Protective effect of Calamintha officinalis Moench leaves against alcohol-induced gastric mucosa injury in rats. Macroscopic, histologic and phytochemical analysis.

Calamintha officinalis Moench (Lamiaceae) is an aromatic plant used since ancient times for its preservative and medicinal properties. The plant, known as 'Mentuccia' in Central Italy, is used in cooking as an aromatizant and to impart aroma and flavour to food. The methanol extract of the leaves was subjected to phytochemical and biological investigations. The extract contains polyphenols, catechic tannins and terpenes and shows radical scavenger activity. By means of HPLC analysis, eriocitrin, eriodyctiol, acacetin, linarin, benzoic acid and some phenolic acids, such as caffeic, chlorogenic, p-coumaric, were determined. The gastroprotective activity of the extract was investigated using ethanol-induced ulcer in rats, with sucralfate as a reference drug. Samples of gastric mucosa, stained by PAS and haematoxylin/eosin, were observed by light microscopy. The efficacy of the extract was comparable to that of the reference drug. Probably the gastroprotective effect depends on a synergistic action of all the compounds occurring in C. officinalis leaves, even if the antioxidant potential of the leaves plays an important role by removing damaging agents from the gastric mucosa.

Ursolic acid plays a role in Nepeta sibthorpii Bentham CNS depressing effects.

The sedative, anticonvulsant and analgesic activity of ursolic acid, a terpenoid bioassay-isolated from Nepeta sibthorpii Bentham, was evaluated in mice. The oral administration of ursolic acid (2.3 mg/kg) produced a significant depressant effect on CNS by reducing spontaneous motor activity and the number and lethality of pentylenetetrazol (PTZ)-induced seizures. Two models of nociception, the writhing test and the hot plate test, were also used to examine the analgesic effect of ursolic acid. At a dose of 2.3 mg/kg, ursolic acid caused an inhibition of acetic acid-induced abdominal constriction, but was inactive in the hot plate test. Treatment at a higher dose (20 mg/kg) significantly increased the reaction time in the hot plate test. This effect, reversed by naloxone, evidently involves opioid receptors, but the analgesic activity of ursolic acid may be related also to the antiinflammatory and antioxidant properties of this compound.

Opuntia ficus indica (L.) Mill. mucilages show cytoprotective effect on gastric mucosa in rat.

Opuntia ficus indica cladodes possess a protective action against ethanol-induced ulcer in the rat. The major components of cladodes are carbohydrate polymers, mainly mucilages and pectin. To clarify the cytoprotective effects of cladodes on experimental ethanol-induced ulcer in rat, mucilages and pectin were extracted and were administered instead of cladodes. The above mentioned effects induced by cladodes may be attributed to mucilages, and not significantly to pectin.

Chiral 3,3'-(1,2-ethanediyl)-bis[2-(3,4-dimethoxyphenyl)-4-thiazolidinones] with anti-inflammatory activity. Part 11: evaluation of COX-2 selectivity and modelling.

Anti-inflammatory/analgesic 3,3'-(1,2-ethanediyl)-bis[2-(3,4-dimethoxyphenyl)-4-thiazolidinones] 1, obtained as racemic mixtures (a) and mesoforms (b), have two equivalent stereogenic centres (C-2 and C-2') and exist as RR, SS and RS isomers. The enantioseparation of 1a provided the single enantiomers that displayed different in vitro cyclooxygenase-1/cyclooxygenase-2 selectivity ratios. In particular the dextrorotatory compound is a highly selective COX-2 inhibitor and the levorotatory one is moderately selective. Instead, RS-meso isomer (1b) exhibited similar levels of inhibitory activity on both COX isozymes. The diastereo- and enantioselectivity has been explained by molecular modelling of RR, SS and RS compounds into COX-1 and COX-2 binding sites. Theoretical results indicated SS>RS>RR affinity order towards COX-2 isoenzyme, in agreement with in vitro and previous in vivo pharmacological results.

Study on the increment of the production of gastric mucus in rats treated with Opuntia ficus indica (L.) Mill. cladodes.

Opuntia ficus indica cladodes are used in traditional medicine of many countries for their cicatrisant activity. The major components of cladodes are carbohydrate-containing polymers, which consist of a mixture of mucilage and pectin. In this paper we studied the cytoprotective effects of cladodes on experimental ethanol-induced ulcer in rat. The O. ficus indica cladodes administration gives rise to cytoprotection phenomena by breaking up the epithelial cells and stimulating an increase in mucus production. When O. ficus indica cladodes are administered as a preventive therapy, keep the gastric mucosa under normal condition by preventing mucus dissolution caused by ethanol and favouring mucus production. An increase of mucus production is also observed during the course of the curative treatment. The treatment with O. ficus indica cladodes provokes an increase in the number of secretory cells. Probably, the gastric fibroblasts are involved in the antiulcer activity.

Anticonvulsant and sedative effects of Salvadora persica L. stem extracts.

The effect of Salvadora persica L. stem extracts on the potentiation of sodium pentobarbital activity and on generalized tonic-clonic seizure produced by pentylenetetrazol (PTZ) on the rat is reported. The extracts of Salvadora persica L. extended sleeping-time and decreased induction-time induced by sodium pentobarbital; in addition it showed protection against pentylenetetrazol-induced convulsion by increasing the latency period and diminishing the death rate.

Biological effect of Opuntia ficus indica (L.) Mill. (Cactaceae) waste matter. Note I: diuretic activity.

In this work we studied in rat the diuretic activity of Opuntia ficus indica (L.) Mill. (Cactaceae) waste matter. The cladodes, flowers and non commerciable fruits were collected in S. Cono (CT, Sicily) cultivation. Acute and chronic diuretic activity of 15% infusion of cladodes, flowers and fruits were assayed. Natriuresis, kaliuresis and the activity on fructose-induced hyperuricemia was also studied. The results show that O. ficus indica cladode, fruit and flower infusions significantly increase diuresis. This effect is more marked with the fruit infusion and it is particularly significant during the chronic treatment. The fruit infusion shows also antiuric effect. In all experiments cladode, flower and fruit infusions showed a modest but not significant increase in natriuresis and kaliuresis.

Synthesis and antiinflammatory, analgesic activity of 3,3'-(1,2-ethanediyl)-bis[2-aryl-4-thiazolidinone] chiral compounds. Part 10.

In this note, the synthesis and structure-activity relationships of a new series of 2R,2'R/2S,2'S and 2R,2'S-meso 3,3'-(1,2-ethanediyl)-bis[2-aryl-4-thiazolidinones] are described. Antiinflammatory activity was investigated by the carrageenin-induced paw edema test and analgesic activity by acetic acid writhing and hot plate tests in rats. All compounds displayed ulcerogenic effects and acute toxicity much lower than indomethacin and phenylbutazone. Meso isomers (b) showed better pharmacological profiles than corresponding racemates (a). Methoxy substitution patterns of the aryls on stereogenic carbons are generally the most favorable on the pharmacological profile.

Anticonvulsant and sedative effects of some 5-substituted bromopyrazolinic spirobarbiturates.

We studied in mice the neuropharmacological effect of some 5-substituted bromopyrazolinic spirobarbiturates. LD50 and CL50 values were estimated for all the investigated compounds. The effect on potentiation of sodium pentobarbital activity and on generalised tonic-clonic seizures produced by PTZ on mice was studied. All the compounds had the same pharmacological profile, they extended sleeping-time induced by sodium pentobarbital and showed protection against PTZ-induced convulsions, decreasing the death rate.

Antiulcer activity of Opuntia ficus indica (L.) Mill. (Cactaceae): ultrastructural study.

In Sicily folk medicine, Opuntia ficus indica (L.) Mill. cladodes are used for the treatment of gastric ulcer. We studied the effect of administration of lyophilized cladodes on experimental ethanol-induced ulcer in rat. In this paper, we report the ultrastructural observations of gastric mucosa. The ultrastructural changes were observed by trasmission electronic microscopy (TEM) confirming the protective effect exercised by administration of lyophilized cladodes. Pre-treatment test in rats revealed a protective action against ethanol-induced ulcer. Probably, the mucilage of Opuntia ficus indica is involved.

Effects of Teucrium divaricatum Heldr. ssp. divaricatum decoction on experimental ulcer in rats.

The effects of chronic intragastric administration of the aerial parts decoction of Teucrium divaricatum Heldr. ssp. divaricatum (Labiateae) on experimental acetylsalicylic acid (ASA)-induced ulcer were studied in rats. The ulcer index and histological mucosa regeneration were evaluated. The ulcer index significantly decreased (U.I. 1.7+/-1.5; P<0.05) after treatment with a lyophilized decoction of T. divaricatum (500 mg/kg os), once daily for 7 days, compared to the control (U.I. 11.4+/-2.3). The ultrastructure modifications of gastric mucosa were observed by transmission electronic microscopy (TEM) confirming the antisecretory effect exercised by administration of the T. divaricatum decoction. Treatment with T. divaricatum seems to block up parietal cell acid secretion and to stimulate in the chief cells the formation of zymogen granules.

In vitro anti-mycotic activity of some medicinal plants containing flavonoids.

Aqueous, ethanolic and petroleum ether extracts of Citrus sinensis L. (Osbeck), Euphrasia officinalis L., Glycyrrhiza glabra L., Matricaria recutita L., Rosa canina L. and Ruta graveolens L. have been studied. The antimycotic activity was evaluated "in vitro" on strains of Candida albicans isolated from clinical samples obtained in the course of acute vaginitis.

Salvadora persica L.: hypolipidemic activity on experimental hypercholesterolemia in rat.

Stems of Salvadora persica are widely used as tooth cleaning sticks in Arabic countries and decoctions show hypocholesterolemic properties. The effects of prolonged administration of a lyophilized stem decoction of Salvadora persica were evaluated in diet-induced rat hypercholesterolemia. The preparation was administered for 15 and 30 days (by gavage at a dose of 500 mg/kg in an aqueous vehicle in a volume of 0.5 ml/100 g b.w.). Cholesterol, HDL, LDL and triglyceride plasma levels were assayed. The results showed that the S. persica decoction significantly lowered cholesterol and LDL plasma levels in rats, proving to be more active at 30 days of treatment. The systemic administration of Triton results in a rise in plasma cholesterol and triglyceride levels. The results obtained show that S. persica decoction was inactive at 18 hr after treatment, whereas at 27 hr, it was able to reduce cholesterol and LDL plasma levels. In all experiments HDL and triglycerides were unchanged.

Antiulcer activity of Salvadora persica L.: structural modifications.

In previous work we observed that the decoction of Salvadora persica L. possessed significant protective action against ethanol and stress-induced ulcers. This study was designed to confirm the antiulcer activity of Salvadora persica decoction using optical microscopy. The elements of gastric mucosa tended to be reestablished normally in treated rats.

Hypoglycemic effects of Salvadora persica L. in the rat.

The stem decoction of Salvadora persica L., a drug widely used as a tooth cleaning stick in Arabian countries, shows, in normal rats, hypoglycemic effects, an increase in plasma immunoreactive insulin (IRI) and an incremented oral-glucose tolerance. The decoction also causes a significant decrease in mean body weight without drastic reduction in food consumption.

Effects of naringin on experimental ulcer in rats.

The effects of chronic intragastric administration of naringin (200 mg/kg) on experimental acetylsalicylic acid (ASA)-induced ulcer were studied in rat. The ulcer index and histological mucosa regeneration were evaluated. The ulcer index significantly decreased after treatment with naringin (200 mg/kg) once daily for seven days. Microscopic observations confirm these results.

3,3'-Bi(1,3-thiazolidin-4-one) system. VIII. 3,3'-(1,2-Ethanediyl) derivatives and corresponding 1,1'-disulfones: synthesis, stereochemistry and antiinflammatory activity.

To deeply investigate the influence of lipophilicity, phenyl substitution patterns and stereo-chemistry on pharmacological profiles of chiral bisarylthiazolidinones, frequently endowed with stereoselective antiinflammatory, analgesic, antihistaminic activities, we synthesized and explored some 3,3'-(1,2-ethanediyl) analogues 1-4, along with their S-oxidized derivatives 5-8. Each derivative can be isolated as 2R, 2'R/2S, 2'S (a) and 2R, 2'S- or 2S, 2'R- meso (b) diastereomers, which were explored by means of carrageenin edema test, acetic acid writhing and hot plate tests, and also tested for gastrolesive potential and LD50. Independently of lipophilic and electronic features, disulfides 3b, 4b and disulfones 7a, 8a, 8b displayed interesting activity levels which appear to be mainly linked to the disubstitution pattern on benzenic rings.

In vitro cytotoxic effect of some medicinal plants containing flavonoids.

Aqueous, ethanolic and petroleum ether extracts of Citrus sinensis L. (Osbeck), Euphrasia officinalis L., Glycyrrhiza glabra L., Matricaria recutita L., Rosa canina L. and Ruta graveolens L. have been studied. The cytotoxicity of the drugs assayed was evaluated "in vitro" by means of the dye test using cells of the Yoshida ascites sarcoma. The aqueous extract of Citrus sinensis L. (Osbeck); the petroleum ether extract of Glycyrrhiza glabra L.; the ethanolic and petroleum ether extracts of Rosa canina L. and the petroleum ether extract of Ruta graveolens L. showed a quite significative cytotoxic effect.

Biological effects of hesperidin, a Citrus flavonoid. (Note III): antihypertensive and diuretic activity in rat.

Hesperidin, the most important flavanone of Citrus sp., obtained from the solid residue of orange peel, showed antihypertensive and diuretic effects on normotensive rats and on spontaneously hypertensive rats (SHR).

Effects of fruit juices of Citrus sinensis L. and Citrus limon L. on experimental hypercholesterolemia in the rat.

In Citrus juices there are various substances of different chemical nature, some of which possess already-known hypocholesterolemic properties. Therefore it has seemed interesting to evaluate the effects of a prolonged administration of lyophilized juices of Citrus sinensis L. Osbeck and Citrus limon L. Burm fil. in diet-induced rat hypercholesterolemia. Lyophilized Citrus juices were administered for 15 days (by gavage, at the dose of 5g/kg in aqueous veicle in a volume of 0.5 ml/100 g body weight) and 30 days ("ad libitum", instead of tap water, 5g/kg in 1 ml opportunely diluted with water in the proportion 1:3). Cholesterol, HDL, LDL and triglyceride plasma levels were assayed. The results obtained showed that Citrus juices significantly increase HDL and lower cholesterol, LDL and triglyceride plasma levels in the rat. In particular, Citrus limon has more marked effect on cholesterol and triglyceride levels, Citrus sinensis is more able to increase HDL levels. Therefore, the prolonged use of Citrus sinensis and Citrus limon juices determines a considerable protection against insurgence of hypercholesterolemia. This experimental design does not allow us to determine the active principles to which pharmacological effects may possibly be attributed; but, on the other hand, it let us reproduce experimentally a situation similar to the inclusion of the Citrus juices in the human diet, which results in low, but continuous, body levels of their active principles.