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Background and Purpose The non-psychotropic cannabinoid cannabichromene is known to activate the transient receptor potential ankyrin-type1 ( TRPA1) and to inhibit endocannabinoid inactivation, both of which are involved in inflammatory processes. We examined here the effects of this phytocannabinoid on peritoneal macrophages and its efficacy in an experimental model of colitis. Experimental Approach Murine peritoneal macrophages were activated in vitro by LPS. Nitrite levels were measured using a fluorescent assay; inducible nitric oxide ( iNOS), cyclooxygenase-2 ( COX-2) and cannabinoid ( CB1 and CB2) receptors were analysed by RT-PCR (and/or Western blot analysis); colitis was induced by dinitrobenzene sulphonic acid ( DNBS). Endocannabinoid (anandamide and 2-arachidonoylglycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography-mass spectrometry. Colonic inflammation was assessed by evaluating the myeloperoxidase activity as well as by histology and immunohistochemistry. Key Results LPS caused a significant production of nitrites, associated to up-regulation of anandamide, iNOS, COX-2, CB1 receptors and down-regulation of CB2 receptors mRNA expression. Cannabichromene significantly reduced LPS-stimulated nitrite levels, and its effect was mimicked by cannabinoid receptor and TRPA1 agonists (carvacrol and cinnamaldehyde) and enhanced by CB1 receptor antagonists. LPS-induced anandamide, iNOS, COX-2 and cannabinoid receptor changes were not significantly modified by cannabichromene, which, however, increased oleoylethanolamide levels. In vivo, cannabichromene ameliorated DNBS-induced colonic inflammation, as revealed by histology, immunohistochemistry and myeloperoxidase activity. Conclusion and Implications Cannabichromene exerts anti-inflammatory actions in activated macrophages - with tonic CB1 cannabinoid signalling being negatively coupled to this effect - and ameliorates experimental murine colitis. [ABSTRACT FROM AUTHOR]

Background Functional dyspepsia (FD) is a highly prevalent gastrointestinal disorder characterized by alterations in gastric motility. Yarrow ( Achillea millefolium L., Fam Asteraceae) preparations are traditional remedies used to treat dyspeptic complaints. Herein, we investigated the effect of a standardized dry water extract obtained from A. millefolium flowering tops (AME) on gastric motility. Methods The effect of AME on motility was evaluated on the resting tone of the isolated gastric antrum and on gastric emptying in vivo (phenol red meal method) both in control mice and in the model of cancer chemotherapy (cisplatin)-induced gastric abnormalities. Key Results The AME contracted mouse and human gastric strips and this action was unaffected by hexamethonium and tetrodotoxin, but strongly reduced by atropine. Among various chemical ingredients in yarrow, choline, but not the flavonoids rutin and apigenin, mimicked the action of AME. Furthermore, AME deprived of choline did not exert a contractile effect. In vivo, AME stimulated gastric emptying both in control and in cisplatin-treated mice, being more active in pathological states. Conclusions & Inferences It is concluded that (i) AME exerts a direct spasmogenic effect on gastric antrum; (ii) choline is the chemical ingredient responsible of such effect; (iii) the prokinetic effect of AME observed in vivo could provide the pharmacological basis underlying its traditional use in the treatment of dyspepsia. [ABSTRACT FROM AUTHOR]

The article discusses a study of the effect of the pineapple stem-derived cysteine protease (CP), Bromelain, on intestinal contractility and transit in mice. The authors stimulated the mouse isolated ileum in an organ bath that has acetylcholine, barium chloride in order to examine the contractility in vitro. They found that CP suppressed the contractions caused by different spasmogenic compounds in the mouse ileum with similar potency. They also observed that Bromelain could be used in reducing diarrhea in inflammatory bowel disease patients.

Background and Purpose: Salvinorin A, the active component of the hallucinogenic herb Salvia divinorum, inhibits intestinal motility through activation of kappa-opioid receptors (KORs). However, this compound may have target(s) other than the KORs in the inflamed gut. Because intestinal inflammation upregulates cannabinoid receptors and endogenous cannabinoids, in the present study we investigated the possible involvement of the endogenous cannabinoid system in salvinorin A-induced delay in motility in the inflamed gut.Experimental Approach: Motility in vivo was measured by evaluating the distribution of a fluorescent marker along the small intestine; intestinal inflammation was induced by the irritant croton oil; direct or indirect activity at cannabinoid receptors was evaluated by means of binding, enzymic and cellular uptake assays.Key Results: Salvinorin A as well as the KOR agonist U-50488 reduced motility in croton oil treated mice. The inhibitory effect of both salvinorin A and U-50488 was counteracted by the KOR antagonist nor-binaltorphimine and by the cannabinoid CB(1) receptor antagonist rimonabant. Rimonabant, however, did not counteract the inhibitory effect of salvinorin A on motility in control mice. Binding experiments showed very weak affinity of salvinorin A for cannabinoid CB(1) and CB(2) and no inhibitory effect on 2-arachidonoylglycerol and anandamide hydrolysis and cellular uptake.Conclusions and Implications: The inhibitory effect of salvinorin A on motility reveals a functional interaction between cannabinoid CB(1) receptors and KORs in the inflamed--but not in the normal--gut in vivo. [ABSTRACT FROM AUTHOR]

Background and purpose:Cannabidiol is a Cannabis-derived non-psychotropic compound that exerts a plethora of pharmacological actions, including anti-inflammatory, neuroprotective and antitumour effects, with potential therapeutic interest. However, the actions of cannabidiol in the digestive tract are largely unexplored. In the present study, we investigated the effect of cannabidiol on intestinal motility in normal (control) mice and in mice with intestinal inflammation.Experimental approach:Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine; intestinal inflammation was induced by the irritant croton oil; contractility in vitro was evaluated by stimulating the isolated ileum, in an organ bath, with ACh.Key results:In vivo, cannabidiol did not affect motility in control mice, but normalized croton oil-induced hypermotility. The inhibitory effect of cannabidiol was counteracted by the cannabinoid CB1 receptor antagonist rimonabant, but not by the cannabinoid CB2 receptor antagonist SR144528 (N-[-1S-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide), by the opioid receptor antagonist naloxone or by the α2-adrenergic antagonist yohimbine. Cannabidiol did not reduce motility in animals treated with the fatty acid amide hydrolase (FAAH) inhibitor N-arachidonoyl-5-hydroxytryptamine, whereas loperamide was still effective. In vitro, cannabidiol inhibited ACh-induced contractions in the isolated ileum from both control and croton oil-treated mice.Conclusions and implications:Cannabidiol selectively reduces croton oil-induced hypermotility in mice in vivo and this effect involves cannabinoid CB1 receptors and FAAH. In view of its low toxicity in humans, cannabidiol may represent a good candidate to normalize motility in patients with inflammatory bowel disease.British Journal of Pharmacology (2008) 154, 1001–1008; doi:10.1038/bjp.2008.177; published online 12 May 2008 [ABSTRACT FROM AUTHOR]

The hallucinogenic plant Salvia divinorum has been used for medical treatments of gastrointestinal disorders. Here, we evaluated the effect of a standardized extract from the leaves of Salvia divinorum (SDE) and of its active ingredient salvinorin A on motility in vivo, both in physiological states and during croton oil-induced intestinal inflammation. SDE (1–100 mg kg−1) significantly inhibited motility only in inflamed, but not in control, mice. In control mice, salvinorin A (0.01–10 mg kg−1) significantly inhibited motility only at the highest doses tested (3 and 10 mg kg−1) and this effect was not counteracted by naloxone or by the κ-opioid receptor (KOR) antagonist nor-binaltorphimine. Inflammation significantly increased the potency of salvinorin A (but not of the KOR agonist U-50488) in reducing motility. The inhibitory effects of both salvinorin A and U-50488 in inflamed mice were counteracted by naloxone or by nor-binaltorphimine. We conclude that salvinorin A may reduce motility through activation of different targets. In physiological states, salvinorin A, at high doses, inhibited motility through a non-KOR mediated mechanism. Gut inflammation increased the potency of salvinorin A; this effect was mediated by KOR, but it was not shared by U-50488, thus suggesting that salvinorin A may have target(s) other than KOR in the inflamed gut. [ABSTRACT FROM AUTHOR]

Salvia divinorum is a widespread hallucinogenic herb traditionally employed for divination, as well as a medicament for several disorders including disturbances of gastrointestinal motility. In the present study we evaluated the effect of a standardized extract from the leaves of S. divinorum (SDE) on enteric cholinergic transmission in the guinea-pig ileum. SDE reduced electrically evoked contractions without modifying the contractions elicited by exogenous acetylcholine, thus suggesting a prejunctional site of action. The inhibitory effect of SDE on twitch response was abolished by the opioid receptor antagonist naloxone and by the κ-opioid antagonist nor-binaltorphimine, but not by naltrindole (a δ-opioid receptor antagonist), CTOP (a μ-opioid receptor antagonist), thioperamide (a H3 receptor antagonist), yohimbine (an α2-receptor antagonist), methysergide (a 5-hydroxytryptamine receptor antagonist), NG-nitro-l- arginine methyl ester (an inhibitor of NO synthase) or apamin (a blocker of Ca2+-activated K+ channels). Salvinorin A, the main active ingredient of S. divinorum, inhibited in a nor-binaltorphimine- and naloxone-sensitive manner electrically induced contractions. It is concluded that SDE depressed enteric cholinergic transmission likely through activation of κ-opioid receptors and this may provide the pharmacological basis underlying its traditional antidiarrhoeal use. Salvinorin A might be the chemical ingredient responsible for this activity. [ABSTRACT FROM AUTHOR]

: Gastrointestinal cancer is one of the leading causes of cancer mortality in the world. Therefore, numerous efforts are being made to find chemoprotective substances able to reduce its incidence. Amongst these, green tea, one of the most popular beverages world-wide, has been reported to provide protective effects against gastrointestinal cancer. : To critically evaluate all epidemiological studies reporting an association between green tea consumption and a reduced risk of gastrointestinal cancer. : Epidemiological studies of green tea consumption in relation to gastrointestinal cancer or preneoplastic lesions were identified through computerized literature searches using the following databases: Medline (Pubmed), Embase, Amed, CISCOM, Phytobase and Cochrane Library. Only epidemiological studies indicating the type of tea (green tea) and the site of either cancer or precancerous lesions (stomach or intestine) were included. No language restrictions were imposed. : Twenty-one epidemiological investigations met our inclusion/exclusion criteria. : These studies seemed to suggest a protective effect of green tea on adenomatous polyps and chronic atrophic gastritis formations. By contrast, there was no clear epidemiological evidence to support the suggestion that green tea plays a role in the prevention of stomach and intestinal cancer. [ABSTRACT FROM AUTHOR]

We propose a novel algorithm for solving multiparametric linear programming problems. Rather than visiting different bases of the associated LP tableau, we follow a geometric approach based on the direct exploration of the parameter space. The resulting algorithm has computational advantages, namely the simplicity of its implementation in a recursive form and an efficient handling of primal and dual degeneracy. Illustrative examples describe the approach throughout the paper. The algorithm is used to solve finite-time constrained optimal control problems for discrete-time linear dynamical systems. [ABSTRACT FROM AUTHOR]

Cimicifuga racemosa is widely employed to relieve menopause symptoms for its hormonal-like action. However, recent experimental studies have not found an estrogenic action by this plant. The purpose of this systematic review is to analyse all experimental studies (in vivo and in vitro) performed on C. racemosa to elucidate its mechanism of action. Animal and in vitro experiments on C. racemosa were identified through a computerised literature searches performed on Medline (PubMed), Embase, Amed, CISCOM and Cochrane Library databases. In addition, bibliographies of the articles thus located were scanned for further relevant publications and manufactures of commercial C. racemosa preparations were asked to contribute published and unpublished material. No language restrictions were imposed. A total of 15 animal and 15 in vitro studies on C. racemosa have been found. Their results suggest that C. racemosa possesses a central activity instead of a hormonal effect. Further biological and chemical investigations are required to define its mechanism of action and to identify the compounds responsible of its actions. [Copyright &y& Elsevier]

Nimesulide, a selective inhibitor of cyclooxygenase-2, has been reported to cause less gastric damage, compared to other NSAIDs. We investigated the effect of nimesulide on basal gastric acid secretion, a contributing factor in NSAID-induced gastric damage, and histamine, pentagastrin, 5-methylfurmethide, isobutyl methylxanthine or high K+ stimulated acid secretion in the isolated mouse stomach. The stomachs, removed from mice, were transferred into an organ bath and continuously perfused. Changes in pH following the addition of secretagogues were measured by a pH electrode system. The effects of nimesulide on basal and secretagogues-stimulated acid secretion were compared to those of indomethacin. Nimesulide (1 μM to 100 μM) produced a rightward concentration-dependent shift and reduction of maximum acid secretion of all the agonist-stimulated acid secretion curves. Indomethacin was only effective at the higher concentration of 100 μM. Compared to their effects singly, nimesulide (20 μM) and famotidine (0.15 μM) together caused a further shift without further reduction in maximum acid output of the histamine-stimulated curve, suggesting that nimesulide was not acting at the histamine H2-receptor. Nimesulide concentration-dependent reduction of stimulated acid secretion in the isolated mouse stomach was not by antagonism of the histamine H2 receptor and is probably beyond the level of adenylate cyclase stimulation. A direct effect on the calcium channel is demonstrated. [Copyright &y& Elsevier]

Background: Constitutive cyclooxygenase‐1 enzyme synthesizes prostaglandins which are thought to play an important role in the functional integrity of the stomach gastric mucosa. Recently, it was shown that cyclooxygenase‐1 deficient mutant mice did not develop spontaneous gastric pathology and appear less sensitive to indomethacin‐induced gastric damage. Aim: To investigate gastric acid secretion in cyclooxygenase‐1 deficient mutant mice. Methods: The basal and histamine or isobutyl methylxanthine‐stimulated acid secretion in stomachs of cyclooxygenase‐1 deficient homozygous mice and the effect of indomethacin was compared with that of heterozygous and wild‐type mice using isolated lumen perfused mouse stomachs, in organ baths, monitored by pH‐electrodes. Results: There was no significant difference in the basal or histamine stimulated gastric acid secretion between wild‐type or heterozygous or homozygous mice. However, isobutyl methylxanthine was more potent in the cyclooxygenase‐1 deficient and heterozygous mice than in wild‐type mice. Indomethacin, at concentrations below 1 mM, had no effect on either basal or histamine stimulated acid secretion in any of the mice populations. Conclusion: Gastric acid secretion is maintained without prostaglandin involvement in cyclooxygenase‐1 deficient mice. The finding that basal and histamine‐stimulated gastric acid secretion was similar in the cyclooxygenase‐1 deficient, compared to wild‐type mice is consistent with the lack of spontaneous gastric pathology in the cyclooxygenase‐1 deficient mice. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on Senna and its laxative effect, by F. Borrelli, G. Aviello, R. Capasso and F. Capasso in the 2006 issue.

Two ethanolic propolis extracts (EPE) with and without the caffeic acid phenethyl ester (CAPE), CAPE and galangin (major components of propolis) were investigated for anti-inflammatory activity in rats using carrageenin foot oedema, carrageenin pleurisy and adjuvant arthritis. In our experiments, EPE with CAPE and CAPE alone significantly inhibited carrageenin oedema, carrageenin pleurisy and adjuvant arthritis. In contrast EPE without CAPE and galangin did not exhibit anti-inflammatory effects in acute and chronic inflammation. These results suggest that the anti-inflammatory activity of propolis is due to CAPE. [Copyright &y& Elsevier]

We have studied the effect of propolis and its main active ingredient caffeic acid phenetyl ester (CAPE) on formation of aberrant crypt foci (ACF) and tumors in the rat colon in vivo. CAPE (50 mg/kg i.p.) reduced the formation of ACF and tumor induced by azoxymethane, while propolis ethanolic extract was without effect. These results suggest a potential anti-carcinogenesis of CAPE but not propolis. [Copyright &y& Elsevier]

Tomatoes are one of the most widely consumed vegetables in the Mediterranean Diet. They are a rich source of antioxidant compounds and their consumption is linked with a reduction of various types of pathologies. In addition to geographical and seasonal variables, cultivar is an important factor affecting the profile and the concentration of antioxidant compounds. “Pomodorino Vesuviano” is a Protected Designation of Origin (PDO) tomato cultivar traditionally grown in Campania (southern Italy), which to the best of our knowledge has never been analyzed for bioactive compounds before. Here we present a study conducted to investigate the carotenoid and flavonoid content in tomatoes from this cultivar. Results indicate that Pomodorino Vesuviano is a rich source of antioxidants, with lycopene (78.6 mg/kg fresh weight (fw)) and quercetin (8.52 mg/kg fw) are the major components. Moreover, cell-based studies have suggested that a synergistic effect among phytochemicals in tomatoes is responsible for their antioxidant activity, since the combination of low concentrations of carotenoids and polyphenols (i.e. per se inactive concentrations) resulted in a significant reduction of reactive oxygen species (ROS) formation. . [ABSTRACT FROM AUTHOR]

Background and Purpose: Allyl isothiocyanate (AITC, mustard oil), a constituent of many common cruciferous vegetables (Brassicaceae), activates transient receptor potential of ankyrin type-1 (TRPA1) channels, claimed to regulate gastrointestinal contractility. In this study, we have investigated the effect of AITC on intestinal motility.Experimental Approach: Effects of AITC were investigated in vivo on upper gastrointestinal transit in mice and in mouse isolated ileum [contractions induced by electrical field stimulation (EFS), acetylcholine and spontaneous contractility]. The contractor activity of AITC was studied in mouse isolated colon. The ability of TRPA1 channel antagonists to block AITC-induced elevation of intracellular Ca(2+) [Ca(2+)](i) was assessed in HEK293 cells transfected with rat TRPA1 channels.Key Results: AITC increased [Ca(2+)](i) in HEK293 cells, reduced ileal contractility (acetylcholine-, EFS-induced contractions and spontaneous contractility), but contracted the isolated colon. Gentamicin and camphor (non-selective TRPA1 channel antagonists), HC-030031 and AP18 (selective TRPA1 channel agonists) inhibited AITC-induced effects in HEK293 cells but not in the ileum or colon. AITC-induced contractions were reduced by tetrodotoxin and strongly reduced by nifedipine, cyclopiazonic acid and ryanodine. In vivo, AITC reduced (following i.p. administration) or increased (following intragastric administration) upper gastrointestinal transit in mice These effects were not affected by HC-030031.Conclusion and Implications: AITC, depending, in vitro, on the regions of gut examined and, in vivo, on the route of administration, exerted both stimulatory and inhibitory effects on intestinal motility, which were not sensitive to TRPA1 channel antagonists. The proposition that TRPA1 channels are the primary targets for AITC to induce contraction should be revised. [ABSTRACT FROM AUTHOR]

Background and Purpose: Endocannabinoids (via cannabinoid CB(1) receptor activation) are physiological regulators of intestinal motility and food intake. However, their role in the regulation of gastric emptying is largely unexplored. The purpose of the present study was to investigate the involvement of the endocannabinoid system in the regulation of gastric emptying in mice fed either a standard diet (STD) or a high-fat diet (HFD) for 14 weeks.Experimental Approach: Gastric emptying was evaluated by measuring the amount of phenol red recovered in the stomach after oral challenge; CB(1) expression was analysed by quantitative reverse transcription-PCR; endocannabinoid (anandamide and 2-arachidonoyl glycerol) levels were measured by liquid chromatography-mass spectrometry.Key Results: Gastric emptying was reduced by anandamide, an effect counteracted by the CB(1) receptor antagonist rimonabant, but not by the CB(2) receptor antagonist SR144528 or by the transient receptor potential vanilloid type 1 (TRPV1) antagonist 5'-iodoresiniferatoxin. The fatty acid amide hydrolase (FAAH) inhibitor N-arachidonoyl-5-hydroxytryptamine (but not the anandamide uptake inhibitor OMDM-2) reduced gastric emptying in a way partly reduced by rimonabant. Compared to STD mice, HFD mice exhibited significantly higher body weight and fasting glucose levels, delayed gastric emptying and lower anandamide and CB(1) mRNA levels. N-arachidonoylserotonin (but not rimonabant) affected gastric emptying more efficaciously in HFD than STD mice.Conclusions and Implications: Gastric emptying is physiologically regulated by the endocannabinoid system, which is downregulated following a HFD leading to overweight. [ABSTRACT FROM AUTHOR]

Patients with ulcerative colitis (UC) using marijuana have been reported to experience symptomatic benefit. Cannabidivarin (CBDV) is a safe non-psychoactive phytocannabinoid able to activate and desensitize TRPA1, a member of the TRP channels superfamily, which plays a pivotal role in intestinal inflammation. Here, we have investigated the potential intestinal anti-inflammatory effect of CBDV in mice and in biopsies from pediatric patients with active UC. Colonic inflammation was induced in mice by dinitrobenzenesulfonic acid (DNBS). The effect of orally administered CBDV on macroscopic and microscopic damage, inflammatory parameters (i.e. myeloperoxidase activity, intestinal permeability and cytokine production) and faecal microbiota composition, was evaluated 3 days after DNBS administration. TRPA1 expression was studied by RT-PCR in inflamed colons of mice as well as in mucosal colonic biopsies of children with active UC, whose response to incubation with CBDV was also investigated. CBDV attenuates, in a TRPA1-antagonist sensitive manner, DNBS-induced signs of inflammation including neutrophil infiltration, intestinal permeability, and cytokine (i.e. IL-1β, IL-6 and the chemokine MCP-1) production. CBDV also alters the dysregulation of gut microbiota associated to colitis. Finally, CBDV lessens cytokine expression in colonic biopsies from pediatric patients with ulcerative colitis, a condition in which TRPA1 was up-regulated. Our preclinical study shows that CBDV exerts intestinal anti-inflammatory effects in mice via TRPA1, and in children with active UC. Since CBDV has a favorable safety profile in humans, it may be considered for possible clinical trials in patients with UC. [ABSTRACT FROM AUTHOR]