the tumor microenvironment of early stage CRC. Our study could suggest a promising role for propolis in complementary medicine as a food supplement to decrease or prevent CRC progression.