Behavioral effects of Euphorbia hirta L.: sedative and anxiolytic properties.

Lyophilised aqueous extract of Euphorbia hirta L. (Euphorbiaceae) has been evaluated for behavioral effects in mice. The extract did not induce any toxic effect when it was administered i.p. and orally. Sedative properties could be confirmed with high doses (100 mg of dried plant/kg, and more), by a decrease of behavioral parameters measured in non-familiar environment tests (activitest and staircase test), whereas anticonflict effects appeared at lower doses (12.5 and 25 mg of dried plant/kg), by an enhancement of behavioral parameters measured in the staircase test and in the light/dark choice situation test. These findings validate the traditional use of E. hirta as a sedative and reveal original anxiolytic properties.

Nickel absorption and distribution from rat small intestine in situ.

The aim of this work was to study the absorption of nickel chloride in rats by means of the intestinal perfusion in situ technique at nickel concentrations of 1, 5, 10, 25, and 100 mg/L. Active transport and facilitated diffusion seem to play an important role in the intestinal absorption of nickel at concentrations < or = 10 mg/L. At higher concentrations, the absorption rate would be limited by saturation of the carriers. The distribution of the absorbed nickel was studied by intestinal perfusion of a 10-mg Ni/L solution for 30 or 60 min. Both in concentration and amount, the jejunum showed the higher values of absorbed nickel, followed by the kidneys and liver. When all of the collected organs (brain, heart, liver, lungs, spleen, kidneys, and testicles) and blood, but not the small intestine, are analyzed following a 60-min perfusion, it was found that 1% of the initial concentration had passed through the intestinal barrier.

Bioavailability and intestinal absorption of aluminum in rats: effects of aluminum compounds and some dietary constituents.

In the present investigation, the deposition of aluminum in intestinal fragment and the appearance in blood were studied in a perfused rat intestine in situ for 1 h with several aluminum forms (16 mM). We observed that aluminum absorption was positively correlated with the theoretic affinity of aluminum and the functional groups of the chelating agent. The absorption of aluminum after ingestion of organic compounds is more important than after ingestion of mineral compounds, with the following order: Al citrate > Al tartrate, Al gluconate, Al lactate > Al glutamate, Al chloride, Al sulfate, Al nitrate. Absorption depends on the nature of the ligands associated with the Al3+ ion in the gastrointestinal fluid. The higher the aluminum retention in intestinal fragment, the lower the absorption and appearance in blood. However, the higher aluminum concentration is always in the jejunal fragment because of the influence of pH variation on this fragment. Another objective of the present study was to determine the influence of several parameters on aluminum citrate absorption: with or without 0.1 mmol dinitrophenol/L, with aluminum concentration from 3.2, 16, 32, and 48, to 64 mmol/L, media containing 0, 3, or 6 mmol Ca/L, with or without phosphorus or glucose. It is concluded that aluminum is absorbed from the gastrointestinal tract by (1) a paracellular energy independent and nonsaturable route, mainly used for high aluminum concentration, which is modified by extracellular calcium, and (2) a transcellular and saturable route, the aluminum level was not modified with enhancement of aluminum quantity in intestinal lumen. This pathway can be similar with calcium transfer through the intestine and is energy dependent because of a decrease of aluminum absorption that follows the removal of glucose and phosphorus.

In vitro and in vivo studies on chelation of manganese.

This work deals with new chelating agents of manganese (Mn). Out of 24 compounds chosen for their chemical structure supposed to be favorable for Mn complexation, six polyaminopolycarboxylic acids proved to be efficient for displacing Mn bound to serum bovine proteins in vitro: TTHA, DTPA, DPTA, DPTA-OH, HBED, EDTA (mobilization > or =50%). The first five compounds were then tested in vivo on rats pretreated with MnCl2. They exhibited only slight to moderate efficacy to diminish Mn in tissues and were ineffective on increased Mn concentration in whole blood; in addition, they had different and specific mobilizing effects on other essential elements (Fe, Zn, Cu). Their limited efficacy in vivo could be due to the formation of very stable complexes between Mn2+ and different molecules such as hemoglobin and certain cytochromes, instead of Fe2+. This could disturb the functioning of the cellular respiratory chain, leading to an incomplete reduction of O2 with formation of free oxygenated radicals, reduction in the energy supply, and disturbance of the cytochromes renewal mechanism. All of these phenomena could accelerate cellular aging and explain the lack of efficacy of the chelating agents towards Mn neurotoxicity (Parkinson's syndrome).

Anti-inflammatory and analgesic effects of an aqueous extract of Harpagophytum procumbens.

The dried aqueous extract of Harpagophytum procumbens (Pedaliaceae) and its main iridoid glycoside, harpagoside, have been evaluated for anti-inflammatory and analgesic effects in mice and rats, in order to validate or invalidate the involvement of this compound in such properties. This extract exerted significant and dose-dependent anti-inflammatory and analgesic effects, from the dose 100 mg of dried secondary roots/kg, the first being obtained on an acute inflammatory process (carrageenan-induced edema test in rats) and the second being obtained against a chemical stimulus (writhing test in mice). Harpagoside does not appear to be involved in anti-inflammatory properties, since this iridoid glycoside did not protect against carrageenan inflammatory effects when it was used at 5 and 10 mg/kg; 5 mg corresponding to the quantity contained in 400 mg of dried secondary roots. The main iridoid glycoside of H. procumbens appears to be implicated in the peripheral analgesic properties of this species, but other compounds have to be involved, since the dose of 10 mg/kg exerted a significant protective effect. The absence of the activity of H. procumbens after an acid treatment (0.1 N hydrochloric acid), stomach, suggests the use of a suitable galenic preparation in order to protect the active principles from the action of the acid released in the stomach.

Analgesic, antipyretic and anti-inflammatory properties of Euphorbia hirta.

Lyophilised aqueous extract of Euphorbia hirta L. (Euphorbiaceae) has been evaluated for analgesic, antipyretic and anti-inflammatory properties in mice and rats, in order to complete its activity profile, after the confirmation of the existence of a central depressant activity particularly expressed by a strong sedative effect, associated with anxiolytic effects. This study leads us to the conclusion that this plant extract exerts central analgesic properties. Such a dose-dependent action was obtained against chemical (writhing test) and thermic (hot plate test) stimuli, respectively, from the doses of 20 and 25 mg/kg and it was inhibited by a naloxone pretreatment, a specific morphinic antagonist compound. An antipyretic activity was obtained at the sedative doses of 100 and 400 mg/kg, on the yeast-induced hyperthermia. Finally, significant and dose-dependent anti-inflammatory effects were observed on an acute inflammatory process (carrageenan-induced edema test in rats) from the dose of 100 mg/kg. On the other hand, plant extract remained inactive on chronic processes such as Freund's adjuvant-induced rheumatoid arthritis, after a chronic treatment during fourteen days at the daily dose of 200 or 400 mg/kg; however, if inefficacy was observed on rat backpaws edema and on loss of weight, the aqueous extract reduced the inflammatory hyperalgia.

Influence of Anisotes trisulcus and Crepis rueppellii extracts on sites of bile formation in the rat.

Anisotes trisulcus and Crepis rueppellii, two medicinal plants from Yemen, have been investigated for their hepatobiliary properties. A study of their choleretic effect and of sites of bile formation was carried out in the rat, by evaluation of bile flow, bile acids output and 14C-erythritol clearance. The data suggest that both extracts of these plants induce hypercholeresis, but Anisotes would stimulate the bile acid-dependent fraction and Crepis the bile acid-independent fraction.

Neurophysiological effects of an extract of Eschscholzia californica Cham. (Papaveraceae).

An aqueous alcohol extract of Eschscholzia californica (Ec) has been evaluated for benzodiazepine, neuroleptic, antidepressant, antihistaminic and analgesic properties, in order to complete the study of the sedative and anxiolytic effects previously demonstrated. The plant extract did not protect mice against the convulsant effects of pentylenetetrazol, and did not cause muscle relaxant effects but appeared to possess an affinity for the benzodiazepine receptor: thus, flumazenil, an antagonist of these receptors, suppressed the sedative and anxiolytic effects of the extract. The Ec extract induced peripheral analgesic effects in mice but did not possess antidepressant, neuroleptic or antihistaminic effects.

Analgesic and behavioural effects of Morinda citrifolia.

The traditional therapeutic indications for the use of Morinda citrifolia L. (Rubiaceae) have been investigated. The lyophilised aqueous extract of roots of M. citrifolia was evaluated for analgesic and behavioural effects in mice. The extract did not exhibit any toxic effects but did show a significant, dose-related, central analgesic activity in the writhing and hotplate tests; this effect was confirmed by the antagonistic action of naloxone. Furthermore, administration of M. citrifolia extract at high dosages decreased all behavioural parameters in the two compartment test, the light/dark choice situation test, and the staircase test; together with the induced sleeping time, these results are suggestive of sedative properties.

An analytical study, anti-inflammatory and analgesic effects of Harpagophytum procumbens and Harpagophytum zeyheri.

The iridoids of Harpagophytum procumbens and Harpagophytum zeyheri were studied by CLHP. Harpagoside is the main iridoid for both drugs whereas 8-p-coumaroylharpagide is a representative iridoid of Harpagophytum zeyheri only. The ratio harpagoside/8-p-coumaroylharpagide can be used to distinguish chemically both species. For commercial dried aqueous extracts this ratio is intermediate because they are probably prepared from a mixture of H. procumbens and H. zeyheri drugs. The aqueous extracts of both drugs show similar analgesic and anti-inflammatory properties. Harpagophytum procumbens and Harpagophytum zeyheri should be accepted as sources for the drug Harpagophyti radix.

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.

Behavioural effects of the American traditional plant Eschscholzia californica: sedative and anxiolytic properties.

Eschsholzia californica Cham. is a traditional medicinal plant of the Indians used by the rural population of California for its analgesic and sedative properties. Our study on the aqueous extract shows that this plant reduced the behavioural parameters measured in a familiar environment test in mice (novelty preference, locomotion and rearings in two compartments test) at doses above 100 mg/kg and in non-familiar environment tests (staircase test) at doses above 200 mg/kg. This finding validates its traditional sedative properties confirmed by the sleeping induction at doses above 100 mg/kg. Furthermore, when administered at a dose a of 25 mg/kg, E. californica appeared to also have an anxiolytic action since it produced an increase of the number of steps climbed by mice in the staircase test (anticonflict effect) and that of the time spent by animals in the lit box when they were confronted with the light/dark choice situation. Before evaluation of the behavioural effects, it was verified that our aqueous extract did not induce any toxic effect when administered i.p. and p.o.