Oral preparation of hyaluronic acid, chondroitin sulfate, N-acetylglucosamine, and vitamin C improves sexual and urinary symptoms in participants with recurrent urinary tract infections: a randomized crossover trial.

BACKGROUND: Intravesical instillation of hyaluronic acid (HA) has been associated with reduced sexual dysfunction in participants with recurrent urinary tract infections (rUTIs), but the efficacy of an oral treatment has never been investigated. AIM: To investigate the efficacy of an oral preparation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C in improving sexual and urinary symptoms in a cohort of reproductive-age participants with rUTI. METHODS: In a monocentric randomized crossover pilot trial, participants with rUTI who were referred to our institute between March 2022 and April 2023 were randomized 1:1 in 2 groups: intervention vs control. All participants had an oral preparation of cranberry, D-mannose, propolis extract, turmeric, and Boswellia twice a day for 3 months. The intervention group also included an oral preparation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C once a day for 3 months. Crossover of treatment occurred at 3 months for an additional 3 months. At baseline and 3 and 6 months, participants were evaluated clinically and with the International Prostate Symptom Score (IPSS) and Female Sexual Function Index (FSFI). Descriptive statistics and logistic regression models tested the impact of the intervention on urinary and sexual symptoms at each follow-up assessment. OUTCOMES: Improvement in sexual and urinary symptoms as measured by the FSFI and IPSS. RESULTS: Overall, 27 (54%) participants had an FSFI score <26.5 at enrollment. At 3 months, FSFI scores were higher in the intervention group vs control (P < .001), but IPSS scores were lower (P = .03). After crossover of treatment, FSFI and IPSS scores remained stable in the intervention group. However, after crossover, the control group showed a significant improvement in IPSS and FSFI scores (all P < .01) vs the 3-month assessment. At last follow-up, urinary and sexual symptoms were comparable between groups. In logistic regression analyses, the intervention group was associated with early improvement in sexual symptoms (odds ratio, 3.9; P = .04) and urinary symptoms (odds ratio, 5.1; P = .01) after accounting for clinical confounders. CLINICAL IMPLICATIONS: Combination treatment with HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C is effective if started immediately or even after a few months from symptoms in participants with rUTI. STRENGTHS AND LIMITATIONS: The main limitation is the lack of long-term follow-up. CONCLUSION: The oral formulation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C could be an effective therapy against urinary and sexual distress in participants with rUTI (NCT06268483; ClinicalTrials.gov).

Propolis: a natural compound with potential as an adjuvant in cancer therapy - a review of signaling pathways.

Propolis is a natural product used in cancer treatment, which is produced by bees via different sources. The chemical composition of Propolis is determined based on the climatic and geographical conditions, as well as harvesting time and method. This compound has been the subject of numerous investigational endeavors due to its expansive therapeutic capacity which includes antibacterial, anti-fungal, anti-inflammatory, anti-oxidant, anti-viral, and anti-cancer effects. The growing incidence rate of different cancers necessitates the need for developing novel preventive and therapeutic strategies. Chemotherapy, radiotherapy, and stem cell therapy have proved effective in cancer treatment, regardless of the adverse events associated with these modalities. Clinical application of natural compounds such as Propolis may confer promise as an adjuvant therapeutic intervention, particularly in certain subpopulations of patients that develop adverse events associated with anticancer regimens. The diverse biologically active compounds of propolis are believed to confer anti-cancer potential by modulation of critical signaling cascades such as caffeic acid phenethyl ester, Galangin, Artepillin C, Chrysin, Quercetin, Caffeic acid, Nymphaeols A and C, Frondoside A, Genistein, p-coumaric acid, and Propolin C. This review article aims to deliver a mechanistic account of anti-cancer effects of propolis and its components. Propolis can prevent angiogenesis by downregulating pathways involving Jun-N terminal kinase, ERK1/2, Akt and NF-ƘB, while counteracting metastatic progression of cancer by inhibiting Wtn2 and FAK, and MAPK and PI3K/AKT signaling pathways. Moreover, propolis or its main components show regulatory effects on cyclin D, CDK2/4/6, and their inhibitors. Additionally, propolis-induced up-regulation of p21 and p27 may result in cell cycle arrest at G2/M or G0/G1. The broad anti-apoptotic effects of propolis are mediated through upregulation of TRAIL, Bax, p53, and downregulation of the ERK1/2 signaling pathway. Considering the growing body of evidence regarding different anti-cancers effects of propolis and its active components, this natural compound could be considered an effective adjuvant therapy aimed at reducing related side effects associated with chemotherapy and radiotherapy.

The Beneficial Effect of Brazilian Propolis for Liver Damage through Endoplasmic Reticulum Stress.

There is evidence that propolis exhibits anti-inflammatory, anticancer, and antioxidant properties. We assessed the potential beneficial effects of Brazilian propolis on liver injury in nonalcoholic fatty liver disease (NAFLD). Our findings demonstrate that Brazilian propolis suppresses inflammation and fibrosis in the liver of mice with NAFLD by inhibiting the expression of genes involved in endoplasmic reticulum (ER) stress. Additionally, Brazilian propolis also suppressed the expression of ER stress-related genes in HepG2 cells treated with an excess of free fatty acids, leading to cell apoptosis. A deeper analysis revealed that kaempferol, one of the components present in Brazilian propolis, induces cell proliferation through the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and protects against oxidative stress. In conclusion, Brazilian propolis exhibits hepatoprotective properties against oxidative stress by inhibiting ER stress in NAFLD-induced model mice.

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.

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.

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.

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.

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 ).

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.

Artepillin C overcomes apalutamide resistance through blocking androgen signaling in prostate cancer cells.

Prostate cancer has a relatively good prognosis, but most cases develop resistance to hormone therapy, leading to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) antagonists and a cytochrome P450 17A1 inhibitor have been used to treat CRPC, but cancer cells readily develop resistance to these drugs. In this study, to improve the therapy of CRPC, we searched for natural compounds which block androgen signaling. Among cinnamic acid derivatives contained in Brazilian green propolis, artepillin C (ArtC) suppressed expressions of androgen-induced prostate-specific antigen and transmembrane protease serine 2 in a dose-dependent manner. Reporter assays revealed that ArtC displayed AR antagonist activity, albeit weaker than an AR antagonist flutamide. In general, aberrant activation of the androgen signaling is involved in the resistance of prostate cancer cells to hormone therapy. Recently, apalutamide, a novel AR antagonist, has been in clinical use, but its drug-resistant cases have been already reported. To search for compounds which overcome the resistance to apalutamide, we established apalutamide-resistant prostate cancer 22Rv1 cells (22Rv1/APA). The 22Rv1/APA cells showed higher AR expression and androgen sensitivity than parental 22Rv1 cells. ArtC inhibited androgen-induced proliferation of 22Rv1/APA cells by suppressing the enhanced androgen signaling through blocking the nuclear translocation of AR. In addition, ArtC potently sensitized the resistant cells to apalutamide by inducing apoptotic cell death due to mitochondrial dysfunction. These results suggest that the intake of Brazilian green propolis containing ArtC improves prostate cancer therapy.

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.

Caffeic acid phenethyl ester suppresses intestinal FXR signaling and ameliorates nonalcoholic fatty liver disease by inhibiting bacterial bile salt hydrolase activity.

Propolis is commonly used in traditional Chinese medicine. Studies have demonstrated the therapeutic effects of propolis extracts and its major bioactive compound caffeic acid phenethyl ester (CAPE) on obesity and diabetes. Herein, CAPE was found to have pharmacological activity against nonalcoholic fatty liver disease (NAFLD) in diet-induced obese mice. CAPE, previously reported as an inhibitor of bacterial bile salt hydrolase (BSH), inhibited BSH enzymatic activity in the gut microbiota when administered to mice. Upon BSH inhibition by CAPE, levels of tauro-ß-muricholic acid were increased in the intestine and selectively suppressed intestinal farnesoid X receptor (FXR) signaling. This resulted in lowering of the ceramides in the intestine that resulted from increased diet-induced obesity. Elevated intestinal ceramides are transported to the liver where they promoted fat production. Lowering FXR signaling was also accompanied by increased GLP-1 secretion. In support of this pathway, the therapeutic effects of CAPE on NAFLD were absent in intestinal FXR-deficient mice, and supplementation of mice with C16-ceramide significantly exacerbated hepatic steatosis. Treatment of mice with an antibiotic cocktail to deplete BSH-producing bacteria also abrogated the therapeutic activity of CAPE against NAFLD. These findings demonstrate that CAPE ameliorates obesity-related steatosis at least partly through the gut microbiota-bile acid-FXR pathway via inhibiting bacterial BSH activity and suggests that propolis enriched with CAPE might serve as a promising therapeutic agent for the treatment of NAFLD.

A Systematic Review of the Potential Effects of Propolis Extracts on Experimentally-induced Diabetes.

Oxidative stress (OS) is involved in the development of diabetes mellitus (DM) and its complications. Thus, OS reduction may be an important strategy for DM therapy. Propolis is bee resins with high antioxidant activity and is used in the treatment of different diseases, including DM. Therefore, in this systematic review, we evaluated the impact of propolis administration in diabetic animals. We used the PRISMA strategy to collect preclinical studies published in English up to November 2021 in three databases (PubMed/Medline, Scopus, and Web of Science). We used the SYRCLE tool to analyze the risk of methodological bias. Our primary search returned 198 studies, of which 14 were considered eligible to be included in this review. The administration of propolis induced a hypoglycemic effect in the treated animals, which is probably due to the reduction of OS. The animals showed restoration of endogenous antioxidant defenses and reduced levels of markers for OS. The administration of propolis resulted in improvement in the lipid profile of treated animals. Our risk of bias assessment showed a methodological quality score of less than 30% due to a lack of randomization, blinding, and proper allocation of animals. Heterogeneity in treatments, lack of results, and use of non-standard extracts are limitations in our data analysis. Despite these limitations, propolis induced a significant hypoglycemic effect in diabetic animals when compared to untreated controls. This effect was associated with a reduction in OS, a process mediated by ROS neutralization and restoration of endogenous antioxidant defenses.

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.

Brazilian Red Propolis Accelerates Gastric Healing and Reduces Gastric Submucosal Layer Inflammation in Ultrasound-Monitored Rats.

Propolis has been used for the treatment of gastric disturbances in folk medicine, nevertheless, the gastric healing effects of Brazilian red propolis have not been unveiled. This study aimed to assess the gastric healing effect of the hydroalcoholic extract of red propolis (HERP) in the acetic acid-induced ulcer model. Rats under acetic acid-induced-ulcer were treated with HERP (100 mg/kg, p.o.) twice a day for seven days. Histological changes, oxidative stress, and inflammatory parameters were analyzed in the gastric tissue. Moreover, the gastric wall thickness was measured by ultrasound. The in vitro cytotoxicity of HERP and cellular migration of fibroblasts were evaluated. The treatment with HERP promoted gastric healing, reducing gastric wall thickness, macroscopic lesion area, and histopathological damages compared to the vehicle. Moreover, HERP reduced oxidative stress and inflammation in the gastric tissue but did not change mucin or collagen levels. HERP did not show signs of toxicity either in vivo or in vitro. HERP displayed a healing effect in vivo by reducing oxidative stress and inflammation. These data contribute to validating the popular use of this product in the treatment of gastric disorders and advance scientific knowledge in the search for new drugs for the management of gastric ulcers.

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 .

Propolis Enhances 5-Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study.

In this study, we investigated the combined treatment of 5-fluorouracil (5-FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase-transfected (Lovo-Luc CRC) cells and healthy colon cells (CCD-18Co) to varying concentrations of 5-FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti-tumor effects of PE and 5-FU using various methods. Our findings showed that the combination of PE and 5-FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti-tumor effectiveness of 5-FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5-FU through iROS generation in a dose-dependent manner.

Anti-hyperglycemic effects of propolis or metformin in type 2 diabetes mellitus.

Background: The aim of this study was to evaluate the effect of propolis or metformin versus placebo on glycemic control in pharmacological treatment-naïve patients with type 2 diabetes mellitus (T2DM). Methods: A double-blind, randomized, placebo-controlled in parallel groups clinical trial was performed in 36 pharmacological treatment-naïve patients with T2DM. They received propolis (300 mg), metformin (850 mg), or placebo twice daily before breakfast and dinner for 12 weeks. At the beginning and end of the study, fasting plasma glucose (FPG), 2-h postload glucose (2-h PG) during a 75-g oral glucose tolerance test, glycated hemoglobin A1c (A1C) and a metabolic profile were measured. Areas under the curve (AUC) of glucose and insulin, total insulin secretion (insulinogenic index), the first phase of insulin secretion (Stumvoll index), and insulin sensitivity (Matsuda index) were calculated. Statistical analyses: Kruskal-Wallis, Mann-Whitney U and Wilcoxon tests. Results: The propolis and metformin groups exhibited significant reductions in FPG (p=0.009 and p=0.001, respectively), 2-h PG (p=0.034 and p=0.001, respectively) levels, AUC of insulin, Stumvoll index, and an increment in the Matsuda index. The comparison of the changes from baseline to the end showed significant differences between placebo and propolis in FPG (p=0.004) and A1C (p=0.049) levels, while between placebo and metformin were in FPG (p=0.002), 2-h PG (p=0.004) and A1C (p=0.007) levels. Conclusions: The administration of propolis and metformin compared to placebo reduced FPG and A1C levels; in addition, metformin decreased 2-h PG, AUC of glucose and insulin, high-density lipoprotein cholesterol, and increased the insulin sensitivity.