34 results on '"Gabriella Aviello"'
Search Results
2. A Mineral Extract from red Algae Ameliorates Chronic Spontaneous Colitis in IL-10 Deficient Mice in a Mouse Strain Dependent Manner
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Gabriella Aviello, Padraic G. Fallon, Sean P. Saunders, and Sylvie Amu
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Pharmacology ,Enterocolitis ,medicine.medical_specialty ,business.industry ,chemistry.chemical_element ,Interleukin ,Calcium ,medicine.disease ,Inflammatory bowel disease ,Interleukin 10 ,Endocrinology ,chemistry ,Internal medicine ,Immunology ,Medicine ,Serum amyloid A ,medicine.symptom ,Colitis ,business ,Serum Amyloid A Protein - Abstract
Inflammatory bowel disease is an urgent public health problem with a high incidence in developed countries. Alterations of lifestyle or dietary interventions may attenuate the disease progression and increase the efficacy of current therapies. Here we tested the effect of chronic supplementation with a mineral extract from red marine algae – rich in calcium (34%), magnesium, phosphorus, selenium and other trace minerals – in a clinically relevant model of spontaneous enterocolitis, interleukin (IL)-10-/- mice. The mineral extract was administered in the drinking water of Il10-/- mice on C57BL/6 J and BALB/c strain backgrounds for 25 weeks commencing from 3 to 4 weeks of age. The mineral extract ameliorated the spontaneous development of colitis and severity of disease in Il10-/- mice on a C57BL/6 J background. Mineral extract-treated Il10-/- C57BL/6 J strain mice had significantly reduced mortality, circulating levels of serum Amyloid A and reduced colonic tissue damage. In contrast, comparable treatment of Il10-/- mice on a BALB/c background with the mineral extract did not alter the course of colitis. These data demonstrate that chronic supplementation with a natural mineral extract selectively ameliorates spontaneous mild–moderate colitis in Il10-/- mice on a C57BL/6 J, but does not attenuate more moderate–severe colitis in BALB/c strain animals. Copyright © 2013 John Wiley & Sons, Ltd.
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- 2013
3. Pharmacological inhibition of MAGL attenuates experimental colon carcinogenesis
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Lucia Morbidelli, Roberta Imperatore, Gabriella Aviello, Lorena Buono, Barbara Romano, Vincenzo Di Marzo, Angelo A. Izzo, Pierangelo Orlando, Raffaele Capasso, Martina Monti, Fabiana Piscitelli, Ester Pagano, Francesca Borrelli, Pagano, Ester, Borrelli, Francesca, Orlando, Pierangelo, Romano, Barbara, Monti, Martina, Morbidelli, Lucia, Aviello, Gabriella, Imperatore, Roberta, Capasso, Raffaele, Piscitelli, Fabiana, Buono, Lorena, Di Marzo, Vincenzo, and Izzo, ANGELO ANTONIO
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0301 basic medicine ,Male ,Cannabinoid receptor ,Colorectal cancer ,Angiogenesis ,Carcinogenesis ,Colon ,Down-Regulation ,Mice, Nude ,Angiogenesis Inhibitors ,Antineoplastic Agents ,Arachidonic Acids ,URB602 ,Cancer prevention ,Glycerides ,03 medical and health sciences ,chemistry.chemical_compound ,Cyclin D1 ,Cell Line, Tumor ,medicine ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Lipid metabolism ,Pharmacology ,Enzyme Inhibitors ,Mice, Inbred ICR ,Neovascularization, Pathologic ,Azoxymethane ,business.industry ,Biphenyl Compounds ,Rectum ,medicine.disease ,Monoacylglycerol Lipases ,Monoacylglycerol lipase ,Vascular endothelial growth factor ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,chemistry ,Biochemistry ,Cancer research ,Female ,business ,Colorectal Neoplasms ,Endocannabinoids - Abstract
Colorectal cancer (CRC) is a major health problem in Western countries. The endocannabinoid 2-arachidonoyl-glycerol (2-AG) exerts antiproliferative actions in a number of tumoral cell lines, including CRC cells. Monoacylglycerol lipase (MAGL), a serine hydrolase that inactivates 2-AG, is highly expressed in aggressive human cancer cells. Here, we investigated the role of MAGL in experimental colon carcinogenesis. The role of MAGL was assessed in vivo by using the xenograft and the azoxymethane models of colon carcinogenesis; MAGL expression was evaluated by RT-PCR and immunohistochemistry; 2-AG levels were measured by liquid chromatography mass spectrometry; angiogenesis was evaluated in tumor tissues [by microvessel counting and by investigating the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) proteins] as well as in human umbilical vein endothelial cells (HUVEC); cyclin D1 was evaluated by RT-PCR. MAGL and 2-AG were strongly expressed in tumor tissues. The MAGL inhibitor URB602 reduced xenograft tumor volume, this effect being associated to down-regulation of VEGF and FGF-2, reduction in the number of vessels and down-regulation of cyclin D1. In HUVEC, URB602 exerted a direct antiangiogenic effect by inhibiting FGF-2 induced proliferation and migration, and by modulating pro/anti-angiogenic agents. In experiments aiming at investigating the role of MAGL in chemoprevention, URB602 attenuated azoxymethane-induced preneoplastic lesions, polyps and tumors. MAGL, possibly through modulation of angiogenesis, plays a pivotal role in experimental colon carcinogenesis. Pharmacological inhibition of MAGL could represent an innovative therapeutic approach to reduce colorectal tumor progression. (C) 2017 Elsevier Ltd. All rights reserved.
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- 2016
4. Tools for Controlling Activity of Neural Circuits Can Boost Gastrointestinal Research
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Gabriella Aviello, Giuseppe D'Agostino, Aviello, G., and D'Agostino, G.
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0301 basic medicine ,Opinion ,Biology ,Bioinformatics ,Institutional support ,Inflammatory bowel disease ,inflammatory bowel diseases ,03 medical and health sciences ,0302 clinical medicine ,optogenetics ,medicine ,Pharmacology (medical) ,Microbiota-gut-brain axi ,Colitis ,microbiota-gut-brain axis ,Pharmacology ,intestinal permeability ,lcsh:RM1-950 ,Inflammatory Bowel Diseases ,medicine.disease ,Chemogenetic ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,Research centre ,Immunology ,DREADD ,chemogenetics ,030217 neurology & neurosurgery - Abstract
We thank Prof U. G. Knaus and T. C. Collin for critical reading of the manuscript. GA is supported by the European Crohn's and Colitis Organization (ECCO) (J/15/2) and by the National Childrens' Research Centre (K/12/1). GD is supported by the University of Aberdeen Wellcome Trust Institutional Support Fund (105625/Z/14Z).
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- 2016
5. Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice
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Francesco Capasso, Fabiana Piscitelli, Barbara Romano, Angelo A. Izzo, Pierangelo Orlando, Vincenzo Di Marzo, Raffaele Capasso, Gabriella Aviello, Laura Gallo, and Francesca Borrelli
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Pharmacology ,Palmitoylethanolamide ,medicine.medical_specialty ,Cannabinoid receptor ,medicine.medical_treatment ,food and beverages ,Biology ,Depolarization-induced suppression of inhibition ,Endocannabinoid system ,Oleoylethanolamide ,chemistry.chemical_compound ,Cannabichromene ,Endocrinology ,chemistry ,Internal medicine ,parasitic diseases ,medicine ,Cannabinoid receptor type 2 ,lipids (amino acids, peptides, and proteins) ,Cannabinoid ,psychological phenomena and processes - Abstract
BACKGROUND AND PURPOSE Cannabichromene (CBC) is a major non-psychotropic phytocannabinoid that inhibits endocannabinoid inactivation and activates the transient receptor potential ankyrin-1 (TRPA1). Both endocannabinoids and TRPA1 may modulate gastrointestinal motility. Here, we investigated the effect of CBC on mouse intestinal motility in physiological and pathological states. EXPERIMENTAL APPROACH Inflammation was induced in the mouse small intestine by croton oil. Endocannabinoid (anandamide and 2-arachidonoyl glycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography-mass spectrometry; TRPA1 and cannabinoid receptors were analysed by quantitative RT-PCR; upper gastrointestinal transit, colonic propulsion and whole gut transit were evaluated in vivo; contractility was evaluated in vitro by stimulating the isolated ileum, in an organ bath, with ACh or electrical field stimulation (EFS). KEY RESULTS Croton oil administration was associated with decreased levels of anandamide (but not 2-arachidonoyl glycerol) and palmitoylethanolamide, up-regulation of TRPA1 and CB1 receptors and down-regulation of CB2 receptors. Ex vivo CBC did not change endocannabinoid levels, but it altered the mRNA expression of TRPA1 and cannabinoid receptors. In vivo, CBC did not affect motility in control mice, but normalized croton oil-induced hypermotility. In vitro, CBC reduced preferentially EFS- versus ACh-induced contractions. Both in vitro and in vivo, the inhibitory effect of CBC was not modified by cannabinoid or TRPA1 receptor antagonists. CONCLUSION AND IMPLICATIONS CBC selectively reduces inflammation-induced hypermotility in vivo in a manner that is not dependent on cannabinoid receptors or TRPA1.
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- 2012
6. Modulation of mouse gastrointestinal motility by allyl isothiocyanate, a constituent of cruciferous vegetables (Brassicaceae ): evidence for TRPA1-independent effects
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Raffaele Capasso, Vincenzo Di Marzo, Barbara Romano, Angelo A. Izzo, Luciano De Petrocellis, Gabriella Aviello, and Francesca Borrelli
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Pharmacology ,chemistry.chemical_classification ,biology ,Cruciferous vegetables ,food and beverages ,Motility ,Brassicaceae ,biology.organism_classification ,Allyl isothiocyanate ,Contractility ,chemistry.chemical_compound ,Transient receptor potential channel ,chemistry ,Biochemistry ,TRPA1 Cation Channel ,Ankyrin - Abstract
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.
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- 2012
7. Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation
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L. De Petrocellis, Gabriella Aviello, Pierangelo Orlando, A Schiano Moriello, Angelo A. Izzo, V. Di Marzo, and Colin Stott
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Physiology ,Cannabigerol ,medicine.medical_treatment ,TRPV1 ,Pharmacology ,Tetrahydrocannabivarin ,TRPV ,Transient receptor potential channel ,chemistry.chemical_compound ,Cannabichromene ,chemistry ,medicine ,Cannabinoid ,Cannabidiol ,medicine.drug - Abstract
Aim Plant cannabinoids, like Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), activate/desensitize thermosensitive transient receptor potential (TRP) channels of vanilloid type-1 or -2 (TRPV1 or TRPV2). We investigated whether cannabinoids also activate/desensitize two other 'thermo-TRP's', the TRP channels of vanilloid type-3 or -4 (TRPV3 or TRPV4), and if the TRPV-inactive cannabichromene (CBC) modifies the expression of TRPV1-4 channels in the gastrointestinal tract. Methods TRP activity was assessed by evaluating elevation of [Ca(2+)](i) in rat recombinant TRPV3- and TRPV4-expressing HEK-293 cells. TRP channel mRNA expression was measured by quantitative RT-PCR in the jejunum and ileum of mice treated with vehicle or the pro-inflammatory agent croton oil. Results (i) CBD and tetrahydrocannabivarin (THCV) stimulated TRPV3-mediated [Ca(2+)](i) with high efficacy (50-70% of the effect of ionomycin) and potency (EC(50∼) 3.7 μm), whereas cannabigerovarin (CBGV) and cannabigerolic acid (CBGA) were significantly more efficacious at desensitizing this channel to the action of carvacrol than at activating it; (ii) cannabidivarin and THCV stimulated TRPV4-mediated [Ca(2+)](i) with moderate-high efficacy (30-60% of the effect of ionomycin) and potency (EC(50) 0.9-6.4 μm), whereas CBGA, CBGV, cannabinol and cannabigerol were significantly more efficacious at desensitizing this channel to the action of 4-α-phorbol 12,13-didecanoate (4α-PDD) than at activating it; (iii) CBC reduced TRPV1β, TRPV3 and TRPV4 mRNA in the jejunum, and TRPV3 and TRPV4 mRNA in the ileum of croton oil-treated mice. Conclusions Cannabinoids can affect both the activity and the expression of TRPV1-4 channels, with various potential therapeutic applications, including in the gastrointestinal tract.
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- 2011
8. Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo
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Kevin Lewellyn, Raffaele Capasso, Livio Luongo, Sabatino Maione, Francesca Borrelli, Gabriella Aviello, Angelo A. Izzo, Maria De Chiaro, Barbara Romano, Jordan K. Zjawiony, Francesca Guida, Aviello, Gabriella, Borrelli, Francesca, F., Guida, Romano, Barbara, K., Lewellyn, M., De Chiaro, L., Luongo, J. K., Zjawiony, S., Maione, Izzo, ANGELO ANTONIO, and Capasso, Raffaele
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Lipopolysaccharides ,Male ,Agonist ,medicine.drug_class ,medicine.medical_treatment ,Anti-Inflammatory Agents ,Nitric Oxide Synthase Type II ,(+)-Naloxone ,Pharmacology ,Nitric Oxide ,κ-opioid receptor ,Diterpenes, Clerodane ,Mice ,chemistry.chemical_compound ,Receptor, Cannabinoid, CB1 ,Rimonabant ,Drug Discovery ,medicine ,Animals ,Edema ,Salvia ,Cells, Cultured ,Genetics (clinical) ,Inflammation ,Mice, Inbred ICR ,Salvinorin ,Macrophages ,Receptors, Opioid, kappa ,Salvinorin A ,chemistry ,Cyclooxygenase 2 ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Cannabinoid ,Inflammation Mediators ,Opioid antagonist ,medicine.drug - Abstract
The hallucinogenic compound, salvinorin A, is a potent κ-opioid receptor (KOR) agonist. However, other target(s) than the KOR, such as the cannabinoid CB1 receptor, have been proposed to explain its multiple pharmacological actions. Here, we have evaluated the effect of salvinorin A in lipopolysaccharide (LPS)-stimulated macrophages as well as in models of inflammation in vivo. Salvinorin A (0.1-10 pM) reduced LPS-stimulated nitrite, TNF-α and IL-10 (but not IL-1β) levels as well as iNOS (but not COX-2) LPS-induced hyperexpression. The effect of salvinorin A on nitrite levels was reverted by the opioid antagonist naloxone, the KOR antagonist nor-binaltorphimine and by the CB1 antagonist rimonabant Salvinorin A also prevented KOR and CB1 hyperexpression induced by LPS. In vivo, salvinorin A reduced the LPS- and the carrageenan-induced paw oedema and formalin-induced inflammatory pain, in a nor-binaltorphimine and rimonabant-sensitive manner. It is concluded that salvinorin A-via KORs and CB1 receptors-exerts ultrapotent actions on macrophages and also shows moderate antinflammatory effects in vivo.
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- 2011
9. Antispasmodic Effects and Structure−Activity Relationships of Labdane Diterpenoids from Marrubium globosum ssp. libanoticum
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Sergio Rosselli, Francesca Borrelli, Daniela Rigano, Angelo A. Izzo, Carmen Formisano, Maurizio Bruno, Felice Senatore, Gabriella Aviello, Raffaele Capasso, Rigano, D, Aviello, G, Bruno, M, Formisano, C, Rosselli, S, Capasso, R, Senatore, F, Izzo, AA, Borrelli, F, Rigano, Daniela, Aviello, Gabriella, Maurizio, Bruno, Formisano, Carmen, Sergio, Rosselli, Capasso, Raffaele, Senatore, Felice, Izzo, ANGELO ANTONIO, and Borrelli, Francesca
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Male ,Antispasmodic effect ,diterpenoid ,Pharmaceutical Science ,Pharmacognosy ,Analytical Chemistry ,Labdane ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Ileum ,Drug Discovery ,Botany ,medicine ,Animals ,Lebanon ,Medicinal plants ,Pharmacology ,Marrubium globosum ssp. libanoticum ,Plants, Medicinal ,Molecular Structure ,biology ,Plant Extracts ,fungi ,Organic Chemistry ,Parasympatholytics ,food and beverages ,Muscle, Smooth ,Settore CHIM/06 - Chimica Organica ,biology.organism_classification ,Acetylcholine ,Terpenoid ,Antispasmodic Agent ,Complementary and alternative medicine ,chemistry ,Molecular Medicine ,Antispasmodic ,Diterpenes ,Diterpene ,Marrubium ,medicine.drug - Abstract
Marrubium globosum ssp. libanoticum is a medicinal plant used in Lebanon to reduce pain and smooth muscle spasms. A chloroform extract obtained from M. globosum aerial parts reduced acetylcholine-induced contractions in the isolated mouse ileum. The purification of this extract identified, among 12 isolated labdane diterpenoids, four new compounds, named 13-epicyllenin A (4), 13,15-diepicyllenin A (5), marrulibacetal (9), and marrulactone (11). Their structures were determined by spectroscopic methods. Compound 9, which exerted antispasmodic activity, is likely the active ingredient of the extract. Preliminary structure-activity relationships for this class of compounds are suggested.
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- 2009
10. Peripheral endocannabinoid dysregulation in obesity: relation to intestinal motility and energy processing induced by food deprivation and re-feeding
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Fabiana Piscitelli, Stefania Petrosino, Francesca Borrelli, Gabriella Aviello, Vincenzo Di Marzo, Angelo A. Izzo, Barbara Romano, and Raffaele Capasso
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Pharmacology ,medicine.medical_specialty ,Cannabinoid receptor ,medicine.medical_treatment ,digestive, oral, and skin physiology ,2-Arachidonoylglycerol ,nutritional and metabolic diseases ,Adipose tissue ,Biology ,Endocannabinoid system ,Energy homeostasis ,Small intestine ,chemistry.chemical_compound ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Internal medicine ,medicine ,lipids (amino acids, peptides, and proteins) ,Cannabinoid ,Pancreatic hormone - Abstract
Background and purpose: Endocannabinoids in tissues controlling energy homeostasis are altered in obesity, thus contributing to metabolic disorders. Here we evaluate endocannabinoid dysregulation in the small intestine of mice with diet-induced obesity (DIO) and in peripheral tissues of Zucker and lean rats following food deprivation and re-feeding. Experimental approach: Intestinal transit, evaluated using rhodamine-B-labelled dextran, and small intestinal endocannabinoid levels, measured by liquid chromatography mass spectrometry, were measured in mice fed normal or high-fat diets (HFDs). Endocannabinoid levels were measured also in various tissues of lean and Zucker rats fed ad libitum or following overnight food deprivation with and without subsequent re-feeding. Key results: After 8 weeks of HFD, baseline intestinal transit was increased in DIO mice and enhanced by cannabinoid CB1 receptor antagonism less efficaciously than in lean mice. Small intestinal anandamide and 2-arachidonoylglycerol levels were reduced and increased respectively. In Zucker rats, endocannabinoids levels were higher in the pancreas, liver and duodenum, and lower in the subcutaneous adipose tissue. Food deprivation increased endocannabinoid levels in the duodenum and liver of both rat strains, in the pancreas of lean rats and in adipose tissues of Zucker rats. Conclusions and implications: Reduced anandamide levels might account for increased intestinal motility in DIO mice. Regulation of endocannabinoid levels in rat peripheral tissues, induced by food deprivation and re-feeding, might participate in food intake and energy processing and was altered in Zucker rats. These data, together with previous observations, provide further evidence for dysregulation of peripheral endocannabinoids in obesity.
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- 2009
11. Inhibitory effect of quercetin on rat trachea contractility in vitro
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Raffaele Capasso, Gabriella Aviello, Barbara Romano, Giuseppina Atorino, Ester Pagano, and Francesca Borrelli
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Pharmacology ,Pharmaceutical Science ,heterocyclic compounds - Abstract
Objectives The effect of quercetin, a naturally occurring flavonoid traditionally used to treat airway diseases such as bronchial asthma, on the contractile response elicited by electrical field stimulation or carbachol in rat isolated trachea was investigated. Methods Isolated tracheal tissue was subjected to contractions by an electrical field stimulation of 5 Hz for 30 s, 400 mA, and the responses in the presence of cumulative concentrations of quercetin (10−6−3 × 10−4 M) were observed. The effect of quercetin was also evaluated after administration of phentolamine plus propranolol (to block α- and β-adrenergic receptors), NG-nitro-L-arginine methyl ester (to block nitric oxide synthesis), capsaicin (to desensitise sensory C fibres), α-chymotrypsin (a proteolytic enzyme that rapidly degrades vasoactive intestinal peptide), SR140333 and SR48968 (tackykinin NK1 and NK2 receptor antagonists, respectively). Key findings Quercetin produced a concentration-dependent inhibition of contractions induced by both carbachol and electrical field stimulation. However, quercetin was more active in inhibiting the contractions produced by electrical field stimulation than those induced by carbachol, suggesting a presynaptic site of action (in addition to a postsynaptic effect, as revealed by the inhibitory action of quercetin on carbachol-induced contractions). The inhibitory effect of quercetin on contractions induced by electrical field stimulation was unaffected by phentolamine plus propranolol, SR 140333 and SR 48968, capsaicin treatment or by the proteolytic enzyme α-chymotrypsin. In contrast, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester significantly reduced the inhibitory effect of quercetin on contractions induced by electrical field stimulation. Conclusions Quercetin inhibits rat tracheal contractility through a presynaptic (involving nitric oxide) and a postsynaptic site of action.
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- 2009
12. Inhibitory effect of quercetin on rat trachea contractility in vitro
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Francesca Borrelli, Giuseppina Atorino, Barbara Romano, Ester Pagano, Raffaele Capasso, and Gabriella Aviello
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Pharmacology ,medicine.medical_specialty ,Carbachol ,biology ,Chemistry ,Proteolytic enzymes ,Pharmaceutical Science ,Inhibitory postsynaptic potential ,Nitric oxide ,Contractility ,Nitric oxide synthase ,chemistry.chemical_compound ,Endocrinology ,Phentolamine ,Internal medicine ,medicine ,biology.protein ,heterocyclic compounds ,Quercetin ,medicine.drug - Abstract
Objectives The effect of quercetin, a naturally occurring flavonoid traditionally used to treat airway diseases such as bronchial asthma, on the contractile response elicited by electrical field stimulation or carbachol in rat isolated trachea was investigated. Methods Isolated tracheal tissue was subjected to contractions by an electrical field stimulation of 5 Hz for 30 s, 400 mA, and the responses in the presence of cumulative concentrations of quercetin (10(-6)-3x10(-4) M) were observed. The effect of quercetin was also evaluated after administration of phentolamine plus propranolol (to block alpha- and beta-adrenergic receptors), NG-nitro-L-arginine methyl ester (to block nitric oxide synthesis), capsaicin (to desensitise sensory C fibres), alpha-chymotrypsin (a proteolytic enzyme that rapidly degrades vasoactive intestinal peptide), SR140333 and SR48968 (tackykinin NK1 and NK2 receptor antagonists, respectively). Key findings Quercetin produced a concentration-dependent inhibition of contractions induced by both carbachol and electrical field stimulation. However, quercetin was more active in inhibiting the contractions produced by electrical field stimulation than those induced by carbachol, suggesting a presynaptic site of action (in addition to a postsynaptic effect, as revealed by the inhibitory action of quercetin on carbachol-induced contractions). The inhibitory effect of quercetin on contractions induced by electrical field stimulation was unaffected by phentolamine plus propranolol, SR 140333 and SR 48968, capsaicin treatment or by the proteolytic enzyme alpha-chymotrypsin. In contrast, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester significantly reduced the inhibitory effect of quercetin on contractions induced by electrical field stimulation. Conclusions Quercetin inhibits rat tracheal contractility through a presynaptic (involving nitric oxide) and a postsynaptic site of action.
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- 2009
13. Inhibitory effect of salvinorin A, from Salvia divinorum , on ileitis-induced hypermotility: cross-talk between κ-opioid and cannabinoid CB1 receptors
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Pietro Marini, K Huben, Francesca Borrelli, Maria Grazia Cascio, V. Di Marzo, A. A. Izzo, Gabriella Aviello, R Capasso, Francesco Capasso, Barbara Romano, and Jordan K. Zjawiony
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Pharmacology ,medicine.medical_specialty ,Cannabinoid receptor ,biology ,medicine.drug_class ,Salvinorin ,medicine.medical_treatment ,digestive, oral, and skin physiology ,biology.organism_classification ,Endocannabinoid system ,κ-opioid receptor ,Salvinorin A ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Opioid receptor ,Internal medicine ,Salvia divinorum ,medicine ,Cannabinoid - Abstract
Background and purpose: Salvinorin A, the active component of the hallucinogenic herb Salvia divinorum, inhibits intestinal motility through activation of κ-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.
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- 2008
14. Cannabidiol, extracted fromCannabis sativa, selectively inhibits inflammatory hypermotility in mice
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Francesco Capasso, Barbara Romano, Gabriella Aviello, Raffaele Capasso, Angelo A. Izzo, Francesca Borrelli, and C Scalisi
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Pharmacology ,medicine.medical_specialty ,Cannabinoid receptor ,medicine.medical_treatment ,(+)-Naloxone ,Biology ,Endocrinology ,Rimonabant ,Fatty acid amide hydrolase ,Internal medicine ,medicine ,Cannabinoid receptor type 2 ,Croton oil ,Cannabinoid ,Cannabidiol ,medicine.drug - Abstract
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-chloro3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide), by the opioid receptor antagonist naloxone or by the a2-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
- Published
- 2008
15. The role of endocannabinoids in the regulation of gastric emptying: alterations in mice fed a high-fat diet
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Angelo A. Izzo, Francesco Capasso, V. Di Marzo, Isabel Matias, Gabriella Aviello, Francesca Borrelli, Stefania Petrosino, Barbara Romano, Pierangelo Orlando, and Raffaele Capasso
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Pharmacology ,medicine.medical_specialty ,Cannabinoid receptor ,Gastric emptying ,medicine.medical_treatment ,digestive, oral, and skin physiology ,TRPV1 ,Anandamide ,Biology ,Endocannabinoid system ,chemistry.chemical_compound ,Endocrinology ,Rimonabant ,chemistry ,Fatty acid amide hydrolase ,Internal medicine ,medicine ,lipids (amino acids, peptides, and proteins) ,Cannabinoid ,medicine.drug - Abstract
Background and purpose: Endocannabinoids (via cannabinoid CB1 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; CB1 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 CB1 receptor antagonist rimonabant, but not by the CB2 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 CB1 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. British Journal of Pharmacology (2008) 153, 1272–1280; doi:10.1038/sj.bjp.0707682; published online 28 January 2008
- Published
- 2008
16. Inhibitory effect of the herbal antidepressant St. John’s wort (Hypericum perforatum) on rat gastric motility
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Francesca Borrelli, Gabriella Aviello, Francesco Capasso, Raffaele Capasso, Angelo A. Izzo, Capasso, Raffaele, Borrelli, Francesca, Aviello, Gabriella, Capasso, Francesco, and Izzo, ANGELO ANTONIO
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Male ,Gastric motility ,Methysergide ,In Vitro Techniques ,Pharmacology ,chemistry.chemical_compound ,In vivo ,Animals ,Medicine ,Rats, Wistar ,Flowering Tops ,Analysis of Variance ,Dose-Response Relationship, Drug ,Gastric emptying ,biology ,Plant Extracts ,business.industry ,Stomach ,Antagonist ,Hypericum perforatum ,Muscle, Smooth ,General Medicine ,biology.organism_classification ,Antidepressive Agents ,Rats ,Hyperforin ,Gastric Emptying ,chemistry ,business ,Hypericum ,medicine.drug - Abstract
St. John's wort (Hypericum perforatum) is a highly popular and effective herbal antidepressant that clinically interacts with a number of conventional drugs. Because alterations in gastric emptying can cause pharmacokinetic interactions, in the present study we evaluated the effect of a standardized extract prepared from the flowering tops of Hypericum perforatum (SJW extract) on rat gastric motility. Orally administered SJW extract delayed gastric emptying in vivo. In vitro studies showed that SJW extract was significantly more active in inhibiting acetylcholine (or prostaglandin E2)-induced contractions than electrical field stimulation (EFS)-induced contractions. The effect of SJW extract on EFS-induced contractions was unaffected by drugs that inhibit intrinsic inhibitory nerves or by tachykinin antagonists, but it was reduced by the 5-hydroxytryptamine antagonist methysergide. The inhibitory effect of SJW extract on acetylcholine-induced contractions was reduced by the sarcoplasmic reticulum Ca2+-ATPase inhibitor cyclopiazonic acid, but not by the L-type Ca2+ channel blocker nifedipine or by methysergide. Among the chemical constituents of SJW extract tested, hyperforin and, to a lesser extent, the flavonoids kaempferol and quercitrin, inhibited acetylcholine-induced contractions. It is concluded that SJW has a direct inhibitory effect on smooth muscle and could also possibly modulate gastric neurotransmission. If extended to humans, the inhibitory effect of SJW extract on gastric emptying in vivo could contribute, at least in part, to the clinical pharmacokinetic interactions between conventional medicines and this herbal antidepressant.
- Published
- 2008
17. Effect of Boswellia serrata on intestinal motility in rodents: inhibition of diarrhoea without constipation
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Raffaele Capasso, Angelo A. Izzo, Gabriella Aviello, Valeria Ascione, Francesca Borrelli, R. Longo, and Francesco Capasso
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Pharmacology ,medicine.medical_specialty ,biology ,digestive, oral, and skin physiology ,Motility ,Ileum ,Zileuton ,biology.organism_classification ,medicine.disease ,Inflammatory bowel disease ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,medicine ,Boswellia serrata ,Verapamil ,Boswellia ,Rolipram ,medicine.drug - Abstract
Clinical studies suggest that the Ayurvedic plant Boswellia serrata may be effective in reducing diarrhoea in patients with inflammatory bowel disease. In the present study, we evaluated the effect of a Boswellia serrata gum resin extract (BSE) on intestinal motility and diarrhoea in rodents. BSE depressed electrically-, acetylcholine-, and barium chloride-induced contractions in the isolated guinea-pig ileum, being more potent in inhibiting the contractions induced by acetylcholine and barium chloride. The inhibitory effect of BSE on acetylcholine-induced contractions was reduced by the L-type Ca(2+) channel blockers verapamil and nifedipine, but not by the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid, by the phosphodiesterase type IV inhibitor rolipram or by the lipoxygenase inhibitor zileuton. 3-acetyl-11-keto-beta-boswellic acid, one of the main active ingredients of B. serrata, inhibited acetylcholine-induced contractions. BSE inhibited upper gastrointestinal transit in croton oil-treated mice as well as castor oil-induced diarrhoea. However, BSE did not affect intestinal motility in control mice, both in the small and in the large intestine. It is concluded that BSE directly inhibits intestinal motility with a mechanism involving L-type Ca(2+) channels. BSE prevents diarrhoea and normalizes intestinal motility in pathophysiological states without slowing the rate of transit in control animals. These results could explain, at least in part, the clinical efficacy of this Ayurvedic remedy in reducing diarrhoea in patients with inflammatory bowel disease.
- Published
- 2006
18. Effect of caffeic acid phenethyl ester on gastric acid secretion in vitro
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Francesco Capasso, Inmaculada Posadas, Francesca Borrelli, Valeria Ascione, Gabriella Aviello, Raffaele Capasso, Borrelli, Francesca, Posadas, I, Capasso, Raffaele, Aviello, Gabriella, Ascione, V, and Capasso, Francesco
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Male ,medicine.medical_specialty ,Nifedipine ,medicine.drug_class ,Physostigmine ,In Vitro Techniques ,Biology ,Gastric Acid ,Mice ,chemistry.chemical_compound ,Caffeic Acids ,Gastrointestinal Agents ,1-Methyl-3-isobutylxanthine ,Muscarine ,Internal medicine ,medicine ,Caffeic acid ,Animals ,Secretion ,Caffeic acid phenethyl ester ,Pharmacology ,Mice, Inbred ICR ,Gastrointestinal agent ,Dose-Response Relationship, Drug ,Stomach ,Phenylethyl Alcohol ,Pentagastrin ,Endocrinology ,Acetylcholinesterase inhibitor ,chemistry ,Gastric Mucosa ,Acetylcholinesterase ,Potassium ,Gastric acid ,Cholinesterase Inhibitors ,Acetylcholine ,Histamine ,medicine.drug - Abstract
Caffeic acid phenethyl ester (CAPE), one of the major components of propolis (honeybee resin), has demonstrated a wide spectrum of activities including suppression of eicosanoids by inhibition of cyclooxygenase-1 and cyclooxygenase-2 enzyme activities. The aim of this study was to investigate the effect of CAPE on basal and secretagogues-stimulated gastric acid secretion in vitro. In the isolated, lumen-perfused, stomach preparation of mouse, CAPE (10–100 μM) did not affect the basal gastric acid secretion nor the secretion stimulated by histamine, pentagastrin, isobutyl methylxanthine and high levels of K + . By contrast, CAPE increased the gastric acid secretion induced by the muscarinic receptor agonist, 5-methylfurmethide (5-MEF). CAPE also inhibited the acetylcholinesterase activity in an in vitro colorimetric assay. Eserine (10 μM), a well known acetylcholinesterase inhibitor, also increased 5-MEF-stimulated acid secretion. Our results show that CAPE increases gastric acid secretion stimulated by an acetylcholine agonist receptor likely through inhibition of acetylcholinesterase activity.
- Published
- 2005
19. Senna and the formation of aberrant crypt foci and tumors in rats treated with azoxymethane
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Raffaele Capasso, G. Di Carlo, Francesca Borrelli, Gabriella Aviello, Francesco Capasso, Angelo A. Izzo, Nicola Mascolo, Borrelli, Francesca, Capasso, Raffaele, Aviello, Gabriella, DI CARLO, G, Izzo, ANGELO ANTONIO, Mascolo, NICOLA DOMENICO C. FERDINANDO, and Capasso, Francesco
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Male ,Senna Plant ,medicine.medical_specialty ,Colorectal cancer ,Senna ,medicine.medical_treatment ,Azoxymethane ,Laxative ,Pharmaceutical Science ,Adenocarcinoma ,Gastroenterology ,chemistry.chemical_compound ,Internal medicine ,Drug Discovery ,Anthraquinones ,medicine ,Animals ,Anticarcinogenic Agents ,Rats, Wistar ,Carcinogen ,Pharmacology ,biology ,Cathartics ,Senna Extract ,medicine.disease ,biology.organism_classification ,digestive system diseases ,Rats ,Complementary and alternative medicine ,chemistry ,Colonic Neoplasms ,Molecular Medicine ,Precancerous Conditions ,Phytotherapy ,Aberrant crypt foci - Abstract
Chronic use of anthraquinone laxatives has been blamed for the induction of habituation and the development of colonic cancer, but there are no definitive studies which have demonstrated this. To evaluate the carcinogenic potential of anthraquinones, the effect of long-term senna pod extract (SE) treatment on either healthy rats or rats treated with an initiating tumor agent (azoxymethane--AOM) has been studied. SE (30 and 60mg/kg), administered for 110 weeks, did not induce the development of aberrant crypt foci (ACF) and tumors in healthy rats. The development of ACF and tumors in rats treated with AOM were significantly reduced by SE (30 and 60 mg/kg). These results suggest that a chronic SE use does not predispose to colon cancer. By contrast, SE might exert an anti-tumoral activity on rat colon carcinogenesis.
- Published
- 2005
20. Farnesoid X receptor agonists attenuate colonic epithelial secretory function and prevent experimental diarrhoea in vivo
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Stephen J. Keely, Joseph B. J. Ward, Magdalena S Mroz, Silvie Amu, Padraic G. Fallon, Mark Donowitz, Gabriella Aviello, Niamh Keating, Rafiquel Sarker, Mroz, M. S., Keating, N., Ward, J. B., Sarker, R., Amu, S., Aviello, G., Donowitz, M., Fallon, P. G., and Keely, S. J.
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Diarrhea ,Male ,medicine.medical_specialty ,Sodium-Hydrogen Exchangers ,medicine.drug_class ,Colon ,Blotting, Western ,Receptors, Cytoplasmic and Nuclear ,Pharmacology ,Biology ,medicine.disease_cause ,Mice ,Antidiarrheal ,Intestinal mucosa ,In vivo ,Isoxazole ,Internal medicine ,Electrodiagnosi ,medicine ,Animals ,Humans ,Intestinal Mucosa ,Receptor ,Antidiarrheals ,Cells, Cultured ,Caco-2 Cell ,Ion Transport ,Bile acid ,Animal ,Sodium-Hydrogen Exchanger 3 ,Electrodiagnosis ,Cholera toxin ,Gastroenterology ,Epithelial Transport ,Isoxazoles ,Cell Biology ,G protein-coupled bile acid receptor ,Intestinal Ion Transport ,Diarrhoea ,Mice, Inbred C57BL ,Endocrinology ,Farnesoid X receptor ,Caco-2 Cells ,Bile Acid ,Ex vivo ,Human - Abstract
Objective Bile acids are important regulators of intestinal physiology, and the nuclear bile acid receptor, farnesoid X receptor (FXR), is emerging as a promising therapeutic target for several intestinal disorders. Here, we investigated a role for FXR in regulating intestinal fluid and electrolyte transport and the potential for FXR agonists in treating diarrhoeal diseases. Design Electrogenic ion transport was measured as changes in short-circuit current across voltage-clamped T84 cell monolayers or mouse tissues in Ussing chambers. NHE3 activity was measured as BCECF fluorescence in Caco-2 cells. Protein expression was measured by immunoblotting and cell surface biotinylation. Antidiarrhoeal efficacy of GW4064 was assessed using two in vivo mouse models: the ovalbumin-induced diarrhoea model and cholera toxin (CTX)-induced intestinal fluid accumulation. Results GW4064 (5 μmol/L; 24 h), a specific FXR agonist, induced nuclear translocation of the receptor in T84 cells and attenuated Cl− secretory responses to both Ca2+ and cAMP-dependent agonists. GW4064 also prevented agonist-induced inhibition of NHE3 in Caco-2 cells. In mice, intraperitoneal administration of GW4064 (50 mg/mL) also inhibited Ca2+ and cAMP-dependent secretory responses across ex vivo colonic tissues and prevented ovalbumin-induced diarrhoea and CTX-induced intestinal fluid accumulation in vivo. At the molecular level, FXR activation attenuated apical Cl− currents by inhibiting expression of cystic fibrosis transmembrane conductance regulator channels and inhibited basolateral Na+/K+-ATPase activity without altering expression of the protein. Conclusions These data reveal a novel antisecretory role for the FXR in colonic epithelial cells and suggest that FXR agonists have excellent potential for development as a new class of antidiarrheal drugs.
- Published
- 2014
21. Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer
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Vincenzo Di Marzo, Fabiana Piscitelli, Laura Gallo, Gabriella Aviello, Barbara Romano, Raffaele Capasso, Francesca Borrelli, Angelo A. Izzo, Aviello, Gabriella, Romano, Barbara, Borrelli, Francesca, Capasso, Raffaele, L., Gallo, F., Piscitelli, V. D., Marzo, and Izzo, ANGELO ANTONIO
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Male ,Cannabinoid receptor ,Colorectal cancer ,TRPV1 ,Azoxymethane ,Antineoplastic Agents ,Pharmacology ,chemistry.chemical_compound ,Mice ,Cell Line, Tumor ,Drug Discovery ,otorhinolaryngologic diseases ,medicine ,Animals ,Cannabidiol ,Humans ,Genetics (clinical) ,Cell Proliferation ,Mice, Inbred ICR ,Cell growth ,medicine.disease ,HCT116 Cells ,Endocannabinoid system ,digestive system diseases ,Colon cancer ,chemistry ,Colonic Neoplasms ,Non-psychotropic cannabinoid ,Molecular Medicine ,Adenocarcinoma cells ,Comet Assay ,Caco-2 Cells ,medicine.drug ,Aberrant crypt foci - Abstract
Colon cancer affects millions of individuals in Western countries. Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis. Thus, we investigated its possible chemopreventive effect in the model of colon cancer induced by azoxymethane (AOM) in mice. AOM treatment was associated with aberrant crypt foci (ACF, preneoplastic lesions), polyps, and tumour formation, up-regulation of phospho-Akt, iNOS and COX-2 and down-regulation of caspase-3. Cannabidiol-reduced ACF, polyps and tumours and counteracted AOM-induced phospho-Akt and caspase-3 changes. In colorectal carcinoma cell lines, cannabidiol protected DNA from oxidative damage, increased endocannabinoid levels and reduced cell proliferation in a CB(1)-, TRPV1- and PPARγ-antagonists sensitive manner. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.
- Published
- 2012
22. Salvinorin A reduces mechanical allodynia and spinal neuronal hyperexcitability induced by peripheral formalin injection
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Livio Luongo, Serena Boccella, Raffaele Capasso, Vito de Novellis, Enza Palazzo, Francesca Guida, Gabriella Aviello, Ida Marabese, Sabatino Maione, Angelo A. Izzo, Maria De Chiaro, Jordan K. Zjawiony, Luisa Gatta, Guida, Francesca, Luongo, Livio, Aviello, G, Palazzo, Enza, De Chiaro, M, Gatta, L, Boccella, S, Marabese, Ida, Zjawiony, Jk, Capasso, R, Izzo, A, DE NOVELLIS, Vito, Maione, Sabatino, Guida, F, Luongo, L, Palazzo, E, Marabese, I, Capasso, Raffaele, Izzo, ANGELO ANTONIO, de Novellis, V, and Maione, S.
- Subjects
Agonist ,Male ,medicine.drug_class ,Formalin injection ,Anti-Inflammatory Agents ,Pain ,Pharmacology ,Salvinorin A ,Nociceptive spinal neurons ,κ-opioid receptor ,Allodynia ,Diterpenes, Clerodane ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Mice ,Formaldehyde ,Glial cells ,medicine ,lcsh:Pathology ,Premovement neuronal activity ,Animals ,Mice, Inbred ICR ,business.industry ,Research ,Chronic pain ,Nociceptors ,medicine.disease ,Anesthesiology and Pain Medicine ,chemistry ,Spinal Cord ,Hyperalgesia ,Nociceptor ,Molecular Medicine ,medicine.symptom ,business ,Neuroscience ,lcsh:RB1-214 - Abstract
Background: Salvinorin A (SA), the main active component of Salvia Divinorum, is a non-nitrogenous kappa opioid receptor (KOR) agonist. It has been shown to reduce acute pain and to exert potent antinflammatory effects. This study assesses the effects and the mode of action of SA on formalin-induced persistent pain in mice. Specifically, the SA effects on long-term behavioural dysfuctions and changes in neuronal activity occurring at spinal level, after single peripheral formalin injection, have been investigated. Moreover, the involvement of microglial and glial cells in formalin-induced chronic pain condition and in SA-mediated effects has been evaluated. Results: Formalin induced a significant decrease of mechanical withdrawal threshold at the injected and contralateral paw as well as an increase in the duration and frequency, and a rapid decrease in the onset of evoked activity of the nociceptive neurons 7 days after formalin injection. SA daily treatment significantly reduced mechanical allodynia in KOR and cannabinoid receptor 1 (CB1R) sensitive manner. SA treatment also normalized the spinal evoked activity. SA significantly reduced the formalin-mediated microglia and astrocytes activation and modulated pro and anti-inflammatory mediators in the spinal cord. Conclusion: SA is effective in reducing formalin-induced mechanical allodynia and spinal neuronal hyperactivity. Our findings suggest that SA reduces glial activation and contributes in the establishment of dysfunctions associated with chronic pain with mechanisms involving KOR and CB1R. SA may provide a new lead compound for developing anti-allodynic agents via KOR and CB1R activation.
- Published
- 2012
23. Garlic: empiricism or science?
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Barbara Romano, Francesca Borrelli, Angelo A. Izzo, Francesco Capasso, Francesca Lembo, Raffaele Capasso, Ludovico Abenavoli, Gabriella Aviello, Aviello, Gabriella, Abenavoli, L., Borrelli, Francesca, Capasso, Raffaele, Izzo, ANGELO ANTONIO, Lembo, Francesca, Romano, B., and Capasso, Francesco
- Subjects
Cardiotonic Agents ,Plant Science ,Alliin ,Pharmacology ,law.invention ,History, 17th Century ,chemistry.chemical_compound ,law ,Alliinase ,Neoplasms ,Drug Discovery ,Antithrombotic ,Medicine ,Animals ,Humans ,Drug Interactions ,Medicinal plants ,Garlic ,Hypolipidemic Agents ,Allicin ,biology ,business.industry ,Botany ,food and beverages ,General Medicine ,Allium sativum ,Atherosclerosis ,Complementary and alternative medicine ,chemistry ,biology.protein ,business ,Phytotherapy - Abstract
Garlic (Allium sativum L. fam. Alliaceae) is one of the best-researched, best-selling herbal remedies and is also commonly used as a food and a spice. Garlic constituents include enzymes (for example, alliinase) and sulfur-containing compounds, including alliin, and compounds produced enzymatically from alliin (for example, allicin). Traditionally, it has been employed to treat infections, wounds, diarrhea, rheumatism, heart disease, diabetes, and many other disorders. Experimentally, it has been shown to exert antilipidemic, antihypertensive, antineoplastic, antibacterial, immunostimulant and hypoglycemic actions. Clinically, garlic has been evaluated for a number of conditions, including hypertension, hypercholesterolemia, intermittent claudication, diabetes, rheumatoid arthritis, common cold, as an insect repellent, and for the prevention of arteriosclerosis and cancer. Systematic reviews are available for the possible antilipidemic, antihypertensive, antithrombotic and chemopreventive effects. However, the clinical evidence is far from compelling. Garlic appears to be generally safe although allergic reactions may occur.
- Published
- 2010
24. Inhibitory effect of caffeic acid phenethyl ester, a plant-derived polyphenolic compound, on rat intestinal contractility
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Caterina Scalisi, Raffaele Capasso, Gabriella Aviello, Francesca Borrelli, Barbara Romano, Angelo A. Izzo, Fileccia R, Aviello, Gabriella, Scalisi, C., Fileccia, R., Capasso, Raffaele, Romano, Barbara, Izzo, ANGELO ANTONIO, and Borrelli, Francesca
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Male ,Muscle Relaxation ,chemistry.chemical_element ,Pharmacology ,Calcium ,In Vitro Techniques ,Apamin ,Potassium Chloride ,chemistry.chemical_compound ,Phentolamine ,Caffeic Acids ,Phenols ,Ileum ,Caffeic acid ,medicine ,Animals ,Channel blocker ,Rats, Wistar ,Caffeic acid phenethyl ester ,Flavonoids ,Voltage-dependent calcium channel ,Polyphenols ,Phenylethyl Alcohol ,Plants ,Rats ,chemistry ,Biochemistry ,Cyclopiazonic acid ,medicine.drug ,Muscle Contraction - Abstract
Caffeic acid phenethyl ester (CAPE) exerts pharmacological actions (e.g. anti-inflammatory, chemopreventive) which are relevant for potential clinical application in the digestive tract. However, no study has been published on its possible effects on intestinal motility, to date. In the present study, we investigated the effect of this plant-derived polyphenolic compound on the spontaneous contractions of the rat isolated ileum. CAPE reduced (in a tetrodotoxin-insensitive manner) spontaneous ileal contractions and this effect was reduced by the l -type Ca 2+ channel blocker nifedipine and the chelant of calcium ethylenediaminetetraacetic acid. However, the effect of CAPE was not modified by a number of inhibitors/antagonists such as of phentolamine plus propranolol, atropine, tetrodotoxin, cyclopiazonic acid, ω-conotoxin, apamin, N G -nitro- l -arginine methyl ester, 3-isobutyl-1-methylxanthine, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or a combination of SR 140333, SR48968 and SR142801. In conclusion our study shows that (i) CAPE relaxed myogenic contractions of rat ileum and that (ii) this effect occurs, at least in part, throughout a mechanism involving l -type Ca 2+ channels.
- Published
- 2010
25. Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis
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Vincenzo Di Marzo, Angelo A. Izzo, Francesco Capasso, Pierangelo Orlando, Gabriella Aviello, Raffaele Capasso, Stefania Petrosino, Federico Guadagno, Barbara Romano, Francesca Borrelli, Francesco Maiello, Borrelli, Francesca, Aviello, Gabriella, Romano, B., Orlando, P., Capasso, Raffaele, Maiello, F., Guadagno, F., Petrosino, S., Capasso, Francesco, Di Marzo, V., and Izzo, ANGELO ANTONIO
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Male ,Cell Survival ,Colon ,medicine.medical_treatment ,Interleukin-1beta ,Gene Expression ,Nitric Oxide Synthase Type II ,Pharmacology ,medicine.disease_cause ,Inflammatory bowel disease ,Antioxidants ,Amidohydrolases ,Lipid peroxidation ,chemistry.chemical_compound ,Mice ,inflammatory bowel disease ,gastrointestinal pharmacology ,Drug Discovery ,Cannabinoid Receptor Modulators ,Medicine ,Animals ,Cannabidiol ,Humans ,Colitis ,Genetics (clinical) ,Cannabis ,Mice, Inbred ICR ,biology ,business.industry ,Cannabinoids ,Gastroenterology ,Organ Size ,medicine.disease ,Ulcerative colitis ,Interleukin-10 ,Nitric oxide synthase ,non-psychotropic cannabinoid ,chemistry ,Cyclooxygenase 2 ,Immunology ,biology.protein ,Molecular Medicine ,Cannabinoid ,Caco-2 Cells ,business ,Oxidative stress ,medicine.drug - Abstract
Inflammatory bowel disease affects millions of individuals; nevertheless, pharmacological treatment is disappointingly unsatisfactory. Cannabidiol, a safe and non-psychotropic ingredient of marijuana, exerts pharmacological effects (e.g., antioxidant) and mechanisms (e.g., inhibition of endocannabinoids enzymatic degradation) potentially beneficial for the inflamed gut. Thus, we investigated the effect of cannabidiol in a murine model of colitis. Colitis was induced in mice by intracolonic administration of dinitrobenzene sulfonic acid. Inflammation was assessed both macroscopically and histologically. In the inflamed colon, cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) were evaluated by Western blot, interleukin-1beta and interleukin-10 by ELISA, and endocannabinoids by isotope dilution liquid chromatography-mass spectrometry. Human colon adenocarcinoma (Caco-2) cells were used to evaluate the effect of cannabidiol on oxidative stress. Cannabidiol reduced colon injury, inducible iNOS (but not cyclooxygenase-2) expression, and interleukin-1beta, interleukin-10, and endocannabinoid changes associated with 2,4,6-dinitrobenzene sulfonic acid administration. In Caco-2 cells, cannabidiol reduced reactive oxygen species production and lipid peroxidation. In conclusion, cannabidiol, a likely safe compound, prevents experimental colitis in mice.
- Published
- 2009
26. Silymarin BIO-C, an extract from Silybum marianum fruits, induces hyperprolactinemia in intact female rats
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Francesco Capasso, Gabriella Aviello, Angelo A. Izzo, Francesco Savino, Francesca Borrelli, Francesca Lembo, Raffaele Capasso, Capasso, Raffaele, Aviello, Gabriella, Capasso, Francesco, F., Savino, Izzo, ANGELO ANTONIO, Lembo, Francesca, and Borrelli, Francesca
- Subjects
Agonist ,medicine.medical_specialty ,medicine.drug_class ,Pharmaceutical Science ,Pharmacology ,Silybum marianum ,Dopamine ,Internal medicine ,Lactation ,Drug Discovery ,medicine ,Animals ,Milk Thistle ,Rats, Wistar ,Bromocriptine ,biology ,Dose-Response Relationship, Drug ,business.industry ,Plant Extracts ,Receptors, Dopamine D2 ,Body Weight ,Reference Standards ,biology.organism_classification ,Prolactin ,Rats ,Hyperprolactinemia ,Dose–response relationship ,Endocrinology ,medicine.anatomical_structure ,Complementary and alternative medicine ,Fruit ,Dopamine Agonists ,Molecular Medicine ,Female ,business ,medicine.drug ,Silymarin - Abstract
Breastfeeding is widely acknowledged to have important health benefits for infants and mothers. Milk thistle (Silybum marianum fruits) has been recently proposed to be used by nursing mothers for stimulating milk production; however, the mode of action of this herbal drug is still unknown. In this paper, we have evaluated the effect of a micronized standardized extract of S. marianum (Silymarin BIO-C=Piulatte) on the serum levels of prolactin in female rats. A 14-day treatment with Silymarin BIO-C (25-200mg/kg, given orally) increased, in a dose dependent manner, the serum prolactin levels. Moreover, after a 66-day discontinuation of Silymarin BIO-C treatment, prolactin levels were still significantly elevated although we observed a trend to decrease that was counteracted by a further 7-day treatment with Silymarin BIO-C. Bromocriptine, a dopamine D(2) receptor agonist, (1-10mg/kg, os) significantly and in a dose dependent manner, reduced the serum prolactin levels; bromocriptine, at the dose of 1mg/kg, significantly reduced the high serum prolactin levels induced by Silymarin BIO-C. In conclusion, we have shown that an extract from S. marianum fruits significantly increases circulating prolactin levels in female rats; this effect seems to involve, at least in part, dopamine D(2) receptors.
- Published
- 2009
27. Potent relaxant effect of a Celastrus paniculatus extract in the rat and human ileum
- Author
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Simona De Marino, Stefania Masone, Giovanni Aprea, Nicola Borbone, Raffaele Capasso, Domenico Montesano, Gabriella Aviello, Francesca Borrelli, Angelo A. Izzo, Borrelli, Francesca, Borbone, Nicola, Capasso, Raffaele, Montesano, D, DE MARINO, Simona, Aviello, Gabriella, Aprea, Giovanni, Masone, S, and Izzo, ANGELO ANTONIO
- Subjects
Nifedipine ,medicine.drug_class ,Muscle Relaxation ,Neurotoxins ,Wistar ,Ileum ,Tetrodotoxin ,Celastrus paniculatus ,omega-Conotoxins ,Dose-Response Relationship ,chemistry.chemical_compound ,Animals ,Calcium Channel Blockers ,Dose-Response Relationship, Drug ,Gastrointestinal Motility ,Humans ,Muscle, Smooth ,Parasympatholytics ,Plant Extracts ,Plant Oils ,Rats ,Rats, Wistar ,Seeds ,Celastrus ,Drug Discovery ,Intestinal motility ,medicine ,Pharmacology ,Celastrus paniculatu ,biology ,Traditional medicine ,Muscle relaxant ,Biological activity ,Omega-Conotoxins ,biology.organism_classification ,Small intestine ,medicine.anatomical_structure ,chemistry ,Muscle-relaxant activity ,Muscle ,Smooth ,Drug ,Cyclopiazonic acid - Abstract
Ethnopharmacological importance: Celastrus paniculatus Willd. (Celastraceae) is an Ayurvedic remedy used for the treatment of a number of diseases, including bowel spasms. Aim of the study: To investigate the mode of the relaxing action of a methanolic extract prepared from the seeds of Celastrus paniculatus (CPE, 0.0001-10 μg/mL) in the rat ileum and to try to confirm on human tissues the intestinal pharmacological activity of the extract. Materials and methods: The relaxant effect of CPE was studied in vitro by evaluating its effect on the spontaneous contractions of the isolated ileum. Results: CPE exerted a tetrodotoxin- and ω-conotoxin-resistant inhibitory effect on rat ileum motility (IC50: 0.24 ± 0.02 μg/mL; Emax: 99.0 ± 0.60%). The inhibitory effect was reduced by nifedipine but not by cyclopiazonic acid. Experiments with specific antagonists enabled us to exclude the involvement of the main endogenous spasmogenic (i.e. acetylcholine and tachykinins) and relaxing (noradrenaline, nitric oxide, ATP) compounds. CPE also relaxed the isolated human ileum (IC50: 0.26 ± 0.02 μg/mL; Emax: 99.1 ± 0.46%). Conclusion: It is concluded that (i) CPE exerted a powerful myogenic and L-type Ca2+-dependent relaxing effect in the isolated rat ileum and that (ii) the human ileum is sensitive to the inhibitory effect of CPE. If confirmed in vivo, our data could explain the traditional use of this herb in the treatment of intestinal spasms. © 2009 Elsevier Ireland Ltd. All rights reserved.
- Published
- 2008
28. The hallucinogenic herb Salvia divinorum and its active ingredient salvinorin A reduce inflammation-induced hypermotility in mice
- Author
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Gabriella Aviello, Francesco Capasso, Raffaele Capasso, Angelo A. Izzo, Francesca Borrelli, Lukasz M. Kutrzeba, Giovanni Sarnelli, Jordan K. Zjawiony, Capasso, Raffaele, Borrelli, F, Zjawiony, J, Kutrzeba, L, Aviello, G, Sarnelli, G., Capasso, Francesco, and Izzo, A
- Subjects
Agonist ,Hallucinogen ,Male ,Physiology ,medicine.drug_class ,Motility ,(+)-Naloxone ,Salvia ,Pharmacology ,Diterpenes, Clerodane ,chemistry.chemical_compound ,Mice ,medicine ,Animals ,Inflammation ,Mice, Inbred ICR ,biology ,Endocrine and Autonomic Systems ,Chemistry ,Plant Extracts ,Receptors, Opioid, kappa ,Gastroenterology ,3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ,Analgesics, Non-Narcotic ,biology.organism_classification ,Salvinorin A ,Plant Leaves ,Opioid ,Salvia divinorum ,Hallucinogens ,Diterpenes ,Gastrointestinal Motility ,medicine.drug - Abstract
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 kappa-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.
- Published
- 2008
29. Effect of Marrubium globosum ssp libanoticum on intestinal motility
- Author
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Francesca Borrelli, Maurizio Bruno, Sergio Rosselli, Gabriella Aviello, Carmen Formisano, Daniela Rigano, Felice Senatore, Aviello, G, Rigano, Daniela, Borrelli, Francesca, Formisano, C, Rosselli, S, Senatore, F, Bruno, M., AVIELLO G, RIGANO D, BORRELLI F, FORMISANO C, ROSSELLI S, SENATORE F, BRUNO M, Aviello, Gabriella, Formisano, Carmen, S., Rosselli, Senatore, Felice, M., Bruno, Aviello, G., and Rosselli, S.
- Subjects
Pharmacology ,Traditional medicine ,biology ,business.industry ,Organic Chemistry ,Pharmaceutical Science ,biology.organism_classification ,Analytical Chemistry ,Intestinal motility ,Complementary and alternative medicine ,Drug Discovery ,Molecular Medicine ,Medicine ,business ,Marrubium - Published
- 2007
30. Spasmolytic activity of Phagnalon saxatile (L.) Cass. on the isolated rat ileum
- Author
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Maurizio Bruno, Felice Senatore, Daniela Rigano, Gabriella Aviello, Carmen Formisano, Raffaele Capasso, Angelo A. Izzo, Aviello, Gabriella, Rigano, Daniela, Formisano, Carmen, Capasso, Raffaele, Izzo, ANGELO ANTONIO, Senatore, Felice, M., Bruno, Aviello, G., Rigano, D., Formisano, C., Izzo, A. A., Senatore, F., and Bruno, M.
- Subjects
Pharmacology ,biology ,Traditional medicine ,business.industry ,Organic Chemistry ,Pharmaceutical Science ,Ileum ,biology.organism_classification ,Analytical Chemistry ,medicine.anatomical_structure ,Complementary and alternative medicine ,Drug Discovery ,medicine ,Molecular Medicine ,business ,Phagnalon saxatile - Published
- 2007
31. Phytochemical and pharmacological studies on the acetonic extract of Marrubium globosum ssp. libanoticum
- Author
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Armando Grassia, Felice Senatore, Daniela Rigano, Gabriella Aviello, Raffaele Capasso, Franco Piozzi, Francesca Borrelli, Maurizio Bruno, Nelly Apostolides Arnold, RIGANO, D, GRASSIA, A, BORRELLI, F, AVIELLO, G, PIOZZI, F, BRUNO, M, ARNOLD, NA, CAPASSO, R, SENATORE, F, Rigano, Daniela, Grassia, A., Borrelli, Francesca, Aviello, G., Piozzi, F., Bruno, M., APOSTOLIDES ARNOLD, N., Capasso, Raffaele, and Senatore, Felice
- Subjects
Male ,Blotting, Western ,Pharmaceutical Science ,Nitric Oxide Synthase Type II ,Pharmacognosy ,LABDANE DITERPENOIDS ,Carrageenan ,Dinoprostone ,Analytical Chemistry ,law.invention ,Labdane ,chemistry.chemical_compound ,Mice ,law ,Drug Discovery ,Botany ,VULGARE ,Animals ,Edema ,Rats, Wistar ,Pharmacology ,biology ,Traditional medicine ,Plant Extracts ,Organic Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,CYLLENEUM ,Plant Components, Aerial ,biology.organism_classification ,Rats ,Complementary and alternative medicine ,chemistry ,Phytochemical ,Macrophages, Peritoneal ,Molecular Medicine ,Lamiaceae ,VELUTINUM ,Diterpene ,Phytotherapy ,Marrubium - Abstract
A new natural labdane diterpene, marrulibanoside, was isolated from the acetonic extract of aerial parts of M. globosum Montbr. et Auch. ex Benth. ssp. libanoticum Boiss. (Lamiaceae). Its structure was determined by spectroscopic methods such as 1D and 2D NMR and mass spectrometry. Pharmacological studies have shown that the extract of M. globosum exerts anti-inflammatory effects in the rat paw oedema induced by carrageenin resulting in reduced paw swelling. This activity, which seems due to marrulibanoside, is a consequence of iNOS and COX-2 activities inhibition.
- Published
- 2006
32. Cytotoxic germacrane sesquiterpenes from the aerial parts of Santolina insularis
- Author
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Federico U Santelia, Orazio Taglialatela-Scafati, Ernesto Fattorusso, Francesca Petrucci, Gabriella Aviello, Francesca Borrelli, Giovanni Appendino, Mauro Ballero, Appendino, G., Aviello, G., Ballero, M., Borrelli, Francesca, Fattorusso, Ernesto, Petrucci, F., Santelia, F. U., and TAGLIALATELA SCAFATI, Orazio
- Subjects
Stereochemistry ,Pharmaceutical Science ,Epoxide ,Stereoisomerism ,Pharmacognosy ,Asteraceae ,Sesquiterpene ,Analytical Chemistry ,chemistry.chemical_compound ,Sesquiterpenes, Germacrane ,Drug Discovery ,Humans ,Nuclear Magnetic Resonance, Biomolecular ,Pharmacology ,Plants, Medicinal ,biology ,Molecular Structure ,Organic Chemistry ,Absolute configuration ,Biological activity ,biology.organism_classification ,Antineoplastic Agents, Phytogenic ,Terpenoid ,Complementary and alternative medicine ,chemistry ,Italy ,Molecular Medicine ,Drug Screening Assays, Antitumor - Abstract
Chemical investigation of Santolina insularis afforded eleven germacrane sesquiterpenes (1-11), four of which (2, 3, 10, and 11) are new. The stereostructures of these compounds have been established by a combination of spectroscopic techniques (mainly NMR), chemical transformations and application of the modified Mosher method. Compounds 8 and 10 showed a potent and selective cytotoxic activity against the human colon carcinoma cell line.
- Published
- 2005
33. Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice
- Author
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Ferdinando Fiorino, G. De Rosa, Ines Fasolino, Gabriella Aviello, Angelo A. Izzo, Francesca Borrelli, Raffaele Capasso, Beatrice Severino, Francesco Capasso, Barbara Romano, and M. Mazzella
- Subjects
Phospholipase C ,Endocrine and Autonomic Systems ,Physiology ,Gastroenterology ,Proteolytic enzymes ,Motility ,Ileum ,Biology ,Pharmacology ,Cysteine protease ,Small intestine ,medicine.anatomical_structure ,Biochemistry ,In vivo ,medicine ,Rolipram ,medicine.drug - Abstract
Background 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. Methods 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. Key Results 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, N1-3-methylbutyryl-N4-6-aminohexanoyl-piperazine (10−4mol 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. Conclusions & Inferences 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.
- Published
- 2011
34. THE ANTIDEPRESSANT ST. JOHN'S WORT (HYPERICUM PERFORATUM) INHIBITS RAT AND HUMAN VAS DEFERENS CONTRACTILITY
- Author
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G. Napodano, Gabriella Aviello, A. Izzo, R. Capasso, V. Montanaro, F. Capasso, and Vincenzo Altieri
- Subjects
Contractility ,medicine.anatomical_structure ,business.industry ,Urology ,Vas deferens ,medicine ,Antidepressant ,Hypericum perforatum ,Pharmacology ,business - Published
- 2006
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