Two cardenolide glycosides, corotoxigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (1) and coroglaucigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (2), were isolated from the seed fairs of Asclepias curassavica. The structures of 1-2 were determined based on the combination of the analysis of their MS, NMR spectroscopic data and acid hydrolysis. The inhibitory effects of compounds 1 and 2 on human colorectal carcinoma cells (HCT116), non-small cell lung carcinoma cells (A549) and hepatic cancer cells (SMMC-7721) were evaluated. The results showed that both compounds 1 and 2 significantly inhibited the viability, proliferation, and migration of A549, HCT116 and SMMC-7721 cells, suggesting that compounds 1 and 2 can be applied in the treatment of lung, colon and liver cancers in clinical practice. This study may not only provide a scientific basis for clarifying the active ingredients in A. curassavica, but also help to understand its antitumor activity, which can promote the application of A. curassavica in clinical treatment of various cancers.
Antineoplastic Agents/pharmacology* ; Asclepias/chemistry* ; Cardenolides/pharmacology* ; Glycosides/pharmacology* ; Humans ; Seeds

AIMTo study the effect of antidigoxin antiserum on oxygen stress induced by myocardial ischemia/reperfusion (MI/R) injury in rats.

METHODSSprauge Dawley rats were submitted to ligate left anterior descending coronary artery 30 min followed by 45 min reperfusion. Experiment animals were randomly divided into seven groups including sham group, MI/R group, normal salina group, verapamil group and three antidigoxin antiserum groups from low to high dose. The left ventricular myocardial tissue sample of ischemia were processed and measured the level of endoxin and malondialdehyde (MDA), the activities of Na+, K(+) -ATPase and superoxin dismutase (SOD). The myocardia morphology was observed.

RESULTSThe levels of endoxin and MDA increased and the activities of Na+, K(+) -ATPase and MDA were inhibited significantly in MI/R and saline groups. Including verapamil group in comparison to MI/R and saline groups, MDA level decreased and SOD activities partly reserved, meanwhile, only in three antidigoxin antiserum groups, the myocardial endoxin level was remarkably decreased, Na+, K(+) -ATPase activities were drastically increased. The myocardial histological morphology was significantly improved.

CONCLUSIONAntidigoxin antiserum, an endoxin mutual clone antibody, had the effect of attenuating the damage of oxygen free radicals induced by MI/R via to antagonizing the inhibition effect of endoxin on myocardial membrane Na+, K(+) -ATPase activities.

Animals ; Cardenolides ; antagonists & inhibitors ; Digoxin ; pharmacology ; Immune Sera ; pharmacology ; Malondialdehyde ; analysis ; Myocardial Reperfusion ; Myocardial Reperfusion Injury ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Saponins ; antagonists & inhibitors ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Superoxide Dismutase ; metabolism

To study the anticancer activity of griffithin from Streptocaulon griffithii Hook. f. and its effect on apoptosis of cancer cells in vitro, the inhibitory effect of griffithin on cell proliferation was studied by MTT assay, the cell apoptosis was observed by AO/EB double decoration assay and flow cytometry. Griffithin exhibited high anticancer activity on four human cancer cell lines, with IC50 ranged from 0.17 - 0.43 microg x mL(-1). Griffithin also induced apoptosis of PC-3 cells. Griffithin had anticancer activity and induced apoptosis of cancer cells.
Antineoplastic Agents, Phytogenic ; chemistry ; isolation & purification ; pharmacology ; Apocynaceae ; chemistry ; Apoptosis ; drug effects ; Cardenolides ; administration & dosage ; chemistry ; isolation & purification ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Flow Cytometry ; HL-60 Cells ; Humans ; Inhibitory Concentration 50 ; Microscopy, Fluorescence ; Molecular Structure ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry

BACKGROUNDEndogenous hydrogen sulfide is a new neuromodulator which takes part in the regulation of central nervous system physiology and diseases. Whether endogenous hydrogen sulfide in the central nervous system regulates cardiovascular activity is not known. In the present study, we observed the hemodynamic changes of hydrogen sulfide or its precursor by intracerebroventricular injection, and investigate the possible roles of endogenous digitalis like factors and sympathetic activity in the regulation.

METHODSNinety-four Sprague-Dawley rats underwent a right cerebroventricular puncture, then the hydrogen sulfide saturation buffer or its precursor injected by intrcerebroventricular catheter. A heperin-filled catheter was inserted into the right femoral artery or into the left ventricle, and changes of blood pressure or cardiac function recorded by a Powerlab/4S instrument. Phentolamine or metoprolol were pre-injected to observe the possible role in autonomic nerve activity. After rats were sacrificed, plasma was collected and endogenous digitalis-like factors were measured with a commercial radioimmunoassay kit. The aortic, cardiac sarcolemmal vesicles were isolated and the activity of Na(+)-K(+)-ATPase was measured as ouabain-sensitive ATP hydrolysis under maximal velocity conditions by measuring the release of inorganic phosphate from ATP. Unpaired Student's t test for two groups or analysis of variances (ANOVA) for multiple groups were used to compare the differences of the changes.

RESULTSIntracerebroventricular injection of hydrogen sulfide induced a transient hypotension, then dramatic hypertenive effects in a dose-dependent manner. Bolus injection of L-cysteine or beta- mercaptopyruvate also increased mean arterial pressure (P < 0.01), whereas hydroxylamine-a cystathionine beta synthase inhibitor decreased the arterial pressure (P < 0.01). Hydrogen sulfide and L-cysteine increased mean arterial pressure, left ventricular develop pressure and left-ventricle maximal rate of systolic and diastolic pressure; these functions were decreased by hydroxylamine (P < 0.01). Glibenclamide (a K(ATP) channel blocker) blocked the transient hypotensive effect, phentolamine (an alpha-adrenergic receptor blocker) blocked the hypertensive effect, and metoprolol (a selective beta 1 receptor blocker) blocked the positive inoptropic effect of central nervous system hydrogen sulfide. The endogenous digitalis-like factors in plasma were elevated (P < 0.01) after treatment with L-cysteine, association with decreasing Na(+)-K(+)-ATPase activity in cardiac or aortic sarcolemmal vesicles (P < 0.01). Hydroxylamine injection reduced the endogenous digitalis-like factors level in plasma association with increasing Na(+)-K(+)-ATPase activity in cardiac and aortic sarcolemmal vesicles.

CONCLUSIONCentral nervous system endogenous hydrogen sulfide upregulated mean arterial pressure and cardiac systolic function by activation of sympathetic nerves or release of endogenous digitalis-like factors.

Animals ; Blotting, Western ; Cardenolides ; metabolism ; Central Nervous System ; drug effects ; metabolism ; Cystathionine beta-Synthase ; metabolism ; Cysteine ; analogs & derivatives ; pharmacology ; Hemodynamics ; drug effects ; Hydrogen Sulfide ; metabolism ; pharmacology ; Male ; Radioimmunoassay ; Rats ; Rats, Sprague-Dawley ; Saponins ; metabolism ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Sulfurtransferases ; metabolism