Bioactives of Melipona rufiventris Propolis: Exploring its Antimicrobial, Anti-Inflammatory, and Antioxidant Activities.

This study explores the potential of propolis, a resinous substance produced by bees, from Melipona rufiventris species. With its composition encompassing resin, wax, pollen, and soil, propolis holds historical significance in traditional medicine within tropical regions. This research is driven by the scarcity of information surrounding M. rufiventris propolis, prompting an investigation into its chemical constituents, in vivo toxicity, and antimicrobial, antioxidant, and anti-inflammatory properties. This exploration could potentially uncover novel applications for this natural product, bolstering both meliponiculture practices and the preservation of native bee populations. The propolis was sampled in Cabo Verde-MG and underwent ethanolic extraction to yield an extract (EEP) for analysis. Chemical assessments (Folin-Ciocalteau, and UHPLC-HRMS) revealed the presence of polyphenols, including flavonoids. The EEP demonstrated higher antimicrobial activity against Gram-positive bacteria and exhibited efficacy against multiresistant strains isolated from complex wounds. Synergistic interactions with commercial antibiotics were also observed. Furthermore, anti-inflammatory evaluations showcased the EEP's potential in reducing NF-kB activation and TNF-α release at non-toxic concentrations. Despite these promising biological activities, the EEP exhibited no antiproliferative effects and demonstrated safety in both the MTS assay and the G. mellonella model. Collectively, these findings highlight the M. rufiventris propolis extract as a valuable reservoir of bioactive compounds with multifaceted potential.

Evaluation of a Standardized Extract Obtained from Cashew Apple (Anacardium occidentale L.) Bagasse in DSS-Induced Mouse Colitis.

Inflammatory bowel diseases (IBD) include Crohn's disease and ulcerative colitis. Several studies relate eating habits to different aspects of IBD, such as progression and worsening of the clinical condition. Therefore, many natural products (NPs) such as polyphenols and carotenoids have been identified as promising agents in supporting IBD. An interesting source for obtaining bioactive NPs is the by-products of the food industry. The present study evaluated the potential beneficial effect of a standardized extract (CAE) obtained from cashew apple bagasse in the dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice. This was the first time that CAE had been evaluated in this experimental model. Chemical evaluation of CAE identified carotenoids (96.28 ± 0.15 mg/100 g), phenolic compounds (37.49 ± 0.64 mg/100 g), and a mixture of anacardic acids (C15:3 = 94.2 ± 0.6 mg/100 g; C15:2 = 108.4 ± 0.1 mg/100 g; C15:1 = 214.8 ± 0.2 mg/100 g). Administration of CAE (500 mg/kg, 4 days, p.o.) after DSS challenge was more effective in delaying disease progression compared with prior treatment (500 mg/kg, 30 days, p.o.), according to the disease activity index. However, no treatment strategy with CAE was able to prevent or inhibit disease progression, since all parameters evaluated (macroscopic, biochemical, and histopathological) in CAE-treated animals were similar to those observed in DSS-challenged animals. Despite the high dose (500 mg/kg), the standardized extract (CAE) did not result in an effective concentration of carotenoids. Furthermore, as some anacardic acids have been reported as histone acetyltransferases inhibitors, there could be a possible antagonistic relationship between carotenoids and anacardic acids. Complementary research will be necessary to test the hypothesis of antagonism. Thus, an optimized extract, with an even higher concentration of carotenoids, obtained from cashew apple bagasse, can be developed as a possible adjuvant food supplement for inflammatory bowel diseases.

Phenolic profile and potential beneficial effects of underutilized Brazilian native fruits on scavenging of ROS and RNS and anti-inflammatory and antimicrobial properties.

Brazilian native fruits (BNF) have aroused interest of researchers and consumers for their great human health benefits. In this study, five BNF (Byrsonima lancifolia, Campomanesia phaea, Jacaratia spinosa, Solanum alternatopinnatum and Acnistus arborescens) were tested for their polyphenolic compounds by LC-ESI-MS/MS, reactive species deactivation (ROO˙, O2˙-, HOCl and NO˙), anti-inflammatory properties in vivo, and in vitro antimicrobial activity - with determination of putative mechanism(s) of action. Eighty-one polyphenols were identified, which exhibited a significant capacity to deactivate both ROS and RNS. C. phaea extract had the highest capacity to scavenge ROO˙ (68.94 µmol TE per g), O2˙- (IC50: 575.36 µg mL-1) and NO˙ (IC50: 16.96 µg mL-1), which may be attributed to the presence of ellagitanins. B. lancifolia decreased neutrophil influx into the peritoneal cavity of mice by 50% as compared to carrageenan and reduced Candida albicans biofilm viability by 3 log10 possibly due to complexation with cell membrane ergosterol. In summary, the BNF presented herein are good sources of bioactive compounds with positive effects on deactivation of biological reactive species, as well as with anti-inflammatory and antimicrobial activities, which can be altogether highly beneficial to human health.

Diacetylcurcumin: a new photosensitizer for antimicrobial photodynamic therapy in Streptococcus mutans biofilms.

This study evaluated the effect of antimicrobial photodynamic therapy (aPDT) on S. mutans using diacetylcurcumin (DAC) and verified DAC toxicity. In vitro, S. mutans biofilms were exposed to curcumin (CUR) and DAC and were light-irradiated. Biofilms were collected, plated and incubated for colony counts. DAC and CUR toxicity assays were conducted with Human Gingival Fibroblast cells (HGF). In vivo, G. mellonella larvae were injected with S. mutans and treated with DAC, CUR and aPDT. The hemolymph was plated and incubated for colony counts. Significant reductions were observed when DAC and CUR alone were used and when aPDT was applied. HGF assays demonstrated no differences in cell viability for most groups. DAC and CUR reduced the S. mutans load in G. mellonella larvae both alone and with aPDT. Systematic toxicity assays on G. mellonella demonstrated no effect of DAC and CUR or aPDT on the survival curve.

Anadenanthera Colubrina vell Brenan: anti-Candida and antibiofilm activities, toxicity and therapeutical action.

We evaluated the antifungal and antibiofilm potential of the hydroalcoholic extract of bark from Anadenanthera colubrina (vell.) Brenan, known as Angico, against Candida spp. Antifungal activity was evaluated using the microdilution technique through the Minimum Inhibitory and Fungicide Concentrations (MIC and MFC). The antibiofilm potential was tested in mature biofilms formed by Candida species and analyzed through the counting of CFU/mL and scanning electron micrograph (SEM). In vivo toxicity and therapeutic action was evaluated in the Galleria mellonella model. The treatment with the extract, in low doses, was able to reduce the growth of planktonic cells of Candida species. MIC values range between 19.5 and 39 µg/mL and MFC values range between 79 and 625 µg/mL. In addition was able to reduce the number of CFU/mL in biofilms and to cause structural alteration and cellular destruction, observed via SEM. A. colubrina showed low toxicity in the in vivo assay, having not affected the viability of the larvae at doses below 100mg/kg and high potential in the treatment of C. albicans infection. Considering its high antifungal potential, its low toxicity and potential to treatment of infections in in vivo model, A. colubrina extract is a strong candidate for development of a new agent for the treatment of oral candidiasis.

Comprehensive characterization of bioactive phenols from new Brazilian superfruits by LC-ESI-QTOF-MS, and their ROS and RNS scavenging effects and anti-inflammatory activity.

Brazilian native fruits (BNF) remain unexplored and underutilized resources with a high potential to improve human health and wellness. In our study, five new BNF (Eugenia stipitata, Sageretia elegans, Byrsonima arthropoda, Spondias mombin andRubus rosaefolius)were evaluated for their phenolic composition by LC-ESI-QTOF-MS; and for their ROS and RNS scavenging effects (ROO, O2-, NO, HOCl); in vivo anti-inflammatory activity (neutrophil migration); and in vivo acute toxicity in Galleria mellonella. Eighty-six phenolic compounds were identified, including hydroxybenzoic acids, hydroxycinnamic acids, flavonoids, anthocyanins and ellagitannins, several of which had never been reported in BNF. The BNF exhibited high antioxidant effects against biologically relevant radicals, and treated animals showed decreased neutrophil influx and NF-kB activation. Thus, these BNF are good sources of antioxidant and anti-inflammatory molecules that can be beneficial for human health as functional foods. Based on their bioactivity, they can be considered as new Brazilian superfruits.

Bioprospection of Eugenia brasiliensis, a Brazilian native fruit, as a source of anti-inflammatory and antibiofilm compounds.

The anti-inflammatory and antibiofilm activities as well as toxicity and chemical profile of Eugenia brasiliensis pulp extract (EBE), were evaluated. EBE chemical profile and phenolic content were determined by LC-MS/MS. EBE was tested for its in vitro and in vivo anti-inflammatory activity, including TNF-α release, NF-кB activation, neutrophil migration and paw edema. The MIC/MBC and antibiofilm activities were tested against methicillin sensitive and resistant Staphylococcus aureus, Escherichia coli, Pseudomona aeruginosa, Streptococcus mutans, and Lactobacillus acidophilus. EBE acute toxicity was evaluated in Galleria mellonella and RAW 264.7 macrophage. EBE total phenolic content was 389.88 ±â€¯3.48 mg GAE/g with identified polyphenols. EBE decreased TNF-α release in vivo and in vitro, NF-кB activation, neutrophil influx into peritoneal cavity, and it showed maximal inhibition of paw edema after 2 h. MIC of EBE ranged from 62.5-500 µg/mL while MBC values were >500 µg/mL, with a decrease in L. acidophilus biofilm formation. EBE showed negligible toxicity in larvae and macrophage cells. Our findings open new perspectives concerning EBE application as source of anti-inflammatory and antibiofilm molecules as a functional food, pharmaceutical lead or agribusiness commodity.

Isoflavonoids from Brazilian red propolis down-regulate the expression of cancer-related target proteins: A pharmacogenomic analysis.

Vestitol and neovestitol are bioactive isoflavonoids isolated from Brazilian red propolis, a unique Apis melifera type of propolis botanically originated from Dalbergia ecastophyllum. Although these molecules have relevant biological effects, including anticancer and immunomodulatory activities, their mechanism(s) of action and the affected pathways remain largely unknown. Here, we carried out a pharmacogenomic analysis to investigate the effects of vestitol and neovestitol on the whole-genome expression in human tumor cells, particularly cancer-related target proteins. HeLa cells were exposed to the compounds at IC20 and genomic information of treated cells was analyzed using the Illumina transcriptome system and GeneGo MetaCore software. Our results showed that vestitol (IC20  = 214.7 µM) reduced the expression of genes enrolled with the alpha tubulin (fold -3.7), tubulin in microtubules (fold -3.7), and histone h3 (fold = -3.03), and that treatment with neovestitol (IC20  = 102.91 µM) downregulated prostaglandin E synthase gene (fold = -3.12), which are considered ideal targets for anticancer therapy. These data open avenues for the study of vestitol and neovestitol as potential promising candidates for anticancer therapy. Toxicological, non-clinical, and clinical validation of the findings presented herein is needed.

Unexplored endemic fruit species from Brazil: Antibiofilm properties, insights into mode of action, and systemic toxicity of four Eugenia spp.

Brazilian endemic fruit species have aroused attention due to their highly valuable, yet unexplored, agro-industrial, food and therapeutic potential. Herein, we describe the antifungal activity of four Eugenia spp. against Candida albicans biofilms, and further demonstrate insights into their potential mode(s) of action and toxicity in vitro and in vivo. Extracts from different parts (seeds, pulps, leaves) of E. leitonii (EL), E. brasiliensis (EB), E. myrcianthes (EM) and E. involucrata (EI) were obtained (S23°23',W45°39') and chemically characterized by GC/MS. The active extracts were tested against C. albicans biofilm viability and architecture, as well as mode of action, and toxicology using RAW 264.7 macrophages and Galleria mellonella larvae. The MIC values ranged from 15.62 to >2000 µg/mL. The most active extracts were EL (seed, 15.62 µg/mL) and EB (leaf and seeds, 31.25 and 15.62 µg/mL, respectively). Treatment with these extracts at 10xMIC reduced biofilm viability by 54-55% (P < 0.0001) as compared to 42% by nystatin. At 10xMIC, all extracts caused damages to biofilm architecture and integrity, and fewer hyphae remained attached to treated biofilms. None of them was found to interfere with cell wall biosynthesis or complexation with ergosterol. The extracts had low toxicity against macrophages in vitro (P > 0.05) and G. mellonella larvae, with mean in vivo LD50 of 1500 mg/kg (EL, seeds); 2500 mg/kg (EB, seeds); and 1250 mg/kg (EB, leaf). The phenolic compounds epicatechin and gallic acid were the major constituents in the extracts. Our findings may open avenues for the application of these yet unexplored native fruits in the food and pharmaceutical industry.

Antioxidant and Anti-Inflammatory Activities of Unexplored Brazilian Native Fruits.

Brazilian native fruits are unmatched in their variety, but a poorly explored resource for the development of food and pharmaceutical products. The aim of this study was to evaluate the phenolic composition as well as the antioxidant and anti-inflammatory activities of the extracts of leaves, seeds, and pulp of four Brazilian native fruits (Eugenia leitonii, Eugenia involucrata, Eugenia brasiliensis, and Eugenia myrcianthes). GC-MS analyses of the ethanolic extracts showed the presence of epicatechin and gallic acid as the major compounds in these fruits. Antioxidant activity was measured using synthetic DPPH free-radical scavenging, ß-carotene bleaching assay, and reactive oxygen species (ROO·, O2·-, and HOCl). The fruit extracts also exhibited antioxidant effect against biologically relevant radicals such as peroxyl, superoxide, and hypochlorous acid. In general, the pulps were the fruit fractions that exhibited the lowest antioxidant activities, whereas the leaves showed the highest ones. The anti-inflammatory activity was assessed in an in vivo model using the carrageenan-induced neutrophil migration assay, which evaluates the inflammatory response in the acute phase. The pulp, seeds, and leaves of these fruits reduced the neutrophil influx by 40% to 64%. Based on these results, we suggest that the anti-inflammatory activity of these native fruits is related to the modulation of neutrophil migration, through the inhibition of cytokines, chemokines, and adhesion molecules, as well as to the antioxidant action of their ethanolic extracts in scavenging the free-radicals released by neutrophils. Therefore, these native fruits can be useful to produce food additives and functional foods.