RESUMO
AbstractGastric ulcer is a prevalent gastrointestinal disease, and the drugs currently used in the treatment produce several adverse effects. In this context, the search for new therapeutic antiulcer agents is essential, and medicinal plants have great potential. Here, we investigated the gastroprotective properties of Copaifera langsdorffii Desf., Fabaceae, hydroalcoholic extract obtained from leaves and its isolated compounds. The phytochemistry studies and the compounds isolations were performed using chromatographic and spectroscopic methodologies. The hydroalcoholic extract was evaluated using ethanol/HCl, non-steroidal anti-inflammatory drug, stress-induced-ulcer and chronic ulcer-model. The effects on gastric content volume, pH, total acidity and mucus stomach production were evaluated in the pylorus ligated-model. The C. langsdorffii extract obtained from leaves (50, 250 or 500 mg/kg) reduced the injured area compared to control group in all experiments. The extract showed a significant decrease in the total gastric juice acidity and an increase in mucus production (500 mg/kg) when compared to vehicle. Among isolated compounds (30 mg/kg) α-humulene, β-caryophyllene and caryophyllene oxide showed greater gastroprotective activity in the ethanol/HCl induced ulcer model. The data herein obtained shown that C. langsdorffii leaves extract and isolated compounds from it, presented gastroprotective properties in different animal models of gastric ulcer. These effects may be associated with the ability of the extract to decrease gastric secretion and increase the mucus production.
RESUMO
Parasitic diseases continue to be a major worldwide health problem, and there is an urgent need for development of therapeutic drugs. This paper describes synthesis of dehydrodiferulic acid dilactone 1 and dehydrodisinapic acid dilactone 2 furofuran lignans by oxidative coupling of ferulic and sinapic acids, respectively. Their schistosomicidal, trypanocidal, and leishmanicidal activities were evaluated in vitro against Schistosoma mansoni adult worms, trypomastigote and amastigotes forms of Trypanosoma cruzi, and promastigote forms of Leishmania amazonensis. Compound 1 did not display significant schistosomicidal activity, but it presented potent trypanocidal activity, since it induced death of trypomastigotes and amastigotes with IC50/24h of 9.3µM and 7.3µM, respectively. Compound 2 had slight trypanocidal and schistosomicidal activities. None of the compounds were active against L. amazonensis. These results demonstrated that furofuran lignans are potentially useful for anti-parasitic drugs development and should be further investigated.
Assuntos
Furanos/síntese química , Furanos/farmacologia , Lignanas/síntese química , Lignanas/farmacologia , Esquistossomicidas/síntese química , Esquistossomicidas/farmacologia , Tripanossomicidas/síntese química , Tripanossomicidas/farmacologia , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Furanos/química , Humanos , Concentração Inibidora 50 , Lactonas/síntese química , Lactonas/química , Leishmania/efeitos dos fármacos , Leishmania mexicana/efeitos dos fármacos , Lignanas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Testes de Sensibilidade Parasitária , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/química , Tripanossomicidas/química , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Three new azaphilones with an unusual methylene bridge, named mycoleptones A, B, and C (2, 4, and 5), were isolated from cultures of Mycoleptodiscus indicus, a fungus associated with the South American medicinal plant Borreria verticillata. Additionally, four known polyketides, austdiol (1), eugenitin (3), 6-methoxyeugenin (6), and 9-hydroxyeugenin (7), were also isolated. The structural characterization of compounds was carried out by nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, electronic circular dichroism spectroscopy, time-dependent density functional theory calculations, and X-ray crystallography. Compounds 1-9 were weakly active when tested in antileishmanial and cytotoxicity assays.
Assuntos
Benzofuranos/isolamento & purificação , Endófitos/química , Policetídeos/isolamento & purificação , Benzofuranos/química , Benzofuranos/farmacologia , Brasil , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Leishmania/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Policetídeos/química , Policetídeos/farmacologia , Rubiaceae/microbiologiaRESUMO
Presently, natural products, such as Piper umbellata L. (Piperaceae), have been evaluated as sources of antimicrobial agents with efficacies against microorganisms. The in vitro antimicrobial activity was performed by broth micro-dilution susceptibility assay, according to the protocols of the National Committee for Clinical Laboratory Standards, and described the antibacterial and antifungal activities of crude ethanolic extract and fractions obtained by partitions sequentially among water-methanol, methylene chloride and ethyl acetate, as well as the major constituent, 4-nerolidylcatechol from the aerial parts of P. umbellata L. Amphotericin B and ciprofloxacin were used as controls. Among the microorganism cultures, hydromethanol fraction demonstrated the pre-eminent antifungal activity. 4-Nerolidylcathecol was the only tested plant component that exhibited activity against all the selected microorganisms, suggesting its great potential as a source for the development of new drugs. In order to estimate the antimalarial activity of P. umbellata L., a micro-dilution method protocol, parasite lactate dehydrogenase assay, with a Plasmodium falciparum Sierra Leone (D6) clone was utilised. The antimalarial agent artemisinin was used as control. 4-Nerolidylcathecol exhibited the best antimalarial activity; however, it was not significant when compared with control. These in vitro results do not justify the use of P. umbellata L. in malaria patients. However, there is a possibility of 4-nerolidylcathecol, after biotransformation, exhibiting a significant antimalarial activity in in vivo assays. However, 4-nerolidylcathecol demonstrated to possess a broad antimicrobial activity which is, in fact, a promising source for the development of new therapeutic agents.
Assuntos
Anti-Infecciosos/farmacologia , Antimaláricos/farmacologia , Catecóis/farmacologia , Piper/química , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Anti-Infecciosos/isolamento & purificação , Antimaláricos/isolamento & purificação , Catecóis/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos , L-Lactato Desidrogenase/metabolismo , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Extratos Vegetais/isolamento & purificaçãoRESUMO
The crude ethanolic extract from aerial parts of Pothomorphe umbellata L. (Piperaceae) and fractions obtained by partitions sequentially among water-methanol, methylene chloride, and ethyl acetate, as well as the major constituent, 4-nerolidylcatechol, were, respectively, evaluated and evidenced for antioxidant and cytotoxic effects through fluorometric microplate and microculture tetrazolium assays in HL-60 cells. The crude ethanolic extract demonstrated the preeminent antioxidant activity (IC50 = 1.2 µg/mL) against exogenous cytoplasmic reactive oxygen species, followed by the water-methanolic (IC50 = 4.5 µg/mL), methylene chloride (IC50 = 5.9 µg/mL), ethyl acetate (IC50 = 8.0 µg/mL), 4-nerolidylcatechol (IC50 = 8.6 µg/mL), and the sterol fractions (IC50 > 12.5 µg/mL). Vitamin C, the positive control used in this assay, presented IC50 value equivalent to 1.7 µg/mL. 4-Nerolidylcatechol (IC50 = 0.4 µg/mL) and methylene chloride fraction (IC50 = 2.3 µg/mL) presented considerable cytotoxicity probably because of the presence of an o-quinone, an auto-oxidation by product of the catechol. Polar compounds, present in the ethanol extract, appear to increase the solubility and stability of the major active constituent, acting synergistically with 4-nerolidylcatechol, improving its pharmacokinetic parameters and increasing significantly its antioxidant activity which, in turn, suggests that the aqueous-ethanolic extract, used in folklore medicine, is safe and effective.
Assuntos
Antioxidantes/farmacologia , Catecóis/farmacologia , Piperaceae/química , Extratos Vegetais/farmacologia , Antioxidantes/análise , Ácido Ascórbico/metabolismo , Catecóis/análise , Citoplasma/metabolismo , Células HL-60 , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Oxigênio/metabolismo , Extratos Vegetais/análise , Folhas de Planta/química , Quinonas/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
(±)-Licarin A (1), a neolignan obtained by the oxidative coupling reaction of isoeugenol, had in this study its enantiomers resolved. A novel, quick and efficient enantiomeric resolution of 1 was directly performed by chiral high-performance liquid chromatography (HPLC-PDA) protocol (CHIRALPACK(®) AD column; 9:1 (v/v) n-hexane:2-propanol; 1.0 mL/min). This method provided a chromatogram profile with a well-resolved peak separation. After isolation of each enantiomer with ee>99.9%, they were analysed in a polarimeter. Compound 2, which showed a retention time (t(r)) of 12.13 min, was the (+)-enantiomer and compound 3 (t(r)=18.90 min) was the (-)-enantiomer.