ABSTRACT
From the leaves of Phellolophium madagascariense Baker (Apiaceae), an endemic herb to Madagascar, three known coumarins (osthol, murraol and meranzin hydrate) have been isolated and identified. This is the first report of these compounds in this species. The structural elucidations were based on the analysis of physical and spectroscopic data. The anticancer activity of the three isolated compounds and of a synthetic sample of osthol was evaluated on L1210 mouse leukemia and on human prostatic cancer hormonosensitive LNCaP and hormonoindependent PC3 and DU145 cell lines.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Apiaceae/chemistry , Coumarins/isolation & purification , Animals , Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Coumarins/chemical synthesis , Coumarins/chemistry , Coumarins/pharmacology , Drug Screening Assays, Antitumor , Humans , Male , Mass Spectrometry , Mice , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Optical Rotation , Plant Leaves/chemistry , Prostatic Neoplasms/drug therapy , Spectrophotometry, Infrared , Spectrophotometry, UltravioletABSTRACT
The fetus is able to exhibit a stress response to painful events, and stress hormones have been shown to modulate pulmonary vascular tone. At birth, the increased level of stress hormones plays a significant role in the adaptation to postnatal life. We therefore hypothesized that pain may alter pulmonary circulation in the perinatal period. The hemodynamic response to subcutaneous injection of formalin, which is used in experimental studies as nociceptive stimulus, was evaluated in chronically prepared, fetal lambs. Fetal lambs were operated on at 128 days gestation. Catheters were placed into the ascending aorta, superior vena cava, and main pulmonary artery. An ultrasonic flow transducer was placed around the left pulmonary artery. Three subcutaneous catheters were placed in the lambs' limb. The hemodynamic responses to subcutaneous injection of formalin, to formalin after fetal analgesia by sufentanil, and to sufentanil alone were recorded. Cortisol and catecholamine concentrations were also measured. Pulmonary vascular resistances (PVR) increased by 42% (P < 0.0001) after formalin injection. Cortisol increased by 54% (P = 0.05). During sufentanil infusion, PVR did not change significantly after formalin. Cortisol increased by 56% (P < 0.05). PVR did not change during sufentanil infusion. Norepinephrine levels did not change during any of the protocols. Our results indicate that nociceptive stimuli may increase the pulmonary vascular tone. This response is not mediated by an increase in circulating catecholamine levels. Analgesia prevents this effect. We speculate that this pulmonary vascular response to nociceptive stimulation may explain some hypoxemic events observed in newborn infants during painful intensive care procedures.
