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.

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 ).

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.

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.

Mouthwashes: Alternatives and Future Directions.

This narrative review summarises "alternative" or "natural" over-the-counter (OTC) mouthwashes not covered elsewhere in this supplement and newly emerging products, as potential mouthwashes of the future. The "natural" mouthwashes reviewed include saltwater, baking soda, coconut oil, charcoal, propolis, seaweeds, and probiotics. Other than essential oils, it is apparent that their clinical effectiveness is still under debate, but there is some evidence to suggest that propolis reduces plaque and gingivitis. This review also covers the host immune response, via novel anti-inmmunomodulant mouthwashes, such as erythropoietin to reduce inflammation with oral mucositis (OM) after radiotherapy. The emerging concept of nanoparticle-containing mouthwashes, such as iron oxide, is further discussed for OM, this agent having the potential for more targeted delivery of chemical antimicrobials. Unfortunately, there are impacts on the environment of widening mouthwash use with more new products, including increased use of packaging, antimicrobial resistance, and possible detrimental effects on marine life. Further, there are roadblocks, relating to regularly approvals and side effects, that still need to be overcome for any OTC deivered immunomodulant or nanoformulation mouthwashes. Despite these caveats, there are many new mouthwashes under development, which could help manage major oral diseases such as caries, gingivitis, and periodontal disease.

Propolis as a Potential Therapeutic Agent to Counteract Age-Related Changes in Cartilage: An In Vivo Study.

Aging is intricately linked to chronic low-grade systemic inflammation, which plays a significant role in various age-related conditions, including osteoarthritis (OA). The aging process significantly influences the development of OA due to alterations in cartilage composition, reduced proteoglycan content, dysregulation of growth factor signaling, and heightened oxidative stress. Propolis, a natural product renowned for its potent antioxidant and anti-inflammatory properties, has the potential to mitigate age-induced changes in cartilage. The primary objective of this study was to rigorously assess the impact of in vivo propolis treatment on the histopathological characteristics of knee articular cartilage in senescent rats. This study involved a cohort of twenty male Sprague-Dawley rats, randomly allocated into four distinct groups for comparative analysis: YR (control group consisting of young rats), SR (senescent rats), SR-EEP (senescent rats treated with an ethanolic extract of propolis, EEP), and SR-V (senescent rats administered with a control vehicle). This study employed comprehensive histological and stereological analyses of knee articular cartilage. Propolis treatment exhibited a significant capacity to alleviate the severity of osteoarthritis, enhance the structural integrity of cartilage, and augment chondrocyte density. These promising findings underscore the potential of propolis as a compelling therapeutic agent to counteract age-related alterations in cartilage and, importantly, to potentially forestall the onset of osteoarthritis.

The effects of propolis supplementation on high-sensitivity C-reactive protein, testosterone hormone, and metabolic profile in women with polycystic ovary syndrome: A randomized, triple-blinded, placebo-controlled clinical trial.

One of the most prevalent ovulation disorders is polycystic ovarian syndrome (PCOS). According to the anti-inflammatory and beneficial effects of propolis, this triple-blind controlled trial was designed to evaluate the effect of propolis on metabolic factors, high-sensitivity C-reactive protein, and testosterone in women with PCOS. Recruited patients from the gynecologist clinic were randomized based on a stratified permuted four-block randomization procedure to supplement with propolis tablets, two tablets/day (500 mg propolis/day) (n = 30) or identical placebo tablets (n = 30) for 12 weeks in 2021 until 2022. Data were collected using a demographic questionnaire, blood samples, and a checklist to record the measured parameters. A total of 57 patients completed the trial. ANCOVA test showed that hip circumference (HC)) p = 0.03), fasting insulin (p = 0.007), homeostatic model assessment for insulin resistance (p = 0.004), testosterone (p = 0.004), and low-density lipoprotein (LDL)/high-density lipoprotein (HDL) (p = 0.02) were significantly decreased in the propolis versus the placebo group after adjustment for confounders. Although fasting blood glucose (p = 0.04) decreased significantly in the propolis group compared to the placebo, after adjusting for confounders, significance was lost (p = 0.09). Supplementation with propolis elicited positive effects on fasting insulin and insulin resistance, in addition to reducing the testosterone level, LDL/HDL, and HC, in PCOS women.

The effect of propolis supplementation on cardiovascular risk factors in women with rheumatoid arthritis: A double-blind, placebo, controlled randomized clinical trial.

Propolis has gained popularity in recent years because of its beneficial properties, which make it a possible preventative and therapeutic agent as well as a valuable food and cosmetic ingredient. The objective of this study was to evaluate the effects of propolis supplementation on cardiovascular risk factors in women with rheumatoid arthritis. This randomized, double-blind, placebo-controlled clinical trial was performed among 48 patients diagnosed with rheumatoid arthritis. Subjects were randomly assigned to placebo and intervention groups, supplemented with 1000 mg/day of propolis for 12 weeks. Cardiovascular risk factors including, high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein (MCP-1), Nitric oxide, blood pressure, and lipid profile were assessed pre-and post-intervention. The atherogenic index of plasma value, as well as total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C, and non-HDL-C/HDL-C ratios, were significantly reduced in the intervention group, compared with the placebo group post-intervention (p < 0.05). Moreover, there was a significant reduction in the serum level of hs-CRP in the intervention group when compared with the placebo group (p = 0.001). Furthermore, propolis supplementation could marginally reduce MCP-1 (p = 0.051). These data indicate that propolis supplementation may be a promising treatment strategy for cardiovascular complications among rheumatoid arthritis patients.

Anti-Inflammatory and Histological Analysis of Skin Wound Healing through Topical Application of Mexican Propolis.

Skin wound healing is a complex biochemical process of tissue repair and remodeling in response to injury. Currently, the drugs used to improve the healing process are inaccessible to the population, are costly, and have side effects, making the search for new treatment alternatives necessary. Propolis is a natural product produced by bees that is widely recognized and used in folk medicine for its multiple biomedical activities. However, therapeutic information regarding Mexican propolis is limited. This study aimed to evaluate the wound-healing effect of the Chihuahua ethanolic extract of propolis (ChEEP). Macroscopic and histological analyses were performed using a mouse wound-healing model. The topic acute toxicity assay showed that propolis at 10% w/v had no toxic effects. ChEEP has antibacterial activity against the Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis. Moreover, it exhibited good anti-inflammatory activity evaluated through mouse ear edema induced by 12-O-tetradeca-noylphorbol-13-acetate (TPA). A full-thickness incision lesion was created in mice and treated topically with 10% ChEEP. At Day 14 post-treatment, it was observed that propolis increased wound contraction and reduced healing time and wound length; furthermore, propolis increased the tensile strength of the wound, as determined with the tensiometric method, and promoted the formation of type I collagen at the site of injury, as evaluated with Herovici stain. These findings suggest that the topical administration of ChEEP can improve skin wound healing, probably due to the synergistic effect of its components, mainly polyphenols, in different steps of the wound-healing process. It should be noted this is the first time that the wound-healing activity of a Mexican propolis has been evaluated.

Clinical effectiveness of α-lipoic acid, myo-inositol and propolis supplementation on metabolic profiles and liver function in obese patients with NAFLD: A randomized controlled clinical trial.

BACKGROUND: To compare the effects of α-lipoic acid (ALA), myo-inositol (MI) and propolis supplementation on metabolic parameters and liver function in obese patients with non-alcoholic fatty liver disease (NAFLD) METHODS: Ninety-two obese patients with NAFLD were randomly allocated into one of the four groups (ALA, MI, propolis, and control groups) for 8 weeks. At pre-and post-intervention, anthropometric measures, metabolic parameters and liver function were assessed. Clinical effectiveness was assessed using Absolute Risk Reduction (ARR) and Number Needed to Treat (NNT). RESULTS: After 8 weeks, apart from waist-to-hip ratio, all studied anthropometric measures decreased significantly in each of the groups over the trial. Although the greatest improvements in glycemic indices were observed in MI group (p < 0.05), the differences among the groups were not significant. Control group showed the greatest reduction in serum triglyceride level (p = 0.026) while the greatest improvements in serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were observed in MI group (p = 0.043, p = 0.019 and p = 0.041, respectively). Alanine aminotransferase (ALT) levels reduced significantly in all groups, particularly in propolis group (p = 0.012). The greatest reduction in serum aspartate transaminase (AST) level was observed in control group (p < 0.001), however, the difference among the groups was statistically marginal (p = 0.058). The estimated NNTs for one grade reduction in liver steatosis for MI, ALA and propolis supplementation compared with control group were 1.5, 2.2 and 3, respectively. CONCLUSION: Dietary recommendation for weight loss accompanied by MI and then ALA supplementation improved metabolic parameters and liver steatosis. "Registered under ClinicalTrials.gov Identifier no: IRCT20100209003320N22".

Ethanol extract of propolis regulates type 2 diabetes in mice via metabolism and gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a traditional natural medicine with various activities such as antioxidant and anti-inflammatory, immunomodulatory, anti-tumour, gastroenteritis treatment and prevention, anti-microbial and parasitic, as well as glucose regulation and anti-diabetes, and is expected to be an anti-diabetic candidate with few side effects, but the mechanism of action of propolis on type 2 diabetes mellitus (T2DM) has not been fully elucidated. AIM OF THE STUDY: The purpose of this study was to investigate the mechanism of the effect of ethanol extract of propolis (EEP) on the regulation of blood glucose in T2DM mice. MATERIALS AND METHODS: We studied the possible mechanism of EEP on T2DM using an animal model of T2DM induced by a combination of a high-fat diet and intraperitoneal injection of streptozotocin (STZ). The experiment was divided into four groups, namely, the normal group (HC), model group (T2DM), EEP and metformin group (MET). Biochemical indexes and cytokines were measured, and the differences of metabolites in the serum were compared by 1H-NMR. In addition, the diversity of intestinal flora in feces was studied by 16S rDNA amplicon sequencing. RESULTS: The results showed that following treatment with EEP and MET, the weight-loss trend of mice was alleviated, and the fasting blood glucose, insulin secretion level, insulin resistance index, C peptide level and oral glucose tolerance level decreased, whereas the insulin sensitivity index increased, thereby EEP effectively alleviated the occurrence of T2DM and insulin resistance. Compared with the T2DM group, the concentrations of pro-inflammatory cytokines interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) decreased significantly in EEP and MET groups, whereas the concentrations of anti-inflammatory cytokine interleukin-10 (IL-10) increased significantly. Metabolomics results revealed that EEP and MET regulate carbohydrate metabolism and restore amino acid and lipid metabolism. Correlation analysis of intestinal flora in mouse feces showed that compared with the HC group, harmful bacteria such as Bilophila, Eubacterium_ventriosum_group, Mucispirillum and Desulfovibrio were found in the T2DM group, whereas the abundance of beneficial bacteria such as Lactobacillus was significantly reduced. Parabacteroides, Akkermansia, Leuconostoc, and Alloprevotella were abundantly present in the EEP group; however, the MET group showed an increase in the genus Parasutterella, which could regulate energy metabolism and insulin sensitivity. CONCLUSIONS: The results showed that EEP and MET reduce fasting blood glucose in T2DM mice, followed by alleviating insulin resistance, improving the inflammatory reaction of mice, regulating the metabolism of mice, and affecting the steady state of gut microbiota. However, the overall therapeutic effect of EEP is better than that of MET.

Influência da via hippo no reparo da mucosite oral quimicamente induzida em modelo murino submetida a tratamento com laser, geleia real ou própolis / Influence of the hippo pathway on the repair of chemically induced oral mucositis in a murine model subjected to treatment with laser, royal jelly or propolis

A via hippo é uma via de transdução de sinal altamente conservada que está implicada no desenvolvimento, homeostase e regeneração celular/tecidual. A YAP tem papel fundamental na via hippo uma vez que junto com a TAZ ativam fatores de transcrição que levam ao crescimento, diferenciação e migração celular. O mecanismo de fosforilação da YAP/TAZ pela LATS1/LATS2 cria um sítio de ligação para manter a YAP no citoplasma (fosforilada) impedindo suas funções a nível nuclear. Diante das importantes funções desta via no reparo e crescimento tecidual, esta pesquisa avaliou se a via hippo exerceu influência na resposta ao tratamento da MO através da expressão das proteínas YAP e LATS2 em mucosite oral (MO) quimicamente induzida pelo 5- fluoracil (5-FU), em modelo murino, tratada com própolis (P), geleia real (GR) ou laser (L) comparadas ao grupo controle (C), sem tratamento. Foram utilizadas amostras de ratos machos wistar divididos nos seguintes grupos: C, P, GR e L (intraoral 6 J/cm2 ) separados em três tempos experimentais: dias 08, 10 e 14. O perfil de imunomarcação foi feito por escores padronizados entre 0 a 3 levando em consideração a marcação nuclear e/ou citoplasmática. Na análise de imunomarcação da YAP, no dia 08, o grupo controle obteve os escore 0 e 1 na maioria das amostras, já nos dias 10 e 14 a maior parte das amostras obteve os escore 2 e 3. Nos grupos experimentais (L, GR e P), o escore 2 prevaleceu em todos os tempos experimentais. Para LATS2 houve prevalência do escore 2 tanto no grupo controle quanto nos grupos teste em todos os tempos experimentais. Em relação a análise estatística da imunoexpressão da proteína YAP, verificou-se diferença estatítica significativa (p= 0,020), apenas no dia 08 entre o grupo controle comparado aos grupos experimentais (L, GR e P). Já para LATS2 nenhuma diferença estatística foi encontrada. Na avaliação estatística dos diferentes tempos experimentais dentro um mesmo grupo, só foi encontrada diferença estatística significativa no grupo laser e apenas para LATS2 (p=0,025). Adicionalmente foi realizada a correlação de spearman, entre YAP e LATS2 para todos os grupos, porém não houve associação estatística significativa. A maior imunoexpressão de YAP e LATS2 (escores 2 e 3) observada nos grupos experimentais, indica que a via hippo é ativada e parece influenciar o processo de reparo nas mucosites orais quimioinduzidas e tratadas pelos diferentes métodos (AU).

The hippo pathway is a highly conserved signal transduction pathway that is implicated in cell/tissue development, homeostasis and regeneration. YAP plays a key role in the hippo pathway since, together with TAZ, they activate transcription factors that lead to cell growth, differentiation and migration. The YAP/TAZ phosphorylation mechanism by LATS1/LATS2 creates a binding site to keep YAP in the cytoplasm (phosphorylated) preventing its functions at the nuclear level. Given the important functions of this pathway in tissue repair and growth, this research evaluated whether the hippo pathway exerted influence on the response to OM treatment through the expression of YAP and LATS2 proteins in oral mucositis (OM) chemically induced by 5-fluororacil (5- FU), in a murine model, treated with propolis (P), royal jelly (GR) or laser (L) compared to the control group (C), without treatment. Samples of male Wistar rats divided into the following groups were used: C, P, GR and L (intraoral 6 J/cm2) separated into three experimental times: days 08, 10 and 14. The immunostaining profile was performed by standardized scores between 0 to 3 taking into account nuclear and/or cytoplasmic labeling. In the YAP immunostaining analysis, on day 08, the control group obtained scores 0 and 1 in most samples, while on days 10 and 14 most samples obtained scores 2 and 3. In the experimental groups (L, GR and P), score 2 prevailed at all experimental times. For LATS2 there was a prevalence of score 2 both in the control group and in the test groups at all experimental times, showing a very heterogeneous expression. Regarding the statistical analysis of YAP protein immunoexpression, there was a statistically significant difference (p= 0.020), only on day 08 between the control group compared to the experimental groups (L, GR and P). As for LATS2, no statistical difference was found. In the statistical evaluation of the different experimental times within the same group, a statistically significant difference was only found in the laser group and only for LATS2 (p=0.025). Additionally, the Spearman correlation was performed between YAP and LATS2 for all groups, but there was no statistically significant association. The greater immunoexpression of YAP and LATS2 (scores 2 and 3) observed in the experimental groups indicates that the hippo pathway is activated and seems to influence the repair process in chemoinduced oral mucositis treated by different methods (AU).

Evaluation of efflux pump inhibitory activity of some plant extracts and using them as adjuvants to potentiate the inhibitory activity of some antibiotics against Staphylococcus aureus.

Background: Antibiotic-resistant pathogens became a real global threat to human and animal health. This needs to concentrate the efforts to minimize and control these organisms. Efflux pumps are considered one of the important strategies used by bacteria to exclude harmful materials from the cell. Inhibition of these pumps can be an active strategy against multidrug resistance pathogens. There are two sources of efflux pump inhibitors that can be used, chemical and natural inhibitors. The chemical origin efflux pump inhibitors have many toxic side effects while the natural origin is characterized by a wide margin of safety for the host cell. Aim: In this study, the ability of some plant extracts like (propolis show rosemary, clove, capsaicin, and cumin) to potentiate the inhibitory activity of some antibiotics such as (ciprofloxacin, erythromycin, gentamycin, tetracycline, and ampicillin) against Staphylococcus aureus pathogen were tested. Methods: Efflux pump inhibitory activity of the selected plant extracts was tested using an ethidium bromide (EtBr) accumulation assay. Results: The results have shown that Propolis has a significant synergistic effect in combination with ciprofloxacin, erythromycin, and gentamycin. While it has no effect with tetracycline or ampicillin. Also, no synergic effect was noticed in a combination of the minimum inhibitory concentration for the selected plant extracts (rosemary, clove, capsaicin, and cumin) with any of the tested antibiotics. Interestingly, according to the results of the EtBr accumulation assay, Propolis has potent inhibitory activity against the S. aureus (MRS usa300) pump system. Conclusion: This study suggests that Propolis might act as a resistance breaker that is able to restore the activity of ciprofloxacin, erythromycin, and gentamycin against S. aureus strains, in case of the efflux-mediated antimicrobial resistance mechanisms.

Brazilian Propolis Intake Decreases Body Fat Mass and Oxidative Stress in Community-Dwelling Elderly Females: A Randomized Placebo-Controlled Trial.

This study aimed to investigate the effects of Brazilian propolis on body fat mass and levels of adiponectin and reactive oxygen species among community-dwelling elderly females. This was a double-blind randomized placebo-controlled trial. Altogether, 78 females aged 66-84 years were randomly assigned to the propolis (PRO; n = 39) or placebo (PLA; n = 39) group. For 12 weeks, the PRO group were given three capsules containing 227 mg of propolis twice a day. Meanwhile, the PLA group were given daily placebo capsules. Of 78 participants, 53 (PLA group: n = 28, PRO group: n = 25) completed the study. Although no changes were observed in absolute or relative fat mass in the PLA group, they showed a significant decline in the PRO group. The level of serum adiponectin in the PLA group did not change, although that of the PRO group significantly increased. The level of d-ROMs in the PLA group significantly increased, whereas that of the PRO group significantly decreased. The serum SOD activity in the PLA group significantly decreased, whereas that of the PRO group tended to increase. These results suggest that propolis supplementation may decrease body fat mass and oxidative stress among community-dwelling elderly females.

Effects of propolis on inflammation markers in patients undergoing hemodialysis: A randomized, double-blind controlled clinical trial.

BACKGROUND AND AIMS: Several studies have been performed in vitro and in animals showing that propolis (a resin made by bees) has excellent anti-inflammatory properties, but no study has been performed in patients with chronic kidney disease (CKD) on hemodialysis (HD). The present study aimed to evaluate the effects of propolis supplementation on inflammatory markers in patients with CKD on HD. METHODS: This is a longitudinal, double-blind, placebo-controlled trial with patients randomized into two groups: propolis (4 capsules of 100 mg/day containing concentrated and standardized dry EPP-AF® green propolis extract) or placebo (4 capsules of 100 mg/day containing microcrystalline cellulose, magnesium stearate and colloidal silicon dioxide) for two months. Routine parameters were analyzed using commercial kits. The plasma levels of inflammatory cytokines were evaluated by flow luminometry. RESULTS: Forty-one patients completed the follow-up, 21 patients in the propolis group (45 ± 12 years, 13 women, BMI, 22.8 ± 3.7 kg/m2) and 20 in the placebo group (45.5 ± 14 years, 13 women, BMI, 24.8 ± 6.8 kg/m2). The obtained data revealed that the intervention with propolis significantly reduced the serum levels of tumour necrosis factor α (TNFα) (p = 0.009) as well as had the tendency to reduce the levels of macrophage inflammatory protein-1ß (MIP-1ß) (p = 0.07). There were no significant differences in the placebo group. CONCLUSION: Short-term EPP-AF® propolis dry extract 400 mg/day supplementation seems to mitigate inflammation, reducing the plasma levels of TNFα and MIP-1ß in patients with CKD on HD. This study was registered at clinicaltrials.gov (NCT04411758).

Ameliorative Effects of Propolis and Royal Jelly against CCl4 -Induced Hepatotoxicity and Nephrotoxicity in Wistar Rats.

Carbon tetrachloride (CCl4 ) is known to have hepatotoxic and nephrotoxic effects. During the two-month CCl4 exposure of Wistar rats, propolis extract (PE) and royal jelly (RJ) were added in order to test the potential protective effect against hepato-renal injury. Ketonuria, proteinuria, high creatinine and urea levels are the result of CCl4 -induced nephrotoxicity. Severe disorders of hematological indicators indicate anemia; high values of leukocytes indicate inflammatory condition. Cytogenetic impairments in hepatocytes, aggregation of platelets, and hypoproteinemia indicate severe liver impairment. Results suggest a more significant protective role of RJ compared to PE. Both extracts regulated proteinuria, ketonuria, hypoproteinemia and reduced platelet aggregation in the hepatic circulation. The increase in the number of erythrocytes (RBC) suggest protective effects against anemia; the decrease in the number of leukocytes can be linked to anti-inflammatory effects. PE and RJ have a beneficial effect against hepato-renal injury, anemia and anti-inflammatory conditions caused by CCl4 .