Phytochemical profiling and characterization of flavonoid derivatives from propolis sample and investigation of cytotoxic and antiprotozoal activities.

Recently, the growth of consumer demand for functional foods with potential nutritional and health benefits led to rapid growth of analytical tools for profiling of bioactive metabolites and assure quality. Bee propolis is one of the most important bee products owing to its myriad health value. As a gummy exudate produced in beehives after harvesting from different plant species, bee propolis contains bioactive secondary metabolites. The current study aims to profiling the chemical composition of propolis samples from Nigeria using HPLC-UV-ELSD and with the aid of NMR-based analysis for assignment of metabolites classes abundant in Nigerian propolis. Red Nigerian propolis samples were subjected to phytochemical analysis using HPLC-UV-ELSD and NMR. Further chromatographic separation of promising fractions was performed by column chromatography and size exclusion chromatography. Screening of the antitrypanosomal and cytotoxic activities against Trypanosoma brucei and human leukemia cell lines (U937), respectively, was performed. The performance of LC-MS permitted identification of the different components from which 13 compound were identified and allowed combination of fractions to afford 9 fractions from which two isoflavonoids were isolated and identified using 1D and 2D NMR analysis with MS as isosativan and Medicarpin. Red Nigerian propolis crude extract showed the highest inhibitory activity at 6.5 µg/ml compared to moderate activity for the isolated compounds with MIC of 7.6 µg/ml and 12.1 µg/ml for medicarpin and isosativan, respectively. Moreover, the fraction RN-6 from the total extract showed the potent cytotoxic effect with IC50 = 26.5 µg/ml compared to standard diminazen which showed IC50 = 29.5 µg/ml.

Characteristics of Indonesian Stingless Bee Propolis and Study of Metabolomic Properties Based on Region and Species.

The chemical compounds found in propolis vary according to plant sources, species, and geographical regions. To date, Indonesian propolis has not yet become standardized in terms of its chemical constituents. Thus, this study aimed to identify the presence of marker compounds and determine whether different classes of Indonesian propolis exist. In this study, yields, total polyphenol content (TPC), total flavonoid content (TFC), and antioxidants were measured. Identification of chemical compounds was carried out with Fourier-transform infrared (FTIR) spectroscopy and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Metaboanalyst 6.0 was employed in conducting principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using the results of the FTIR and LC-MS/MS. The propolis with the highest TFC, TPC, and antioxidant activity was Geniotrigona thoracica from North Sumatra. The results of propolis compound mapping based on region with discriminant analysis revealed that types of propolis from Java have similar characteristics. Then, based on species, the types of propolis from Tetragonula laeviceps and Heterotrigona itama have special characteristics; the samples from these species can be grouped according to similar characteristics. In conclusion, 10 potential marker compounds were identified in Indonesian propolis, enabling regional and species-specific varieties of Indonesian propolis to be classified based on chemical composition mapping.

The Clinical Effect of a Propolis and Mangosteen Extract Complex in Subjects with Gingivitis: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

This study investigated the efficacy and safety of a propolis-mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and incipient periodontitis. A multicentered, randomized, double-blind, placebo-controlled trial involving 104 subjects receiving either PMEC or placebo for eight weeks was conducted. The primary focus was on the changes in inflammatory biomarkers from gingival crevicular fluid (GCF), with clinical parameters as secondary outcomes. The results revealed that the PMEC group showed a significantly reduced expression of all measured GCF biomarkers compared to the placebo group (p < 0.0001) at 8 weeks, including substantial reductions in IL-1ß, PGE2, MMP-8, and MMP-9 levels compared to the baseline. While clinical parameters trended towards improvement in both groups, the intergroup differences were not statistically significant. No significant adverse events were reported, indicating a favorable safety profile. These findings suggest that PMEC consumption can attenuate gingival inflammation and mitigate periodontal tissue destruction by modulating key inflammatory mediators in gingival tissue. Although PMEC shows promise as a potential adjunctive therapy for supporting gingival health, the discrepancy between biomarker improvements and clinical outcomes warrants further investigation to fully elucidate its therapeutic potential in periodontal health management.

Protective effect of propolis in protecting against radiation-induced oxidative stress in the liver as a distant organ.

Stresses caused by ionizing radiation can also damage tissues and organs through the circulatory system. In this study, we aimed to determine the radioprotective effect of propolis, a natural and powerful antioxidant product, against oxidative liver damage caused by cranial irradiation. Thirty-two male albino Sprague-Dawley rats, divided into four groups, were designed as sham group, irradiation (IR) group, propolis plus IR, control group of propolis. Biochemical parameters were measured in liver tissue of rats. While Total enzymatic superoxide scavenging activity (TSSA) and non-enzymatic superoxide scavenging activity (NSSA), glutathione peroxidase (GSH-Px) activities of all groups were statistically significantly higher than rats receiving only-irradiation, Glutathione-S-transferase (GST) activity in the IR group was significantly lower than in the sham control group and IR + propolis group. Superoxide dismutase (SOD) activity in the IR group was found to be significantly higher than both the sham control group and the propolis control group, but lower than the IR + propolis group. Malondialdehyde level and xanthine oxidase activity were higher in the IR group than in the other groups. Compared to the sham control group, in the group treated with propolis, a significant elevation in antioxidant parameters, specifically TSSA, NSSA, SOD, and GST activities, was noted, with corresponding increases of 32.3%, 23.2%, 47.6%, and 22.6%, respectively. Our findings show that propolis can be a radioprotective agent against ionized radiation damage by increasing antioxidant activity and reducing oxidant stress in liver tissue.

Effects of Propolis Consumption on Liver Enzymes and Obesity Indices in Adults: A Systematic Review and Dose-Response Meta-Analysis.

Background: Propolis, a natural resin produced by bees, has been studied for its potential effects on liver enzymes and obesity indices. However, a meta-analysis is necessary to comprehensively understand the impact of propolis on obesity and liver function. Objectives: This meta-analysis of randomized controlled trials (RCTs) sought to evaluate the effects of propolis consumption on liver enzymes and obesity indices in adults. Methods: A systematic literature search up to December 2023 was completed in PubMed/Medline, Scopus, and Web of Science, to identify eligible RCTs. Heterogeneity tests of the selected trials were performed using the I 2 statistic. Random-effects models were assessed on the basis of the heterogeneity tests, and pooled data were determined as weighted mean differences (WMDs) with a 95% confidence interval (CI). Results: A pooled analysis of 24 trials showed that propolis consumption led to a significant reduction in alanine aminotransferase (ALT) (WMD: -2.58; 95% CI: -4.64, -0.52; P = 0.01), aspartate aminotransferase (AST) (WMD: -1.84; 95% CI: -3.01, -0.67; P = 0.002), and alkaline phosphatase (ALP) (WMD: -24.90; 95% CI: -42.13, -7.67; P = 0.005) in comparison with the control group. However, there were no significant effects on gamma-glutamyl transferase (GGT), body weight, BMI (in kg/m2), fat mass, body fat percentage, fat-free mass, adiponectin, waist circumference, hip circumference, and waist-hip ratio in comparison with the control group. Conclusions: We discovered that consuming propolis can lead to a significant decrease in ALT, AST, and ALP levels, without causing significant changes in GGT, anthropometric indices, and adiponectin levels. However, future well-designed RCTs with large numbers of participants and extended durations, focusing on precise propolis dosage and ingredients, are necessary.

The effects of MIND diet and propolis supplementation on metabolic syndrome: A randomized controlled clinical trial.

The MIND is a novel eating plan preserves cognitive function. Propolis is a resinous substance that has several biological and medicinal properties. This study examines the effect of the MIND diet and propolis supplementation on MetS indices among metabolic syndrome subjects. This RCT study, was conducted on adults with metabolic syndrome who were referred to the Hazrat Ali Health Center in Isfahan. 84 eligible subjects were divided into 3 groups. Including MIND diet + Propolis supplement, MIND diet + placebo, and control group. The data obtained from the subjects was analyzed in two descriptive and analytic levels. The Shapiro-Wilk test and examination of skewness were conducted to assess the normality of the distribution of quantitative variables. Quantitative variables were reported using either the mean (SD). SPSS Statistics software version 26 was used for statistical analysis of data. In this study the MIND + Propolis group compared to the control group after adjusting variables showed a significant decrease (p-value < 0.05) in weight, BMI, WC, SBP, DBP, and TG by 0.97 times (3%), 0.97 times (3%), 0.98 times (2%), 0.93 times (7%), 0.94 times (6%), and 0.75 times (25%), respectively; this significant change was also observed in FBS (p-value < 0.001) by 0.85 times (15%), and HDL-C (mg/dl) has shown a significant increase (p-value < 0.05) by 1.17 times (17%). MIND group compared to the control group after adjusting variables showed a significant decrease (p-value < 0.05) in BMI, WC, and SBP by 0.98 times (2%), 0.98 times (2%), and 0.95 times (5%), respectively; this significant change (p-value < 0.001) was also observed in DBP, FBS, and TG by 0.92 times (8%), 0.83 times (17%), and 0.71 times (29%), respectively; HDL-C has shown a significant increase (p-value < 0.001) by 1.21 times (21%), and weight has shown a non-significant decrease (p-value = 0.055) by 0.98 times (2%). This study indicated that the MIND diet + Propolis supplement and MIND diet compared to the control group can significantly decrease BMI, WC, SBP, DBP, FBS, TG, and weight (non-significant for the MIND group), and also increase HDL-C.

Antihypertensive effect of a nanoemulsion of baccharis dracunculifolia leaves extract in sodium-dependent hypertensive rats.

Baccharis dracunculifolia (DC) is an important botanical source of Brazilian green propolis and have many compounds with potential antihypertensive activity. However, little is known about the specific antihypertensive properties of DC, or the mechanisms involved. Here we aimed to chemically characterise an ethanolic DC extract (eDC), test its antihypertensive properties and the involvement of neurogenic mechanisms using an animal model of salt-dependent hypertension. The chemical analysis of the eDC revealed the presence of many antihypertensive compounds. Administering the eDC in a nanoemulsion formulation (25 to 50 mg/kg) effectively normalised blood pressure in hypertensive rats. The result also suggested that neurogenic mechanisms are involved in the antihypertensive action of eDC. The treatment with p-coumaric acid (0.32 to 3 mg/kg), a polyphenol abundant in the eDC, produced no significant antihypertensive effect. The findings indicate that the eDC has antihypertensive properties, and that these effects may be mediated through neurogenic pressor mechanisms.

Productions of Th2 cytokines, IL-4 and IL-10, were enhanced via the function of IL-2 from anti-CD3 antibody-stimulated mouse spleen cells treated with caffeic acid phenethyl ester.

OBJECTIVES: Interleukin (IL)-2 production by mouse spleen cells stimulated with an anti-CD3 antibody is significantly enhanced by caffeic acid phenethyl ester (CAPE), a major constituent of Chinese propolis (CP). In this study, we evaluated the functional significance of IL-2 in CAPE-treated activated spleen cells. METHODS: Mouse spleen cells were stimulated with an anti-CD3 monoclonal antibody in the presence of CAPE. Cytokine production was examined using an enzyme-linked immunosorbent assay (ELISA). Messenger RNA level expression was examined via reverse transcription quantitative polymerase chain reaction (RT-PCR). IL-2 function was assessed using IL-2 and a neutralizing antibody. Spleen cell subsets were identified and characterized using flow cytometry. RESULTS: CAPE treatment of anti-CD3 antibody-stimulated spleen cells reduced IFN-γ production, then enhanced IL-2 production, followed by enhancement of IL-4 and IL-10 production. The Th2 cytokine production enhancing effects of CAPE were completely abolished by addition of an anti-IL-2 neutralizing antibody. In the absence of CAPE, exogenously added IL-2 could enhance IL-4 production to a lesser degree, but did not stimulate IL-10 production, in stimulated spleen cells. Interestingly, CAPE significantly reduced the proportions of CD4+ and CD8+ cells, and increased those of CD4-CD8- cells among anti-CD3 stimulated spleen cells, in the presence or absence of anti-IL-2 neutralizing antibody treatment. CONCLUSIONS: CAPE reduced IFN-γ production, then enhanced IL-4 and IL-10 production via the activity of specifically elevated IL-2 in stimulated spleen cells. CAPE exerted these effects in a CD4- CD8- cell specific manner.

Effects of propolis extract administration on immune parameters, faecal consistency scores, and growth performance of Holstein-Friesian calves.

The purpose of the study was to investigate the effect of Ethanolic Extract of Propolis (EEP) administration on immune parameters, faecal consistency scores, growth performance, and feed efficiency of Holstein Friesian calves. A total of 24 calves were divided into two different groups, control (n = 12) and EEP (n = 12). Both groups consisted of 6 male and 6 female calves. The calves were fed milk amounting to 10% of their birth weight each day until they reached 60 days of age. Additionally, they were given starter feed and dry hay once a day. Calves assigned to the EEP group received 4 ml of EEP daily. Use of EEP increased (P < 0.05) the serum IgG and IgM levels at 2 months of age compared to the control group. EEP also showed efficacy (P < 0.01) in reducing faecal consistency in calves throughout the study. The levels of IL-1ß, IL-6, TNF-α and NF-κB expression in calves treated with EEP were lower (P < 0.05) throughout the EEP application period. On the other hand, IGF-1 mRNA transcript levels were (P < 0.01) higher in EEP group calves than in the control group. Furthermore, EEP-fed calves consumed less dry matter for 1 kg of live weight gain during the weaning-4 months (P < 0.01) and birth-4 months (P < 0.05) periods. These results indicate that EEP supplementation, through its immunostimulatory effects, plays a crucial role in the control of neonatal calf diarrhoea. Growth and development as well as IGF-1, which stimulates growth in almost all somatic cells, was also significantly increased by EEP supplementation. The combined effect of the rich bioactive compounds found in EEP appears to have a significant impact on health and well-being, resulting in improved early life performance in dairy calves.

Evaluation of the cytotoxic activity of chemically characterized propolis originating from different geographic regions and vitamin D co-supplementation against human ovarian cancer cells.

Ovarian cancer is the second most common and lethal gynecologic malignancy. Among natural product-based therapy, the honeybee products, particularly propolis, serve a valuable source contributing directly to human nutrition and health.In the present study, we determined the chemical composition of different types of propolis originating from Egypt, Germany and France using liquid chromatography-tandem mass spectrometry. The compounds identified belong to different metabolite classes, including flavonoids, cinnamic acid, chalcones, terpenoids, phenolic lipids, stilbenes, phenolic compounds, carbohydrates, vitamins, coumarins, polyprenylated benzophenone, benzoic acids, fatty acid methyl ester, and coumaric acid, and their derivatives. The most active extract is from France then Egypt and Germany.Afterwards, we treated the human ovarian cancer cells, OVCAR4, with different concentrations (1-400 µg/mL) of variable propolis types supplemented or not with vitamin D (0.0015-0.15 µg/mL) in order to evaluate the efficacy and the cytotoxic activities of our local P as compared to other types collected from different geographic regions. Importantly, the combinatorial treatment of OVCAR4 cancer cells with propolis and vitamin D in the same concentration ranges resulted in enhanced cell viability inhibition. Furthermore, such co-supplementation with vitamin D inhibits predominately the proliferative activity of cell population with the French propolis type as manifested by Ki67 expression, while it reduces considerably its expression, particularly with the German type, followed by the Egyptian one.Nowadays, scientists are interested by natural products which have risen to the forefront of drug discovery. Chemically characterized propolis showing cell viability inhibition and antiproliferative potential seems a valuable extract for further consideration as anti-carcinogenic agent.

The Effects of Propolis Consumption on Body Composition and Blood Pressure: A Systematic Review and Dose-Response Meta-Analysis.

Introduction and Aim: Research on the effects of propolis consumption on body composition, and blood pressure (BP) has produced inconsistent results. This systematic review and dose-response meta-analysis was carried out to compile the data from the randomized controlled trials (RCTs) on how propolis supplementation affects body composition, and BP level in adults. Materials and Methods: A systematic literature search was conducted using electronic databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane library, up to January 2024. The RCTs, evaluating the effects of propolis consumption on weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), fat mass (FM), systolic BP (SBP), and diastolic BP (DBP), were included in the study. We used the random-effects model to establish the pooled effect size. Results: A total of 22 RCTs involving 1082 participants were included in the study. Propolis supplementation demonstrated significant reductions in weight (weighted mean difference [WMD]: -0.37 kg; 95% confidence interval [CI]: -0.63 to -0.12), and BMI (WMD: -0.11 kg/m2; 95% CI: -0.13 to -0.09). However, there were no significant effects on WC, WHR, FM, HC, SBP, and DBP levels. The dose-response analysis revealed a significant nonlinear relationship between propolis dosage and WC (P = 0.020). Moreover, the BMI (P = 0.047) and WC (P = 0.004) reduction trend continues until 8 weeks of intervention and then this impact plateaued. Conclusions: Supplementation with propolis seems to be effective in reducing weight and BMI. However, it should be noted that the anti-obesity properties of propolis supplementation were small and may not reach clinical importance. Therefore, future well-designed studies with a large sample size are needed to investigate the effect of propolis on body composition and BP in adults.

Oral Propolis Nanoemulsions Modulate Gut Microbiota to Balance Bone Remodeling for Enhanced Osteoporosis Therapy.

The discovery of the bone-gut axis linking bone metabolism to gut microbiota (GM) dysbiosis has revolutionized our understanding of managing degenerative skeletal diseases. Targeting GM regulation has emerged as a promising approach to osteoporosis treatment. Herein, we develop propolis nanoemulsions (PNEs) with enhanced gastrointestinal stability and oral bioavailability for GM-based osteoporosis therapy. Orally administered PNEs exhibit superior antiosteoporosis efficacy in an ovariectomized (OVX) mouse model by modulating the GM structure and metabolites and restoring the intestinal barrier function. Multiomics analysis reveals that a reduction in Streptococcus abundance and an increase in the GM metabolite l-arginine are key factors in osteoporosis management. These changes suppress osteoclast activity and enhance osteoblast function, leading to balanced bone remodeling and, thus, significant antiosteoporotic effects via the gut-bone axis. Our results deepen insights into the intricate relationship between GM and bone remodeling, suggesting a promising strategy that maintains the homeostasis of the GM structure and metabolite for osteoporosis treatment.

Novel composite of nano zinc oxide and nano propolis as antibiotic for antibiotic-resistant bacteria: a promising approach.

This study proposes an innovative approach to combat the escalating threat of antibiotic resistance in bacteria by introducing a novel ZnO-propolis nanocomposite (ZnO-P NCs). The overuse of antibiotics, particularly during events like the COVID-19 pandemic, has intensified bacterial resistance, necessitating innovative solutions. The study employs a cost-effective and controllable biosynthesis method to produce ZnO nanoparticles (ZnO-NPs), with propolis extract crucially contributing to the reduction and stabilization of Zn2+ ions. A biodegradable nano-propolis matrix is then created by incorporating ZnO-NPs, forming the ZnO-P NCs. Structural stability is confirmed through FT-IR and Zeta potential analysis, while nanoscale properties are validated via TEM, SEM, and XRD analyses. The antimicrobial efficacy of various substances, including propolis, nano propolis, ethanolic propolis extract, ZnO-NPs, and ZnO-P NCs, is assessed against Gram-negative and Gram-positive bacteria, alongside a comparison with 28 antibiotics. Among the bacteria tested, Pseudomonas aeruginosa PAO1 ATCC15692 was more sensitive (40 mm) to the biosynthesized nanocomposite ZnO-P NCs than to ZnO-NPs (38 mm) and nanopropolis (32 mm), while Escherichia coli was resistant to nanopropolis (0 mm) than to ZnO-NPs (31 mm), and ZnO-P NCs (34 mm). The study reveals a synergy effect when combining propolis with green-synthesized ZnO-NPs in the form of ZnO-P NCs, significantly improving their efficiency against all tested bacteria, including antibiotic-resistant strains like E. coli. The nanocomposite outperforms other materials and antibiotics, demonstrating remarkable antibacterial effectiveness. SEM imaging confirms the disruption of bacterial cell membranes by ZnO-NPs and ZnO-P NCs. The study emphasizes the potential applications of ZnO-NPs integrated into biodegradable materials and underscores the significance of the zinc oxide-propolis nanocomposite in countering antimicrobial resistance. Overall, this research offers a comprehensive solution to combat multidrug-resistant bacteria, opening avenues for novel approaches in infection control.

Polyprenylated Benzophenones from Brazilian Red Propolis: Analytical Characterization and Anticancer Activity.

The present work describes the extraction of a polyprenylated benzophenone-rich extract from Brazilian red propolis (ERPB), the development and validation of an RP-HPLC-UV method to characterize it, and its evaluation against breast cancer cell lines MCF-7 and MDA-MB-231, as well as the normal counterpart MCF-10A. A mixture of gutifferone E and xanthochymol (1+2), and isolated oblongifolin B (3) were used as chemical standards for ERPB and were also evaluated. The concentrations of 1+2 and 3 corresponded to 16.68% and 42.25% of the total content of the extract, respectively, and the validation parameters evaluated were satisfactorily met. The cytotoxic effects of ERPB were assessed, and the obtained IC50 values were 19.58 µg/mL (MCF-10A), 11.56 µg/mL (MCF-7), and 5.22 µg/mL (MDA-MB-231). In conclusion, ERPB exhibits promising cytotoxic effects on the tested breast cell lines. However, further investigation to elucidate its potential therapeutic applications and safety profile should be conducted.

Efficacy of toothpaste containing Brazilian green propolis extracts with an optimal kaempferide/betuletol ratio for improving oral microbiota: A randomized, controlled, paired crossover study.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a resinous substance collected by honeybees from various plant sources and has been used in traditional folk medicine for centuries. Propolis has various biological properties, including antibacterial, antiviral, anti-inflammatory, and anti-tumor properties. The use of propolis in oral health care is attributable to its antimicrobial and anti-inflammatory effects. However, limited evidence exists on the in vivo efficacy of propolis against periodontal pathogens. AIM OF THE STUDY: We aimed to evaluate the efficacy of Brazilian green propolis (BGP)-containing toothpaste for improving the oral environment and define its antibacterial compounds. MATERIALS AND METHODS: Overall, 48 student volunteers aged 18-40 years (24 females and 24 males) were randomly categorized into the BGP and placebo groups. The BGP and placebo groups received toothpaste with and without BGP, respectively. After a baseline assessment, the plaque index (PI) score, gingival index (GI) score, and proportion of periodontal pathogens on the tongue surface were analyzed at 0, 1, and 2 weeks. Antibacterial compounds were identified using liquid-liquid partitioning, high-performance liquid chromatography purification, and nuclear magnetic resonance methods. RESULTS: The concentration of BGP in the toothpaste was set at 0.0347 w/v%. Compared with the placebo group, the BGP group demonstrated a reduction in the PI score (p < 0.05) but not in the GI score, as well as a reduction in Porphyromonas gingivalis (Pg)/Total bacteria (Tb), Fusobacterium nucleatum (Fn)/Tb, and Aggregatibacter actinomycetemcomitans (Aa)/Tb (p < 0.05) but not in Streptococcus salivalius/Tb. Effect sizes for Pg, Fn and Aa were 0.360, 0.556, and 0.164, respectively. The antibacterial compounds of the BGP-containing toothpaste included a mixture of kaempferide/betuletol. CONCLUSIONS: We confirmed the efficacy of propolis toothpaste with an optimal kaempferide/betuletol ratio for improving oral microbiota, thereby suggesting that BGP toothpaste is clinically useful in maintaining oral health and preventing periodontal disease.

Countercurrent chromatography isolation of green propolis biomarkers: Potential blockers of SARS-COV-2 RBD and ACE2 interaction.

Propolis is a natural resinous mixture produced by honeybees with numerous biological activities. Considering the recently reported potential of propolis as an adjuvant in COVID-19 treatment, a methodology for the fractionation of the hexane extract of Brazilian green propolis (HEGP) was developed for the obtention of prenylated biomarkers by countercurrent chromatography. The inhibition of the interaction between the receptor binding domain (RBD) of spike and ACE2 receptor was evaluated by the Lumitᵀᴹ immunoassay. Fractionation of HEGP was performed by both normal (CCC1 and CCC2, with extended elution) and reversed (CCC3) phase elution-extrusion modes with the solvent system hexane-ethanol-water 4:3:1. The normal elution mode of CCC1 (471 mg HEGP in a 80 mL column volume, 1.6 mm id) was scaled-up (CCC5, 1211 mg HEGP in a 112 mL column volume, 2.1 mm id), leading to the isolation of 89.9 mg of artepillin C, 1; 52.7 mg of baccharin, 2; and 26.6 mg of chromene, with purities of 93 %, 83 % and 88 %, respectively, by HPLC-PDA. Among the isolated compounds, artepillin C, 1, and baccharin, 2, presented the best results in the Lumitᵀᴹ immunoassay, showing 67% and 51% inhibition, respectively, at the concentration of 10 µM. This technique proved to be of low operational cost and excellent reproducibility.

Bioaccessibility and bioavailability of Pb and Cd in rice is affected by propolis and its extracts and Fe intervention.

Increasing the intake of dietary supplements containing antioxidant components can reduce the oral bioavailability of lead (Pb) and cadmium (Cd) and benefit human health. In this study, the effects of propolis and its extracts (kaempferol (KAE), quercetin (QR), and caffeic acid phenethyl ester (CAPE)) in conjunction with proanthocyanidins (PA) on Pb and Cd bioaccessibility (BAC) and the relative bioavailability (RBA) in brown and polished rice are investigated. The results of in vitro tests showed that propolis and its extracts were effective in reducing Pb BAC in both brown and polished rice. A medium dose of PA had a significant reduction effect on Cd BAC (76 %) and RBA in both brown and polished rice. Based on mouse bioassays, the supplementation of propolis and its extracts significantly (p < 0.05) reduced the Pb-RBA in brown rice, resulting in a decrease in Pb RBA from 25 % in the control group to 16.5-17.6 %. The results showed that the BAC and RBA of Pb in brown rice with dietary supplements decreased significantly, which may be related to the enhanced inhibitory effect of high Fe. It was also found that the Pb RBA was negatively correlated with the Fe content in mice kidneys. This result provided evidence that antioxidants better inhibit the bioavailability of heavy metals, highlighting that propolis and PA may be alternative dietary supplements for intervening in human Pb and Cd exposure.

The potential protective effect of propolis on diabetic nephropathy induced by streptozotocin in adult albino rats.

Diabetes mellitus is a common metabolic disorder. It is associated with serious life-threatening complications if not properly managed. The current study aimed at investigating the possible protective role of propolis on streptozotocin-induced diabetic nephropathy. A diabetic rat model was induced by a single intraperitoneal injection of 55 mg/kg streptozotocin. After 4 days, the diabetic rats received oral propolis (300 mg/kg/day) via gastric gavage for 28 days. Biochemical, histopathological and ultrastructural evaluations were performed. The results showed that: streptozotocin-induced diabetes was associated with a marked decrease in the serum high-density lipoproteins and antioxidant enzymes. However, a significant elevation in the levels of serum creatinine, blood urea nitrogen, uric acid, cholesterol, triglycerides and low-density lipoproteins was detected. Furthermore, streptozotocin treatment induced histopathological alterations of the renal cortex; in the form of distorted glomerular capillaries, widened Bowman's space and signs of epithelial tubular degeneration. Ultra-structurally, thickening and irregularity of the glomerular basement membrane and podocytes foot processes effacement were observed. The tubular epithelial cells showed swollen vacuolated mitochondria, scarce basal infoldings and loss of microvilli. Conversely, propolis partially restored the normal lipid profile, antioxidant biomarkers and renal cortical morphology. Propolis exhibited a sort of renoprotection through hypoglycemic, anti-hyperlipidemic and antioxidant effects.

Efficacy of propolis and royal jelly in attenuating cadmium-induced spermatogenesis and steroidogenesis dysregulation, causing infertility in rats.

Bee-derived pharmaceutical products, including propolis (PRO) and royal jelly (ROJ), possess outstanding pharmacological properties. However, their efficiency in counteracting the deleterious influences of cadmium (Cd) in testes and the relevant mechanisms entail further investigations. Therefore, this study sheds light on the therapeutic efficacy of PRO and ROJ against testicular dysfunction and infertility induced by Cd. Toward this end, 30 mature male Wistar albino rats were randomly divided into six groups (5 animals/group), including (I) control, (II) Cd, (III) PRO, (IV) ROJ, (V) PRO + Cd, and (VI) ROJ + Cd groups. Furthermore, antioxidant factors, semen quality, hormonal levels, steroidogenic enzymes, and genotoxicity were assessed. Moreover, histopathological and ultrastructural attributes and offspring rates were investigated. The Cd-treated group revealed marked reductions in reduced glutathione (GSH), total antioxidant capacity (TAC), and superoxide dismutase (SOD) with an amplification of lipid peroxidation in testes, indicating disruption of the antioxidant defense system. Furthermore, myeloperoxidase (MPO) activity and DNA damage were significantly heightened, implying inflammation and genotoxicity, respectively. Moreover, steroidogenic enzymes, including 17ß-Hydroxy Steroid Dehydrogenase 3 (HSD17b3), 3ß-Hydroxy Steroid Dehydrogenase 2 (HSD3b2), 17α-hydroxylase/17,20-lyase (CYP17A1), and steroid 5α-reductase 2 (SRD5A2) were markedly diminished accompanied with disorders in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Besides, spermatozoa quality was reduced, associated with a diminution in the diameter of seminiferous tubules. By contrast, PRO or ROJ significantly protected and/or counteracted the Cd-induced pathophysiological consequences, ameliorating antioxidant and inflammatory biomarkers, steroidogenic enzymes, hormonal levels, and sperm properties, along with lessening DNA impairments. Critically, histological and ultrastructural analyses manifested several anomalies in the testicular tissues of the Cd-administered group, including the Leydig and Sertoli cells and spermatozoa. Conversely, PRO or ROJ sustained testicular tissues' structure, enhancing spermatozoa integrity and productivity. Interestingly, treatment with PRO or ROJ improved fertility indices through offspring rates compared to the Cd-animal group. Our data suggest that PRO is a more effective countermeasure than ROJ against Cd toxicity for securing the delicate testicular microenvironment for spermatogenesis and steroidogenesis.

Effects of short- and long-term use of propolis extracts on liver and kidney in rats.

Propolis is widely used as a supplementary food product for its health benefits. The aim of this study was to determine the effects of commercial propolis extracts on the liver and kidney. Propolis extracts (250 mg/kgbw/day) were administered orally to adult male Wistar albino rats in solvents of ethanol, propylene glycol, water, and olive oil. Liver enzyme levels were determined biochemically in blood samples, and histopathological examinations were performed on the liver. Damage rate in both kidney tissue in the propolis-ethanol extract group increased significantly compared with the other groups after 30 and 90 days of application (p < .05). According to the results, ethanol, used as a common solvent in propolis products, may adversely affect the liver in long-term use. The data indicate that propolis-olive oil extract may be an essential alternative due to its effective and reliable properties.