Jejunal Contractions Research Articles

An Investigation of Novel Series of 2-Thioxo-1,3-dithiol-carboxamides as Potential Antispasmodic Agents: Design, Synthesis via Coupling Reactions, Density Functional Theory Calculations, and Molecular Docking.

This study reports the synthesis of 2-thioxo-1,3-dithiol-carboxamides (TDTCAs) under mild conditions at room temperature using HBTU as a coupling agent, which significantly improved amide bond formation. The synthesized compounds were characterized using several analytical techniques, including 1H and 13C NMR spectroscopy, and HRMS, confirming their intended structures and structural integrity. A DFT computational study at the B3LYP/6-31G(d,p) level was conducted on the four synthesized compounds to compare their electronic properties and molecular structures. The results showed that these compounds demonstrated antispasmodic effects on jejunum contractions. Molecular docking revealed that compounds c and d displayed the highest docking scores on potassium and voltage-gated calcium channels and adrenergic receptors. In summary, compounds c and d exhibit antispasmodic effects, potentially blocking alpha-adrenergic receptors and calcium channels, thus providing a scientific basis for their potential use in treating gastrointestinal disorders.

Oral Vitamin C Intake Ameliorates Crude Oil-Polluted Water-Induced Jejunal Contractile Dysfunctions in Wistar rats

Inhabitants of rural Niger-Delta oil communities in Nigeria often, unintentionally, consume crude oil polluted water (COCW) due to crude oil spills in the region. The impact of vitamin C supplementation during COCW ingestion on the contractile mechanism of the jejunum is not fully known. Hence, this study investigates the outcomes of COCW water and vitamin C intake on the smooth muscle activity of the jejunum in Wistar rats using standard techniques. Data obtained showed that jejunal tissue SOD concentration was significantly reduced, while jejunal tissue MDA concentration was significantly increased in the COCW-only treated group. Contraction mediated by acetylcholine was significantly increased in the COCW-only treated rats. Calcium and potassium ion influx significantly increased jejunal contraction in the COCW-only rats. Incubation of the jejunal tissue in nifedipine, indomethacin, and L-NAME significantly increased acetylcholine-mediated contractions in the jejunal tissue of the COCW-only treated rats when compared to other groups. COCW causes free radical-induced jejunal damage that results in impaired jejunal contractile activity mediated by the M2 muscarinic receptor, nitric oxide synthase activity, voltage-gated large-conductance calcium channels, potassium channels, and prostaglandins. However, the oral intake of Vitamin C supplementation significantly ameliorated impairments by enhancing jejunal antioxidant activity.

Myorelaxant and antispasmodic effects of the essential oil of Artemisia campestris L., and the molecular docking of its major constituents with the muscarinic receptor and the L-type voltage-gated Ca2+channel.

Gastrointestinal disorders are among the most common diseases that cause discomfort to people who are affected. In Morocco, aromatic and medicinal plants are widely used to calm these pains and eliminate their symptoms. Among these plants, Artemisia campestris L. which is used in eastern Morocco to treat digestive system problems. Our study aimed to experimentally verify the traditional use of this plant by evaluating the myorelaxant and antispasmodic effects of the essential oil of Artemisia campestris L. (EOAc). Gas Chromatography-Mass Spectrometry analysis (GC-MS) was performed to identify the compounds present in the EOAc. Then, these molecules were subjected to the in silico study for molecular docking. The myorelaxant and antispasmodic evaluation of the EOAc were tested in vitro on an isolated rabbit and rat jejunum mounted on an organ bath. Then, an isotonic transducer connected to an amplifier recorded the graph related to intestinal contractility. GC-MS analysis of the essential oil of Artemisia campestris L. showed the presence of m-Cymene (17.308%), Spathulenol (16.785%), β Pinene (15.623%), α Pinene (11.352%), α.-Campholenal (8.848%) as main constituents. The EOAc gave a dose-dependent and reversible myorelaxant effect on the spontaneous contractions of jejunum isolated from rabbits, with an IC50 equal to 72.16±15.93μg/mL. This effect did not occur through adrenergic receptors. The EOAc has an antispasmodic effect on the contractions of rat jejunal induced by a medium with low (25mM) or high concentration (75mM) of KCl, and carbachol 10-6M. The obtained inhibitory effects are comparable to those of a non-competitive antagonist of cholinergic receptors. The major compounds of EOAc allowed the establishment of a relationship between these phytoconstituents and the antispasmodic effect found by the EOAc. The obtained results are also supported by a docking study. The obtained results confirm favorably the use of Artemisia campestris L. in traditional Moroccan medicine for the treatment of digestive tract illness, which gives us a new route to valorize the effects obtained by a phytomedicine specific for the digestive tract.

Ethanol Extract of Glycyrrhiza uralensis Fisch: Antidiarrheal Activity in Mice and Contraction Effect in Isolated Rabbit Jejunum.

To evaluate the antidiarrheal effect of ethanol extract of Glycyrrhiza uralensis Fisch root (GFR) in vivo and jejunal contraction in vitro. In vivo, 50 mice were divided into negative control, positive control (verapamil), low-, medium- and high-dose GFR (250, 500, 1,000 mg/kg) groups by a random number table, 10 mice in each group. The antidiarrheal activity was evaluated in castor oil-induced diarrhea mice model by evacuation index (EI). In vitro, the effects of GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) on the spontaneous contraction of isolated smooth muscle of rabbit jejunum and contraction of pretreated by Acetylcholine (ACh, 10 µmol/L) and KCl (60 mmol/L) were observed for 200 s. In addition, CaCl2 was accumulated to further study its mechanism after pretreating jejunal smooth muscle with GFR (1 and 3 g/L) or verapamil (0.03 and 0.1 µmol/L) in a Ca2+-free-high-K+ solution containing ethylene diamine tetraacetic acid (EDTA). GFR (500 and 1,000 mg/kg) significantly reduced EI in castor oil-induced diarrhea model mice (P<0.01). Meanwhile, GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) inhibited the spontaneous contraction of rabbit jejunum (P<0.05 or P<0.01). Contraction of jejunums samples pretreated by ACh and KCl with 50% effective concentration (EC50) values was 1.05 (0.71-1.24), 0.34 (0.29-0.41) and 0.15 (0.11-0.20) g/L, respectively. In addition, GFR moved the concentration-effect curve of CaCl2 down to the right, showing a similar effect to verapamil. GFR can effectively against diarrhea and inhibit intestinal contraction, and these antidiarrheal effects may be based on blocking L-type Ca2+ channels and muscarinic receptors.

Anti-diarrhoeal effects of Garcinia kola (Heckel-Holl) seed methanolic extract and its fractions in animal models

This study investigated the In vitro spasmolytic and In vivo anti-diarrhoeal effects of Garcinia kola seed extract/fractions. Extraction was done by maceration in 70% methanol, serially partitioned in ethyl acetate and n-hexane. Qualitative phytochemical screening was carried out on the crude extract/fractions. The In vitro spasmolytic effect of the extract and fractions at different concentrations (0.5×103, 0.2×103,0.1×103, 0.6×102 mg/ml) were investigated against spontaneous and acetylcholine-induced contractions in isolated rabbit jejunum as well as histamine-induced contractions using isolated guinea pig ileum. The In vivo anti-diarrhoeal effect of the extract was evaluated using three diarrhoeal models: castor oil-induced diarrhoea, charcoal meal gastrointestinal transit time and castor oil-induced enteropooling. In each model, 25 mice were randomly divided into five groups of 5 mice each. Group I served as the untreated control, while group II was a positive control. Groups III-V were administered 125, 250 and 500 mg/kg of the crude methanol extract, respectively. The crude extract, ethyl acetate and aqueous fractions at 0.5×103 mg/ml respectively exhibited 14.4%, 12.9% and 12.2% spasmolytic activities against acetylcholine-induced rabbit jejunum contractions. Histamine-induced guinea pig ileum contractions were inhibited by crude extract (6.2%), ethyl acetate (6.2%), aqueous fraction (7.2%) at 0.6×102 mg/ml. For castor oil-induced diarrhoea, the crude extract at 500 mg/kg produced a significant (p &lt; 0.05) decrease in the diarrhoeal index and faecal weight with a percentage inhibition of 70.4% compared with controls. Similarly, the crude extract (500 mg/kg) significantly (p &lt; 0.05) decreased the charcoal meal gastrointestinal transit time with a percentage inhibition of 33.9% and elicited significant (p &lt; 0.05) intraluminal fluid reduction (9.1%) in castor oil-induced enter pooling test when compared with the untreated group. In conclusion, the anti-motility and anti-secretory activities of the crude extract were attributed to the phytochemical constituents present.

The Spasmolytic, Bronchodilator, and Vasodilator Activities of Parmotrema perlatum Are Explained by Anti-Muscarinic and Calcium Antagonistic Mechanisms.

Parmotremaperlatum is traditionally used in different areas of Pakistan to treat gastrointestinal, respiratory, and vascular diseases. This study evaluates the underlying mechanisms for traditional uses of P. perlatum in diarrhea, asthma, and hypertension. In vitro pharmacological studies were conducted using isolated jejunum, trachea, and aortic preparations, while the cytotoxic study was conducted in mice. Crude extract of P. perlatum(Pp.Cr), comprising appreciable quantities of alkaloids and flavonoids, relaxed spontaneously contracting jejunum preparation, K+ (80 mM)-induced, and carbachol (1 µM)-induced jejunum contractions in a concentration-dependent manner similar to dicyclomine and dantrolene. Pp.Cr showed a rightward parallel shift of concentration-response curves (CRCs) of Cch after a non-parallel shift similarto dicyclomine and shifted CRCs of Ca+2 to rightward much likeverapamil and dantrolene, demonstrating the coexistence of antimuscarinic and Ca+2 antagonistic mechanism. Furthermore, Pp.Cr, dicyclomine, and dantrolene relaxed K+ (80 mM)-induced and Cch (1 µM)-induced tracheal contractions and shifted rightward CRCs of Cch similar to dicyclomine, signifying the dual blockade. Additionally, Pp.Cr also relaxed the K+ (80 mM)-induced and phenylephrine (1 µM)-induced aortic contraction, similarly to verapamil and dantrolene, suggesting Ca+2 channel antagonism. Here, we explored for the first time thespasmolytic and bronchodilator effects of Pp.Crand whether they maybe due to the dual blockade of Ca+2 channels and muscarinic receptors, while the vasodilator effect might be owing to Ca+2 antagonism. Our results provide the pharmacological evidence that P. perlatum could be a new potential therapeutic option to treat gastrointestinal, respiratory, and vascular diseases. Hence, there is a need for further research to explore bioactive constituent of P. perlatum as well as further investigation by suitable experimental models are required to further confirm the importance and usefulness of P. perlatum in diarrhea, asthma, and hypertension treatment.

Myorelaxant and antispasmodic effect of an aqueous extract of Artemisia campestris L. via calcium channel blocking and anticholinergic pathways.

Intestinal spasms are violent contractions that occur in the intestine, which cause discomfort to people who have them. Medicinal plants are widely used in traditional Moroccan medicine to treat these problems, among these being Artemisia campestris L. This study aims to evaluate the relaxant and antispasmodic effects of an aqueous extract of this plant (ACAE). It was performed in vitro on isolated segments of both isolated rat and rabbit jejunum mounted in an organ bath and tension recordings made via an isotonic transducer. ACAE caused a myorelaxant effect on baseline rabbit jejunum contractions in a dose-dependent and reversible manner with an IC50 of 1.52 ± 0.12 mg/ml. This extract would not act via adrenergic receptors pathway. On the other hand, the extract caused a dose-dependent relaxation of the jejunum tone in rat jejenum segments pre-contracted with either Carbachol (CCh; 10−6 M) or high K+ (KCl 75 mM) with an IC50 = 0.49 ± 0.02 mg/ml and 0.36 ± 0.02 mg/ml respectively. In the presence of different doses of the extract, the maximum response to CCh and CaCl2 was significantly reduced. This demonstrates that ACAE acts on both muscarinic receptors and voltage-dependent calcium channels. Thus, the plant extract acted on both muscarinic and nicotinic receptors and acts on the guanylate cyclase pathway, but not the nitric oxide pathway. These results indicate the mechanism by which Artemisia campestris L. acts as an effective antispasmodic agent in traditional Moroccan medicine.

Ethnopharmacological basis for folkloric claims of Anagallis arvensis Linn. (Scarlet Pimpernel) as prokinetic, spasmolytic and hypotensive in province of Punjab, Pakistan

Ethnopharmacological relevanceThe conventional naturopaths of Punjab Province (Pakistan) have trivial usage of Anagallis arvensis Linn.(Primulaceae) for cure of diarrhea, constipation, asthma as well as hypertension. AimPresent research was focused to discover comprehensive mechanism of spasmogenic, spasmolytic, bronchorelaxant and hypotensive folkloric usage of Anagallis arvensis Linn.. MethodologyThe crude extract of Anagallis arvensis Linn. (Aa.Cr) & its (aqueous & organic) portions tested in-vitro on isolated jejunum, ileum, trachea, aorta, paired atria preparations as well as in-vivo in mice & normotensive anaesthetized rats. The responses have been noted by transducers (isotonic & isometric) coupled to Power Lab. ResultAnagallis arvensis Linn. (Aa.Cr; crude aqueous-alcoholic extract) produced contractile action at low concentrations but relaxant action was observed by increasing concentrations on spontaneous contractions of isolated jejunum of rabbit. But, pre-treatment of tissue with atropine prior extract caused suppression of contractile effect indicating presence of cholinergic muscarinic response of Aa.Cr. It also triggered relaxation of high Potassium -stimulated contractions of jejunum with subsequent non-parallel right move in Ca++ CRCs. Moreover, Aa.Cr relaxed carbachol - & high Potassium - stimulated contractions in trachea of rabbit but observed relaxant effect was powerful against CCh (1 μM)- stimulated contractions with rightside parallel move of CCh-curves succeeded by non-parallel move, like Dicyclomine, having dual activities. The Aa.Cr also showed relaxant result on Phenylephrine and High Potassium -prompted contractions in endothelium intact aorta. The fractionation revealed segregations of contractile & relaxant effects in relevant aqueous & organic portions. The Intravenous administration of Aa.Cr to ketamine-diazepam anaesthetized normo-tensive albino rats resulted in decreased MABP, SBP & DBP. The Aa.Cr applied negative (−) inotropic & chronotropic action on paired atria. The Aa.Cr also exhibited anti-diarrheal action in mice against castor oil prompted diarrhea and also mitigated distance covered by charcoal meal in gastrointestinal tract in a manner comparable with loperamide. ConclusionThese results revealed presence of CCB and selective muscarinic agonist activity in Aa.Cr, hence validating folkloric practice of Anagallis arvensis Linn. in diarrhea, constipation, asthma & hypertension.

Reference Values and Repeatability of Transabdominal Ultrasonographic Gastrointestinal Tract Thickness and Motility in Healthy Donkeys (Equus asinus)

The present study aimed to provide reference ranges for the wall thickness and motility pattern of the gastrointestinal tract from a sample of donkeys (Equus asinus) population using B-mode ultrasonography. In the present study, 30 clinically healthy donkeys (Equus asinus) (15 males and 15 females), aged 2–20 year old and weighed 100–280 kg were randomly selected for B-mode ultrasonographic scanning of the abdomen. The wall thickness of the stomach, duodenum, jejunum, left colon, right colon, and cecum was assessed. Moreover, the motility pattern of the duodenum, jejunum, left colon, right colon, and cecum was evaluated over a period of 3 minutes. Abdominal ultrasonographic scanning of the gastrointestinal tract of healthy donkeys explored that the stomach, duodenum, jejunum, left colon, right colon, and cecum could be visualized easily. The wall thickness of the stomach, duodenum, jejunum, left colon, right colon, and cecum was 7.0 ± 0.9 mm, 3.3 ± 1.0 mm, 5.4 ± 0.6 mm, 5.1 ± 0.5 mm, 5.4 ± 0.5 mm, and 5.4 ± 0.6 mm, respectively. The thickest part of the gastrointestinal tract is the stomach, whereas the thinnest part is the duodenum. The motility pattern of the duodenum, jejunum, left colon, right colon, and cecum was 7.7 ± 1.3 contractions/3 minutes, 6.9 ± 1.1 contractions/3 minutes, 4.1 ± 1.2 contractions/3 minutes, 5.5 ± 1.3 contractions/3 minutes, and 4.0 ± 0.8 contractions/3 minutes, respectively. Both the duodenum and jejunum contractions were significantly higher than that of the left colon, right colon, and cecum. This is the first study reporting the reference values for both the wall thickness and motility pattern of the gastrointestinal tract in healthy donkeys (Equus asinus) in Egypt. Good knowledge of these standard and reference values of the wall thickness and motility pattern of gastrointestinal tract structures represents a step in the early diagnosis of the gastrointestinal disorders, including colic in such animal species.

Dose-dependent effects of two inulin types differing in chain length on the small intestinal morphology, contractility and proinflammatory cytokine gene expression in piglets

ABSTRACTInulin is a linear fructose polymer which may affect small intestinal physiology. The effects of dietary level of two inulin types on morphology, contractility and proinflammatory cytokine gene expression in the small intestine of piglets were investigated. Fifty six piglets were divided into seven groups fed diets without inulin addition or with 1%, 2% or 3% of inulin with an average degree of polymerisation of 10 (IN10) or 23 (IN23). All diets were offered from day 10 of life for 40 d. Feeding IN10 diets did not affect villous height to crypt depth ratio in the duodenum, while in the jejunum the 2% IN10 diet increased it as compared to other groups. Jejunal muscle contractions induced by electrical field stimulation were impaired by the 2% and 3% IN10 diets. The ileal expression of interleukin-12p40 was decreased by the 2% IN10 diet. There was no effect of IN23 level on villous height to crypt depth ratio in any segment of the small intestine as well as on jejunal motility. The 2% and 3% IN23 diets decreased the jejunal expression of tumour necrosis factor-α. In conclusion, IN10 is more active in the small intestine than IN23. At the 2% dietary level, it increases absorptive area in the jejunum, but may slightly impair smooth muscle contractions.

Effects of 7,8-dihydroxyflavone on rat jejunal dynamics subjected to ischaemia-reperfusion injury.

It is known that 7,8-dihydroxyflavone (7,8-DHF), a synthetic agonist specific for TrkB, promotes intestinal cholinergic contraction. However, after intestinal ischaemia-reperfusion (IR) injury, how 7,8-DHF affects intestinal contractile dynamics is unknown. In this study, an IR injury model was prepared with rats subjected to 45minutes clamping of the superior mesenteric artery. The IR injury decreased postoperative food intake and body weight, delayed defecation time, lowered intestinal propulsive rate and decreased cholinergic contraction of jejunal muscle strips, indicating the occurrence of injured jejunal contraction after IR. Feeding rats with 7,8-DHF improved these intestinal activities injured by IR, which exhibited the in vivo effect of 7,8-DHF. To explore its molecular mechanism, the expression and phosphorylation of TrkB, PLC γ1, Akt, and ERK1/2 in the jejunal strips were examined with western blots. The IR injury significantly decreased the expression and phosphorylation levels of all factors studied here. However, 7,8-DHF feeding specifically enhanced the phosphorylation of TrkB, PLC γ1 and Akt factors in both sham- and IR-operated rats, indicating that 7,8-DHF may have activated TrkB which then activated its downstream PLC γ1 and Akt. Finally, we found that 7,8-DHF augmented cholinergic receptor M3 expression somehow. These results imply a possibility that 7,8-DHF might be capable of alleviating the jejunal contractile damage caused by IR through activation of TrkB and augmentation of M3 expression.

Abstract P1123: The Pharmacological Basis for Vasodilator Effect of Sisymbrium Irio Linn. Validates it's Folkloric Use in Hypertension

Traditionally seeds of Sisymbrium irio Linn has been used in different regions of Pakistan for the treatment of gastrointestinal, airways and vascular system ailments. To insight the pharmacological basis in vitro study was conducted in order to validate its folkloric uses in hypertension. 70% aqueous-methanolic extract of seeds from Sisymbrium irio (Si.MEs) was tested on isolated rabbit aorta, jejunum and trachea strip hanged in tissue bath having physiological solutions aerated with carbogen and their responses were measured and recorded via Power Lab. The Si.MEs exhibited the transient spasmogenic effect (0.01-1.0 mg/mL) on spontaneous jejunum contractions, followed by the spasmolytic effect. The addition of atropine resulted in blocking in spasmogenic effect while the spasmolytic effect was originated, suggesting the presence of an antimuscarinic effect. Likewise verapamil, Si.MEs (0.03-5 mg/mL) repressed the high concentration K + (80 mM)-induced contraction and also drifted the Ca 2+ concentration-response curves toward right (0.3-3.0 mg/mL), possibly signifying the Ca 2+ channel blockade. Furthermore, Si.MEs exhibited nonspecific relaxant effect on carbachol (1 μM)- and high concentration K + (80 mM)-induced tracheal contractions in a way comparable to dicyclomine, suggesting the coexistence of Ca 2+ antagonistic and/or antimuscarinic properties. Additionally, Si.MEs also relaxed the phenylephrine(1 μM)- and high concentration K + (80 mM)-induced aortic contraction (0.01-3 mg/mL), suggesting blockade of Ca 2+ channel. Moreover, oral administration of Si.MEs, as high as 6 g per kg, did not produce lethality among the treated groups of mice. Aqueous-methanolic extract of seeds from S. irio (Si.MEs) exhibited the bronchodilator and gut modulator (spasmogenic and spasmolytic) activities, probably through dual blockade of muscarinic receptors and Ca 2+ channels, whereas, vasodilator effect may be due to Ca 2+ channels blockade validates its use in hypertension.

English

Many patients in Africa often utilize herbal medicine for the management of hyperactive gut disorders such as diarrhea and abdominal colic. There is therefore a need to scientifically evaluate efficacy of this herbal remedies. This study investigated the myorelaxant effect of Carissa edulis (Forssk.) Vahl and its possible mechanism of action using isolated rabbit jejunum preparations. Pieces of jejunum were isolated from adult New Zealand white rabbits. They were then mounted in an organ bath containing Tyrode’s solution. The rate and force of jejunal contraction were recorded and analyzed using a Powerlab that was coupled to Chart5 software for windows. The effects of the extract (0.1-10.0 mg/ml) on spontaneous contraction were investigated. Its effect (3.0 mg/ml) was also studied in the presence of LG-NAME (nitric oxide synthase inhibitor), methylene blue (soluble guanylyl cyclase inhibitor) and propranolol (non-selective β adrenergic receptors antagonist). The extract dose-dependent significantly decreased the force but not the rate of spontaneous rabbit jejunal contraction. Among the blockers used, only LG -NAME significantly blocked the effect of the extract. Aqueous root bark extracts of C. edulis possess significant myorelaxant effect on isolated rabbit jejunum. This appears to be mediated through stimulation of nitric oxide release by nitric oxide synthase. Key words: Carissa edulis, diarrhea, jejunum, motility, myorelaxant.

Pharmacological Studies Pertaining to Smooth Muscle Relaxant, Platelet Aggregation Inhibitory and Hypotensive Effects of Ailanthus altissima.

Objective This in vitro and in vivo study was conducted to rationalize some of traditional medicinal uses of Ailanthus altissima in gastrointestinal, respiratory, and cardiovascular systems. Materials Crude extract of Ailanthus altissima (Aa.Cr) and its fractions were prepared and utilized in in vitro and in vivo studies. For in vitro studies, Aa.Cr was investigated on isolated rabbit jejunum, isolated tracheal strip, and isolated aorta of rat suspended in tissue organ bath. Platelet rich and platelet poor plasma were used to study platelet aggregation inhibitory activity. In vivo antidiarrheal effect of Aa.Cr was investigated on balb/c mice pretreated with castor oil to induce diarrhea and SD rats were used to study hypotensive activity. Results Concentration dependent spasmolytic effects of Aa.Cr and its DCM fraction (Aa.DCM) were observed on spontaneous and spasmogen induced contractions in jejunum isolated from rabbit, but effect against high potassium (high-K+) induced contractions was more potent. Moreover Aa.Cr showed parallel shifting of calcium response curve to the right side. While its aqueous fraction (Aa.aq) caused spasmogenesis of isolated rabbit jejunum, this effect was blocked partially with prior administration of atropine (1μM). Concentration dependent protection against castor oil induced diarrhea was also observed. Relaxant effect was observed by the application of Aa.Cr and Aa.DCM against high-K+ and carbachol (CCh) induced contractions in tracheal strips isolated from SD rats, while Aa.Aq caused partial relaxation of high-K+ induced contractions, but no effect was observed against CCh induced contractions. Relaxation of rat aorta by the application of Aa.Cr and its fractions was also observed. Inhibition of force of contraction in rabbit atrium was also observed. Inhibition of platelet aggregation was observed against epinephrine and ADP induced aggregation. Conclusion Keeping in view the observed results, it is concluded that smooth muscle relaxant, platelet aggregation inhibitory and hypotensive effect may be due to the blockage of calcium channels.

Antidiarrheal potential of Distemonanthus benthamianus Baillon. extracts via inhibiting voltage-dependent calcium channels and cholinergic receptors

Objective: To evaluate spasmolytic mechanisms of aqueous and methanolic extracts from Distemonanthus benthamianus trunk-bark. Methods: Spasmolytic activities of extracts were evaluated in vitro on spontaneous and potassium chloride-induced jejunum contractions, or against cholinergic [acetylcholine (0.3 μmol/L)] stimulations. High performance liquid chromatography analysis of both extracts was performed in reference to standard compounds. Results: Extracts developed concentration-dependent inhibitory activities. The methanolic extract, which revealed better activity, produced spasmolytic and myorelaxant effects at concentrations of 0.01-0.30 mg/mL with EC50 of 0.06 and 0.09 mg/mL (95% CI: 0.03-0.3 mg/mL), respectively. Its anticholinergic effect was obtained at the same concentrations with EC50 of 0.11 mg/mL (95% CI: 0.03-0.3 mg/mL). Chromatograms showed the presence of gallic acid in both extracts, rutin being only detected in the aqueous extract. Conclusions: Distemonanthus benthamianus extracts exhibit verapamil and atropine-like activities, thus highlighting calcium channels and muscarinic receptors blocking potentials, which may be conveyed by some phenolic compounds. These results confirm the antidiarrheal activity of Distemonanthus benthamianus extracts.

English

Guiera senegalensis is a medicinal plant that is widely used in West Africa against many illnesses. In this work, the antiasthmatic properties of ethanol leaf extract of the G. senegalensis were evaluated by using various in vitro animal models. In vitro models like isolated guinea pig tracheal chain preparation, isolated guinea pig ileum and rabbit jejunum preparations were studied to evaluate possible mechanism by which extract shows relaxant activity. The preliminary phytochemical screening of the extract revealed the presence of alkaloids, anthraquinones, flavonoids, saponins and tannins. The study showed that the extract contained phytochemicals such as flavonoids, alkaloids, steroids, tannins and saponins. Isolated tracheal smooth muscles contractions induced by histamine was significantly (p&lt;0.01) reduced by the extract, so also that induced by acetylcholine at concentrations of 4 and 8 mg/ml. The findings were similar to that of 0.4 &micro;g/ml isoprenaline. Guinea pig and rabbit jejunum contractions induced by histamine and acetylcholine were significantly (p&lt;0.01) reduced by the extract. These observed effects can be attributed to the presence of phytochemicals such as flavonoids, alkaloids and steroids in the extract. The results of these studies indicated ethanol extract of G. senegalensis possess antiasthmatic activity. Key words: Antiasthmatic activity, bronchoconstriction, Guiera senegalensis, guinea pig ileum. &nbsp

Differential Inhibition of the Rhythm and Amplitude of Acetylcholine-Dependent Contraction in the Murine Jejunum and Ileum &amp;lt;i&amp;gt;In Vitro&amp;lt;/i&amp;gt; by Thiamin and Quinine

Previously, the effects of several bitter substances have been investigated in the contraction of the murine jejunum and ileum, reporting that these independently suppress the rhythm generation of the interstitial cells of Cajal. Recently, it was reported that thiamin, which binds to a bitter taste receptor, modifies the early phase of the ileum contraction, whereas the physiological effects on the rhythm and amplitude of jejunum and ileum contractions remain unclear. In this study, it was investigated the physiological effects of thiamin and quinine on the in vitro contraction of the murine jejunum and ileum using mice for all experiments. the periodic contraction of the jejunum was observed before the administration of acetylcholine (Ach) and other substances, and the tonic amplitudes induced by the substances. These bitter substances variably affect the Ach-induced rhythmic contraction of the jejunum and ileum in vitro. In addition, quinine hydrochloride (Qui) and thiamin hydrochloride (Thi) variably affect the Ach-induced rhythmic contraction of the jejunum and ileum in vitro. Both Qui and Thi markedly increase the rhythmic contraction in the jejunum. Although Thi does not change the rhythmic contraction in the ileum, it gradually reduces the amplitude in the jejunum. Conversely, Qui gradually reduces the amplitude and almost inhibits the contraction in the jejunum. Furthermore, an antagonist of the adrenalin-beta3 receptor, SR59230A, enhances the Qui-induced inhibition of the contraction in the jejunum.

Potential usefulness of methyl gallate in the treatment of experimental colitis.

Methyl gallate is a gallotannin widely distributed in nature. Previous studies have demonstrated its antioxidant, anti-inflammatory, antimicrobial and anti-tumor activities. In the present study, the activity of methyl gallate on experimental models of inflammatory bowel disease has been investigated. Experimental colitis was induced in Sprague-Dawley rats through the intracolonic instillation of an acetic acid solution (2mL, 4% v/v). Methyl gallate (100 and 300mg/kg, p.o.) and the reference drug mesalazine (100mg/kg, p.o.) were tested. Methyl gallate induced a significant reduction in the colon weight/length ratio and macroscopic lesion score. Besides, the malondialdehyde content and the GSSG/GSH ratio were remarkably decreased. Furthermore, the administration of methyl gallate reduced the expression of COX2, IL-6, TNFα and the severity of microscopic tissue damage induced by acetic acid, while the mean goblet cell density was significantly higher in both the group treated with methyl gallate and the one treated with mesalazine, in comparison with untreated animals. The Na+K+ATPase pump activity was recovered in treated groups (control: 827.2±59.6, colitis: 311.6±54.8, methyl gallate 100mg/kg: 642.2±175.0, methyl gallate 300mg/kg: 809.7±100.6, mesalazine: 525.3±81.7). Methyl gallate was also found to induce a significant reduction in the castor oil-induced intestinal motility in Swiss mice, decreasing the peristalsis by 74.5 and 58.82% at 100 and 300mg/kg p.o., respectively. This compound also antagonized the jejunum contractions induced by Ach and CaCl2. This study demonstrates that methyl gallate exerts beneficial effects in a preclinical model of intestinal disorders.

Role of Cyclic Nucleotides in the Effect of Hydrogen Sulfide on Contractions of Rat Jejunum.

We studied the role of cyclic nucleotides in the influence of hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS, 200 μM), on motor activity of rat jejunum. NaHS reduced spontaneous and carbachol-induced contractions of rat jejunum segment, which suggests that H2S can act through mechanisms involving muscarinic receptor activation. Against the background of a membrane-penetrating non-hydrolyzable cAMP analogue or under conditions of adenylate cyclase blockade, the inhibitory effect of NaHS on the carbachol-induced contractions was maintained. Against the background of elevated cGMP concentration or guanylate cyclase inhibition, the reduction of carbachol-induced contractions upon exposure to NaHS was less pronounced than in control. It was hypothesized that H2S induces relaxation of carbachol-induced jejunum contractions, affecting protein kinase G targets or activating cGMP synthesis.

Evaluation of a poly-herbal preparation for the treatment of peptic ulcer

The aim of this study was to validate the traditional uses of ulcerene, a poly-herbal formulation in ethanol, aspirin and stress-induced gastric ulcer model of rat. The extent of gastric ulcer formation was studied, using ulcer score, ulcer index, percentage cure through gross examination and histopathological evaluation. A significant (p&lt;0.001) dose-dependent anti-ulcerant effect was observed in ulcerene (50 and 100 mg/kg)-treated group with highest effectiveness against ethanol-induced ulcer. The concentration-dependent spasmolytic effect was seen in spontaneously contracting, high K+ (80 mM) and carbachol (1 µM)-induced jejunum contractions (10, 0.3 and 1 mg/mL), similar to dicyclomine (10, 1 and 3 µM), indicated non-specific spasmolytic mechanism behind the effect. By considering these results, ulcerene can be suggested for the treatment of peptic ulcer.