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1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35560772

RESUMO

This study investigates the effect of the hydroalcoholic extract of Brazilian green propolis on lipid metabolism in hypercholesterolemic guinea pigs. This product has been considered an important source of bioactive compounds with potential health benefits. Thirty-six guinea pigs, Cavia porcellus (male), 90 days old, weight of 400 g, were divided into six groups of six animals each and fed a standard AIN-93 M diet (C), hypercholesterolemic diet (H), hypercholesterolemic diet + hydroalcoholic extract (75 mg/kg body weight [HEtOH1]; 150 mg/kg body weight [HEtOH2], and 300 mg/kg body weight [HEtOH3]), or hypercholesterolemic diet + simvastatin (1.5 mg/kg body weight) (HS) for 10 weeks. The group-specific diet and water were provided ad libitum throughout the experimental period. Blood and liver tissue samples were collected for biochemical analysis and histopathology. Statistical analysis was performed using GraphPad Prism software version 5.0. The experimental protocol for the use of animals was approved by the Ethics Committee on Animal Use of the University of São Paulo (N°18.1.999.60.0). Animals in the H groups had a lower food intake than in the C group. Fecal excretion was regulated by the administration of extracts, being higher in these groups when compared to H and HS groups. Liver weights were influenced by the diet and administration of the hydroalcoholic extract of green propolis. Hypercholesterolemic diets determined an increase of about 2 times in the relative weight of this organ when compared to the C group, being more expressive in the groups of animals that received the hydroalcoholic extract. A significant increase in serum levels of total and non-HDL cholesterol was observed in H group, concomitant with a reduction in the concentration of cholesterol-HDL when compared to group C. However, these high levels of total cholesterol were reduced when simvastatin and extracts were administered with the hypercholesterolemic diet. The same was observed for the non-HDL cholesterol fraction, where administration with simvastatin and extracts significantly reduced the concentration of these fractions, especially in HS and HEtOH3 groups when compared to group H. Analysis of the HDL fraction demonstrates that the animals submitted to the hypercholesterolemic diet had the lowest levels for this parameter when compared to the groups that received the control diet and/or extracts and simvastatin. There was a significant reduction in serum triacylglycerol levels in the HEtOH2 and HEtOH3 groups. However, a change in liver metabolism was observed, favoring the deposition of lipids in the liver, a different profile from what was observed when administering simvastatin. C group presented a histological aspect compatible with the normality of the organ. The H and HS groups presented moderate to severe fat degeneration, with a slight degeneration in the HS group when compared to the H group. A profile similar to that of the HS group was observed in the HEtOH2 group. Our results suggest that the Brazilian green propolis extract induces positive effects on dyslipidemia.

2.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35554092

RESUMO

Brazilian green propolis from Baccharis dracunculifolia ("alecrim do campo"), stands out for the majority presence of phenolic acids with therapeutic properties well-described in the literature, such as anti-inflammatory, antioxidant, and antitumor. However, its direct application, like many natural products, is limited due to its unfavorable physicochemical properties. Thus, we hypothesize that the encapsulation of these compounds in nanostructured systems is a suitable instrument to overcome these limitations. In this work, an oil/water (O/W) nanoemulsion containing Brazilian green propolis extract (NE-BGP) was developed, and its bioactivity was evaluated in vivo and in vitro experimental models. Quantitative analysis by HPLC showed the presence of coumaric acid, artepelin C and baccharin in the standardized extract obtained, corresponding to 3.2%, 16.8% and 2.3% (w/w), respectively. The developed nanoemulsion showed high stability evaluated for 90 days, with the size around 130 nm, PdI less than 0.3, and negatively charged zeta potential (-20 mV). The encapsulation efficiency of the markers evaluated in NE-BGP determined by the validated UPLC-MS method was superior to 97% for 90 days. Morphological analysis using transmission electron microscopy (TEM) showed globular and spherical shapes. The cytotoxicity was evaluated in 3T3 (murine fibroblasts) and AMJ2-C11 (murine alveolar macrophages) cells and showed IC50 between 20.88 and 49.32 µg/mL after 24 hours of treatment by the neutral red method, respectively. The in vitro anti-inflammatory activity in AMJ2-C11 cells stimulated with LPS 5 µg/mL showed a significant reduction in the levels of nitric oxide (NO), as well as cytokines quantified by CBA (Cytometric Bead Array), IFN-γ, IL-4, and IL-6 in cells treated with NE-BGP (15 µg/ml) when compared to the control group. Male Balb/C mice (n=5) were used to evaluate the in vivo anti-inflammatory activity. NE-BGP administered orally at 100mg/Kg showed a reduction in edema, in the number of inflammatory cells in the joints, and an increase in the mechanical threshold reducing nociceptive stimuli in zymosan-induced mice arthritis. These results indicate that the developed formulation is an exciting system to encapsulate green propolis extract with high physicochemical stability, anti-inflammatory and analgesic effects, suggesting NE-BGP is a possible candidate for the arthritis treatment.

3.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35554657

RESUMO

Propolis is a natural product extensively used in the drug and food industry around the world due to its medicinal properties. Among the most prominent types of propolis in the world there is the red type, and one of its production centers is the Brazilian northeast. Several biological activities from Brazilian red propolis have been studied and its efficacy has been proved; however, there are few studies that report the safety of its use. This study assessed the biochemical and morphological long-term effects of oral consume (90 days) of Brazilian red propolis extract in Wistar rats (Rattus norvegicus, males and females). Animals were divided into three groups: vehicle (polyethylene glycol 15%), red propolis (1000 mg/kg body weight - limit test described by the OECD 408, 2018) (n=10 per group), and satellite (treated with propolis at the same dose) (n=5 per group). The satellite group had a recovery period of 30 days after daily oral gavage of 90 days, before euthanasia. During the treatment period, water and food consumption and animal weight analysis were monitored. After the experimental period, animals were euthanized and samples were collected for biochemical and histopathological analyses. Statistical analysis was performed using GraphPad Prism software version 6.0. The experimental protocol for the use of animals was approved by the Ethics Committee on Animal Use (N° 9701030418). Alterations in the weight of males treated with red propolis were observed (propolis and satellite), being the groups with lower body mass during the experiment. The red propolis group also presented an increased water intake, compared to the other groups. On the other side, the males of the satellite group presented lowest food consumption compared to the other groups. A greater relative mass of the liver in animals of red propolis groups of both sexes were noticed. However, biochemical alterations in hepatic and renal parameters were detected just in the males. Urea levels increased in the propolis and satellite groups, whereas creatinine decreased just on the propolis group. The alanine aminotransferase (ALT) levels increased on the red propolis group, and the aspartate aminotransferase (AST) values increased on the satellite group. Total protein content decreased on animals of propolis and satellite groups of both sexes. Similarly, on the propolis and satellite males, the triglycerides levels decreased. Despite the detection of biochemical alterations, no histopathological changes were detected in the organs of any group. In conclusion, Brazilian red propolis extract in a higher dose, showed no signs of immediate toxicity. However, some alterations in the relative weight of the liver and on some renal and hepatic function indicators were observed. These results, suggests that the chemical composition -isoflavonoids, pterocarpans and polyprenylated benzophenones-, and the higher dosage may be strongly related to the potential sub-chronic toxic effects observed in this study and that its action may be sex-dependent manner.

4.
Life Sci ; 299: 120497, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35339508

RESUMO

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.


Assuntos
Antineoplásicos , Carcinoma de Ehrlich , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma de Ehrlich/patologia , Caspase 3/metabolismo , Ciclina D1/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Interleucina-6/metabolismo , Proteína Jagged-1 , Camundongos , NF-kappa B/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Naturwissenschaften ; 109(2): 18, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35226184

RESUMO

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/farmacologia
6.
Parasitol Res ; 121(2): 775-780, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35048211

RESUMO

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 farmacológico
7.
J Sci Food Agric ; 2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35066883

RESUMO

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.

8.
Nat Prod Res ; : 1-7, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34963393

RESUMO

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.

9.
Antibiotics (Basel) ; 10(7)2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34356734

RESUMO

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.

10.
Chem Biodivers ; 18(9): e2100310, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34231306

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 in vitro and in 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 in 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 fármacos
11.
Chem Biodivers ; 18(8): e2100307, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34086414

RESUMO

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 oblongifolin 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 <100 µg mL-1 . Compounds 8 and 9 displayed the lowest MIC values (0.98 to 31.25 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 6.25 µg mL-1 . The molecular docking results indicated that 8 and 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/fisiologia
12.
J Ethnopharmacol ; 278: 114255, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34062248

RESUMO

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 & purificação
13.
Chem Res Toxicol ; 34(4): 1024-1033, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33720704

RESUMO

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-Zebra
14.
Chem Biodivers ; 17(9): e2000277, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32578329

RESUMO

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 in 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) µg mL-1 at 72 h against adult worms of S. mansoni. The major isolated compounds were inactive with IC50 values >100 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) 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 in 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.


Assuntos
Própole/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Animais , Brasil , Relação Dose-Resposta a Droga , Estrutura Molecular , Fenótipo , Própole/química , Própole/isolamento & purificação , Relação Estrutura-Atividade
15.
J Nat Prod ; 83(6): 1980-1989, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32453565

RESUMO

Our previous study showed that kaempferitrin, the main flavonoid from Bauhinia forficata Link leaves, induces diuresis and saluresis when orally given to rats. Since afzelin (AFZ) and kaempferol (KFL) are active compounds from the biometabolism of kaempferitrin, the diuretic and renal protective properties of these two compounds were evaluated. While the acute treatment with AFZ evoked a diuretic action associated with an increase in Cl- excretion and a Ca2+-sparing effect, KFL did not present any activity. The pretreatment with a muscarinic receptor blocker or with an inhibitor of the cyclooxygenase fully avoided AFZ-induced diuresis. AFZ also induced a prolonged (7-day treatment) diuretic effect in normotensive (NTR) and hypertensive rats (SHR), with an increase of urinary Na+ and Cl- excretion, while it decreased the elimination of Ca2+. AFZ was able to decrease ROS and nitrite generation on kidney homogenates in comparison with the SHR group treated with the vehicle, as well as mitigated the changes in the renal corpuscle region (glomerulus and Bowman's capsule). Moreover, AFZ significantly reduced calcium oxalate crystal formation in urine, with inhibition rates of 41% for the NTR and 92% for the SHR group. Taken together, this study shows that AFZ exerts acute and prolonged diuretic effects plus protective renal properties.


Assuntos
Diuréticos/farmacologia , Hipertensão/tratamento farmacológico , Quempferóis/farmacologia , Nefropatias/prevenção & controle , Manosídeos/farmacologia , Proantocianidinas/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/farmacologia , Bauhinia/química , Cálcio/metabolismo , Cloretos/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Nefropatias/patologia , Estrutura Molecular , Antagonistas Muscarínicos/farmacologia , Folhas de Planta/química , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
16.
J Pharm Pharmacol ; 71(10): 1520-1531, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385306

RESUMO

OBJECTIVE: This study proposed to use the nanotechnology to deliver glycoalkaloidic extract (AE) to bladder cancer cells, evaluating their activity in 2D and 3D models and the biological mechanism of cell death. METHODS: NPs were prepared by nanoprecipitation method using polylactic acid (PLA) and characterized considering their size, charge, particle concentration and stability. The cytotoxicity was evaluated in 2D and 3D model, and the apoptosis and cell cycle were investigated using flow cytometry. KEY FINDINGS: NPs loading AE (NP-AE) had diameter around 125 ± 6 nm (PdI <0.1) and negative charge. The encapsulation efficiency of SM and SS was higher than 85% for both compounds. The obtained formulation showed a significant in-vitro cytotoxic effect against RT4 cells in a dose-dependent manner with IC50 two fold lower than the free AE. The cytotoxic effect of NP-AE was mediated by apoptosis and cell cycle arrested in the S phase. RT4 cells cultured under 3D conditions exhibited a higher resistance to the treatments (IC50 ~ three fold higher than in 2D cell culture). CONCLUSION: The NP-AE might be a promising nanocarrier to load and deliver glycoalkaloids against bladder cancer.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Nanopartículas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Humanos , Nanotecnologia/métodos , Tamanho da Partícula , Poliésteres/química , Fase S/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacos
17.
Chem Biodivers ; 16(10): e1900334, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31448497

RESUMO

Cernumidine (CER) is a guanidinic alkaloid isolated from Solanum cernuum leaves. In this work, we investigated the cytotoxicity, chemosensitizing effect of cernumidine to cisplatin (cDDP) and the possible mechanism of action of the combination on bladder cancer cells. Cernumidine showed cytotoxicity and could sensitize bladder cancer cells to cisplatin. The combination of CER+cDDP inhibited cell migration on T24 cells. CER+cDDP down-regulated MMP-2/9 and p-ERK1/2, while it increased EGFR activity corroborating the observed cell migration inhibition. Down-regulation of Bcl-2 and up-regulation pro-apoptotic Bax and further depletion of the mitochondrial membrane potential (ΔΨm) indicates that mitochondria play a central role in the combination treatment inducing the mitochondrial signaling pathway of apoptosis in T24 cells. Our data showed that the alkaloid cernumidine is worthy of further studies as a chemosensitizing agent to be used in complementary chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ácidos Cafeicos/farmacologia , Guanidinas/farmacologia , Solanum/química , Neoplasias da Bexiga Urinária/tratamento farmacológico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Ácidos Cafeicos/química , Ácidos Cafeicos/isolamento & purificação , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Guanidinas/química , Guanidinas/isolamento & purificação , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia de Fluorescência , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Folhas de Planta/química , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
18.
Phytochem Anal ; 30(3): 364-372, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30648323

RESUMO

INTRODUCTION: Galloylquinic acid derivatives and flavonoids are the main phenolic metabolites found in Copaifera langsdorffii leaves (Leguminosae, Detarioideae), a medicinal plant with potential therapeutic application in the treatment of kidney stones. The factors that affect metabolite production in this plant species are not well understood but may include environmental and genetic factors. OBJECTIVE: To quantify the variation in metabolite production over a 12-month period for 10 groups of C. langsdorffii cultivated under the same environmental conditions. METHODS: Copaifera langsdorffii seeds were collected from 10 different regions in southeast, Brazil and grown in the same field. HPLC-UV was used to quantify nine galloylquinic acid derivatives and two flavonoids in leaf samples from mature trees. Climate data for humidity, radiation, precipitation and temperature were provided by the National Institute of Meteorology, Brazil. Multivariate analyses were performed to correlate chemical and environmental variables. RESULTS: The overall effect of environmental factors on the production of phenolic metabolites was uniform among C. langsdorffii groups. Chemical variation between groups was present, but small, and probably due to differences in their genetics and physiology. Seasonal changes influenced the production of the major phenolic metabolites, with increases in temperature and radiation levels favouring metabolite production. CONCLUSION: When C. langsdorffii trees are cultivated in the same environment, the production of the major secondary metabolites found in their leaves is very similar quantitatively, varying based on geographic location of original population and seasonal changes. This favours the standardisation of plant raw material for the production of a phytomedicine.


Assuntos
Fabaceae/metabolismo , Fenóis/análise , Folhas de Planta/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Geografia , Fenóis/metabolismo , Fenóis/normas , Padrões de Referência , Estações do Ano , Espectrofotometria Ultravioleta/métodos
19.
Chem Biodivers ; 16(1): e1800305, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30335227

RESUMO

Six dibenzylbutyrolactonic lignans ((-)-hinokinin (1), (-)-cubebin (2), (-)-yatein (3), (-)-5-methoxyyatein (4), dihydrocubebin (5) and dihydroclusin (6)) were isolated from Piper cubeba seed extract and evaluated against Schistosoma mansoni. All lignans, except 5, were able to separate the adult worm pairs and reduce the egg numbers during 24 h of incubation. Lignans 1, 3 and 4 (containing a lactone ring) were the most efficient concerning antiparasitary activity. Comparing structures 3 and 4, the presence of the methoxy group at position 5 appears to be important for this activity. Considering 1 and 3, it is possible to see that the substitution pattern change (methylenedioxy or methoxy groups) in positions 3' and 4' alter the biological response, with 1 being the second most active compound. Computational calculations suggest that the activity of compound 4 can be correlated with the largest lipophilicity value.


Assuntos
Anti-Helmínticos/farmacologia , Lignanas/farmacologia , Piper/química , Extratos Vegetais/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Teoria da Densidade Funcional , Feminino , Lignanas/química , Lipídeos/química , Masculino , Camundongos Endogâmicos BALB C , Modelos Teóricos , Simulação de Acoplamento Molecular , Estrutura Molecular , Contagem de Ovos de Parasitas , Extratos Vegetais/química , Espectroscopia de Prótons por Ressonância Magnética , Schistosoma mansoni/química , Eletricidade Estática , Tubulina (Proteína)/química
20.
Phytochemistry ; 156: 214-223, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30321792

RESUMO

In this study, ent-kaurenoic acid derivatives were obtained by microbial transformation methodologies and tested against breast cancer cell lines (MCF-7). A multivariate quantitative-structure activity relationship (QSAR) analysis was performed taking into account both microbial transformation derivatives and other analogues previously reported in literature to give some insight into the main features behind the cytotoxic activity displayed by kaurane-type diterpenes against MCF-7 cells. The partial least square regression (PLS) method was employed in the training set and the best PLS model was built with a factor describing 69.92% of variance and three descriptors (logP, εHOMO and εHOMO-1) selected by the Ordered Predictors Selection (OPS) algorithm. The QSAR model provided reasonable regression (Q2 = 0.64, R2 = 0.72, SEC = 0.29 and SEV = 0.33). The model was validated by leave-N-out cross-validation, y-randomization and external validation (R2pred = 0.89 and SEP = 0.27). The selected descriptors indicated that the activity was mainly related to electronic parameters (HOMO and HOMO-1 molecular orbital energies), as well as to logP. These findings suggest that higher activity values are directly related with both higher logP and frontier orbital energy values. The positive relationship between these orbitals and the activity suggests that the ent-kaurenoic acid analogues interaction with the target involves charge displacement, which is entirely consistent with the literature. Based on these findings, three compounds were proposed and one of them was synthesized and tested. The experimental result confirmed the activity predicted by the model.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Diterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Fabaceae/química , Feminino , Humanos , Células MCF-7 , Relação Quantitativa Estrutura-Atividade , Teoria Quântica
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