ABSTRACT
Effect of strophanthidin (Str) on intracellular calcium concentration ([Ca2+]i) was investigated on isolated ventricular myocytes of guinea pig. Single ventricular myocytes were obtained by enzymatic dissociation technique. Fluorescent signal of [Ca2+]i was detected with confocal microscopy after incubation of cardiomycytes in Tyrode' s solution with Fluo3-AM. The result showed that Str increased [Ca2+]i in a concentration-dependent manner. The ventricular myocytes began to round-up into a contracture state once the peak level of [Ca2+]i was achieved in the presence of Str (10 micromol L(- 1)), but remained no change in the presence of Str (1 and 100 nmol L(-1)). Tetrodotoxin (TTX), nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str (1 and 100 nmol L(-1)) , but had no obvious effects on the action of Str (10 micromol L(-1)). The elevation of [Ca2+]i caused by Str at all of the detected concentrations was partially antagonized by rynodine (10 micromol L(-1)) or the removal of Ca2+ from Tyrode's solution. In Na+, K+ -free Tyrode' s solution, the response of cardiomycytes in [Ca2+]i elevation to Str (10 micromol L(-1)) was attenuated, while remained no change to Str (1 and 100 nmol L(-1)). TTX, nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str at all of the detected concentrations in Na+, K+ -free Tyrode's solution. The study suggests that the elevation of [Ca2+]i by Str at the low (nomomolar) concentrations is partially mediated by the extracellular calcium influx through Ca2+ channel or a "slip mode conductance" of TTX sensitive Na+ channel. While the effect of Str at high (micromolar) concentrations was mainly due to the inhibition of Na+, K+ -ATPase. Directly triggering the release of intracellular Ca2+ from sarcoplasmic reticulum (SR) by Str may be also involved in the mechanism of [Ca2+]i elevation.
Subject(s)
Animals , 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester , Pharmacology , Aequorin , Pharmacology , Calcium , Metabolism , Calcium Channel Blockers , Pharmacology , Calcium Channels , Metabolism , Fura-2 , Pharmacology , Guinea Pigs , Myocardium , Pathology , Nifedipine , Pharmacology , Ryanodine , Pharmacology , Sarcolemma , Metabolism , Pathology , Sarcoplasmic Reticulum , Metabolism , Sodium-Calcium Exchanger , Sodium-Potassium-Exchanging ATPase , Strophanthidin , Pharmacology , Tetrodotoxin , Pharmacology , Thapsigargin , PharmacologyABSTRACT
Three known cardenolides [Strophanthidin [1], Corchoroside A [2] and Olitoriside [3]] were isolated from the seed-leaves of Corchorus olitorius L. [Tiliaceae]. The cytotoxic activity was evaluated against six cancer cell lines. Compounds 2 and 3 were very potent and their EC50 values against A549 [human lung carcinoma] were 0.06 mug/ml and 0.025 mug/ml, respectively. These compounds were isolated for the first time from the seed-leaves of the plant and this was the first report of the cytotoxicity of compounds 2 and 3
Subject(s)
Plant Leaves/chemistry , Seeds/chemistry , Plants , Strophanthidin , Plant ExtractsABSTRACT
The hydroalcoholic extract of the powdered bark of the Indian-snuff Maquira sclerophylla Ducke was purified by column chromatography in silica-gel and the major cardenolide isolated from preparative TLC was identified by 1H-NMR, 1 2 C-NMR and IR analyses. The spectra showed that the active substance has strophanthidin as aglicone.