RESUMO
OBJECTIVES: The effects and molecular mechanisms of brassinin (BR), an indole phytoalexin from cruciferous vegetables, on monocyte-to-macrophage differentiation and inflammatory responses were investigated in this study. METHODS: Inflammatory responses from RAW264.7 cells and THP-1 were stimulated by lipopolysaccharide (1 µg/ml), and monocyte-to-macrophage differentiation of THP-1 was induced by phorbol myristate acetate (50 ng/ml). The production of inflammatory mediators was determined by ELISA, Western blot or real-time PCR. Reactive oxygen species were examined by DCFH-DA assay. KEY FINDINGS: Brassinin at 50 µm suppressed lipopolysaccharide-induced production of nitric oxide synthase, cyclooxygenase-2, prostaglandin E2 and reactive oxygen species by 90%, 69%, 52% and 41%, respectively, in RAW264.7 cells. In THP-1 cells, BR inhibited phorbol myristate acetate-induced monocyte-to-macrophage differentiation by suppressing cluster of differentiation molecule ß and CD36. In addition, BR suppressed translocation of nuclear factor 'kappa-light-chain-enhancer' of activated B cells (NF-κB) into the nucleus. However, BR activated the nuclear factor erythroid-derived 2-like 2 (Nrf2) and its target molecules hemoxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1), with an increase in nuclear translocation of Nrf2. CONCLUSIONS: Brassinin suppressed monocyte-to-macrophage differentiation and inflammatory responses by differentially regulating Nrf2 and NF-κB signallings.
Assuntos
Indóis/farmacologia , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Tiocarbamatos/farmacologia , Animais , Brassica/química , Diferenciação Celular/efeitos dos fármacos , Humanos , Indóis/isolamento & purificação , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Macrófagos/patologia , Camundongos , Monócitos/citologia , Monócitos/patologia , Células RAW 264.7 , Espécies Reativas de Oxigênio , Células THP-1 , Tiocarbamatos/isolamento & purificaçãoRESUMO
Two new boldine derivatives: the 3-thiocarbamateboldine (3) and the 2,9-O,O-diacetyl-3-thiocarbamateboldine (4) have been synthesized and their cytotoxicity evaluated.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Aporfinas/química , Aporfinas/síntese química , Peumus/química , Tiocarbamatos/química , Tiocarbamatos/síntese química , Aporfinas/isolamento & purificação , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Humanos , Tiocarbamatos/isolamento & purificaçãoRESUMO
Phytoalexins are low molecular weight antimicrobial compounds that are synthesized and accumulated in plants after their exposure to pathogenic microorganisms (bacteria, fungi, viruses and protozoans). They are extensively studied now as promising antifungal, potentially anticancer and plant diseases controlling agents. The article pertains to a group of indole-derived phytoalexins--brassinins, containing at least one sulfur atom in the side chain or in the ring(s), isolated from the cruciferous plants. Up today more than 20 compounds, closely related biogenetically, but exhibiting diversified biological activity have been identified. The survey summerises most promising recent results pertaining practical application of brassinins and camalexins.
Assuntos
Extratos Vegetais/química , Triptofano/química , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Indóis/química , Indóis/isolamento & purificação , Indóis/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Plantas/metabolismo , Sesquiterpenos , Enxofre/química , Terpenos , Tiazóis/química , Tiazóis/isolamento & purificação , Tiazóis/metabolismo , Tiocarbamatos/química , Tiocarbamatos/isolamento & purificação , Tiocarbamatos/metabolismo , Triptofano/metabolismo , FitoalexinasRESUMO
Three known thiocarbamate (TC)- and isothiocyanate (ITC)-related compounds have been isolated from the leaves of Moringa oleifera, a traditional herb in southeast Asia, as inhibitors of tumor promoter teleocidin B-4-induced Epstein-Barr virus (EBV) activation in Raji cells. Interestingly, only niaziminin among 10 TCs including 8 synthetic ones showed considerable inhibition against EBV activation. The structure-activity relationships indicated that the presence of an acetoxy group at the 4'-position of niaziminin is important and indispensable for inhibition. On the other hand, among the ITC-related compounds, naturally occurring 4-[(4'-O-acetyl-alpha-L-rhamnosyloxy)benzyl]ITC and commercially available allyl- and benzyl-ITC significantly inhibited activation, suggesting that the isothiocyano group is a critical structural factor for activity.
Assuntos
Herpesvirus Humano 4/efeitos dos fármacos , Folhas de Planta/química , Plantas Medicinais/química , Tiocarbamatos/farmacologia , Ativação Viral/efeitos dos fármacos , Linhagem Celular , Herpesvirus Humano 4/fisiologia , Humanos , Relação Estrutura-Atividade , Tiocarbamatos/química , Tiocarbamatos/isolamento & purificaçãoRESUMO
Allyl isothiocyanate (AITC) is a constituent of cruciferous vegetables. It occurs widely in the human diet as a natural ingredient or food additive. AITC possesses numerous biochemical and physiological activities. It is cytotoxic and tumorigenic at high doses and also is a modulator of enzymes involved in metabolism of xenobiotics, including carcinogens. It is plausible that the wide consumption of dietary AITC may have profound effects on human health. To facilitate investigations of the effects of dietary AITC in humans, a method of measuring its uptake is needed. In this study, a urinary marker was developed for quantifying AITC uptake in humans. Four adult volunteers were asked to eat a meal containing brown mustard as the source of AITC. The 48-h urine samples were collected from these individuals and analyzed by reverse phase high performance liquid chromatography. A major urinary metabolite was found, which was identified as N-acetyl-S-(N-allylthiocarbamoyl)-L-cysteine, the N-acetylcysteine conjugate of AITC, by comparing its retention time and UV, nuclear magnetic resonance, and mass spectra with those of the synthetic standard. After ingestion of mustard, the AITC conjugate was detected in urine collected from 0 to 12 h. No conjugate was found in urine samples collected after 12 h. The major portion of this metabolite was excreted within 8 h. The average total excretion of AITC conjugate was 5.4 +/- 1.7 (SD) mg after consumption of 10 g of mustard and 12.8 +/- 2.0 mg when 20 g of mustard was consumed. Thus, a dose-dependent excretion of this metabolite was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)