Pharmacological studies on aqueous extract of Launaea arborescens from southwest Algeria.

ETHNOPHARMACOLOGICAL RELEVANCE: Launaea arborescens, its vernacular name is Mol-albina belonging to asteracaea family origin of the southwest of Algeria. This plant is used in folk medicines to treat gastroenteritis, diabetes, child aliment and other diseases; it is taken macerated or boiled. AIM: This study aims to evaluate the anti-inflammation an analgesic activity of the aqueous extract of Launaea arborescens (AqELA) and its pathway of action. METHODS: the investigation of anti-inflammatory and analgesic effects were done using formalin test, acetic acid test. For mechanism investigation, it was used hot plate test to induce opioid receptors, a histamine and serotonin test to induce edema paw, finally, for the TRPV1 receptor, it was used the capsaicin test. RESULTS: The aqueous extract of Launaea arborescens showed a significant inhibition of abdominal writhing test 95% and 100% inhibition of licking paw using acid acetic test and formalin test respectively (EC: 47 mg/kg and 104 mg/kg). The analgesic effect of the aqueous extract of Launaea arborescens showed inhibition of sensation of pain after 120 min compared to morphine effect. The aqueous extract of Launaea arborescens reduced paw volume after 180 min and 120 min for histamine and serotonin respectively with dose-dependent. Concerning of TRPV1 receptors, the inhibition was showed at doses 100 mg and 300 mg. CONCLUSION: Our results contribute towards validation of the traditional use of Launaea arborescens for inflammation ailment.

Anti-Inflammatory and Analgesic Activities of the Complex of Flavonoids from Lychnis chalcedonica L.

Anti-inflammatory and analgesic activities of the complex of flavonoids from Lychnis chalcedonica L. were studied in the models of acute aseptic inflammation induced by carrageenan, histamine, and serotonin and acetic acid-induced painful chemical stimulation. It is demonstrated that course treatment with flavonoids derived from Lychnis chalcedonica L. produced a stable pharmacological effect comparable with that of the reference anti-inflammatory drug diclofenac.

Protective role of the triterpenoid-enriched extract of Trichosanthes dioica root against experimentally induced pain and inflammation in rodents.

Trichosanthes dioica Roxb. (Cucurbitaceae), called pointed gourd in English, is a dioecious climber grown in the Indian subcontinent. This study evaluated the anti-nociceptive and anti-inflammatory effects of triterpenoid-enriched extract of T. dioica root (CETD) in rodents at the doses of 50 and 100 mg kg(-1) body weight po. Anti-nociceptive activity was evaluated by acetic acid-induced writhing and tail flick methods in Swiss albino mice. CETD was evaluated for anti-inflammatory activity in experimental acute (carrageenan-, histamine- and serotonin-induced paw oedema) and chronic models (cotton pellet-induced granuloma) in Wistar albino rats. In writhing test, CETD dose dependently and significantly inhibited writhes; in tail flick test, CETD demonstrated significant increase in reaction time (after 60 and 120 min). In all the anti-inflammatory models, CETD exhibited promising anti-inflammatory activity in a dose-dependent manner. Therefore, T. dioica root afforded remarkable anti-nociceptive and anti-inflammatory protections in the tested rodent models.

Anxiolytic-like effect of a serotonergic ligand with high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors.

S-(-)-2-[[4-(napht-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-alpha]-pyrazine (CSP-2503) is a serotonin (5-HT) receptor ligand with selectivity and high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors. CSP-2503 reduced rectal temperature and 5-HT neuronal hypothalamic activity in mice, decreased electrical activity of raphe nuclei cells in rats and blocked the enhancement of adenylate cyclase activity induced by forskolin in HeLa cells transfected with the human 5-HT1A receptor. This compound also blocked head-twitches induced by the 5-HT(2A/2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Contractions of guinea pig ileum induced by the 5-HT3 receptor agonist 2-methyl-5-HT were prevented by CSP-2503. Moreover, it reduced the bradycardia reflex induced by 2-methyl-5-HT in anaesthetized rats. In the light/dark box and social interaction tests, CSP-2503 presented anxiolytic activity, an action shared by 5-HT1 agonists and 5-HT3 antagonists. Taken together, these results suggest that CSP-2503 is a new 5-HT1 receptor agonist with 5-HT2A and 5-HT3)receptor antagonist activities that might be useful in a number of conditions associated with anxiety.

Laxative and anti-diarrheal activity of polycarbophil in mice and rats.

We investigated the laxative and anti-diarrheal activity of polycarbophil, an insoluble hydrophilic polymer, in comparison with other agents used for treating functional bowel disorder (FBD). In naive rats, polycarbophil (500 mg/kg) increased fecal weight and water contents without producing diarrhea. Carboxymethylcellulose (CMC) did not produce evident changes in bowel movement. Picosulfate markedly produced diarrhea. Loperamide, trimebutine and granisetron decreased stool output dose-dependently. Constipation, indicated by decrease in fecal weight, was produced by loperamide and clonidine in rats. Polycarbophil (500 mg/kg) and CMC increased fecal weight without diarrhea. Conversely trimebutine further decreased fecal weight in constipated rats. Polycarbophil (500 mg/kg) suppressed diarrhea induced by castor oil, and at 250-500 mg/kg, it produced shaped stools in animals with stools loosened by prostaglandin E2, serotonin or carbachol in mice. Polycarbophil (500 mg/kg) also reduced stools in rats with stool output increased by wrap restraint stress (WRS). CMC had no effect in the diarrhea models, except for carbachol-induced diarrhea, and WRS-induced evacuation. Loperamide, trimebutine and granisetron inhibited diarrhea production and WRS-induced evacuation, except for carbachol-induced diarrhea. The results show that polycarbophil prevents constipation and diarrhea without inducing diarrhea or constipation, which is different from the other agents. Hydrophilic polymers such as polycarbophil will be promising agents for the treatment of FBD.

Effects of Cistus laurifolius L. flowers on gastric and duodenal lesions.

The flowers and flower buds of Cistus laurifolius L. are used for the treatment of peptic ulcers. Through the bioassay-guided fractionation of the material, using water immersion and immobilisation-induced stress ulcer model, the EtOH-precipitated part from the aqueous extract (E-H2O decreases) was determined to be the active fraction. For the evaluation of the mode of action, the activity of E-H2O decreases was tested using various ulcer models in rats and mice and this fraction was found active against pylorus ligation-, abs. ethanol-, indomethacin-, indomethacin plus HCl/EtOH-induced gastric and cysteamine-induced duodenal lesions while ineffective against serotonin-induced gastric lesions. The active fraction showed its activity not only on per os administration but also after subcutanous injection. According to the results of biochemical studies, the active fraction showed a potent antiacid activity. In addition, histopathological, and toxicological studies were conducted with the active fraction.

Methamphetamine-induced serotonin neurotoxicity is mediated by superoxide radicals.

Methamphetamine (METH) causes deleterious effects in brain monoaminergic systems. Evidence has accumulated to suggest that these effects may be mediated via the overproduction of the superoxide radicals. We have recently shown that METH-induced dopamine (DA) depletion is attenuated in copper-zinc superoxide dismutase (CuZnSOD) transgenic (Tg) mice. In the present study, we have used receptor autoradiographic studies of [125I]RTI-55 labeled serotonin (5-HT) uptake sites to evaluate the effect of a two dosing schedule (5 mg/kg or 10 mg/kg x 4) of METH on striatal 5-HT uptake sites in nontransgenic (Non-Tg), heterozygous (Hetero) and homozygous (Homo) SOD-Tg mice. The low dose caused no significant changes in striatal 5-HT uptake sites in any of the groups. The high dose caused marked decreases (-74%) in striatal 5-HT uptake sites in Non-Tg mice. In contrast, 5-HT uptake sites showed only a 31% decrease in homozygous SOD-Tg mice whereas heterozygous SOD-Tg mice showed 63% depletion. These results show that increased SOD activity can protect against METH-induced neurotoxicity in striatal serotonergic terminals. These data provide further evidence for a role of oxidative stress in the neurotoxic effects of METH.

Inhibition by actinomycin D of neurogenic mouse ear oedema.

We have investigated the effects of actinomycin D on mouse ear oedema induced by capsaicin, neuropeptides, and established inflammatory mediators. Actinomycin D (0.5 mg/kg, i.v.) significantly (P < 0.01) inhibited ear oedema induced by topical application of capsaicin, while adriamycin (6.0 mg/kg, i.v.) and cycloheximide (6.0 mg/kg, i.v.) had no effect on oedema. The ear oedema induced by intradermal injection of neuropeptides such as mammalian tachykinins, calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP), was markedly (P < 0.05, P < 0.01 or P < 0.001) suppressed by actinomycin D. The drug was also effective (P < 0.01 or P < 0.001) in inhibiting bradykinin (BK)- and compound 48/80-induced ear oedema, but did not inhibit oedema induced by histamine, 5-HT, leukotriene C4 (LTC4), and platelet activating factor (PAF) at a dose of 1 mg/kg. In mast cell-deficient W/WV mice, actinomycin D (1.0 mg/kg, i.v.) failed to inhibit substance P (SP)-induced ear oedema whereas spantide (0.5 mg/kg, i.v.) was an effective (P < 0.01) inhibitor of oedema formation. Furthermore, actinomycin D (10-100 microM) dose-dependently prevented histamine release from rat peritoneal mast cells evoked by SP, compound 48/80, and the ionophore A23182, respectively. These results strongly suggest that an inhibitory effect of actinomycin D on neurogenic inflammation is due primarily to the prevention of mast cell activation mediated by neuropeptides, rather than an interaction with DNA or receptors of neuropeptides.

Assessment of the developmental toxicity of ascorbic acid, sodium selenate, coumarin, serotonin, and 13-cis retinoic acid using FETAX.

The developmental toxicity of five compounds was evaluated with the Frog Embryo Teratogenesis Assay: Xenopus (FETAX) and the results were compared to mammalian literature. Small cell Xenopus laevis blastulae were exposed to ascorbic acid, sodium selenate, coumarin, serotonin and 13-cis retinoic acid for 96 hr. Three separate static-renewal assays were conducted for each compound. Teratogenic potential of the test materials was determined based on Teratogenic Index values [TI = LC50/EC50 (malformation)], types and severity of induced malformations and embryo growth. Ascorbic acid had little or no teratogenic potential. Sodium selenate and coumarin tested as having moderately positive teratogenic potential. Serotonin scored as having moderately strong teratogenic potential and 13-cis retinoic acid scored as having strong teratogenic potential. Results were consistent with mammalian data and support the use of FETAX for the screening of developmental toxicants.

[The radioprotective properties of the liposomal form of mexamine]. / Radiozashchitnye svoistva liposomnoi formy meksamina.

Encapsulation of mexamine (5 methoxytryptamine) in large monostratal lecithin-cholesterol liposomes was shown to cause a 1.4-fold reduction of acute toxicity of the preparation and to prolong its radioprotective efficacy from 15 min to 2 h.

[Effect of blockaders of biogenic amine receptors on experimental ulcer development]. / Vliianie blokatorov retseptorov biogennykh aminov na éksperimental'nyi ul'tserogenez.

The effects of serotonin antagonist peritol, cholinolytic atropine, H2-receptor blocker cimetidine and dopaminergic receptor blocker metoclopramide on stress- and exogenous serotonin-induced gastric ulcerogenesis in rats were studied. Peritol was shown to inhibit significantly serotonin- an stress-induced hemorrhagic effect. Similar but less pronounced inhibit produced by metoclopramide and cimetidine. Atropine decreased gastric hemorrhages induced by serotonin but failed to affect stress-induced hemorrhagic lesions. All antagonists tested decreased stress-induced erosions. Erosive lesions stimulated by exogenous serotonin were significantly decreased by atropine only. Metoclopramide known for its cholinomimetic action increased serotonin-induced erosions. It was concluded that serotonin plays an essential role in the pathogenesis of gastric lesions, and its effects suggest the involvement of acetylcholine, histamine and dopamine.

Gastrointestinal studies of Pyrenacantha staudtii leaf extracts.

The main constituents of the ethanol extract of Pyrenacantha staudtii leaves were identified to be triterpenoid saponins and orally this extract was shown to protect rats from developing gastric ulcers induced by various experimental models: drugs (indomethacin, serotonin), cold-restraint stress and Shay rat. The protection was shown to be dose-dependent in the case of indomethacin-induced ulcers. The mechanisms by which the triterpenoids of P. staudtii may exhibit anti-ulcer activities are discussed.

Serotonergic modulation of the feeding behavior of the medicinal leech.

Hungry medicinal leeches, Hirudo medicinalis, bite warm surfaces and ingest blood meals averaging 890% of their weight. Satiation lasts 12-18 months during which leeches avoid warm surfaces and will not bite. The segmental nervous system of the leech is distinguished by a population of neurons which contain serotonin (5-Hydroxytryptamine, 5-HT) at high concentrations. Some of these identified 5-HT neurons directly activate the effectors responsible for three physiological components of feeding: salivary secretion, bite-like movements and pharyngeal peristalsis. A localized warming of the lip is sufficient to initiate ingestion and synaptically excites anterior 5-HT cells into high frequency impulses or bursts. Distension of the body wall terminates ingestion and also hyperpolarizes these 5-HT neurons. Serotonin treatment produces hyperphagic behavior by the leech, while a specific pharmacological lesion of its 5-HT cell produces the anorexic behavior of satiation. This anorexia is transiently reversed by 5-HT treatment. Serotonin plays an obligatory role in the initiation and expression of leech feeding behavior by its differential modulation of central neuronal networks and peripheral glands and muscles.