ABSTRACT
ABSTRACT A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and spectral comparison with related compounds, leading to complete assignment of the 1H and 13C NMR spectra.
Subject(s)
Plant Leaves/chemistry , Bauhinia/chemistry , Lactones/isolation & purification , Lactones/chemistry , Reference Values , Stereoisomerism , Molecular Structure , Carbon-13 Magnetic Resonance Spectroscopy/methods , Proton Magnetic Resonance Spectroscopy/methodsABSTRACT
Background: Domperidone is widely prescribed in patients with gastrointestinal disorders but some cardiac adverse effects have been recently reported. Aim: To evaluate the risk of QT prolongation, ventricular arrhythmias and sudden cardiac death associated with the use of oral domperidone in adults without cancer. Material and Methods: Systematic searches in MEDLINE, LILACS, SciELO, the Cochrane Library and regulatory agencies websites were performed, followed by a manual search of cited references. The search strategy consisted of combining free and indexed text words without any date or language restriction. Results: Three case-control studies met the inclusion criteria; none of them evaluated QT interval prolongation. With low risk of bias, each study quantified the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD). The odds ratios for these events in these studies were 4.7 (95% confidence interval (CI): 1.4-16), 1.59 (95% CI: 1.28-1.98) and 11.02 (95% CI: 2.02-62.3) respectively. A significantly increased risk was observed in patients older than 60 years of age or receiving doses > 30 mg/day. Conclusions: Heterogeneity between selected studies did not allow the computation of a summary measure. However, evidence was found that an increased risk of VA/SCD is associated with the use of oral domperidone in adults.
Subject(s)
Animals , Female , Humans , Mice , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Diterpenes/administration & dosage , Epoxy Compounds/administration & dosage , Paclitaxel/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/chemistry , Apoptosis/drug effects , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Diterpenes/chemistry , Drug Synergism , Epoxy Compounds/chemistry , Lactones/administration & dosage , Lactones/chemistry , Mice, Nude , Oxidative Stress/drug effects , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Transcriptional Activation/drug effects , Tumor Burden , Xenograft Model Antitumor AssaysABSTRACT
Cholangiocarcinoma (CC) is a chemoresistant intrahepatic bile duct carcinoma with a poor prognosis. The aims of this study were to identify molecular pathways that enhance sesquiterpene lactone parthenolide (PTL)-induced anticancer effects on CC cells. The effects of PTL on apoptosis and hemoxygenase-1 (HO-1) induction were examined in CC cell lines. The enhancement of PTL-mediated apoptosis by modulation of HO-1 expression and the mechanisms involved were also examined in an in vitro cell system. Low PTL concentrations (5 to 10 micrometer) led to Nrf2-dependent HO-1 induction, which attenuated the apoptogenic effect of PTL in Choi-CK and SCK cells. PTL-mediated apoptosis was enhanced by the protein kinase C-alpha inhibitor Ro317549 (Ro) through inhibition of expression and nuclear translocation of Nrf2, resulting in blockage of HO-1 expression. Finally, HO-1 silencing resulted in enhancement of apoptotic cell death in CC cells. The combination of PTL and Ro efficiently improved tumor growth inhibition compared to treatment with either agent alone in an in vivo subcutaneous tumor model. In conclusion, the modulation of HO-1 expression substantially improved the anticancer effect of PTL. The combination of PTL and Ro could prove to be a valuable chemotherapeutic strategy for CC.
Subject(s)
Humans , Active Transport, Cell Nucleus/drug effects , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Nucleus/metabolism , Cholangiocarcinoma/drug therapy , Drug Resistance, Neoplasm/drug effects , Enzyme Activation , Enzyme Inhibitors/pharmacology , Heme Oxygenase-1/genetics , Lactones/chemistry , NF-E2-Related Factor 2/genetics , Protein Kinase C-alpha/antagonists & inhibitors , RNA, Small Interfering/genetics , Sesquiterpenes/chemistry , Signal Transduction/drug effectsABSTRACT
Sesquiterpene lactones of the plants Viguiera sylvatica and Decachaeta thieleana (Asteraceae) modulate nitric oxide production and phagocytosis of macrophages cell line RAW. Different species of the Asteraceae family are a potential source of sesquiterpene lactones with anti-inflammatory properties. Macrophages play a central role in the regulation of immune responses. In the present study, the in vitro effect of two sesquiterpene lactones, a millerenolide and a thieleanin, was assessed by measuring the production of nitric oxide (NO) by cell line RAW (murine macrophages) using the Griess reagent. Additionally, the effect of these sesquiterpene lactones on phagocytic capacity of latex particles and the reduction of nitroblue tetrazolium (NBT) were evaluated microscopically. Treatment of macrophages with >2.5 µg/ml of both sesquiterpene lactones, reduced the production of NO. A decreased number of macrophages able to reduce NBT were observed when these cells were treated with 3 µg/ml of millerenolide or 7.5 µg/ml of thieleanin. Treatment of macrophages with 4 µg/ml of millerenolide or 7.5 µg/ml of thieleanin, reduced the phagocytic capacity of macrophages. Cytotoxic effects on the macrophages were only observed when the concentration was increased to 8 µg/ml of millerenolide or 25 µg/ml of thieleanin. Our results suggest that these sesquiterpene lactones could be useful compounds in the elaboration of anti-inflammatory drugs. Rev. Biol. Trop. 56 (3): 1063-1073. Epub 2008 September 30.
Las plantas de la familia Asteraceae son una fuente potencial de lactonas sesquiterpénicas con propiedades antiinflamatorias. Los macrófagos son células que desempeñan una función central en la regulación de la respuesta inmune. Este estudio evaluó el efecto in vitro de dos lactonas sesquiterpénicas, un millerenólido y thieleanina, sobre la producción de óxido nítrico (NO) en una línea celular de macrófagos de ratón (RAW), utilizando el reactivo de Griess. Además, se estudió el efecto sobre la capacidad fagocítica de RAW, evaluando al microscopio la fagocitosis de partículas inertes de látex y la reducción de nitroazul de tetrazolio (NBT). Se observó que los macrófagos tratados con lactona sesquiterpénica (>2.5 µg/ml) disminuyeron la producción de NO. Además, se observó una disminución de la cantidad de macrófagos capaces de reducir NBT, después que fueron tratados con millerenólido (3 µg/ml) o thieleanina (7.5 µg/ ml). Por otro lado, la exposición a 4 µg/ml de millerenólido ó 7.5 µg/ml de thieleanina redujo la cantidad promedio de partículas de látex fagocitadas. No se observaron diferencias entre tratamientos y control en cuanto al porcentaje de células fagocíticas. Sólo se observaron efectos citotóxicos sobre los macrófagos, cuando la concentración de millerenólido se incrementó a 8 µg/ml o la de thieleanina se aumentó a 25 µg/ml. Estos resultados sugieren que el millerenólido y la thieleanina podrían ser compuestos útiles en la elaboración de drogas antiinflamatorias.
Subject(s)
Animals , Mice , Asteraceae/chemistry , Lactones/pharmacology , Macrophages/drug effects , Nitric Oxide/biosynthesis , Phagocytosis/drug effects , Sesquiterpenes/pharmacology , Cell Line , Lactones/chemistry , Lactones/isolation & purification , Macrophages/physiology , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purificationABSTRACT
Background: Natural products are used in the production of therapeutic drugs due to their wide diversity and excellent adaptability to biological structures. Sesquiterpene ¡aciones are the active constituents of several plants from the Asteraceae family. Aim: To assess the in vitro effect of a sesquiterpene lactone (millerenolide). Material and methods: The drug effect was assessed measuring the proliferation of lymphocytes using the 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonylJ-2H-tetrazolium hydroxide (XTT) technique. Changes on the cell cycle were analyzed on a FACSort flow cytometer The effect of millerenolide on the production of nitric oxide (NO) by macrophages was evaluated using the Griess reagent. Additionally, phagocytosis of latex particles and nitroblue tetrazolium (NBT) reduction by macrophages were evaluated microscopically. Results: Treatment of human peripheral blood mononuclear cells (PBMC) with millerenolide decreases the proliferation of lymphocytes, decreases the percentage of cells in S, and G2/Mphases, and increases the proportion of cells in GO/Gl phase. Treatment of macrophages with millerenolide, reduces the production of NO, the phagocytic capacity and the number of cells able to reduce NBT. Cytotoxic effects of the lactone on human PBMC were only observed when the concentration was increased to 6 fig/ml. Conclusions: Millerenolide could be considered as a potential therapeutic agent with immunosuppressiveproperties.
Subject(s)
Humans , Immunosuppressive Agents/pharmacology , In Vitro Techniques , Lactones/pharmacology , Leukocytes, Mononuclear/drug effects , Lymphocyte Activation/drug effects , Nitric Oxide/biosynthesis , Sesquiterpenes/pharmacology , Analysis of Variance , Asteraceae/chemistry , Cytotoxicity Tests, Immunologic , Lactones/chemistry , Lactones/toxicity , Leukocytes, Mononuclear/physiology , Lymphocyte Activation/physiology , Phagocytosis/drug effects , Phagocytosis/physiology , Plant Extracts/chemistry , Plant Extracts/toxicity , Sesquiterpenes/chemistry , Sesquiterpenes/toxicityABSTRACT
Complex physalin metabolites present in the capsules of the fruit of Physalis angulata L. have been isolated and submitted to a series of assays of antimicrobial activity against Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, S. aureus ATCC 25923, S. aureus ATCC 6538P, Neisseria gonorrhoeae ATCC 49226, Escherichia coli ATCC 8739; E. coli ATCC 25922, Candida albicans ATCC 10231 applying different methodologies such as: bioautography, dilution broth, dilution agar, and agar diffusion techniques. A mixture of physalins (pool) containing physalins B, D, F, G inhibit S. aureus ATCC 29213, S. aureus ATCC 25923, S. aureus ATCC 6538P, and N. gonorrhoeae ATCC 49226 at a concentration of 200 mg/æl, using agar dilution assays. The mixture was inactive against P. aeruginosa ATCC27853, E. coli ATCC 8739; E. coli ATCC 25922, C. albicans ATCC 10231 when applying bioautography assays. Physalin B (200 æg/ml) by the agar diffusion assay inhibited S. aureus ATCC 6538P by n 85 percent; and may be considered responsible for the antimicrobial activity.