Characterization of GQA as a novel ß-lactamase inhibitor of CTX-M-15 and KPC-2 enzymes.

ß-lactam resistance is a significant global public health issue. Outbreaks of bacteria resistant to extended-spectrum ß-lactams and carbapenems are serious health concerns that not only complicate medical care but also impact patient outcomes. The primary objective of this work was to express and purify two soluble recombinant representative serine ß­lactamases using Escherichia coli strain as an expression host and pET101/D as a cloning vector. Furthermore, a second objective was to evaluate the potential, innovative, and safe use of galloylquinic acid (GQA) from Copaifera lucens as a potential ß-lactamase inhibitor.In the present study, blaCTX-M-15 and blaKPC-2 represented genes encoding for serine ß-lactamases that were cloned from parent isolates of E. coli and K. pneumoniae, respectively, and expression as well as purification were performed. Moreover, susceptibility results demonstrated that recombinant cells became resistant to all test carbapenems (MICs; 64-128 µg/mL) and cephalosporins (MICs; 128-512 µg/mL). The MICs of the tested ß-lactam antibiotics were determined in combination with 4 µg/mL of GQA, clavulanic acid, or tazobactam against E. coli strains expressing CTX-M-15 or KPC-2-ß-lactamases. Interestingly, the combination with GQA resulted in an important reduction in the MIC values by 64-512-fold to the susceptible range with comparable results for other reference inhibitors. Additionally, the half-maximal inhibitory concentration of GQA was determined using nitrocefin as a ß-lactamase substrate. Data showed that the test agent was similar to tazobactam as an efficient inhibitors of the test enzymes, recording smaller IC50 values (CTX-M-15; 17.51 for tazobactam, 28.16 µg/mL for GQA however, KPC-2; 20.91 for tazobactam, 24.76 µg/mL for GQA) compared to clavulanic acid. Our work introduces GQA as a novel non-ß-lactam inhibitor, which interacts with the crucial residues involved in ß-lactam recognition and hydrolysis by non-covalent interactions, complementing the enzyme's active site. GQA markedly enhanced the potency of ß-lactams against carbapenemase and extended-spectrum ß-lactamase-producing strains, reducing the MICs of ß-lactams to the susceptible range. The ß-lactamase inhibitory activity of GQA makes it a promising lead molecule for the development of more potent ß-lactamase inhibitors.

Larvicidal Activity of Constituents from the Main Brazilian Propolis Types: Green, Red, and Brown against Aedes aegypti.

In search of environmentally benign and mammalian-friendly mosquito-mitigating compounds, we conducted an investigation into the constituents isolated from Brazilian red, brown, and green propolis. Additionally, we synthetically modified active constituents to explore the role of lipophilicity in enhancing their larvicidal activity. Honeybees collect plant resins from their habitats, mix them with saliva, and utilize them to seal their beehives. The constituents present in propolis exhibit a unique composition specific to the geographical location and the fauna of the region. As part of the plant's natural defense mechanism, propolis compounds demonstrate antibacterial, insecticidal, and phytotoxic properties. Given that several insecticides target the enzyme acetylcholinesterase, we conducted in silico studies to examine the interactions between propolis compounds and acetylcholinesterase through molecular docking. In this study, we present the mosquito larvicidal activities of propolis constituents.

Rational design of solid lipid-polymer hybrid nanoparticles: An innovative glycoalkaloids-carrier with potential for topical melanoma treatment.

Despite the promising potential of Solanum plant glycoalkaloids in combating skin cancer, their clinical trials have been halted due to dose-dependent toxicity and poor water solubility. In this study, we present a rational approach to address these limitations and ensure colloidal stability of the nanoformulation over time by designing solid lipid-polymer hybrid nanoparticles (SLPH). Leveraging the biocompatible and cationic properties of polyaspartamides, we employed a new polyaspartamide derivative (P1) as a raw material for this class of nanostructures. Subsequently, we prepared SLPH through a one-step process involving hot-melt emulsification followed by ultrasonication. The physicochemical properties of the SLPH were thoroughly characterized using dynamic light scattering (DLS), ζ-potential analysis, nanoparticle tracking analysis (NTA), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). The optimized formulation exhibited long-term stability over six months under low temperatures, maintaining a particle size around 200 nm, a polydispersity index (PdI) lower than 0.2, and a ζ-potential between +35-40 mV. Furthermore, we evaluated the cytotoxic effect of the SLPH against human cutaneous melanoma cells (SK-MEL-28) compared to human foreskin fibroblast cells (HFF-1). Encapsulation of glycoalkaloids into the nanoparticles (SLPH-GE) resulted in a two-fold greater selective cytotoxic profile for melanoma cells than glycoalkaloids-free (GE). The nanoparticles disrupted the stratum corneum barrier with a penetration depth of approximately 77 µm. These findings underscore the potential of the developed nanosystem as an effective glycoalkaloid carrier with suitable colloidal and biological properties for further studies in topical treatment strategies for cutaneous melanoma.

A validated ultra-performance liquid chromatography with tandem mass spectrometry method for the quantification of Brazilian green propolis main compounds.

Brazilian green propolis is used in folk medicine because of its various biological properties. The hydroalcoholic extract of Brazilian green propolis is characteristic for possessing several pharmacological properties. Phytochemical investigations have attributed some of these properties to the presence of compounds, which were chosen as analytical markers. This paper reports the development and analytical validation using UPLC-MS/MS in MRM mode. Veratraldehyde was used as an internal standard in qualitative and quantitative analyses of the extracts. Relative standard deviation values obtained for intra-day and inter-day precision were lower than 4%. Of the five parameters for robustness, wavelength detection and flow rate were the critical ones. Limits of detection and quantification ranged from 0.300 to 39.500 ng.mL-1 and from 1.400 to 85.00 ng.mL-1, respectively. The recoveries were between 94.00 and 119.00%, with relative standard deviation values around 5.0%. The developed method is precise, sensitive, and reliable for analysing Brazilian green propolis.

In vitro Evaluation of the Antileishmanial and Antischistosomal Activities of p-Coumaric Acid Prenylated Derivatives.

We have evaluated eight p-coumaric acid prenylated derivatives in vitro for their antileishmanial activity against Leishmania amazonensis promastigotes and their antischistosomal activity against Schistosoma mansoni adult worms. Compound 7 ((E)-3,4-diprenyl-4-isoprenyloxycinnamic alcohol) was the most active against L. amazonensis (IC50=45.92 µM) and S. mansoni (IC50=64.25 µM). Data indicated that the number of prenyl groups, the presence of hydroxyl at C9, and a single bond between C7 and C8 are important structural features for the antileishmanial activity of p-coumaric acid prenylated derivatives.

Copaifera langsdorffii Oleoresin-Loaded Nanostructured Lipid Carrier Emulgel Improves Cutaneous Healing by Anti-Inflammatory and Re-Epithelialization Mechanisms.

The skin is essential to the integrity of the organism. The disruption of this organ promotes a wound, and the organism starts the healing to reconstruct the skin. Copaifera langsdorffii is a tree used in folk medicine to treat skin affections, with antioxidant and anti-inflammatory properties. In our study, the oleoresin of the plant was associated with nanostructured lipid carriers, aiming to evaluate the healing potential of this formulation and compare the treatment with reference drugs used in wound healing. Male Wistar rats were used to perform the excision wound model, with the macroscopic analysis of wound retraction. Skin samples were used in histological, immunohistochemical, and biochemical analyses. The results showed the wound retraction in the oleoresin-treated group, mediated by α-smooth muscle actin (α-SMA). Biochemical assays revealed the anti-inflammatory mechanism of the oleoresin-treated group, increasing interleukin-10 (IL-10) concentration and decreasing pro-inflammatory cytokines. Histopathological and immunohistochemical results showed the improvement of re-epithelialization and tissue remodeling in the Copaifera langsdorffii group, with an increase in laminin-γ2, a decrease in desmoglein-3 and an increase in collagen remodeling. These findings indicate the wound healing potential of nanostructured lipid carriers associated with Copaifera langsdorffii oleoresin in skin wounds, which can be helpful as a future alternative treatment for skin wounds.

Polyalthic Acid from Copaifera lucens Demonstrates Anticariogenic and Antiparasitic Properties for Safe Use.

This study aimed at evaluating the potential of Copaifera lucens, specifically its oleoresin (CLO), extract (CECL), and the compound ent-polyalthic acid (PA), in combating caries and toxoplasmosis, while also assessing its toxicity. The study involved multiple assessments, including determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against cariogenic bacteria. CLO and PA exhibited MIC and MBC values ranging from 25 to 50 µg/mL, whereas CECL showed values equal to or exceeding 400 µg/mL. PA also displayed antibiofilm activity with minimum inhibitory concentration of biofilm (MICB50) values spanning from 62.5 to 1000 µg/mL. Moreover, PA effectively hindered the intracellular proliferation of Toxoplasma gondii at 64 µg/mL, even after 24 h without treatment. Toxicological evaluations included in vitro tests on V79 cells, where concentrations ranged from 78.1 to 1250 µg/mL of PA reduced colony formation. Additionally, using the Caenorhabditis elegans model, the lethal concentration (LC50) of PA was determined as 1000 µg/mL after 48 h of incubation. Notably, no significant differences in micronucleus induction and the NDI were observed in cultures treated with 10, 20, or 40 µg/mL of CLO. These findings underscore the safety profile of CLO and PA, highlighting their potential as alternative treatments for caries and toxoplasmosis.

Brazilian red propolis extract free and encapsulated into polymeric nanoparticles against ovarian cancer: formulation, characterisation and biological assays in 2D and 3D models.

Cancer incidence worldwide is alarming and among the cancers that affect women ovarian cancer is the most fatal. Many side effects are associated with conventional therapies and none of them are completely effective, so the development of new treatments is necessary. Brazilian red propolis extract is a natural product with complex composition and great potential for cancer treatment. However, its clinical application is harmed due to unfavourable physicochemical characteristics. To enable its application encapsulation in nanoparticles can be used. OBJECTIVES: The aims of this work were to develop polymeric nanoparticles with Brazilian red propolis extract and compare their action with the free extract against ovarian cancer cells. METHODS: Box Behnken design was used and nanoparticles were characterised using the techniques dynamic light scattering, nanoparticle tracking analysis, transmission electron microscopy, differential scanning calorimetry and encapsulation efficiency. Activity against OVCAR-3 was also tested on 2D and 3D models. KEY FINDINGS: Nanoparticles' sizes were ~200 nm with monomodal size distribution, negative zeta potential, spherical shape and with extract molecularly dispersed. Encapsulation efficiency was above 97% for the biomarkers chosen. Nanoparticles had greater efficacy in comparison with free propolis in OVCAR-3. CONCLUSIONS: So far, the nanoparticles here described have the potential to be a chemotherapy treatment in the future.

Brazilian Red Propolis Presents Promising Anti-H. pylori Activity in In Vitro and In Vivo Assays with the Ability to Modulate the Immune Response.

Helicobacter pylori is a Gram-negative, microaerophilic, curved-rod, flagellated bacterium commonly found in the stomach mucosa and associated with different gastrointestinal diseases. With high levels of prevalence worldwide, it has developed resistance to the antibiotics used in its therapy. Brazilian red propolis has been studied due to its biological properties, and in the literature, it has shown promising antibacterial activities. The aim of this study was to evaluate anti-H. pylori from the crude hydroalcoholic extract of Brazilian red propolis (CHEBRP). For this, in vitro determination of the minimum inhibitory and bactericidal concentration (MIC/MBC) and synergistic activity and in vivo, microbiological, and histopathological analyses using Wistar rats were carried out using CHEBRP against H. pylori strains (ATCC 46523 and clinical isolate). CHEBRP presented MIC/MBC of 50 and 100 µg/mL against H. pylori strains (ATCC 43526 and clinical isolate, respectively) and tetracycline MIC/MBC of 0.74 µg/mL. The association of CHEBRP with tetracycline had an indifferent effect. In the stomach mucosa of rats, all treatments performed significantly decreased the number of H. pylori, and a concentration of 300 mg/kg was able to modulate the inflammatory response in the tissue. Therefore, CHEBRP showed promising anti-H. pylori in in vitro and in vivo assays.

Novel Preclinical Study of Galloylquinic Acid Compounds from Copaifera lucens with Potent Antifungal Activity against Vaginal Candidiasis Induced in a Murine Model via Multitarget Modes of Action.

Vaginal candidiasis is a medical condition characterized by the overgrowth of Candida spp. in the vaginal cavity with complex recurrent pathogenicity as well as tolerance to antifungal therapy and hence is awaiting more safe and effective treatments. This work aimed to assess the potential antifungal activity of galloylquinic acid compounds (GQAs) from Copaifera lucens leaves against vaginal Candida albicans. The antifungal susceptibility test was performed against 20 isolates of multidrug-resistant (MDR) C. albicans using agar diffusion and broth microdilution assays. The results showed that GQAs exhibited strong antagonistic activity against the test isolates, with inhibition zone diameters ranging from 26 to 38 mm and low MICs (1 to 16 µg/mL) as well as minimum fungicidal concentrations (2 to 32 µg/mL). The MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay confirmed the safety of GQAs against the Vero cell line, showing a 50% inhibitory concentration (IC50) of 168.17 mg/mL. A marked difference in the growth pattern of the treated and untreated pathogens was also observed, where a concentration-dependent reduction in the growth rate occurred. Moreover, a pronounced fungicidal effect was demonstrated 6 h after treatment with 1× the minimum fungicidal concentration (MFC), as evidenced by time-kill assays, where the number of survivors was decreased a 6-fold. GQAs effectively inhibited and eradicated about 80% of C. albicans biofilm at 6 µg/mL and 32 µg/mL, respectively. Interestingly, GQAs disturbed the fungal membrane integrity, induced cell lysis, and reduced the virulence factors (proteinase and phospholipase) as well as the catalase activity. Moreover, the ergosterol content in the plasma membrane decreased in a concentration-dependent manner. Additionally, the altered mitochondrial membrane potential was associated with an increased release of cytochrome c from mitochondria to the cytosol, suggesting the initiation of early apoptosis in GQA-treated cells. Transcriptional analysis revealed that all test genes encoding virulence traits, including SAP1, PLB1, LIP1, HWP1, and ALS1, were markedly downregulated in GQA-treated cells compared to the control. The in vivo murine model of vaginal candidiasis further confirmed the therapeutic activity of GQAs (4 mg/kg of body weight) against C. albicans. This work comprehensively evaluated the antifungal, antivirulence, and antibiofilm activities of GQAs against C. albicans isolates using in vitro and in vivo models, providing molecular-level insights into the antifungal mechanism of action and experimental evidence that supports the potential use of GQAs for the treatment of vaginal candidiasis. IMPORTANCE Our work presents a new perspective on the potential use of GQAs as safe and highly effective phytochemicals against MDR C. albicans. This microorganism colonizes the human vaginal epithelium, causing vaginal candidiasis, a condition characterized by recurrent pathogenicity and tolerance to traditional antifungal therapy. Based on the results of in vitro tests, our study reports GQAs antifungal modes of action. These compounds exhibited an anticandidal effect by deactivating the fungal hydrolytic enzymes, reducing ergosterol content in the plasma membrane, altering the potential of the mitochondrial membrane, and inducing apoptosis. Additionally, GQAs showed high activity in eradicating the biofilm formed by the fungus via the downregulation of HWP1, ALS, SAP, PLB, and LIP genes, which are constitutively expressed in the biofilm. In an in vivo murine model of vaginal candidiasis, GQAs further demonstrated strong evidence of their effectiveness as an antifungal therapy. In this regard, our findings provide novel insights into the potential therapeutic use of these phytoactive molecules for vaginal candidiasis treatment.

A reliable validated high-performance liquid chromatography-photodiode array detection method for quantification of terpenes in Copaifera pubiflora, Copaifera trapezifolia, and Copaifera langsdorffii oleoresins.

The Copaifera oleoresins are widely used in folk medicine to treat various diseases. The goal of this study was to develop a validated reverse-phase high-performance liquid chromatography method with photodiode array detection (RP-HPLC-PDA) to quantify eight terpenes: ent-hardwickiic acid, ent-copalic acid, ent-7α-acetoxy hardwickiic acid, ent-16-hydroxy-3,13-clerodadiene-15,18-dioic acid, ent-5,13-labdadiene-15-oic acid, junenol, ent-kaurenoic acid, and 13E-ent-labda-7,13-dien-15-oic acid in the oleoresins of Copaifera pubiflora L. (OCP), Copaifera trapezifolia L. (OCT) and Copaifera langsdorffii L. (OCL). The linearity of the method was confirmed in the range of 20.00-500 µg.mL-1 (r2 > 0.999). The limit of quantification was between 1,05 and 16.89 µg.mL-1. Precision and accuracy ranges were found to be %RSD <0.2 and 96% to 110%, respectively. Based on the obtained results, the developed analytical method is rapid, precise, accurate, and sensitive for quantifying these terpenes in Copaifera's oleoresins.

In vivo schistosomicidal activity of (±)-licarin A-loaded poly(ε-caprolactone) nanoparticles.

Schistosomiasis mansoni is an infectious parasitic disease caused by worms of the genus Schistosoma, and praziquantel (PZQ) is the medication available for the treatment of schistosomiasis. However, the existence of resistant strains reinforces the need to develop new schistosomicidal drugs safely and effectively. Thus, the (±)-licarin A neolignan incorporated into poly-Ɛ-caprolactone (PCL) nanoparticles and not incorporated were evaluated for their in vivo schistosomicidal activity. The (±)-licarin A -loaded poly(ε-caprolactone) nanoparticles and the pure (±)-licarin A showed a reduction in the number of worm eggs present in spleens of mice infected with Schistosoma mansoni. In addition, the (±)-licarin A incorporated in the concentration of 20 mg/kg and 200 mg/kg reduced the number of worms, presenting percentages of 56.3% and 41.7%, respectively.

In vitro comparison between antimicrobial and antibiofilm effects of Green Propolis and Baccharis dracunculifolia against Staphylococcus pseudintermedius isolate.

Staphylococcus pseudintermedius is the leading cause of canine pyoderma. Honeybee products are common to treat this and other types of infections. High average annual population loss of bees has been observed. This study evaluated antibacterial and antibiofilm profile of Green Propolis and Baccharis dracunculifolia against S. pseudintermedius and the chemical similarities among both. Ethanolic extracts were produced and chemically characterized. The isolates were subjected to treatment with the extracts in both planktonic and sessile forms. Green propolis minimum inhibitory concentration (MIC) was 0.156 mg / mL, and minimum bactericidal concentration (MBC) was 0.312mg / mL. Baccharis dracunculifolia extract MIC and MBC was 0.312mg / mL and 2.5 mg / mL, respectivelly. Both extracts reduced SD55 formation of biofilm at minimum inhibitory concentration and at 1/8 minimum inhibitory concentration. The results observed in relation to ED99, were similar for both extracts. Besides that, similar chemical indicators between both extracts, including the presence of Artepellin C, suggest that the Baccharis dracunculifolia extract could be an alternative to the Green Propolis extract in the treatment of staph infections.

Novel antitumor activity of the combined treatment of galloylquinic acid compounds with doxorubicin in solid Ehrlich carcinoma model via the Notch signaling pathway modulation.

AIMS: This study aims to investigate the potential synergistic effect of the combined treatment of galloylquinic acid compounds from Copaifera lucens with doxorubicin via the modulation of the Notch pathway in solid Ehrlich carcinoma-bearing mice model. MAIN METHODS: The solid tumor model was induced by subcutaneous inoculation of Ehrlich carcinoma cells in the right hind limb of mice, after serial syngeneic cell passages in the peritoneal cavity. Sixty mice were allocated into five groups including treated groups with galloylquinic acid compounds, doxorubicin, and their combination. Normal and tumor control groups were also assigned. Tissue homogenates were collected to measure the levels of the Notch-1, Hes-1, Jagged-1, TNF-α, IL-6 and VEGF, as well as SOD, MDA, and GSH. Histopathological and immunohistochemical examinations of tumor or control tissues were also performed for the levels of NF-κB p65, cyclin D1 and caspase 3 activity. KEY FINDINGS: Our results showed that the combined treatment of galloylquinic acid compounds with doxorubicin significantly decreased the levels of the Notch-1, Hes-1, Jagged-1, TNF-α, IL-6, VEGF, NF-κB p65, and cyclin D1 in tumor tissues. Moreover, the compounds induced cancer cell death as evidence by increasing the caspase 3 activity, and they possessed potent inhibitory effects on oxidative stress. SIGNIFICANCE: Galloylquinic acid compounds exhibited promising antineoplastic effects and promoted the chemosensitivity of doxorubicin, mainly by modulating the Notch signaling pathway and its downstream effectors. These compounds may be considered in solid tumors treatment for improving the efficacy and reducing the side effects of chemotherapeutic agents.

A new species of jewel beetle (Coleoptera, Buprestidae, Agrilus) triggers the production of the Brazilian red propolis.

Red propolis is a substance produced by bees by mixing resins from plants with wax, oils, and other secretions to protect the hive against natural enemies. Dalbergia ecastaphyllum (L.) Taub. (Fabaceae) is the primary botanical source of the Brazilian red propolis, where bees Apis mellifera L. collect a reddish resin from the stems to produce propolis. This species occurs in coastal dune and mangrove ecosystems, where local beekeepers install their beehives for propolis production. The induction of propolis production was virtually unknown. Previous reports and field evidence suggested that the reddish resin available in D. ecastaphyllum stems was not produced spontaneously but induced by the presence of a parasitic insect that feeds on the plant's stems. Research in the apiaries of the beekeepers' association of Canavieiras, Bahia, Brazil, led to the capture of a jewel beetle of an unknown species of the genus Agrilus Curtis (Buprestidae). It was confirmed that this jewel beetle is a red propolis production inductor. The adult and immature of this new species, Agrilus propolis Migliore, Curletti, and Casari sp. nov. are here described and illustrated. Behavioral information on the biology and chemical ecology confirms that the reddish resin of D. ecastaphyllum is directly related to the beetle attack and only occurs when Agrilus propolis sp. nov. adults emerge from the plant stem. This information is very important for Brazilian propolis producers interested in expanding red propolis production, which can have favorable effects on the economy of mangrove communities, promoting income generation, creating new business opportunities, and helping to sustain local communities and families.

Brazilian green propolis reduces worm burden and hepatic granuloma formation in a Schistosoma mansoni experimental murine model.

Characterized as an acute and chronic parasitic disease, schistosomiasis mansoni has as its central pathology the formation of hepatic granulomas in response to the parasite's eggs trapped in the host's liver. In recent years, research on propolis has grown; however, there is little anthelmintic work on this bee product. In the propolis scenario, Brazilian ones receive attention, with green and red propolis standing out. This study aims to evaluate in vivo the standardized extract of Brazilian green propolis (Pex) against Schistosoma mansoni. The in vivo antiparasitic activity of Pex was conducted in female BALB/c mice infected with S. mansoni and of the three groups treated with Pex (300 mg/kg); G2 (35th to 42nd dpi) reduced the total worm burden by 55.32%, followed by G3 (42nd to 49th dpi) and G4 (49th to 56th dpi), with about 46%. Furthermore, G2 significantly reduced the total egg load in the ileum (59.33%) and showed an increase in the dead eggs. Similarly, histological analysis of the livers showed a significant reduction in the number and diameter of the granulomas. Based on these results, there is an interesting schistosomicidal activity of Pex and its potential against the formation of hepatic granulomas, paving the way for more detailed studies of propolis in the animal model of schistosomiasis mansoni.

Chemical characterization of Brazilian propolis using automated direct thermal desorption-gas chromatography-mass spectrometry.

BACKGROUND: Propolis, produced by honey bees, is used around the world, displaying several corroborated biological activities. Brazil is one of the leading producers of propolis, with a great diversity of types, each with a characteristically chemical fingerprint influenced by the flora of the local region. The secondary metabolite's composition of propolis strongly impacts its biological properties, and its chemical characterization is of great importance for its quality control. Several chromatographic techniques have been applied to characterize propolis, highlighting the extraction of its volatiles and its analysis through gas chromatography. Fourteen Brazilian propolis samples collected in four states, including brown, green and red propolis types, were chemically characterized using the automated direct thermal desorption-gas chromatography-mass spectrometry (DTD-GC-MS). RESULTS: Red propolis type was characterized by acyclic saturated hydrocarbons, fatty alcohols, terpenes, and phenylpropanoids as nonacosane, α-copaene, ß-amyrin acetate, anethole, and 7-O-methylvestitol. Brown propolis presented hydrocarbons, monoterpenes, and sesquiterpenes, as α-pinene and α-bisabolol. Brazilian green propolis presented polycyclic aromatic hydrocarbons and sesquiterpenes, including 1-methyl-octahydroanthracene, 2,5-dimethyl-γ-oxo-benzenebutanoic acid, nerolidol, and spathulenol. Principal component analysis (PCA) was performed, allowing for clustering brown and red propolis types, indicating a divergence with the chemical composition of the green propolis samples. The hierarchical cluster analysis (HCA) allowed the chemical fingerprint of each propolis type to be differentiated. CONCLUSION: Red propolis was characterized by sesquiterpenes, pterocarpans, and isoflavans; brown propolis was characterized by hydrocarbons, aldehydes, and monoterpenes, while green propolis samples were characterized by the presence of polycyclic aromatic hydrocarbons, sesquiterpenes, and naphthalene derivatives. © 2022 Society of Chemical Industry.

Evaluation of lignan-loaded poly(ε-caprolactone) nanoparticles: synthesis, characterization, in vivo and in silico schistosomicidal activity.

Lignan dinitrohinokinin displays important biological activities, which led to the preparation of its poly-ε-caprolactone nanoparticles. Kinetics analysis revealed initially slow drug release followed by a prolonged, moderate release 6 h later due to DNHK diffusion through the polymeric matrix. Molecular dynamics simulations show that DNHK molecules that interact stronger with other DNHK molecules near the PCL/DNHK surface are more difficult to dissociate from the nanoparticle. The smaller diameter nanocapsules with negative surface charge conferred good colloidal stability. The formulations showed a size distribution with monodisperse systems formation. In vivo evaluation of schistosomicidal activity against Schistosoma mansoni showed that DNHK, when incorporated into nanoparticles, caused egg number reduction of 4.2% and 28.1% at 40 mg/kg and 94.2% and 84.4% at 400 mg/kg in the liver and the spleen, respectively. The PCL nanoparticles were stable in aqueous dispersion and could be optimized to be used as a promising lignan release agent.

Effectiveness of Oil-Based Denture Dentifrices-Organoleptic Characteristics, Physicochemical Properties and Antimicrobial Action.

Denture dentifrices must be effective and not deleterious to prosthetic devices. This study formulated and evaluated dentifrices based on oils of Copaifera officinalis, Eucalyptus citriodora, Melaleuca alternifolia, Pinus strobus, and Ricinus communis. Organoleptic characteristics (appearance, color, odor, taste), physicochemical properties (pH, density, consistency, rheological, abrasiveness, weight loss, and surface roughness) and antimicrobial (Hole-Plate Diffusion-HPD)/anti-biofilm (Colony Forming Units-CFU) action against Staphylococcus aureus, Streptococcus mutans, and Candida albicans were evaluated. Formulations were compared with water (negative control) and a commercial dentifrice (positive control). The data were analyzed by Kruskal-Wallis and Dunn tests (α = 0.05). The organoleptic and physicochemical properties were adequate. All dentifrices promoted weight losses, with high values for C. officinalis and R. communis, and an increase in surface roughness, without differing from each other. For antimicrobial action, C. officinalis and E. citriodora dentifrices were similar to positive control showing effectiveness against S. mutans and C. albicans and no dentifrice was effective against S. aureus; regarding the anti-biofilm action, the dentifrices were not effective, showing higher CFU counts than positive control for all microorganisms. The dentifrices presented satisfactory properties; and, although they showed antimicrobial action when evaluated by HPD, they showed no effective anti-biofilm action on multispecies biofilm.