Showing papers by "María José Alcaraz published in 2006"

Flavonoids from Artemisia copa with anti-inflammatory activity.

Abstract: Bioactivity-guided fractionation of the dichloromethane and ethanol extracts from the aerial parts of Artemisia copa led to the isolation of the flavonoids spinacetin, jaceosidin, axillarin, penduletin, tricin and chrysoeriol. These compounds were studied for possible inhibitory activity on the generation of inflammatory mediators in a cell line of mouse macrophages (RAW 264.7) stimulated with lipopolysaccharide. Spinacetin and jaceosidin weakly inhibited nitric oxide production whereas all flavonoids reduced prostaglandin E2 levels to different extents. The most active flavonoid was jaceosidin that inhibited cyclooxygenase-2 activity in a concentration-dependent manner with an IC50 value of 2.8 microM. In addition, the other flavonoids partially inhibited synovial phospholipase A2 activity. These mechanisms may provide a basis for explaining the anti-inflammatory activity of this plant.

Pharmacodynamic properties of methotrexate and aminotrexate™ during weekly therapy

Abstract: 4-amino-pteroyl-glutamic acid (AminotrexateTM; AMT) has several advantages over the related antifolate methotrexate (MTX), including greater potency, complete oral bioavailability, and greater accumulation by leukemic blasts in vitro. We compared the pharmacodynamic properties of AMT (given orally at 4 mg/m2 in two divided doses per week) and MTX (100 mg/m2 in four divided doses per week) among children with acute lymphoblastic leukemia. We find AMT and MTX to have equivalent penetration into the bone marrow compartment of these patients, as indicated by the steady-state concentrations within mature red blood cells (RBCs). However, MTX concentrations in the cerebrospinal fluid after oral dosage are significantly greater than AMT. To confirm these clinical observations, mice were treated four weekly injections of AMT or MTX, at a 1:20 dosage ratio, and tissue antifolate content was then determined over the subsequent 22 days. We confirm the selective exclusion of AMT from the CNS compartment, while showing equivalent accumulation of AMT and MTX in the RBCs, liver, spleen, kidneys and testes. Finally, we demonstrate that AMT, MTX, and their predominant polyglutamate species are equipotent inhibitors of their target intracellular enzyme dihydrofolate reductase, emphasizing the critical nature of steady-state tissue accumulation in determining the relative cytotoxic potency of these two antifolates.

Marine sponge metabolites for the control of inflammatory diseases.

Abstract: Marine organisms are a rich source of bioactive metabolites. A number of potential anti-inflammatory compounds have been isolated from marine invertebrates that exhibit phospholipase A2 inhibitory activity. A wide range of marine compounds have been investigated for their anti-inflammatory properties. Cacospongionolide B and petrosaspongiolide M are representative examples of anti-inflammatory compounds in experimental models of acute or chronic inflammation. The mechanisms of action of these compounds include phospholipase A, inhibition as well as the control of nuclear factor-B activation and inflammatory gene expression. Although many marine compounds exhibit interesting anti-inflammatory properties, few have entered clinical trials. The future development of this class of compounds as anti-inflammatory drugs requires the introduction of novel molecular targets of therapeutic relevance in addition to biotechnological approaches for the production of these molecules.