Evaluation of epirubicin-induced acute oxidative stress toxicity in rat liver cells and mitochondria, and the prevention of toxicity through quercetin administration.

Anticancer therapy with epirubicin (EPI) results in acute hepatotoxicity, likely due to the generation of free radicals. However, the oxidative status of rat liver cells and mitochondria after EPI toxicity has not been investigated. In the present study, we first investigated the pro-oxidant effect of EPI on both hepatic cells and mitochondrial function. Injection of EPI into rats at a dose of 9mg/kg (cumulative dose in human chemotherapy), induced hepatic dysfunction, as revealed by a significant increase in serum glutamate oxaloacetate transaminases (SGOT) and glutamate pyruvate transaminases (SGPT). Oxidative stress in liver cells and mitochondria was provoked by EPI because a statistically significant reduction of catalase (CAT), superoxide dismutase (SOD) and cytosolic glutathione (GSH) levels, and a significant increase in malonedialdehyde (MDA) levels - an indicator of lipid peroxidation that can perforate biological membranes - were observed. Second, the protective effect of quercetin (QE) (0.33mg/kg) against EPI-induced oxidative stress was also investigated. Indeed, the pretreatment of rats with QE protected liver cells and mitochondria from oxidative stress. This treatment prevented hepatic dysfunction by maintaining normal levels of serum transaminases following the inhibition of their hepatic leakage by preventing lipid peroxidation. Thus, QE works through the prevention of cellular membrane perforation and the antioxidant defense system of mitochondria from liver cells, which represent compartments for the permanent production of reactive oxygen species (ROS) through the respiratory chain.

Chemical composition and antioxidant potential of Ruta montana L. essential oil from Algeria.

The essential oil of aerial parts of Ruta montana L. growing in the Oran region in the west of Algeria was obtained by hydrodistillation with a 1.63% yield on a dry weight basis. Gas chromatography (GC) and GC/mass spectrometry (MS) analyses were carried out to identify the chemical composition of R. montana essential oil. Moreover, spectrophotometric analyses were employed to highlight the scavenger capacity of this oil using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. Twenty compounds were identified by GC and CG/MS analyses, and the bulk of the compounds of the oil were undecan-2-one (32.8%), nonan-2-one (29.5%), nonanol-2-acetate (18.2%), and psoralen (3.5%). The results obtained using the DPPH test show that R. montana essential oil possesses antiradical activity in a concentration-dependent manner. Thus, a linear correlation (correlation coefficient R(2) = 0.971, P < .001) was found between the reduction of DPPH stable free radical and the concentration of R. montana essential oil.

Preliminary study on immunological and behavioural effects of Thymus broussonetii Boiss., an endemic species in Morocco.

In the present work, we had tried to evaluate the immunotropic and behavioural effects of Thymus broussonetii Boiss. So, we tested the neurostimulant effects of four extracts. This preliminary study allowed to identify both the immunostimulant and the neurotropic antistress effects of the studied extracts. Among the four extracts, only the aqueous and ethyl acetate ones showed an apparent effect on the tested biological activities, whereas the butanolic extract and the essential oil did not show any interesting effect (data not shown). These results showed that the aqueous and ethyl extracts of this endemic species are of interest for two reasons: stimulation of the immunizing system and protection against the stress by a neurotropic activity. Thyme extracts increased in vivo the number of leucocyte categories studied including polynuclears, total lymphocytes, TCD4+, TCD8+ and NK cells. These data suggest that the intraperitoneal administration of Thymus broussonetii extract has a potent direct effect on leucocytes in vivo. The elevation of leucocyte and thrombocyte counts produced by thyme in the peripheral blood was already reported in the literature. These results could be of practical importance in the field of phytotherapy in the treatment of some cases of human immunodeficiency such as cancer, leukaemia and AIDS.

Consumption of argan oil (Morocco) with its unique profile of fatty acids, tocopherols, squalene, sterols and phenolic compounds should confer valuable cancer chemopreventive effects.

The aim of this study was to evaluate the fatty acids, tocopherols, squalene, sterols and phenolic antioxidants in three types of argan oil (Moroccan food, Moroccan aesthetic and a French commercial variety) along with a basic comparison with extra virgin olive and sunflower oil. The fatty acid profiles in the argan oils were very similar, with oleic acid (43%) and linoleic acid (36%) and their respective monoacylglycerols predominating. The major vitamer identified was -tocopherol with a mean of 483+/-11 mg/kg, in contrast to -tocopherol, which is the major vitamer in olive (190+/-1 mg/kg) and sunflower oil (532+/-6 mg/kg). The squalene content of the argan oils was very similar with a mean of 313+/-4 mg/100 g, which is lower than that of the olive oil (499 mg/100 g) but significantly higher than in the sunflower oil (6 mg/100 g). In contrast to olive and sunflower oils in which -sitosterol is predominant, the major sterols detected in the argan oils were schottenol (mean 147+/-10 mg/kg) and spinasterol (mean 122+/-10 mg/kg). The only phenolic compounds other than the tocopherol vitamers which could be readily detected and quantitated were vanillic, syringic and ferulic (probably conjugated to glucose) acids along with tyrosol. In contrast to the extra virgin olive oil (793 mg/kg), the concentration of total phenolic compounds is extremely low (<5.0 mg/kg). Nevertheless, argan oil with its high content of the vitamer -tocopherol, squalene and oleic acid is likely to enhance the cancer prevention effects of the Moroccan diet.

Neurotropic, immunological and gastric effects of low doses of Atropa belladonna L., Gelsemium sempervirens L. and Poumon histamine in stressed mice.

Previous studies realized in the laboratory have indicated that application of experimental stress (such as unavoidable footshock) induced significant behavioral, gastric and immunological alterations in mice. The aim of this study was to evaluate effects of low doses of Atropa belladonna L., Gelsemium sempervirens L. and Poumon histamine on stress-induced behavioral, immunological and gastric alterations. Locomotor, postural and exploratory activities have been evaluated by two behavioral tests: light/dark box and staircase tests. Immunological studies were investigated to count white blood cells subpopulations (lymphocytes, neutrophils, monocytes and basophils) by coulter counter. The severity of gastric erosions was evaluated by microscopic technique in mice after experimental stress. The results have demonstrated that low doses of G. sempervirens L. and A. belladonna L. had a significant neurotropic and protective effects on behavioral and gastric alterations induced by experimental stress. The immunological protective effects observed were probably induced via their neurotropic effects. The P. histamine showed a significant immunoprotective and gastroprotective effect in mice exposed to experimental stress.

Behavioral and pharmaco-toxicological study of Papaver rhoeas L. in mice.

A lyophilized ethanolic aqueous extract of Papaver rhoeas petals was evaluated for its behavioral and pharmaco-toxicological effects in mice and its chemical composition was studied using thin layer chromatography (TLC). In this study, chemical analysis by TLC showed that the petals contain some anthocyanins, whereas no alkaloids were detected. The toxicological effect of alcoholic and aqueous plant extract administered intraperitoneally was determined in mice. The toxicological results obtained indicated that 2000 mg/kg is LD10 and 4000 mg/kg is LD50. Behavioral and pharmacological studies of ethanolic and aqueous extract showed that the plant extract reduced locomotory, exploratory and postural behavior of mice. This was evaluated through two specific behavioral tests; a non-familiar environment test (the Staircase test) and a familiar environment test (Free exploratory test). These behavioral and pharmacological effects are more pronounced when the solvent used for extraction is 10% ethanol and is not antagonized by benzodiazepines, opioids, dopaminergic and cholinergic compounds (flumazenil, naloxone, sulpuride and atropine). The plant extract did not induce sleep in mice after treatment with an infrahypnotic dose of pentobarbital. This finding shows that the plant extract has a sedative effect at a 400 mg/kg dosage.

A new flavonoid from the aerial parts of Chrysanthemum viscidehirtum.

From the aerial parts of Chrysanthemum viscidehirtum, a new flavonoid, 2"-glucosyl-8-C-glucosyl-4'-O-methylapigenin (1) was isolated.

Antibacterial and molluscicidal activities of the essential oil of Chrysanthemum viscidehirtum.

The volatile fraction of Chrysanthemum viscidehirtum aerial parts, consisting mainly of limonene, beta-farnesene and many oxygenated sesquiterpenes, was screened for activity against 21 microbial strains. This essential oil exhibited activity against all germs tested, in particular Salmonella typhi and Proteus mirabilis. It also showed molluscicidal activity against Bulinus truncatus.

Behavioural effects of Passiflora incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse.

Lyophilised hydroalcoholic and aqueous extracts of the aerial parts of Passiflora incarnata L. (Passifloraceae) (Passion-flower), as well as chemical constituents of the plant, indole alkaloids (harman, harmin, harmalin, harmol, and harmalol) maltol and flavonoids (orientin, isoorientin, vitexin and isovitexin) were assessed for behavioral effects in mice. The accordance with the traditional use of P. incarnata, psychotropic properties were confirmed by some behavioral tests in mice. The anxiolytic properties of hydroalcoholic extract were confirmed at 400 mg/kg by the increase of rears and steps climbed in the staircase test (non-familiar environmental test), and the increase in locomotion and time spent in light side in the light/dark box choice test (non-familiar environmental test). The sedative properties of aqueous extract were confirmed at 400 g/kg by decrease of rears and steps climbed in the staircase test and the decrease of rears and locomotion in the free exploratory test. Moreover, the aqueous extract induced sleep in mice after treatment with a sub-hypnotic dose of pentobarbital.

The role of stomachal digestion on the pharmacological activity of plant extracts, using as an example extracts of Harpagophytum procumbens.

Various researchers have described anti-inflammatory activity of aqueous extracts of devil's-claw (Harpagophytum procumbens DC.). In this study the extent of the anti-inflammatory activity of an aqueous extract prepared from cryoground fresh plant and administered intraperitoneally, per os (by gavage), and intraduodenally was determined in rats. The anti-inflammatory properties were assessed by applying the carrageenan-induced edema test. The results obtained indicated that intraperitoneal pretreatment with an aqueous extract of H. procumbens significantly reduced the carrageenan-induced edema at 400 and 800 mg/kg 4 h after carrageenan injection (45 and 65% inhibition, respectively). When administered orally (by gavage), the extracts were inefficient. This result could be attributed to the time in transition in the stomach, where the pH is acidic, causing a decrease of the activity of the extract. This inference is consistent with the results obtained by other authors, showing the absence of extract activity when it was treated in an environment of pH 1 and 37 degrees C (similar to the physicochemical conditions found in the stomach) and then administered intraperitoneally. Intraduodenal pretreatment with the aqueous extract significantly reduced the carrageenan-induced edema at 200, 400, and 1600 mg/kg 6-9 h after carrageenan injection (43, 60, and 41% inhibition, respectively). The presence of extract activity after intraduodenal administration supports the assumption that transition of the extract through the stomach leads to loss of activity.

Neurotropic action of the hydroalcoholic extract of Melissa officinalis in the mouse.

A lyophilised hydroalcoholic extract of Melissa officinalis L. (Lamiaceae) has been evaluated for behavioral effects in mice. According to the traditional use of M. officinalis, sedative properties have been confirmed for low doses by the decrease of behavioral parameters measured in a non-familiar environment test (staircase test) and in a familiar environment test (two compartment test). With high doses, a peripheral analgesic activity was obtained by reducing the acetic acid-induced pain (writhing test); moreover, the plant extract induced the sleep in mice after treatment with an infrahypnotic dose of pentobarbital and potentialised the sleep induced by a hypnotic dose of pentobarbital.

Hepatoprotective and anti-inflammatory effects of a traditional medicinal plant of Chile, Peumus boldus.

Dried hydro-alcoholic extract of Peumus boldus (Monimiaceae) has been evaluated for hepatoprotective, choleretic and anti-inflammatory effects in mice and rats, in order to validate or to invalidate traditional therapeutic indications. This extract exerted a significant hepatoprotection of tert-butyl hydroperoxide-induced hepatotoxicity in isolated rat hepatocytes (in vitro technique) by reducing the lipid peroxidation and the enzymatic leakage of LDH; this in vitro efficacy was reinforced by a significant hepatoprotection on CCl4-induced hepatotoxicity in mice (in vivo technique), the plant extract reducing the enzymatic leakage of ALAT. Boldine, the main alkaloid of P. boldus appears to be implicated in this hepatoprotective activity. Choleretic effects, often mentioned in traditional indications, have not been confirmed in rats. Finally, significant and dose-dependent anti-inflammatory effects were obtained on an acute inflammatory process (carrageenan-induced edema test in rats). Boldine does not appear to be involved in such properties.