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The circular smooth muscles of the middle colon of the rabbit generate giant contractions of high amplitude and low frequency. Flavone, at various concentrations, reduces the giant contractions and the tonic contraction induced by 10 µM carbachol and 80 mM KCl. The contractions induced by dequalinium and tetraethylammonium are reduced by flavone (30 µM). At 100 µM, flavone decreases the contraction induced by 100 µM methylene blue and 1 mM orthovanadate. These results suggest that flavone inhibit the giant contractions by (1) inhibition of voltage-dependent Ca 2+ channels, (2) activation of guanyl cyclase, (3) opening of K + channels and (4) inhibition of tyrosines kinases.

The spontaneous mechanical activity of the proximal, middle and distal colon of the rabbit shows in vitro two types of contractions: phasic contractions with low amplitude and high frequency, giant contractions (GCs) with high amplitude and low frequency. Both patterns of contractions did not present differences according to the region. Investigations on the neural control of giant contractions in the middle colon gave the following results. (1) GCs are insensitive to muscarinic antagonism by atropine and ganglionic blockade by hexamethonium; (2) GCs are converted into phasic contractions following the inhibition of acetylcholinesterase by neostigmine, and are abolished for a short period by dimethyl-phenyl-piperazinium, a ganglionic nicotinic receptor agonist; (3) application of l -arginine, the substrate of nitric oxide (NO) synthase prolonged the duration of GCs without affecting their amplitude; sodium nitroprusside, a donor of NO, reduced both the amplitude and frequency of GCs; (4) inhibition of guanylate cyclase by methylene blue converted GCs into phasic contractions; (5) blockade of K+ channels with the non-selective blocker, tetraethylammonium, or with the more selective apamin-sensitive Ca2+-dependent K+ channels blocker, dequaliniun, increased the resting tone and decreased the amplitude of contractions; whereas opening of ATP-sensitive K+ channels by diazoxide abolished any rhythmic contractile activity. These data taken together suggest that the amplitude and frequency of GCs are controlled by the endogenous release of NO which activates guanylate cyclase, the subsequent formation of cGMP activates in turn the opening of Ca2+-dependent K+ channels. The cholinergic input seems to be responsible of the resting tone, and an increase of this tone is prone to impose the phasic contractions pattern to the tissue.

Flavonoids are known to relax precontracted intestinal smooth muscle and to delay intestinal transit. We therefore investigated the effects of quercetin, naringenin, apigenin and genistein on intestinal peristalsis in vitro. Peristalsis in fluid-perfused segments of the guinea pig small intestine was recorded through the intraluminal pressure changes associated with the peristaltic waves. Alterations of distension sensitivity were reflected by changes in the peristaltic pressure threshold and alterations of peristaltic performance by changes in the maximal acceleration, amplitude and residual baseline pressure of the peristaltic waves. Quercetin, naringenin, apigenin and genistein (10–300 µmol/l) depressed intestinal peristalsis in a structure- and concentration-dependent manner. The flavonoid-evoked changes in peristalsis parameters made it possible to distinguish between two patterns of peristaltic motor inhibition: a decrease in distension sensitivity and peristaltic performance (apigenin and genistein) and a decrease in distension sensitivity without a major change in peristaltic performance (quercetin and naringenin). The antiperistaltic effect of quercetin was partially prevented by apamin (0.5 µmol/l), N-nitro-L-arginine methylester (100 µmol/l) and naloxone (0.5 µmol/l), whereas the effect of genistein was hardly affected by these drugs. Peristaltic motor activity suppressed by quercetin (300 µmol/l), but not genistein (100 µmol/l), was partially restored by apamin. In contrast, neostigmine (0.3 µmol/l) caused a significant recovery of peristalsis from blockade by genistein but failed to reverse peristaltic motor blockade due to quercetin. These observations suggest that naringenin and quercetin inhibit peristalsis by facilitating inhibitory enteric pathways, whereas apigenin and genistein interfere with muscle excitation or excitation-contraction coupling.

Three new hydrolyzable tannins, cocciferins D(1) (1), D(2) (2), and T(1) (4), were isolated from the leaves of Quercus coccifera. Cocciferin D(2) (2) and two additional new tannins, cocciferins D(3) (3) and T(2) (5), were also obtained from the leaves of Quercus suber. Their oligomeric structures were elucidated on the basis of spectroscopic methods and chemical evidence. Compounds 2, 3, and 5 were rare oligomers possessing glucose cores with both open-chain and pyranose forms.

The gastric cytoprotective properties of natural honey (monofloral and polyfloral specimens) and of a glucose-fructose-sucrose-maltose mixture (GFSM) was evaluated in the rat using absolute ethanol, indomethacin and acidified acetylsalicylic acid (ASA-HCl) as necrotising agents. Prior gastric administration of honey (2.5 g/kg) to animals induced a net reduction of hemorrhagic lesions length of the mucosa. Protection of the stomach elicited by both types of honey and GFSM was almost total against ethanol-induced lesions. Similar results were also observed when using ASA-HCl except that the percent protection was 87%. The percent reduction of indomethacin-induced gastric lesions was variable according to the nature of the test solution: GFSM mixture (41.1%) < polyfloral honey (55.2%) < monofloral honey (64.0%). Perfusion of the stomach with isotonic honey resulted in (1) a 70% reduction of the area of the lesions caused by ethanol, (2) the failure to prevent the transmural potential difference fall induced by ethanol, (3) an increase of basal and histamine-stimulated acid secretion. These results suggest that sugar rich solutions (GFSM and honey) may prevent gastric damage by a mechanism involving the release of some protective agents.

Summary Background: We have previously shown that natural honey is able to protect the rat stomach against acute ethanol- and indomethacin-induced lesions. The present investigations were undertaken to examine the role of intraluminal osmolality in this protective effect. Methods: Mannitol, glucose-fructose-sucrose-maltose mixture (GFSM) and natural honey (300, 600, 1800 mOsmol/kg water) were given orally to rats 30 min before administration of 70% ethanol for a further 15-min period. Lesions area of the excised stomachs were evaluated. Pylorus-ligated stomachs were filled with mannitol, GFSM mixture and honey (1800 mOsmol/kg water) to test the effect of the hyperosmolar solutions on gastric fluid content and acid secretion. The rate of gastric emptying of the three test solutions (1800 mOsmol/kg) was measured by the phenol red method. Results: Intragastric administration of mannitol, GFSM mixture or honey prevented the formation of mucosal lesions in an osmolality-dependent manner. Using the pylorus-ligated stomach model, the test solutions led to a net increase of luminal fluid volume without affecting acid content. Hyperosmolar solutions presented a delayed gastric emptying if compared to a nonnutrient solution made of carboxymethyl cellulose. Conclusions: The observed results suggest that hyperosmolar solutions can prevent the formation of hemorrhagic lesions by luminal dilution of the necrotising agent and acid, an effect which may be potentiated by a lowered gastric emptying rate.

The gastroprotective effect of tannic acid and the aqueous extract of Quercus ilex L. root bark, Punica granatum L. fruit peel and Artemisia herba-alba Asso leaves was investigated in the rat against ethanol-induced damage. Tannic acid, Q. ilex and P. granatum extracts gave 100% precipitation of ovine haemoglobin in vitro, whereas A. herba-alba extract was devoid of any protein-binding property. Oral administration of these plant extracts or tannic acid induced a significant decrease in gastric lesions (47.7%-76%). The observed protection was more pronounced when the test solution was given at the same time with ethanol, except for Q. ilex extract. The acid content of the stomach was significantly increased by P. granatum (368%) and A. herba-alba (251%) extracts prepared in ethanol. It is suggested that monomeric and polymeric polyphenols can strengthen the gastric mucosal barrier.

The cytoprotective properties of various natural honey specimens and of a glucose-fructose-sucrose-maltose mixture (GFSM) against gastric ethanol-induced lesions have been evaluated in rats. GFSM mixture and honey (2.5 g kg-1) were given orally 30 min before administration of 100% ethanol (5 ml kg-1) for a further 15-min period. Animal pretreatment with GFSM or honey prevented the formation of gastric lesions. The number and severity of haemorrhagic lesions were reduced by 98%. Stomach acid content increased by 110-703% according to honey specimens. The similar protective effects of honey and GFSM mixture suggest that carbohydrates at high concentrations behave as mild irritants that can induce adaptive cytoprotection.