Toxicity and neuropharmacological effects of elenine.

Elenine is the aglycone of elenoside, a cytotoxic arylnaphthalene lignan (NSC 644013-W/1) derived from Justicia hyssopifolia. (Family: Acanthaceae). Elenoside is a ß-D-glucoside, with a similar chemical structure to etoposide, exhibiting central depressant activity. In the present study, elenine was given to mice and rats at doses of 10, 20, and 40 mg/kg. Acute toxicity (24 h) and general behaviour in mice was studied as well as its effects on muscular relaxant activity, locomotor activity (Varimex test), and the open-field test and were compared with 10 mg/kg of chlorpromazine. Elenine produced a reduction in the permanence time in muscular relaxant activity (traction test). Spontaneous activity was lower in the Varimex test. The ambulation and rearing were lower compared with the control group, and an increase in boluses was observed in the open-field test. Thus, it can be concluded that elenine has central sedative effects at lower doses than those used with elenoside and has a possible application in conditions of anxiety.

Elenoside increases intestinal motility.

AIM: To study the effects of elenoside, an arylnaph-thalene lignan from Justicia hyssopifolia, on gastro-intestinal motility in vivo and in vitro in rats. METHODS: Routine in vivo experimental assessments were catharsis index, water percentage of boluses, intestinal transit, and codeine antagonism. The groups included were vehicle control (propylene glycol-ethanol-plant oil-tween 80), elenoside (i.p. 25 and 50 mg/kg), cisapride (i.p. 10 mg/kg), and codeine phosphate (intragastric route, 50 mg/kg). In vitro approaches used isolated rat intestinal tissues (duodenum, jejunum, and ileum). The effects of elenoside at concentrations of 3.2 x 10(-4), 6.4 x 10(-4) and 1.2 x 10(-3) mol/L, and cisapride at 10(-6) mol/L were investigated. RESULTS: Elenoside in vivo produced an increase in the catharsis index and water percentage of boluses and in the percentage of distance traveled by a suspension of activated charcoal. Codeine phosphate antagonized the effect of 25 mg/kg of elenoside. In vitro, elenoside in duodenum, jejunum and ileum produced an initial decrease in the contraction force followed by an increase. Elenoside resulted in decreased intestinal frequency in duodenum, jejunum, and ileum. The in vitro and in vivo effects of elenoside were similar to those produced by cisapride. CONCLUSION: Elenoside is a lignan with an action similar to that of purgative and prokinetics drugs. Elenoside, could be an alternative to cisapride in treatment of gastrointestinal diseases as well as a preventive therapy for the undesirable gastrointestinal effects produced by opioids used for mild to moderate pain.

Central nervous activity of elenoside.

Elenoside is a cytotoxic arylnapthalene lignan (NSC 644013-W/1) derived from Justicia hyssopifolia (Family: Acanthaceae). The neuropharmacological activity of this lignan, a beta-D-glucoside was studied. The LD50 (24 h) of elenoside in mice is 305 +/- 7 mg/kg by i.p. route. In the present study elenoside was given to rats at doses of 25 and 50 mg/kg, and its effects on locomotor activity (Varimex test), muscular relaxant activity, open-field test and with chlorpromazine, 10 mg/kg was compared. On Varimex test, spontaneous activity was reduced. Elenoside produced a reduction in the permanence time on muscular relaxant activity (traction test). On open-field test, ambulation and rearing were reduced compared with the control group and an increase in boluses of dose-dependent rate was obtained. Thus it can be concluded that elenoside has central sedative effects and possible application in anxiety conditions.

Constancia diacrónica de las aguas minerales de Firgas (Islas Canarias) y usos terapéuticos / Diachronic stability of mineral waters from Firgas (Canary Islands) and therapeutics uses

Mediante los trabajos aportados por diferentes historiadores del siglo XIX y XX, se estudian las características de los manantiales de la Cuenca del Barranco de La Virgen en Gran Canaria. Con los análisis físico-químicos y químicos de las Aguas Minerales de Firgas Obtenidos de los Laboratorios de AGuas Minerales de Firgas S.A. y realizados entre 1869-2001, se estudia la evolución iónica de dichas aguas. Con los informes sobre medicina popular y los estudios farmacológicos y terapéuticos obtenidos de las Bibliotecas del Museo Canario (Gran Canaria), de la Facultad de Medicina de la Universidad de La Laguna y realizados entre 1844-1974, se estudian las acciones farmacológicas y usos terapéuticos de las Aguas Minerales de Firgas. En este estudio se aporta, por primera vez, la constancia diacrónica de los iones contenidos en las Aguas Minerales de Firgas, así como la recopilación y análisis de informes sobre medicina popular, acciones farmacológicas e indicaciones clínicas descritas por diversos investigadores desde mitad del siglo XVII hasta la actualidad, para esta clase de aguas (AU)

General behavior, toxicity, and cytotoxic activity of elenoside, a lignan from Justicia hyssopifolia.

Cytotoxicity, acute toxicity, and general pharmacological effects in mice of an arylnaphthalene lignan isolated from Jisticia hyssopifolia were studied. Elenoside was cytotoxic to human cancer cell lines in a range of concentrations from 10(-5) to 10(-4)M. It has an LD(50), ip in mice, of 305 mg/kg and central depressive properties at doses of 25, 50, and 100 mg/kg. Thus, elenoside appears to be a sedative with broad spectrum cytotoxicity.

Pharmacological effects of elenoside, an arylnaphthalene lignan.

Acute toxicity (24 h) and general behavior in mice of a lignan from Justicia hyssopifolia, a beta-D-glucoside (elenoside), was studied, and the cytotoxic activity was performed. Elenoside (arylnaphthalene lignan) in mice showed a moderate toxicity order (305 mg/kg) and central depressive properties at doses of 25, 50, and 100 mg/kg. It also displayed cytotoxic activity in a range of concentration of 10(-5)-10(-4) M when studied in the human tumor cell line panel of the US National Cancer Institute (NCI). The results indicated that elenoside has central depressant effects, and the cytotoxic activity of elenoside suggests that this compound and its genin derivatives merit further investigation as antitumoral drugs.

Behavioral despair in mice after prenatal stress.

Maternal stress during pregnancy produced behavioral alterations in both sexes with regard to sexual behavior, aggressive, maternal, lateralization and depression. In the present paper, sex differences for depression in mice was studied. No sex differences between female and male mice groups were observed either in swimming-induced immobility or in the open-field test (ambulation, rearing and boluses). Prenatal stress produced: 1) an increase of immobility time in female mice for swimming-induced immobility, but not in male mice; 2) an increase of ambulation in female mice for open-field test, but not in male mice; 3) there were no significant differences in rearing and boluses between stress and control groups either for female or male mice. Prenatal stress increases the risk of depression and locomotor activity in adult female mice.

Cardiovascular activity of a methanolic extract of Digitalis purpurea spp. heywoodii.

The paper deals with the effects of a glycosidal extract of Digitalis heywoodii, ssp. of Digitalis purpurea L., (Schrophulariaceae) grown in Badajoz (Spain), on isolated cardiac auricle of rabbits, urinary excretion of rats, as well as its emetic effect in pigeons. These effects using vehicle (propylene glycol-ethanol-water, 40:10:50) and digoxin as standards are presented. The extract at concentrations of 20 and 40 microg/ml produced an increase in the contraction force of auricles in a dose-dependent way. At doses of 15 and 30 mg/kg a slight diuretic and natriuretic effect was observed. The active dose range for emesis was 0.5-4 mg/kg and a decrease of the emesis time within 10 min of injection in dose-dependent manner was obtained. The pharmacological activity of the extract is related to gitoxin derivatives (digitalinum verum and strospeside), the most abundant compounds obtained from the leaves of Digitalis purpurea spp. heywoodii.

Action of antidepressant drugs on maternal stress-induced hypoactivity in female rats.

It has been reported that rats forced to swim in a restricted space assume, after initial frenzied attempts to escape, an immobile posture. Porsolt et al. referred to this phenomenon as "behavioral despair", an animal model of depression. Prenatal stress induces an increase of behavioral depression in adult female offspring. This study presents new evidence supporting the hypothesis that maternal stress during gestation increases the risk of depression in the offspring since immobility time was modified by antidepressant drugs (tricyclics and an atypical antidepressant). In rats, amitriptyline (5 mg/kg), imipramine (5 mg/kg) and nomifensine (1 mg/kg) decreased the immobility time in Porsolt test in offspring of mothers stressed during gestation. Moreover, increasing doses of amitriptyline (1, 5, 25 and 40 mg/kg) reduced depression in the forced swimming test in dose-dependent manner.

Motor lateralization, behavioral despair and dopaminergic brain asymmetry after prenatal stress.

This paper presents data suggesting a relationship between rat behavioral despair in the Porsolt test and motor lateralization in the T-maze test. In addition, experimental evidence suggests a functional coupling among dopaminergic systems, behavioral despair and motor lateralization. In the first experiment, female, not male, rats with a high level of behavioral despair showed a low level of behavioral lateralization. The inverse relationship was found in female offspring of mothers stressed during gestation. In comparison with unstressed-mother rats, the female offspring of stressed mothers showed an increase of dopamine (DA) and a decrease of dihydroxyphenylacetic acid (DOPAC) and Homovanillic (HVA) levels and of DOPAC:DA and HVA:DA indexes in the n. accumbens of the right side of the brain. No significant differences were found in the n. accumbens of the left brain. Taken together, the present data provide evidence of a relation between behavioral despair and motor lateralization, suggesting that the biological dopaminergic inervation of n. accumbens could be the basis for this functional coupling. Because the stress of gestant mothers modified these biochemical and behavioral variables, the present study also suggests that lateralization of behavior and emotion during adulthood can be modified by prenatal variables.

A new irregular phenylpropanoid from Apollonias barbujana.

In addition to the known compounds (+/-)-threo-guaiacylglycerol and the phenethyl alcohols, 3-methoxy-4-dihydroxyphenethyl alcohol and 3,4-dimethoxyphenethyl alcohol, a new irregular phenylpropanoid 2-(3-methoxy-4-hydroxyphenyl)-1,3-propanediol was isolated from the ethanolic extract of the leaves of Apollonias barbujana (Lauraceae). Their structures were elucidated on the basis of spectroscopic methods and chemical transformations.

Permanent dopaminergic alterations in the n. accumbens after prenatal stress.

It has been suggested that stress during the initial stages of human life may serve as a predisposing factor to mental illness. Recently, we reported that in pregnant rats, stress induces an increase of behavioral depression in the female offsprings when adult. This article describes the effect of prenatal stress on central dopaminergic transmission during adulthood. The offspring of stressed mothers showed an increase of behavioral depression in the Porsolt test and a reduction of DOPAC, HVA, and DOPAC/DA index in the n. accumbens. The effect on the right accumbens was more marked than on the left. A great body of information exists to suggest that depression is related to a decrease of dopaminergic neurotransmission, and the present data provide new evidence in support of the hypothesis that maternal stress during gestation increases the risk of depression in the offspring. We are also reporting a hitherto uncommented relationship between behavioral depression in the Porsolt test and the decrease of dopamine transmission in the n. accumbens.

Effects of maternal stress during pregnancy on forced swimming test behavior of the offspring.

It has been reported that gonadal steroids modulate brain and behavioral sex differentiation during development. Prenatal maternal restraint also alters development by affecting gonadal steroid levels in the fetus. Prenatal maternal restraint of animals decreases sex differences for sexual behavior, locomotion, aggression, etc. In recent work on animal models, we reported that, like humans, laboratory rats show sex differences in depression. From the present study, performed on Sprague-Dawley rats, we conclude that: 1) there are sex differences for depression in two different animal models (swimming-induced immobility and natatory tests); 2) there are also sex differences in open-field behavior; 3) prenatal maternal restraint decreases sex differences for depression but does not affect sex differences in open-field behavior; 4) prenatal maternal restraint affects female but not male behavior in the two depression tests used. These results suggest that: 1) sex differences reported in animal models of depression are under the control of gonadal steroids during prenatal brain development; 2) stress during early phases of development increases the risk for depression in adulthood.

Sex differences in behavioral despair: relationships between behavioral despair and open field activity.

Many studies have reported sex differences in the rates of depression in humans. Due to experimental problems, the nature of these sexual differences is still unknown. In the present study, we quantify the sex differences in depression using two animal models. Both the Porsolt et al. test and the Hilakivi and Hilakivi forced swimming test have shown that the duration of immobility is higher in the male than in the female. Sexual differences in the animal models of depression are probably unrelated to general activity differences because there is no significant correlation between activity in both tests. However, the correlation between the two models of depression used reached statistical significance. Finally, the immobility levels in the Porsolt test were similar in the different stages of the estrous cycle.