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1.
Pesqui. vet. bras ; 38(5): 967-972, May 2018. graf
Article in English | ID: biblio-955413

ABSTRACT

Nerium oleander is an ornamental cardiotoxic plant found in tropical and subtropical areas of the World. Its toxicity is related to the content of cardioactive glycosides, mainly oleandrin, found throughout the plant. The present study aimed to describe a new and improved method for oleandrin detection in tissue samples. The determination of oleandrin was made after extraction with a modified QuEChERS technique and measurement by UFLC-MS/MS. A total of 36 guinea pigs (Cavia porcellus) were distributed into 3 groups (n=12): control group that received only water orally (CON), and two treated groups that received hydroalcoholic oleander extract at doses of 150mg.kg-1 (OLE 150) and 300mg.kg-1 (OLE 300) in single oral dose. After three hours, fragments of heart, kidneys, liver and brain were collected for determination of oleandrin levels. The extraction and chromatographic procedures were effective for oleandrin detection and quantification in tissues, with retention time of 1.2 min and detection limit of 0.001μg g-1. The chromatographic analysis of treated guinea pigs indicated that oleandrin is distributed equally among the analyzed tissues. The developed methodology is a reliable, effective and rapid form of diagnosis of N. oleander poisoning based on necropsy tissue samples.(AU)


Nerium oleander é uma planta cardiotóxica ornamental encontrada em áreas tropicais e subtropicais do mundo. Sua toxicidade é relacionada á presença de glicosídeos cardioativos, principalmente a oleandrina, encontrada em toda a planta. O presente estudo objetiva descrever um novo e aprimorado método para detecção da oleandrina em amostras de tecido. A determinação da oleandrina foi feita após extração utilizando técnica modificada de QuEChERS e mensuração por UFLC-MS/MS. Um total de 36 cobaios (Cavia porcellus) foi distribuído em três grupos (n=12): grupo controle que recebeu apenas água por via oral (CON), e dois grupos tratados que receberam extrato hidroalcóolico de oleander nas doses de 150mg.kg-1 (OLE 150) e 300mg.kg-1 (OLE 300) em uma única dose oral. Após três horas, fragmentos do coração, rins, fígado e cérebro foram coletados para determinação dos níveis de oleandrina. A extração e procedimentos cromatográficos foram eficientes na detecção e quantificação da oleandrina nos tecidos, com tempo de retenção de 1,2min e limite de detecção de 0,001μg g-1. A análise cromatográfica dos animais tratados indicou que a oleandrina é distribuída de forma equalizada pelos tecidos analisados. A metodologia desenvolvida representa uma forma de diagnóstica segura, efetiva e rápida da intoxicação por N. oleander a partir de amostras de tecidos de necropsia.(AU)


Subject(s)
Chromatography, Liquid/instrumentation , Chromatography, Liquid/statistics & numerical data , Nerium/toxicity , Cardenolides/analysis
2.
Rev. colomb. biotecnol ; 16(1): 51-61, ene.-jun. 2014. tab
Article in Spanish | LILACS | ID: lil-715298

ABSTRACT

Digitalis purpurea L. es una de las principales fuentes de cardenólidos tales como digoxina y digitoxina. Estos fármacos son ampliamente usados en la disfunción cardíaca y para regular las arritmias del corazón. El presente trabajo se realizó con el objetivo de estudiar el efecto de tres elicitores en el cultivo de brotes de Digitalis purpurea var. Roter Berggold para incrementar la producción in vitro de cardenólidos. La elicitación es una estrategia para incrementar la producción de biomasa y metabolitos secundarios en el cultivo in vitro. Los elicitores evaluados fueron ChitoPlant (0,001; 0,01; 0,1 g.L-1); SilioPlant (0,01; 0,1; 1,0 g.L-1) y Jasmonato de metilo (60, 80 y 100 µM), descritos por primera vez para el incremento de cardenólidos. Se demostró que la elicitación es una estrategia viable para el incremento de cardenólidos en brotes de D. purpurea. El ChitoPlant®, redujo la altura sin afectación en el resto de las variables morfológicas evaluadas. Además indujo un incremento significativo en el contenido de cardenólidos. El SilioPlant® (0,01 g.L-1) no provocó afectaciones en la biomasa e incrementó significativamente la síntesis de cardenólidos en los brotes en 3,6 y 6,9 veces el contenido de digoxina y digitoxina respectivamente. La elicitación con el jasmonato de metilo provocó una reducción de la biomasa. Los contenidos de digoxina y digitoxina se incrementaron ligera y significativamente con 80 y 100 µM de jasmonato de metilo respectivamente. El mejor resultado integral se obtuvo con 0,01 g.L-1 de SilioPlant, el cual indujo la mayor producción neta de cardenólidos por frasco de cultivo (4,72 µg digoxina y 88,27 µg digitoxina).


Digitalis purpurea L. is one of the main sources of cardenolides such as digitoxin and digoxin. These drugs are widely used to strengthen cardiac diffusion and to regulate heart rhythm. The aim of this study was to evaluate the influence of three elicitors on shoots of Digitalis purpurea var. Roter Berggold in semisolid media in order to increase cardenolides biosynthesis. Elicitation is a strategy to increase biomass and secondary metabolites production on in vitro cultures. The elicitors evaluated were ChitoPlant (0,001; 0,01; 0,1 g.L-1); SilioPlant (0,01; 0,1; 1,0 g.L-1) and Methyl jasmonate (60, 80, 100 µM), which are reported here to induce cardenolide production for first time. Elicitation resulted an effective strategy to increase cardenolide production on D. purpurea shoot cultures. ChitoPlant induced a decrease in shoots length, but had no effect on the rest of morphological parameters evaluated. As well, ChitoPlant increased cardenolide content. SilioPlant (0,01 g.L-1) did not affect biomass production and at the same time, increased in 3,6-fold and 6,9-fold digoxin and digitoxin content respectively. Elicitation with Methyl jasmonate resulted in decreased biomass production. Digoxin and digitoxin content was slight and significantly increased by Methyl jasmonate 80 and 100 µM respectively. The best integral result was reached with 0,01 g.L-1 of SilioPlant, which induced the highest net yields per culture flask (4,72 µg of digoxin and 88,27 µg of digitoxin).


Subject(s)
Cardenolides , Digitalis , Digitoxin , Digoxin
3.
Article in English | WPRIM | ID: wpr-819821

ABSTRACT

OBJECTIVE@#To investigate possible mechanism of toxicarioside A in HS-5 bone stromal cells.@*METHODS@#HS-5 bone stromal cells were cultured in media supplemented with various concentrations of toxicarioside A or control DMSO (not treatment). Endoglin and TGF-β were detected by Northern and Western blot analysis and quantified in a standard method. Downstream molecules of endoglin and TGF-β (Smad1, Smad2 and their active phosphorylated counterparts, pSmad1 and pSmad2) were also detected and quantified by Western blot analysis. In addition, cell proliferation assay and small interfering RNA (siRNA) against endoglin were used to certificate the function of endolgin in the HS-5 cells.@*RESULTS@#Compared with the not treated (0 μg/mL) or DMSO treated control HS-5 cells, HS-5 cells treated with toxicarioside A were found significant attenuation of endolgin and TGF-β expression. Significant inhibition of cell proliferation was also found in the HS-5 cells treated with toxicarioside A. ALK1-related Smad1 and ALK5-related Smad2 were decreased in HS-5 cells treated with toxicarioside A. In addition, phosphorylated Smad1 (pSmad1) and Smad2 (pSmad2) were also found attenuation in toxicarioside A-treated HS-5 cells. RNA interference showed that blockage of endoglin by siRNA also decreased Smad1 and Smad2 expression in HS-5 cells.@*CONCLUSIONS@#Our results indicate that toxicarioside A can influence bone marrow stromal HS-5's function and inhibit HS-5 cell proliferation by alteration of endoglin-related ALK1 (Smad1) and ALK5 (Smad2) signaling.


Subject(s)
Antiaris , Antigens, CD , Metabolism , Blotting, Northern , Blotting, Western , Bone Marrow Cells , Metabolism , Cardenolides , Pharmacology , Cell Line , Cell Proliferation , Endoglin , Humans , Male , Receptors, Cell Surface , Metabolism , Signal Transduction , Smad1 Protein , Metabolism , Smad2 Protein , Metabolism , Stromal Cells , Transforming Growth Factor beta , Metabolism
4.
Damascus University Journal for Health Sciences. 2012; 28 (1): 181-194
in English | IMEMR | ID: emr-132802

ABSTRACT

Salinity is involved in decline of plant production in arid and semi-arid lands. It is believed that Ca[2+] maintains the structural integrity of the plasmo membrane by cross linking the negatively charged head groups of the plasmo membrane. In this paper we study the effect of salinity on cardinolid synthesis in Adonis autumnalis plants. Plants of Adonis autumnalis [Aleppo] were grown in three salinity conditions: 25, 50 and 100 mM NaCl, during 22 weeks. Leaves of stressed plants had a higher K[+] and Na[+] contents and a lower Ca content than leaves of control plants, K[+]/Na[+] ratio of leaves of stressed plants become a lower than 1 when the senescence was started. Na[+]/Ca[2+] ratio became a higher the higher the salinity conditions were and the longer the time of stress. The roots of stressed plants had lower K[+] content in higher salinity and as longer the time of stress. The Na[+] content of roots of stressed plants was higher than the Na[+] content in roots of control plants, but decreased at the end of experiment due to necrosis and loss of young parts of roots. Ca[2+] content in roots was lower as the salinity stress was higher. The Na[+]/Ca[2+] ratio in roots was maintained low, due to necrosis and loss of young parts of roots. Salinity and ionic disequilibrium did not interfered significantly on cardinolids metabolism. The content of cardinolids did not changed significantly in salinity conditions until the death of the plants. The slight ionic imbalance, which reaches weak levels of salinity, leads to the activation of the cadiotonic glycosides accumulation in the leaves of Adonis autumnalis, and in doing so, it leads to increasing the concentrations of the cardionolides in the leaves and roots of Adonis autumnalis which have been treated at at the salinity of 25mM.


Subject(s)
Salinity , Sodium Chloride , Plant Leaves , Plant Roots , Cardenolides
5.
Chinese Medical Journal ; (24): 3468-3475, 2011.
Article in English | WPRIM | ID: wpr-336545

ABSTRACT

<p><b>BACKGROUND</b>Endogenous 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.</p><p><b>METHODS</b>Ninety-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.</p><p><b>RESULTS</b>Intracerebroventricular 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.</p><p><b>CONCLUSION</b>Central 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.</p>


Subject(s)
Animals , Blotting, Western , Cardenolides , Metabolism , Central Nervous System , Metabolism , Cystathionine beta-Synthase , Metabolism , Cysteine , Pharmacology , Hemodynamics , Hydrogen Sulfide , Metabolism , Pharmacology , Male , Radioimmunoassay , Rats , Rats, Sprague-Dawley , Saponins , Metabolism , Sodium-Potassium-Exchanging ATPase , Metabolism , Sulfurtransferases , Metabolism
6.
Article in Chinese | WPRIM | ID: wpr-253099

ABSTRACT

<p><b>AIM</b>To study the effect of antidigoxin antiserum on oxygen stress induced by myocardial ischemia/reperfusion (MI/R) injury in rats.</p><p><b>METHODS</b>Sprauge 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>Antidigoxin 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.</p>


Subject(s)
Animals , Cardenolides , Digoxin , Pharmacology , Immune Sera , Pharmacology , Malondialdehyde , Myocardial Reperfusion , Myocardial Reperfusion Injury , Rats , Rats, Sprague-Dawley , Saponins , Sodium-Potassium-Exchanging ATPase , Metabolism , Superoxide Dismutase , Metabolism
7.
Acta Pharmaceutica Sinica ; (12): 104-107, 2007.
Article in Chinese | WPRIM | ID: wpr-281917

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Phytogenic , Chemistry , Pharmacology , Apocynaceae , Chemistry , Apoptosis , Cardenolides , Chemistry , Pharmacology , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Cell Survival , Dose-Response Relationship, Drug , Drugs, Chinese Herbal , Chemistry , Pharmacology , Flow Cytometry , HL-60 Cells , Humans , Inhibitory Concentration 50 , Microscopy, Fluorescence , Molecular Structure , Plant Roots , Chemistry , Plants, Medicinal , Chemistry
8.
Indian J Exp Biol ; 2004 Apr; 42(4): 413-8
Article in English | IMSEAR | ID: sea-62566

ABSTRACT

Active compound oleandrin extracted from Nerium indicum (Lal Kaner) leaf has potent piscicidal activity. The piscicidal activity of oleandrin on freshwater fish C. punctatus was both time and dose dependent. Exposure to sub-lethal doses of oleandrin for 24hr and 96hr to fish caused significant alteration in the level of total protein, total free amino acid, nucleic acid, glycogen, pyruvate, lactate and enzyme protease, phosphatases, alanine aminotransferase, aspartate aminotransferase and acetylcholinesterase activity in liver and muscle tissues. The alterations in all the above biochemical parameters were also significantly time and dose dependent. The results show a significant recovery in all the above biochemical parameters, in both liver and muscle tissues of fish after the 7th day of the withdrawal of treatment. Toxicity persistence test of oleandrin on juvenile Labeo rohita shows that fish seed of common culturing carp can be released into rearing ponds after three days of oleandrin treatment. It supports the view that the oleandrin is safer and may be useful substitute of other piscicides for removing the unwanted freshwater fishes from aquaculture ponds.


Subject(s)
Acetylcholinesterase/metabolism , Alanine Transaminase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Cardenolides/chemistry , Cardiac Glycosides/chemistry , Dose-Response Relationship, Drug , Glycogen/metabolism , India , Lactic Acid/metabolism , Lethal Dose 50 , Liver/chemistry , Muscles/chemistry , Perciformes/physiology , Plant Extracts/toxicity , Plant Leaves/toxicity , Pyruvic Acid/metabolism
9.
Neurol India ; 2002 Sep; 50(3): 340-7
Article in English | IMSEAR | ID: sea-121359

ABSTRACT

A family with coexistence of hypotension, recurrent respiratory infection, motor tics, obsessive compulsive disorder, major depressive disorder, early onset osteoporosis, low body mass index, bulimia nervosa and healthy aging with longevity is described. The family members had hyposexual behavior, less tendency for spirituality, had no insomnia but a tendency towards increased somnolence, no addictive behaviour, had more bonding and affectionate behavior and were less creative with an average IQ. There was no vascular thrombosis, systemic neoplasm and neuronal degeneration in the index family. All members of the family were left hemispheric dominant. The level of serum digoxin, HMG CoA reductase activity and dolichol was found to be decreased in all with a corresponding increase in RBC Na(+)-K(+) ATPase activity and serum ubiquinone magnesium level. There was increase in tyrosine catabolites and a reduction in tryptophan catabolites in serum. Total and individual glycosaminoglycan fractions, carbohydrate residues of glycoproteins, glycolipids, activity of GAG degrading enzymes and glycohydrolases were decreased in serum. The concentration of RBC membrane total GAG and carbohydrate residues of glycoproteins increased while cholesterol : phospholipid ratio of membrane decreased. The activity of free radical scavenging enzymes were increased while the concentration of free radicals decreased significantly. The same biochemical patterns were observed in left hemispheric dominance as opposed to right hemispheric dominance. The significance of these findings in the pathogenesis of these disorders is discussed.


Subject(s)
Cardenolides , Depressive Disorder, Major/genetics , Digoxin/blood , Dolichols/metabolism , Dominance, Cerebral , Family Health , Female , Humans , Hydroxymethylglutaryl CoA Reductases/metabolism , Male , Obsessive-Compulsive Disorder/genetics , Pedigree , Saponins/blood , Sodium-Potassium-Exchanging ATPase/metabolism , Ubiquinone/metabolism
10.
J Indian Med Assoc ; 1999 Oct; 97(10): 407-10
Article in English | IMSEAR | ID: sea-99176

ABSTRACT

Yellow oleander (Thevetia neriifolia) is a commonly grown tree found widely in Eastern India. The seeds of yellow oleander are highly poisonous and contain three glycosides--thevetin, thevetoxin and peruvoside. Yellow oleander seed ingestion is usually with suicidal intent in Eastern India. Manifestations range from mild to potentially fatal. It has significant cardiovascular effects with varying rhythm abnormalities. Effects of yellow oleander seed ingestion (YOI) were studied in 300 patients from 1986 to 1990 at BS Medical College, Bankura. Majority i.e., 246 (82%) were females and 226 (75.33%) were young in the age group 11-20 years. Most reported for treatment 6 to 8 hours after ingestion of seeds. The number of seeds swallowed varied from half to fifteen. Two hundred and ninety-two (97.33%) ingested seeds in the crushed form; 156 (52%) were asymptomatic, 92 (30.66%) had vomiting and 36 (12%) had palpitation. In electrocardiogram (ECG), 138 (46%) revealed varying types of arrhythmias including sinus bradycardia in 68 cases (49.27%). Ischaemic changes were present in 118 cases (39.33%). Number of seeds ingested did not bear any relationship with ECG changes in YOI. All 14 cases of death were autopsied. Subendocardial and perivascular haemorrhage with focal myocardial oedema was present in all. Median hospital stay was 5 days (range 2 to 24). During discharge, 256 (85.33%) had normal ECG, 14 (4.66%) had sinus bradycardia and 16 (5.33%) demonstrated ischaemic changes.


Subject(s)
Adolescent , Adult , Age Distribution , Aged , Arrhythmias, Cardiac/chemically induced , Cardenolides/poisoning , Child , Electrocardiography , Female , Humans , India/epidemiology , Length of Stay/statistics & numerical data , Male , Middle Aged , Plant Poisoning/epidemiology , Plants, Toxic/poisoning , Seeds/chemistry , Sex Distribution , Suicide, Attempted/statistics & numerical data
12.
Bulletin of Faculty of Pharmacy-Cairo University. 1998; 36 (3): 147-9
in English | IMEMR | ID: emr-47810

ABSTRACT

The ethanolic extract of the flowers of the Egyptian species of Cheiranthus cheiri L. [Cruciferae] showed significant cytotoxicity against 2 different cancer cell lines. Bioassay-guided fractionation led to the isolation of 2 cardenolides, strophanthidin 1, and helveticoside 2, where the latter demonstrated potent activity against 6 cell lines tested, especially A-549 [human lung carcinoma]. This study was the first report for the isolation of cardenolides from the flower of Cheiranthus cheiri L. and the first report for cytotoxicity of helveticoside


Subject(s)
Cardenolides/isolation & purification , Cytotoxicity Tests, Immunologic , Plants
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