F Capasso’s research while affiliated with Jadavpur University and other places

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.

Bromelain (BR) is a cysteine protease with inhibitory effects on intestinal secretion and inflammation. However, its effects on intestinal motility are largely unexplored. Thus, we investigated the effect of this plant-derived compound on intestinal contractility and transit in mice. Contractility in vitro was evaluated by stimulating the mouse isolated ileum, in an organ bath, with acetylcholine, barium chloride, or electrical field stimulation. Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine. Transit was also evaluated in pathophysiologic states induced by the pro-inflammatory compound croton oil or by the diabetogenic agent streptozotocin. Bromelain inhibited the contractions induced by different spasmogenic compounds in the mouse ileum with similar potency. The antispasmodic effect was reduced or counteracted by the proteolytic enzyme inhibitor, gabexate (15 × 10(-6)  mol L(-1) ), protease-activated receptor-2 (PAR-2) antagonist, N(1) -3-methylbutyryl-N(4) -6-aminohexanoyl-piperazine (10(-4) mol L(-1) ), phospholipase C (PLC) inhibitor, neomycin (3 × 10(-3) mol L(-1) ), and phosphodiesterase 4 (PDE4) inhibitor, rolipram (10(-6)  mol L(-1) ). In vivo, BR preferentially inhibited motility in pathophysiologic states in a PAR-2-antagonist-sensitive manner. Our data suggest that BR inhibits intestinal motility - preferentially in pathophysiologic conditions - with a mechanism possibly involving membrane PAR-2 and PLC and PDE4 as intracellular signals. Bromelain could be a lead compound for the development of new drugs, able to normalize the intestinal motility in inflammation and diabetes.

Croton oil is known to contain a potent tumour-promoting factor, 12-O-tetradecanoylphorbol 13-acetate (TPA), which is responsible for generation of oxygen free radicals and in turn the free radicals lead to lipid peroxidation. Such lipid peroxidation is assumed to induce severe inflammatory changes, increased vascular permeability and generation of proinflammatory hydroperoxides. Commonly used antioxidants are known to inhibit TPA. Our earlier results obtained from studies with Pluchea indica indicated that the methanolic fraction of the root extract possess significant anti-inflammatory and antioxidant activity.The present study was designed to assess the degree of inhibitory effect of P. indica on croton oil-induced mouse ear oedema, lipid hydroperoxide formation, peroxidizability of the epidermal layer and also in-vitro lipid peroxidation (using FeCl3/ADP/NADPH and CCl4 systems).

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Abstract The effect of ricinoleic acid on nitric oxide synthase (NOS) activity has been investigated in the rat. NOS, determined by the oxidation of oxyhemoglobin to methemoglobin or by the formation of citrulline, was detected in homogenates of both ileal and colonic tissue. Ricinoleic acid (10−5–10−3 M) incubated with intestinal tissue for 15 min, increased NOS activity (P <0.05–0.01); however the effect was more evident in the ileum than in the colon. A pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 6.25–25 mg kg−1 i.p., 15 min before the removal of tissue) inhibited the increase in NOS activity (P < 0.05). These findings confirm an involvement of NO in the laxative effect of ricinoleic acid (castor oil).

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. 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. 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. 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.

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. 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. 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 alpha2-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. 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.

Phytotherapic agents, such as herbal formulations containing Matricariae recutita flowers (chamomile) extract, Foeniculum vulgare fruit (fennel) extract and Melissa officinalis aerial parts (lemon balm) extract have beneficial effects on gastrointestinal tract in colicky infants. However, the mechanism is largely unexplored and, particularly, it is not clear if it affects intestinal motility. The aim of this experimental study was to evaluate the effect of different herbal formulations containing Matricariae recutita extract, Foeniculum vulgare extract and Melissa officinalis extract on upper gastrointestinal transit in mice in vivo. Gastrointestinal transit was measured in male ICR mice and in croton oil-treated mice after the oral administration of herbal formulations containing chamomile, fennel and lemon balm (ColiMil) and chamomile and lemon balm (ColiMil experimental). The herbal formulations tested (0.4-0.8 mL/mouse) dose-dependently and significantly inhibited gastrointestinal transit both in control and in croton oil-treated mice. Chamomile extract and lemon balm extract reduced significantly intestinal motility, but not fennel. At similar concentration ColiMil evoked a more consistent response than ColiMil experimental. Our findings directly demonstrate in vivo the effect of a combination of herbal formulations on intestinal motility. The observed inhibitory effect might be studied with clinical studies to test the efficacy of these compounds in the treatment of colicky infants.

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. 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. 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. Gastric emptying is physiologically regulated by the endocannabinoid system, which is downregulated following a HFD leading to overweight.