RESUMO
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 200â¯nm, a polydispersity index (PdI) lower than 0.2, and a ζ-potential between +35-40â¯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.
Assuntos
Lipídeos , Melanoma , Nanopartículas , Polímeros , Humanos , Nanopartículas/química , Lipídeos/química , Melanoma/tratamento farmacológico , Melanoma/patologia , Polímeros/química , Polímeros/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Tamanho da Partícula , Alcaloides/química , Alcaloides/farmacologia , Linhagem Celular Tumoral , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Administração Tópica , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Propriedades de SuperfícieRESUMO
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.
RESUMO
We have evaluated eight p-coumaric acid prenylated derivatives inâ 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=45.92â µM) and S. mansoni (IC50=64.25â 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.
Assuntos
Antiprotozoários , Ácidos Cumáricos , Leishmania , Testes de Sensibilidade Parasitária , Schistosoma mansoni , Animais , Schistosoma mansoni/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/química , Leishmania/efeitos dos fármacos , Antiprotozoários/farmacologia , Antiprotozoários/química , Antiprotozoários/síntese química , Relação Estrutura-Atividade , Prenilação , Propionatos/farmacologia , Propionatos/química , Estrutura Molecular , Esquistossomicidas/farmacologia , Esquistossomicidas/química , Esquistossomicidas/síntese química , Relação Dose-Resposta a DrogaAssuntos
Nanopartículas , Própole , Própole/farmacologia , Leucócitos Mononucleares , Expressão Gênica , CitocinasRESUMO
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.
Assuntos
Fabaceae , Reepitelização , Ratos , Animais , Ratos Wistar , Pele/patologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Fabaceae/química , LipídeosRESUMO
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.
RESUMO
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.
Assuntos
Nanopartículas , Neoplasias Ovarianas , Própole , Feminino , Humanos , Própole/farmacologia , Brasil , Apoptose , Neoplasias Ovarianas/tratamento farmacológico , Linhagem Celular Tumoral , Polímeros , Nanopartículas/química , BioensaioRESUMO
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.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Própole , Ratos , Animais , Própole/farmacologia , Própole/uso terapêutico , Brasil , Ratos Wistar , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Imunidade , Tetraciclinas/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologiaRESUMO
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-Æ-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.
Assuntos
Nanopartículas , Esquistossomose mansoni , Esquistossomicidas , Animais , Caproatos , Lactonas , Lignanas , Camundongos , Poliésteres , Schistosoma mansoni , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/parasitologia , Esquistossomicidas/farmacologia , Esquistossomicidas/uso terapêuticoRESUMO
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.
Assuntos
Anti-Infecciosos , Baccharis , Própole , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Baccharis/química , Biofilmes , Cães , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Folhas de Planta/química , Própole/química , Própole/farmacologia , StaphylococcusRESUMO
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.
Assuntos
Besouros , Dalbergia , Própole , Animais , Brasil , Dalbergia/química , Ecossistema , Própole/química , Própole/farmacologiaRESUMO
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.
Assuntos
Própole , Esquistossomose mansoni , Animais , Modelos Animais de Doenças , Feminino , Granuloma/tratamento farmacológico , Fígado , Camundongos , Camundongos Endogâmicos BALB C , Schistosoma mansoni , Esquistossomose mansoni/tratamento farmacológicoRESUMO
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.
Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Própole , Sesquiterpenos , Animais , Brasil , Cromatografia Gasosa-Espectrometria de Massas/métodos , Monoterpenos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Própole/química , Sesquiterpenos/análiseRESUMO
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.
Assuntos
Lignanas , Nanopartículas , Esquistossomicidas , Portadores de Fármacos , Lignanas/farmacologia , PoliésteresRESUMO
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.
RESUMO
Propolis is a bee product that has been used in medicine since ancient times. Although its anti-inflammatory, antioxidant, antimicrobial, antitumor, and immunomodulatory activities have been investigated, its anti-parasitic properties remain poorly explored, especially regarding helminths. This review surveys the results obtained with propolis around the world against human parasites. Regarding protozoa, studies carried out with the protozoa Trypanosoma spp. and Leishmania spp. have demonstrated promising results inâ vitro and inâ vivo. However, there are fewer studies for Plasmodium spp., the etiological agent of malaria and less so for helminths, particularly for Fasciola spp. and Schistosoma spp. Despite the favorable inâ vitro results with propolis, helminth assays need to be further investigated. However, propolis has shown itself to be an excellent natural product for parasitology, thus opening new paths and approaches in its activity against protozoa and helminths.
Assuntos
Antiparasitários/farmacologia , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Própole/química , Animais , Antiparasitários/química , Antiparasitários/isolamento & purificação , Brasil , Helmintos/efeitos dos fármacos , Leishmania/efeitos dos fármacos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Fenóis/química , Fenóis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plasmodium/efeitos dos fármacos , Trypanosoma/efeitos dos fármacosRESUMO
Brazilian green and red propolis stand out as commercial products for different medical applications. In this article, we report the antimicrobial activities of the hydroalcoholic extracts of green (EGP) and red (ERP) propolis, as well as guttiferone E plus xanthochymol (8) and oblongifolinâ B (9) from red propolis, against multidrug-resistant bacteria (MDRB). We undertook the minimal inhibitory (MIC) and bactericidal (MBC) concentrations, inhibition of biofilm formation (MICB50 ), catalase, coagulase, DNase, lipase, and hemolysin assays, along with molecular docking simulations. ERP was more effective by displaying MIC and MBC values <100â µg mL-1 . Compoundsâ 8 andâ 9 displayed the lowest MIC values (0.98 to 31.25â µg mL-1 ) against all tested Gram-positive MDRB. They also inhibited the biofilm formation of S. aureus (ATCC 43300 and clinical isolate) and S. epidermidis (ATCC 14990 and clinical isolate), with MICB50 values between 1.56 and 6.25â µg mL-1 . The molecular docking results indicated thatâ 8 andâ 9 might interact with the catalase's amino acids. Compounds 8 and 9 have great antimicrobial potential.
Assuntos
Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Própole/química , Anti-Infecciosos/química , Anti-Infecciosos/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Benzofenonas/química , Benzofenonas/isolamento & purificação , Benzofenonas/metabolismo , Benzofenonas/farmacologia , Sítios de Ligação , Biofilmes/efeitos dos fármacos , Brasil , Catalase/química , Catalase/metabolismo , Domínio Catalítico , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Própole/metabolismo , Própole/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Green propolis is produced by Apis mellifera honeybees using Baccharis dracunculifolia D.C. (Asteraceae) as substrate. This Southern Brazilian native plant and green propolis have been used in traditional medicine to treat gastric diseases, inflammation and liver disorders. AIM OF THE STUDY: Investigate the effects of baccharin (Bac) or p-coumaric acid (pCA) isolated from B. dracunculifolia D.C. (Asteraceae) over the inflammation induced by lipopolysaccharide (LPS) in vivo. MATERIALS AND METHODS: Inflammation was induced by LPS injection into air-pouches in mice, which were subsequently treated with Bac or pCA. Lavage fluid was collected from air pouches for the quantification of cellular influx via microscopy, and quantification of inflammatory mediators via colorimetric methods, ELISA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: LPS-induced inflammation increased cellular influx and increased the levels of parameters related to vascular permeability and edema formation, such as nitric oxide (NO) and protein extravasation. Moreover, LPS increased the levels of cytokines and eicosanoids in the air-pouches. Importantly, both Bac and pCA suppressed the infiltration of neutrophils, production of NO and protein extravasation. Notably, the compounds promote differential regulation of cytokine and eicosanoid production. CONCLUSIONS: Our results suggest that Bac from green propolis directly affects inflammation by inhibiting the production of cytokines and eicosanoids, while pCA may exert direct, but also indirect effects on inflammation by stimulating the production of regulatory effectors such as interkeukin-10 in vivo.
Assuntos
Baccharis/química , Ácidos Cumáricos/farmacologia , Própole/metabolismo , Tricotecenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Abelhas , Brasil , Ácidos Cumáricos/isolamento & purificação , Citocinas/metabolismo , Eicosanoides/metabolismo , Feminino , Inflamação/tratamento farmacológico , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Tricotecenos/isolamento & purificaçãoRESUMO
Propolis is one of the most widely used products in traditional medicine. One of the most prominent types of Brazilian propolis is the red one, whose primary botanical source is Dalbergia ecastaphyllum (L.) Taub. Despite the potential of Brazilian red propolis for developing new products with pharmacological activity, few studies guarantee safety in its use. The objective of this study was the evaluation of the possible toxic effects of Brazilian red propolis and D. ecastaphyllum, as well as the cytotoxicity assessment of the main compounds of red propolis on tumoral cell lines. Hydroalcoholic extracts of the Brazilian red propolis (BRPE) and D. ecastaphyllum stems (DSE) and leaves (DLE) were prepared and chromatographed for isolation of the major compounds. RP-HPLC-DAD was used to quantify the major compounds in the obtained extracts. The XTT assay was used to evaluate the cytotoxic activity of the extracts in the human fibroblast cell line (GM07492A). The results revealed IC50 values of 102.7, 143.4, and 253.1 µg/mL for BRPE, DSE, and DLE, respectively. The extracts were also evaluated for their genotoxic potential in the micronucleus assay in Chinese hamster lung fibroblasts cells (V79), showing the absence of genotoxicity. The BRPE was investigated for its potential in vivo toxicity in the zebrafish model. Concentrations of 0.8-6.3 mg/L were safe for the animals, with a LC50 of 9.37 mg/L. Of the 11 compounds isolated from BRPE, medicarpin showed a selective cytotoxic effect against the HeLa cell line. These are the initial steps to determine the toxicological potential of Brazilian red propolis.
Assuntos
Dalbergia/química , Extratos Vegetais/farmacologia , Própole/farmacologia , Animais , Brasil , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Própole/química , Própole/isolamento & purificação , Peixe-ZebraRESUMO
The chemotherapy of schistosomiasis remains centered in the use of praziquantel, however, there has been growing resistant parasites to this drug. Thus, the aim of this work was to evaluate inâ vitro schistosomicidal activity of the hexanes/dichloromethane 1 : 1 extract of Brazilian green propolis (Pex), as well as its major isolated compounds artepillin C, caffeic acid, coumaric acid and drupanin against Schistosoma mansoni. The Pex was active by displaying an IC50 value of 36.60 (26.26-51.13)â µg mL-1 at 72 h against adult worms of S. mansoni. The major isolated compounds were inactive with IC50 values >100â µM, however, the combination of the isolated compounds (CM) in the same range found in the extract was active with an IC50 value of 41.17 (39.89-42.46)â µg mL-1 at 72 h. Pex and CM induced alteration in the tegument of S. mansoni, and caffeic acid caused alteration in egg's maturation. Pex displayed inâ vitro activity against adult worms' and eggs' viability of S. mansoni, which opens new perspectives to better understand the synergistic and/or additive effects promoted by both Pex extract and CM against schistosomiasis features.