Search Results (69)

Objective: This study aimed to evaluate the effects of local use of Brazilian Green Propolis (BGP), either as an ethanolic extract (the most common formulation) or incorporated into lipid-based nanostructures, as an adjuvant therapy for non-surgical periodontal treatment in managing experimental periodontitis (EP) in ovariectomized rats. Methods: Fifty-six female Wistar rats underwent bilateral ovariectomies. After 10 weeks, a cotton ligature was placed around the lower first molar and remained in place for two weeks to induce EP. The ligature was removed, and the rats were randomly assigned in the groups NLT (n = 14), SRP (n = 14), SRP-BGPee (n = 14), and SRP-BGPlns (n = 14). In the NLT group, no local treatment was performed. The SRP group received scaling and root planing (SRP), along with irrigation using a physiological saline solution. The SRP-BGPee group underwent SRP and irrigation with ethanolic extract of BGP. The SRP-BGPlns group underwent SRP and irrigation with BGP-loaded lipid nanostructure (BGPlns). Each group received one SRP session followed by four irrigation sessions with the specified solutions, which were conducted immediately after SRP and subsequently after 2, 4, and 6 days. Euthanasia was performed at 7 and 28 days following the removal of the ligatures. The hemimandibles were processed for the following analyses: microtomographic analysis; histological analysis; histometric analysis of the percentage of bone tissue in the furcation region (PBT); and immunohistochemical analysis for tartrate-resistant acid phosphatase activity (TRAP), transforming growth factor beta 1 (TGFβ1), and osteocalcin (OCN). Results: The SRP-BGPlns group demonstrated superior periodontal tissue repair, reduced alveolar bone loss, fewer TRAP-positive cells (at 7 days), and higher levels of immunolabeling for TGFβ1 (at both 7 and 28 days) and OCN (at 28 days) compared to the other experimental groups. Conclusions: The irrigation with BGP is an effective adjuvant therapy for non-surgical periodontal treatment in managing EP in ovariectomized rats. Its application in lipid-based nanostructures proved to be more effective than the ethanolic extract form. Full article

This study presents the first comprehensive characterization of Brazilian propolis residue, revealing its rich content of bioactive compounds, essential nutrients, and volatile substances, showcasing its potential for sustainable utilization. The term “residue” refers to the solid by-product remaining after ethanolic extraction of raw propolis, which is typically discarded, despite retaining significant nutritional value. HPLC-ESI-MS/MS analysis identified significant concentrations of p-coumaric acid (637.80 mg/kg), chlorogenic acid (497.93 mg/kg), kaempferol (295.82 mg/kg), and caffeic acid (115.11 mg/kg); while HPLC-DAD revealed also artepillin-C (56.56 mg/kg), illustrating strong antioxidant properties. Nutritional analyses showed high moisture content (37.08%), protein (12.56%) and dietary fiber (24.2%). Additionally, the mineral profile highlighted potassium (9800 mg/kg), phosphorus (2520 mg/kg), and calcium (2100 mg/kg). Volatile compounds analysis via HS-SPME-GC-MS identified a diverse class of components, predominantly terpenoids such as α-pinene (20.09%) and caryophyllene (9.76%), suggesting potential applications in fragrance and flavor industries. The multifunctional nature of propolis residue aligns with circular economy principles and highlights its value as a resource for diverse applications. Full article

Group A rotavirus (RV) causes gastrointestinal disease in infants worldwide, and there is currently no specific treatment to eliminate the virus. Due to its chemical properties, propolis is a promising compound for improving gastrointestinal infections. This study aimed to evaluate the action of stingless bee propolis against RV. The method involved determining the concentrations of the extracts that do not exhibit cytotoxicity in colon adenocarcinoma cells using the MTT assay and measuring the reduction in infectivity through a focus forming assay. The results showed that stingless bee propolis was non-cytotoxic up to 200 µg/mL. The reduction in RV infectivity exceeded 99% when using propolis from Plebeia droryana and Melipona quadrifasciata. Brazilian stingless bee propolis, whose active components are known for their activity against various viruses, was experimentally tested and demonstrated effective antiviral activity against RV, supporting its potential application as an antiviral agent. Full article

Background/Objectives: Melanoma is one of the most aggressive forms of skin cancer and is frequently associated with the B-Raf⁶⁰⁰E mutation, which constitutively activates the MAPK signaling pathway. Although selective inhibitors such as Vemurafenib offer clinical benefits, their long-term efficacy is often hindered by resistance mechanisms and adverse effects. In this study, twelve phytochemicals from Brazilian green propolis were evaluated for their potential as selective B-Raf⁶⁰⁰E inhibitors using a computational approach. Methods: Physicochemical, ADME, and electronic properties were assessed, followed by molecular docking using the B-Raf⁶⁰⁰E crystal structure (PDB ID: 3OG7). Redocking validation and 500 ns molecular dynamics simulations were performed to investigate the stability of the ligand-protein complexes, and free energy calculations were then computed. Results: Among the tested compounds, Artepillin C exhibited the strongest binding affinity (−8.17 kcal/mol) in docking and maintained stable interactions with key catalytic residues throughout the simulation, also presenting free energy of binding ΔG of −20.77 kcal/mol. HOMO-LUMO and electrostatic potential analyses further supported its reactivity and selectivity. Notably, Artepillin C remained bound within the ATP-binding site, mimicking several critical interactions observed with Vemurafenib. Results: Among the tested compounds, Artepillin C exhibited the strongest binding affinity (−8.17 kcal/mol) and maintained stable interactions with key catalytic residues throughout the simulation. HOMO-LUMO and electrostatic potential analyses further supported its reactivity and selectivity. Notably, Artepillin C remained bound within the ATP-binding site, mimicking several critical interactions observed with Vemurafenib. Conclusions: These findings indicate that Artepillin C is a promising natural compound for further development as a selective B-Raf⁶⁰⁰E inhibitor and suggest its potential utility in melanoma treatment strategies. This study reinforces the value of natural products as scaffolds for targeted drug design and supports continued experimental validation. Full article

Background: Inflammation plays a critical role in the progression of coronary heart disease (CHD). Low-dose colchicine has shown promise in reducing cardiovascular events, and green Brazilian propolis extract (EPP-AF® (standardized Brazilian green propolis extract) was provided by Apis Flora Indl. Coml. Ltda, Ribeirão Preto, SP, Brazil), known for its anti-inflammatory properties, may offer additional therapeutic benefits. This pilot study aimed to evaluate whether six weeks of EPP-AF^® supplementation improves functional capacity assessed by treadmill exercise testing. Methods: This was a randomized, double-blind, placebo-controlled pilot study conducted at a coronary disease clinic in Brazil. Patients aged ≥ 18 years with stable CHD receiving optimized medical therapy were randomized in a 2:1 ratio to receive either 200 mg of EPP-AF^® or placebo twice daily for six weeks. The primary outcome was the change in treadmill exercise duration (in seconds). Secondary outcomes included total exercise time, functional capacity (measured in metabolic equivalents of task [METs]), high-sensitivity C-reactive protein (hs-CRP) levels, the Seattle Angina Questionnaire (SAQ), and the Canadian Cardiovascular Society (CCS) angina classification. Statistical analysis was performed on an intention-to-treat basis. Results: A total of 59 patients were randomized, with a median follow-up of 6.5 weeks. There was no significant difference in the primary endpoint between groups: the median change in treadmill test time was 39 s in the EPP-AF^® group versus 30 s in the placebo group (p = 0.83). No improvements were observed in METs, hs-CRP levels, SAQ scores, or CCS class in the EPP-AF^® group. No major adverse cardiovascular events occurred during the study. Conclusions: EPP-AF^® did not improve functional capacity, inflammatory markers, or angina symptoms in patients with stable CHD compared to placebo. Full article

Brazilian propolis is a natural bee product with a unique and diverse chemical composition. It is especially rich in phenols and terpenoids that show a range of significant biological properties. Due to the growing scientific interest, its strong anti-inflammatory and anticancer activity has been highlighted. In vitro and in vivo studies demonstrate its potential to modulate inflammatory pathways by inhibiting pro-inflammatory cytokines, such as tumour necrosis factor (TNF-α) and interleukin 6 (IL-6), as well as by regulating oxidative stress. Additionally, active compounds in Brazilian propolis have the potential to inhibit tumour cell proliferation, induce apoptosis and modulate the tumour microenvironment. Depending on the botanical source and region of occurrence, different types of Brazilian propolis are distinguished, including green, red and brown, which differ in composition and biological activity. Green propolis, rich in artepilin C and phenolic acids, shows strong anti-inflammatory and anticancer properties. Red propolis contains isoflavones and quercetin that enhance its antioxidant and immunomodulatory activities. Brown propolis, rich in cinnamic acids and benzophenones, exerts cytotoxic effects against certain lines of cancer cells. This article discusses the current state of knowledge on the mechanisms of action of different types of Brazilian propolis and their potential uses as supportive therapy in inflammatory and cancerous diseases in combination with nanotechnology. Full article

Background: The majority of gliomas are astrocytic in nature. Gliomas have the lowest survival rate among all tumors of the central nervous system (CNS), characterized by high aggressiveness and poor response to treatment. The tumor microenvironment is a source of cytokines such as IL-6, IFN-γ, VEGF, and PDGF-BB, secreted mainly by tumor and immune cells. These cytokines play a significant role in angiogenesis, invasion, and metastasis formation. In vitro and in vivo studies have shown that Brazilian green propolis, derived from Baccharis dracunculifolia DC and rich in artepillin C, exhibits anti-inflammatory, antimicrobial, chemopreventive, and anticancer activities. Additionally, it can penetrate the blood–brain barrier, demonstrating neuroprotective effects. The aim of the present study was to determine the concentration of selected cytokines produced by astrocytes of the CCF-STTG1 cell line, isolated from the brain of a patient with stage IV glioma (astrocytoma). Methods: The cytotoxicity of the EEP-B was evaluated using the MTT assay. Astrocytes were stimulated with LPS at a final concentration of 200 ng/mL and/or IFN-α at 100 U/mL, followed by incubation with EEP-B (25–50 µg/mL) and artepillin C (25–50 µg/mL) under 2-h hypoxia and normoxia conditions. Cytokine concentrations were measured using the xMAP Luminex Multiplex Immunoassay and the Multiplex Bead-Based Cytokine kit. Results: The absence of cytotoxic effects of EEP-B and artepillin C on human astrocytes of the CCF-STTG1 lineage was demonstrated. Stimulation with LPS, IFN-α, and their combination (LPS + IFN-α) significantly increased the secretion of the tested cytokines compared to the control cell line. The most pronounced and statistically significant reduction in cytokine levels, particularly IL-6 and VEGF, was observed following EEP-B treatment at both tested concentrations under both hypoxic and normoxic conditions. Conclusions: Brazilian green propolis may serve as a potential immunomodulator in combination therapies for gliomas of varying malignancy grades. Full article

Propolis is a valuable natural resource for extracting various beneficial compounds. This study explores a sustainable extraction approach for Brazilian green propolis. First, supercritical fluid extraction (SFE) process parameters were optimized (co-solvent: 21.11% v/v CPME, and temperature: 60 °C) to maximize yield, total phenolic content (TPC), antioxidant capacity, and LOX (lipoxygenase) inhibitory activity. GC–MS analysis identified 40 metabolites in SFE extracts, including fatty acids, terpenoids, phenolics, and sterols. After selecting the optimum SFE process parameters, a sequential high-pressure extraction (HPE) approach was developed, comprising SFE, pressurized liquid extraction (PLE) with EtOH/H₂O, and subcritical water extraction (SWE). This process was compared to a similar sequential extraction using low-pressure extractions (LPE) with a Soxhlet extractor. The HPE process achieved a significantly higher overall yield (80.86%) than LPE (71.43%). SFE showed higher selectivity, resulting in a lower carbohydrate content in the non-polar fraction, and PLE extracted nearly twice the protein amount of LPE–2. Despite the HPE selectivity, LPE extracts exhibited better acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and LOX inhibition, demonstrating that the neuroprotective and anti-inflammatory activity of the extracts may be associated with a symbiosis of a set of compounds. Finally, a comprehensive greenness assessment revealed that the HPE process proved more sustainable and aligned with green chemistry principles than the LPE method. Full article

Green propolis, particularly from the unique flora of the Brazilian Caatinga biome, has gained significant interest due to its diverse chemical composition and biological activities. This study focuses on the chemical characterization and antimicrobial evaluation of Caatinga green propolis. Twelve compounds were isolated through different chromatographic techniques, including flavanones (naringenin, 7-O-methyleriodictyol, sakuranetin), flavones (hispidulin, cirsimaritin), flavonols (quercetin, quercetin-3-methyl ether, kaempferol, 6-methoxykaempferol, viscosine, penduletin), and one chalcone (kukulkanin B). Using liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (LC-QToF-MS), a total of 55 compounds excluding reference standards were tentatively identified, which include flavonoids, phenolic acids derivatives, and alkaloids, with flavonols, flavanones, and flavones being predominant. Antimicrobial testing against pathogens revealed that the crude extract exhibited low inhibitory activity, against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) (IC₅₀: 148.4 and 120.98 µg/mL, respectively). Although the isolated compounds showed limited individual activity, a fraction containing sakuranetin and penduletin (Fraction 8) exhibited moderated activity against Cryptococcus neoformans (IC₅₀: 47.86 µg/mL), while a fraction containing quercetin and hispidulin showed moderated activity against VRE (IC₅₀: 16.99 µg/mL). These findings highlight the potential application of Caatinga green propolis as an antimicrobial agent, particularly against resistant bacterial strains, and underscore the importance of synergistic interactions between compounds in enhancing biological effects. Full article

This study evaluates the antimicrobial, antioxidant, and anticancer effects of Brazilian red propolis extract (BRPE) and its nanoencapsulated form (NCBRPE) to address bacteria and conditions associated with the ovarian cancer microenvironment. The NCBRPE showed an average size of 178.3 ± 3.3 nm, a polydispersity index (PdI) of 0.06, and an encapsulation efficiency exceeding 97% for the main bioactive compounds of propolis. Antimicrobial assays revealed that BRPE exhibited minimum inhibitory concentrations (MICs) ranging from 4 to 256 mg/L against seven bacterial strains, while NCBRPE demonstrated sustained efficacy, with a biofilm inhibitory concentration (BIC) of 128 mg/L against Burkholderia cepacia. In clonogenic assays, NCBRPE reduced long-term cancer cell proliferation, achieving a 10-fold decrease in colony formation compared to untreated controls, significantly outperforming BRPE. Flow cytometry indicated that NCBRPE induced apoptosis in 29% ± 0.4 of ovarian cancer cells (OVCAR-3). Additionally, the DPPH assay confirmed the antioxidant activity of NCBRPE, demonstrating that it retained most of the extract’s original antioxidant capacity. This was further supported by oxidative burst assays, which showed a significant reduction in reactive oxygen species (ROS) production in neutrophils. These findings position NCBRPE as a multi-functional therapeutic candidate for managing infections, oxidative stress, and tumor progression in the ovarian cancer microenvironment. Full article

Background/Objectives: Treating chronic wounds incurs substantial costs for Brazil’s Unified Health System. Natural compounds, particularly propolis, are increasingly explored as low-cost alternatives due to their healing properties. Brazilian green propolis, distinct in its chemical composition, has garnered scientific interest. This study aimed to assess the healing effects of green propolis ointment on lower-limb ulcers from leprosy. Methods: A blinded, randomized clinical trial included 18 wounds in two groups: propolis ointment (G1) and control (G2), with evaluations conducted weekly for 61 days. Wound progress was monitored using morphometry and the Pressure Ulcer Scale for Healing (PUSH). Results: No participants exhibited sensitivity to the propolis. G1 showed significant initial healing: average wound area reduction (%) for G1 vs. G2 included 56.38 vs. 6.13–p < 0.001 (week 1); 79.51 vs. 24.16–p = 0.022 (week 4); and 84.33 vs. 39.73–p = 0.051 (week 7). In G1, the PUSH scores decreased from the beginning, whereas in G2, reductions were observed after three weeks. By week 5, 71.4% of G1 wounds scored below eight points, versus 33.3% in G2. G1 wounds exhibited a reduced area and exudate, as well as revitalized granulation tissue without adverse effects. Conclusions: The findings suggest that green propolis ointment is safe, supports tissue repair and may offer cost-effective treatment benefits. Standard wound dressings are selected to support all healing stages, with an emphasis on antimicrobial action, hemostasis to reduce exudate, and pain-reducing and non-irritant properties. Green propolis ointment meets these criteria, offering a cost-effective treatment that accelerates lesion reduction and encouraging leprosy patients to follow the therapeutic regimen. Full article

Background/Objectives: Brazilian red propolis has attracted attention for its pharmacological properties. However, signs of toxicity were recently observed in long-term studies using the hydroalcoholic extract of red propolis (RPHE), likely due to polyprenylated benzophenones. This study aimed to develop a benzophenone-free red propolis extract (BFRP) and validate an HPLC-PDA method to quantify its main constituents: isoliquiritigenin, vestitol, neovestitol, medicarpine, and 7-O-methylvestitol. Methods: BFRP’s toxicity was assessed in zebrafish larvae through a vibrational startle response assay (VSRA) and morphological analysis. Genotoxicity was evaluated using the micronucleus test in rodents, and the extract’s effects on chemically induced preneoplastic lesions in rat colon were studied. An HPLC-PDA method was used to quantify BFRP’s main compounds. Results: BFRP primarily contained vestitol (128.24 ± 1.01 μg/mL) along with isoliquiritigenin, medicarpin, neovestitol, and 7-O-methylvestitol. Zebrafish larvae exposed to 40 µg/mL of BFRP exhibited toxicity, higher than the 10 µg/mL for RPHE, though no morphological differences were found. Fluorescent staining in the notochord, branchial arches, and mouth was observed in larvae treated with both BFRP and RPHE. No genotoxic or cytotoxic effects were observed up to 2000 mg/kg in rodents, with no impact on hepatotoxicity or nephrotoxicity markers. Chemoprevention studies showed a 41.6% reduction in preneoplastic lesions in rats treated with 6 mg/kg of BFRP. Conclusions: These findings indicate that BFRP is a safe, effective propolis-based extract with potential applications for human health, demonstrating reduced toxicity and chemopreventive properties. Full article

Artepillin C, drupanin, and plicatin B are prenylated phenylpropanoids that naturally occur in Brazilian green propolis. In this study, these compounds and eleven of their derivatives were synthesized and evaluated for their in vitro antimicrobial activity against a representative panel of oral bacteria in terms of their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Plicatin B (2) and its hydrogenated derivative 8 (2′,3′,7,8-tetrahydro-plicatin B) were the most active compounds. Plicatin B (2) displayed strong activity against all the bacteria tested, with an MIC of 31.2 μg/mL against Streptococcus mutans, S. sanguinis, and S. mitis. On the other hand, compound 8 displayed strong activity against S. mutans, S. salivarius, S. sobrinus, Lactobacillus paracasei (MIC = 62.5 μg/mL), and S. mitis (MIC = 31.2 μg/mL), as well as moderate activity against Enterococcus faecalis and S. sanguinis (MIC = 125 μg/mL). Compounds 2 and 8 displayed bactericidal effects (MBC: MIC ≤ 4) against all the tested bacteria. In silico studies showed that the complexes formed by compounds 2 and 8 with the S. mitis, S. sanguinis, and S. mutans targets (3LE0, 4N82, and 3AIC, respectively) had energy score values similar to those of the native S. mitis, S. sanguinis, and S. mutans ligands due to the formation of strong hydrogen bonds. Moreover, all the estimated physicochemical parameters satisfied the drug-likeness criteria without violating the Lipinski, Veber, and Egan rules, so these compounds are not expected to cause problems with oral bioavailability and pharmacokinetics. Compounds 2 and 8 also had suitable ADMET parameters, as the online server pkCSM calculates. These results make compounds 2 and 8 good candidates as antibacterial agents against oral bacteria. Full article

Helicobacter pylori is associated with gastrointestinal diseases, and its treatment is challenging due to antibiotic-resistant strains, necessitating alternative therapies. Brazilian red propolis (BRP), known for its diverse bioactive compounds with pharmaceutical properties, was investigated for its anti-H. pylori activity, focusing on biofilm formation inhibition and eradication. BRP was tested against H. pylori (ATCC 43526) using several assays: time–kill, nucleotide leakage, biofilm formation inhibition (determining the minimum inhibitory concentration of biofilm of 50%—MICB₅₀, and cell viability), and biofilm eradication (determining the minimum eradication concentration of biofilm of 99.9%—MBEC). Standardization of H. pylori biofilm formation was also conducted. In the time–kill assay, BRP at 50 µg/mL eliminated all H. pylori cells after 24 h. The nucleotide leakage assay showed no significant differences between control groups and BRP-treated groups at 25 µg/mL and 50 µg/mL. H. pylori formed biofilms in vitro at 10⁹ CFU/mL after 72 h. The MICB₅₀ of BRP was 15.6 µg/mL, and at 500, 1000, and 2000 µg/mL, BRP eradicated all bacterial cells. The MBEC was 2000 µg/mL. These findings suggest that BRP has promising anti-H. pylori activity, effectively inhibiting and eradicating biofilms. Further studies are necessary to elucidate BRP’s mechanisms of action against H. pylori. Full article

Propolis is a resinous bee product with a very complex composition, which is dependent upon the plant sources that bees visit. Due to the promising antimicrobial activities of red Brazilian propolis, it is paramount to identify the compounds responsible for it, which, in most of the cases, are not commercially available. The aim of this study was to develop a quick and clean preparative-scale methodology for preparing fractions of red propolis directly from a complex crude ethanol extract by combining the extractive capacity of counter-current chromatography (CCC) with preparative HPLC. The CCC method development included step gradient elution for the removal of waxes (which can bind to and block HPLC columns), sample injection in a single solvent to improve stationary phase stability, and a change in the mobile phase flow pattern, resulting in the loading of 2.5 g of the Brazilian red propolis crude extract on a 912.5 mL Midi CCC column. Three compounds were subsequently isolated from the concentrated fractions by preparative HPLC and identified by NMR and high-resolution MS: red pigment, retusapurpurin A; the isoflavan 3(R)-7-O-methylvestitol; and the prenylated benzophenone isomers xanthochymol/isoxanthochymol. These compounds are markers of red propolis that contribute to its therapeutic properties, and the amount isolated allows for further biological activities testing and for their use as chromatographic standards. Full article