Nanoparticles In Treatment Of Thermal Injured Rats: Is It Safe?

The aim of this study was to assess whether thermal trauma induced oxidative stress altered the balance between oxidant and antioxidant systems in the blood of burn wound rats in the absence and presence of silver nanoparticles and S-nitrosoglutathione, GSNO. Free silver nanoparticles, free GSNO and silver nanoparticles + GSNO had no cytotoxic effects. Under anesthesia, the shaved dorsum of the rats was exposed to 90°C (burn group) water bath. Studied compounds were administered topically immediately and at 28 days after the burn injury, four times a day. Silver nanoparticles and silver nanoparticles + GSNO were no toxic in vitro and in vivo. There were no significant differences in the levels of urea, creatinine, aminotransferases and hematological parameters, in control-burn groups (free silver nanoparticles) and treated-burn groups (free GSNO or silver nanoparticles + GSNO). There were no differences in lipid peroxidation and in the levels of protein carbonyls and glutathione, used as oxidative stress markers. A little inflammatory cell response, papillary dermis vascularization, fibroblasts differentiated into contractile myofibroblasts and the presence of a large amount of extracellular matrix were evidenced in treated groups following skin injury. These results indicate that silver nanoparticles and GSNO may provide an effective action on wound healing.3041Tian, J., Wong, K.K.Y., Ho, C.M., Lok, C.N., Yu, W.Y., Che, C.M., Chiu, J.F., Tam, P.K.H., (2007) J. Chem. Med. Chem., 2, p. 129Teli, M.K., Mutalik, S., Rajanikant, G.K., (2010) Cur. Pharm. Design., 16, p. 1882Schaller, M., Laude, J., Bodewaldt, H., Hamm, G., Korting, H.C., (2004) Skin Pharmacol. Physiol., 17, p. 31Seabra, A.B., Da Silva, R., De Souza, G.F.P., De Oliveira, M.G., (2008) Artif. Organs, 32, p. 262Seabra, A.B., Pankotai, E., Fehér, M., Somlai, A., Kiss, L., Bíró, L., Szabó, C., Lacza, Z., (2007) Br. J. Dermatol., 156, p. 814Seabra, A.B., Martins, D., Simes, M.M.S.G., Da Silva, R., Brocchi, M., De Oliveira, M.G., (2010) Artif. Organs, 34, p. 204Durán, N., Marcato, P.D., Alves, O.L., De Souza, G.I.H., Esposito, E., (2005) J. Nanobiotechnol., 3, p. 1Durán, N., Marcato, P.D., De Souza, G.I.H., Alves, O.L., Esposito, E., (2007) J. Biomed. Nanotechnol., 3, p. 203Amadeu, T.P., Seabra, A.B., De Oliveira, M.G., Costa, A.M.A., (2007) J. Eur. Acad. Dermatol. Venereol., 21, p. 629Amadeu, T.P., Seabra, A.B., De Oliveira, M.G., Costa, A.M.A., (2008) J. Surg Res., 149, p. 84Correa, D.H.A., Melo, P.S., De Carvalho, C.A.A., De Azevedo, M.B.M., Durán, N., Haun, M., (2005) Eur. J. Pharmacol., 510, p. 17De Conti, R., Oliveira, D.A., Fernandes, A.M.A.P., Melo, P.S., Rodriguez, J.A., Haun, M., Castro, S.L., Durán, N., (1998) Vitro Mol. Toxicol, 11, p. 153Borefreund, E., Puerner, J.A., (1984) J. Tissue Cult. Methods, 9, p. 7Denizot, F., Lang, R., (1986) J. Immunol. Methods, 89, p. 271Michailidis, Y., Jamurta, A.Z., Nikolaidis, M.G., Fatouros, I.G., Koutedakis, Y., Papassotiriou, I., (2007) Med. Sci. Sport Exerc., 39, p. 1107Davis, T.A., Amare, M., Naik, S., Kovalchuk, A.L., Tadaki, D., (2007) Wound Repair Regen., 15, p. 57

Evaluation Of The Antiulcerogenic Activity Of Violacein And Its Modulation By The Inclusion Complexation With β-cyclodextrin

The effects of β-cyclodextrin (βCD) inclusion complexation on the ability of violacein to prevent gastric ulceration in mice were studied. Violacein-βCD inclusion complexes were prepared in 1:1 and 1:2 molar ratios and analysed by differential scanning calorimetry and powder X-ray diffractometry. Violacein previously administered orally at 10 mg/kg significantly reduced indomethacin-induced gastric lesions, as well as 100 mg/kg of cimetidine (positive control). However, βCD complexation in both molar ratios significantly potentiated the protective action of violacein. In the HCl-ethanol-induced gastric ulcer model, violacein and the 1:2 inclusion complex (10 mg/kg, p.o.) inhibited gastric damage by almost 85%, whereas a 63% reduction was observed for the positive control, lansoprazole, at 30 mg/kg. In contrast, treatment with the 1:1 inclusion complex resulted in almost total disappearance of the antiulcer activity in this model. No significant changes in stress-induced gastric injury were found. In addition, the 1:2 inclusion complex improved the antilipoperoxidant activity of violacein in rat liver cells exposed to t-butyl hydroperoxide, whereas the 1:1 complex was less active than violacein. In summary, the 1:2 βCD inclusion complex has gastroprotective properties similar to or higher than that of violacein. An increase in mucosal defensive mechanisms and protection against peroxidative damage might be involved.814387396Ahmed, M.O., El-Gibaly, I., Ahmed, S.M., Effect of cyclodextrins on the physicochemical properties and antimycotic activity of clotrimazole (1998) Int. J. Pharm., 171, pp. 111-121Al-Shabanah, O.A., Raza, M., Al-Harbi, M.M., Al-Bekairi, A.M., Al-Gharably, N.M., Qureshi, S., Effect of ninhydrin on the biochemical and histopathological changes induced by ethanol in gastric mucosa of rats (2000) Life Sci., 67, pp. 559-566Atay, S., Tarnawski, A.S., Dubois, A., Eicosanoids and the stomach (2000) Prostaglandins Other Lipid Mediat, 61, pp. 105-124Bibby, D.C., Davies, N.M., Tucker, I.G., Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems (2000) Int. J. Pharm., 197, pp. 1-11Blandizzi, C., Natale, G., Gherardi, G., Lazzeri, G., Marveggio, C., Colucci, R., Carignani, D., Del Tacca, M., Acid-independent gastroprotective effects of lansoprazole in experimental mucosal injury (1999) Dig. Dis. Sci., 44, pp. 2039-2050Brunton, L.L., Fármacos para controle da acidez gástrica e tratamento de úlceras pepticas (1996) As Bases Farmacológicas da Terapêutica. 9th Ed., pp. 662-673. , Edited by J.G. Hardman and L.E. Limbird. McGraw-Hill, México City, MéxicoChatjigakis, A.K., Donzé, C., Coleman, A.W., Solubility behavior of β-cyclodextrin in water/cosolvent mixtures (1992) Anal. Chem., 64, pp. 1632-1634Connors, K.A., The stability of cyclodextrin complexes in solution (1997) Chem. Rev., 97, pp. 1325-1358Croft, K.D., The chemistry and biological effects of flavonoids and phenolic acids (1998) Ann. N.Y. Acad. Sci., 854, pp. 435-442Das, D., Bandyopadhyay, D., Bhattacharjee, M., Banerjee, R., Hydroxyl radical is the major causative factor in stress-induced gastric ulceration (1997) Free Rad. Biol. Med., 23, pp. 8-18De Azevedo, M.B.M., Alderete, J.B., Lino, A.C.S., Loh, W., Faljoni-Alario, A., Durán, N., Violacein/β-cyclodextrin inclusion complex formation studied by measurements of diffusion coefficient and circular dichroism (2000) J. Incl. Phenom. Mol. Recognit. Chem., 37, pp. 67-74De Azevedo, M.B.M., Alderete, J., Rodriguez, J.A., Souza, A.O., Rettori, D., Torsoni, M.A., Faljoni-Alario, A., Durán, N., Biological activities of violacein a new antitumoral indole derivative in an inclusion complex with β-cyclodextrin (2000) J. Incl. Phenom. Mol. Recognit. Chem., 37, pp. 93-101Desai, J.K., Parmar, N.S., Gastric and duodenal antiulcer activity of sulpiride, a dopamine D 2 receptor antagonist, in rats (1994) Agents Action, 42, pp. 149-152Durán, N., Menck, C.F.M., Chromobacterium violaceum: A review of pharmacological and industrial perspectives (2001) Crit. Rev. Microbiol., 27, pp. 201-222Evangelista, S., Meli, A., Influence of antioxidants and radical scavengers on ethanol-induced gastric ulcers in the rat (1985) Gen. Pharmacol., 16, pp. 285-286Florence, A.T., Jani, P.U., Novel oral drug formulations. Their potential in modulating adverse effects (1994) Drug Saf., 10, pp. 233-266Glavin, G.B., Szabo, S., Experimental gastric mucosal injury: Laboratory models reveal mechanisms of pathogenesis and new therapeutic strategies (1992) FASEB J., 6, pp. 825-831Goa, K.L., Monk, J.P., Enprostil: A preliminary review of its pharmacodynamics and pharmacokinetic properties and therapeutic efficacy in the treatment of peptic ulcer disease (1987) Drugs, 3, pp. 539-559Gracioso, J.S., Vilegas, W., Hiruma-Lima, C.A., Souza Brito, A.R.M., Effects of tea from Turnera ulmifolia L. on mouse gastric mucosa support the Turneraceae as a new source of antiulcerogenic drugs (2002) Biol. Pharm. Bull., 25, pp. 487-491Gremse, D.A., Lansoprazole: Pharmacokinetics, pharmacodynamics and clinical uses (2001) Expert. Opin. Pharmacother., 2, pp. 1663-1670Grover, J.K., Vats, V., Proton pump inhibitors (1999) Trop. Gastroenterol., 20, pp. 16-28Guguen-Guillouzo, C., Guillouzo, A., (1986) Isolated and Culture Hepatocytes, pp. 1-12. , Edited by A. Guillouzo and C. Guguen-Guillouzo. Les Editions INSERM, Paris, and John Libbey Eurotext, LondonHalliwell, B., Gutteridge, J.M.C., (1999) Free Radicals in Biology and Medicine. 3rd Ed., pp. 1-936. , Clarendon Press, Oxford, U.KHayden, L.J., Thomas, G., West, G.B., Inhibitors of gastric lesions in the rat (1978) J. Pharmacol., 30, pp. 244-246Hiruma-Lima, C.A., Gracioso, J.S., Nunes, D.S., Souza Brito, A.R.M., Effects of an essential oil from the bark of Croton cajucara Benth. on experimental gastric ulcer models in rats and mice (1999) J. Pharm. Pharmacol., 51, pp. 341-346Hiruma-Lima, C.A., Gracioso, J.S., Rodriguez, J.A., Haun, M., Nunes, D.S., Souza Brito, A.R.M., Gastroprotective effect essential oil from Croton cajucara Benth. (Euphorbiaceae) (2000) J. Ethnopharmacol., 69, pp. 229-234Hiruma-Lima, C.A., Gracioso, J.S., Toma, W., Almeida, A.B.A., Paula, A.C.B., Brasil, D.S.B., Müller, A.H., Souza Brito, A.R.M., Gastroprotective effect of aparisthman, a diterpene isolated from Aparisthmium cordatum, on experimental gastric ulcer models in rats and mice (2001) Phytomedicine, 8, pp. 94-100Hiruma-Lima, C.A., Toma, W., Gracioso, J.S., Almeida, A.B.A., Batista, L.M., Magri, L., Paula, A.C.B., Souza Brito, A.R.M., Natural trans-crotonin: The antiulcerogenic effect of another diterpene isolated from the bark of Croton cajucara Benth (2002) Biol. Pharm. Bull., 25, pp. 452-456Horáková, L., Stolc, S., Antioxidant and pharmacodynamic effects of pyridoindole stobadine (1998) Gen. Pharmac., 30, pp. 627-638Ito, M., Inaguma, K., Suzuki, Y., Segami, T., Suzuki, Y., Healing-promoting action of zinc-cimetidine complex on acetic acid-induced gastric ulcers in rats (1995) Jpn. J. Pharmacol., 68, pp. 287-295Ito, M., Suzuki, Y., Ishihara, M., Suzuki, Y., Anti-ulcer effects of antioxidants: Effect of probucol (1998) Eur. J. Pharmacol., 354, pp. 189-196Joyeux, M., Rolland, A., Fleurentin, J., Mortier, F., Dorfman, P., Tert-butyl hydroperoxide-induced injury in isolated rat hepatocytes: A model for studying anti-hepatotoxic crude drugs (1990) Planta Med., 56, pp. 171-174Kaneko, T., Baba, N., Protective effect of flavonoids on endothelial cells against linoleic acid hydroperoxide-induced toxicity (1999) Biosci. Biotechnol. Biochem., 6, pp. 323-328Kovacs, T.O., Campbell, D., Haber, M., Rose, P., Jennings, D.E., Richter, J., Double-blind comparison of lansoprazole 15 mg, lansoprazole 30 mg, and placebo in maintenance of healed gastric ulcer (1998) Dig. Dis. Sci., 43, pp. 779-785Levine, R.J., A method for rapid production of stress ulcer in rats (1971) Peptic Ulcer, pp. 92-97. , Edited by C.J. Pfeiffer. Munksgaard, CopenhagenLewis, D.A., Hanson, P.J., (1991) Progress in Medicinal Chemistry, pp. 201-231. , Edited by G.P. Ellis and G.B. West. Elsevier Science Publishers, AmsterdamLien, E.J., Ren, S., Bui, H.H., Wang, R., Quantitative structure-activity relationship analysis of phenolic antioxidants (1999) Free Rad. Biol. Med., 26, pp. 285-294Ligumsky, M., Sestieri, M., Okon, M., Ginsburg, I., Antioxidants inhibit ethanol-induced gastric injury in the rat. Role of manganese, glycine, and carotene (1995) Scand. J. Gastroenterol., 30, pp. 854-860Lissi, E.A., Faure, M., Montoya, N., Videla, L.A., Reactivity of indole derivatives towards oxygenated radicals (1991) Free Radical Biol. Commun., 15, pp. 211-222Loftsson, T., Brewster, M.E., Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization (1996) J. Pharm. Sciences, 85, pp. 1017-1025Malterud, K.E., Diep, O.H., Sund, R.B., C-methylated dihydrochalcones from Myrica gale L: Effects as antioxidants and as scavengers of 1,1-diphenyl-2-picrylhydrazyl (1996) Pharmacol. Toxicol., 78, pp. 111-116McGuigan, J.E., Peptic ulcer and gastritis (1991) Harrison's Principles of Internal Medicine. 12th Ed., pp. 1229-1243. , Edited by J.D. Wilson, E. Braun Wald, K.J. Isselbacher, R.G. Petersdorf, J.B. Martin, A.S. Fauchi, and R.K. Root. McGraw-Hill, New YorkMirossay, L., Kohút, A., Antiulcerogenic effect of pentacaine, chlorpromazine and stobadine on ethanol- and indomethacin-induced stomach lesions in rats (1991) Physiol. Pharmacol., 40, pp. 441-444Mirossay, L., Kohút, A., Effect of stobadine on indomethacin- and ethanol-induced stomach lesions and gastric secretion (1991) Physiol. Phramacol., 40, pp. 437-440Mizui, T., Doteuchi, M., Effect of polyamines on acidified ethanol-induced gastric lesion in rats (1983) Jpn. Pharmacol., 33, pp. 939-945Mizui, T., Doteuchi, M., Lipid peroxidation: A possible role in gastric damage induced by ethanol in rats (1986) Life Sci., 38, pp. 2163-2167Mizui, T., Sato, H., Hirose, F., Doteuchi, M., Effect of antioxidants drugs on gastric damage induced by ethanol in rats (1987) Life Sci., 41, pp. 755-763Mura, P., Faucci, M.T., Parrini, P.L., Furlanetto, S., Pinzauti, S., Influence of the preparation method on the physicochemical properties of ketoprofen-cyclodextrin binary systems (1999) Int. J. Pharm., 179, pp. 117-128Olfert, E.D., Cross, B.M., McWilliam, A.A., (1993) Guide to the Care and Use of Experimental Animals, 1, pp. 1-213. , Canadian Council on Animal Care. OttawaPhull, P.S., Green, C.J., Jacyna, M.R., A radical view of the stomach: The role of oxygen-derived free radicals and antioxidants in gastroduodenal disease (1995) Eur. J. Gastroenterol. Hepatol., 7, pp. 265-274Ren, X., Xue, Y., Liu, J., Zhang, K., Zheng, J., Luo, G., Guo, C., Shen, J., A novel cyclodextrin-derived tellurium compound with glutathione peroxidase (2002) Chembiochem., 3, pp. 356-363Rettori, R., Durán, N., Production, extraction and purification of violacein: An antibiotic pigment produced by Chromobacterium violaceum (1998) World J. Microbiol. Biotechnol., 14, pp. 685-688Robert, A., Nezamis, J.E., Lancaster, C., Hanchar, A.J., Cytoprotection by prostaglandins in rats. Prevention of gastric necroses produced by alcohol, HCl, NaOH, hypotonic and thermal injury (1979) Gastroenterology, 77, pp. 433-443Robert, A., Lancaster, C., Davis, J.P., Field, J.P., Nezamis, J.E., Distinction between antiulcer effect and cytoprotection (1984) Scand. J. Gastroenterol., 101, pp. 69-73Scheiman, J., Agents used in the prevention and treatment of nonsteroidal anti-inflammatory drug-associated symptoms and ulcers (1998) Am. J. Med., 105, pp. 32S-38SShii, D., Inaguma, K., Ito, M., Suzuki, Y., Role of oxygen radicals in healing process of acetic acid-induced ulcers in rats with limited food-intake-time and effects of oxygen radical scavengers on the healing (1992) Exp. Ulcer, 19, pp. 105-109Souza Brito, A.R.M., How to study the pharmacology of medicinal plants in underdeveloped countries (1996) J. Ethnopharmacol., 54, pp. 131-138Souza Brito, A.R.M., Rodriguez, J.A., Hiruma-Lima, C.A., Haun, M., Nunes, D.S., Anti-ulcerogenic activity of dehydrocrotonin, a diterpene isolated from Croton cajucara Benth (1998) Planta Med., 64, pp. 126-129Stella, V.J., Rajewski, R.A., Cyclodextrins: Their future in drug formulation and delivery (1997) Pharm. Res., 14, pp. 556-567Stella, V.J., Rao, V.M., Zannou, E.A., Zia, V.V., Mechanisms of drug release from cyclodextrin complexes (1999) Adv. Drug Deliv. Rev., 36, pp. 3-16Szejtli, J., Medicinal applications of cyclodextrins (1994) Med. Res. Rev., 14, pp. 353-386Szejtli, J., Bolla-Pusztai, E., Tardy-Lengyel, M., Szabo, P., Preparation, properties and biological activity of β-cyclodextrin inclusion complex of menadione (1983) Pharmazie, 38, pp. 189-193Szelenyi, I., Thiemer, K., Distention ulcer as a model for testing of drugs for ulcerogenic side effects (1978) Arch. Toxicol., 41, pp. 99-105Terano, A., Hiraishi, H., Ota, S., Shiga, J., Sugimoto, T., Role of superoxide and hydroxyl radicals in rat gastric mucosal injury induced by ethanol (1989) Gastroenterol. Jpn., 24, pp. 488-493Thompson, D.O., Cyclodextrins enabling excipients: Their present and future use in pharmaceuticals (1997) Crit. Rev. Ther. Drug Carrier Syst., 14, pp. 1-104Toma, W., Gracioso, J.S., Andrade, F.D.P., Hiruma-Lima, C.A., Vilegas, W., Souza Brito, A.R.M., Antiulcerogenic activity of four extracts obtained from the bark wood of Quassia amara L. (Simaroubaceae) (2002) Biol. Pharm. Bull., 25, pp. 1151-1155Uekama, K., Hirayama, F., Irie, T., Cyclodextrin drug carrier systems (1998) Chem. Rev., 98, pp. 2045-2076Vane, J.R., Botting, R.M., New insights into the mode of action of anti-inflammatory drugs (1995) Inflamm. Res., 44, pp. 1-10Vora, J., Boroujerdi, M., Enhanced aqueous solubility of phenolic antioxidants using modified beta-cyclodextrin (1995) Drug Develop. Ind. Pharm., 21, pp. 495-502Wallace, J.L., Nonsteroidal anti-inflammatory drugs and the gastrointestinal tract. Mechanisms of protection and healing: Current knowledge and future directions (2001) Am. J. Med., 110, pp. 19S-23SWallace, J.L., Granger, D.N., The cellular and molecular basis of gastric mucosal defense (1996) FASEB J., 10, pp. 731-740Wallace, J.L., Ma, L., Inflammatory mediators in gastrointestinal defense and injury (2001) Exp. Biol. Med., 226, pp. 1003-1115Yoshikawa, T., Naito, Y., Kishi, A., Tomii, Y., Kaneko, T., Iinuma, S., Ichikawa, H., Kondo, M., Role of active oxygen lipid peroxidation and antioxidants in the pathogenesis of gastric mucosal injury induced by indomethacin in rats (1993) Gut, 34, pp. 732-737Zimmermann, A.E., Katona, B.G., Lansoprazole: A comprehensive review (1997) Pharmacotherapy, 17, pp. 308-32

Gastroprotective Effect Of The Ethanolic Extract And Fractions Obtained From Syngonanthus Bisulcatus Rul

Syngonanthus bisulcatus Rul., popularly known in Brazil as "sempre-vivas chapadeira", is a plant of the family Eriocaulaceae, it is found in the states of Minas Gerais and Bahia. In this work, the ethanolic extract (EtOHE), flavonoid-rich (FRF), and flavonoid-deficient (FDF) fractions obtained from scapes of S. bisulcatus were investigated for gastroprotection in both rats and mice. The activity was evaluated in models for induced gastric ulcer (absolute ethanol, stress, non-steroidal anti-inflammatory drugs, and pylorus ligation). The participation of mucus and prostaglandin E2 were also investigated. Sb-EtOHE (50, 100, and 250 mg/kg, p.o.), Sb-FRF (100 mg/kg, p.o.), and Sb-FDF (100 mg/kg, p.o.) significantly reduced gastric injuries in all models. Sb-FRF altered gastric juice parameters after pylorus ligation. Sb-FRF and Sb-FDF (100 mg/kg each, p.o.) significantly increased the amount of adherent mucus in the gastric mucosa. Sb-FRF maintained the mucosal levels of prostaglandin after the administration of indomethacin. The results indicate that Sb-EtOHE, Sb-FRF and Sb-FDF have significant gastroprotective activity. The observed gastroprotective effects of S. bisulcatus probably involve the participation of both mucus and prostaglandins, integral parts of the gastrointestinal mucosa's cytoprotective mechanisms against aggressive factors. © 2013 Reproduction is free for scientific studies.713544Vonkeman, H.E., Klok, R.M., Postma, M.J., Brouwers, J.R., van de Laar, M.A., Direct medical costs of serious gastrointestinal ulcers among users of NSAID (2007) Drugs Aging, 24, pp. 681-690Alqasoumi, S., Al-Sohaibani, M., Al-Howiriny, T., Al-Yahya, M., Rafatullah, S., Rocket Eruca sativa: A salad herb with potential gastric anti-ulcer activity (2009) World J Gastroenterol, 15, pp. 1958-1965Hoogerwerf, W.A., Pasricha, P.J., Agents used for the control of gastric acidity and treatment of peptic ulcers and gastroesopahgeal reflux diseases (2001) Goodman and Gilman's: The Pharmacological Basis of Therapeutics, pp. 1005-1019. , In: J.G Hardman., L.E Limbrid, C.S. Goodman, B.T Gilman. (eds.), 10th ed. New York: McGraw-HillLima, Z.P., Severi, J.A., Pellizzon, C.H., Brito, A.R.M.S., Solis, P.N., Caceres, A., Giron, L.M., Hiruma-Lima, C.A., Can the aqueous decoction of mango flowers be used as antiulcer agent? (2006) J Ethnopharmacol, 106, pp. 29-37Sostres, C., Gargallo, C.J., Arroyo, M.T., Lanas, A., Adverse effects of nonsteroidal anti-inflammatory drugs(NSAIDs, as pirin and coxibs) on upper gastrointestinal tract. Best Practice and Research (2010) Clinical Gastroenterology, 24, pp. 121-132Valle, D.L., Peptic ulcer diseases and related disorders (2005) Harrison's Principles of Internal Medicine, 16, pp. 1746-1762. , In: E. Braunwald, A. S. Fauci, D. L Kasper, S. L Hauser, D.L Longo, J. L. Jameson. (Eds.), McGraw-Hill, New YorkBighetti, A.E., Antônio, M.A., Kohn, L.K., Rehder, V.L.G., Foglio, M.A., Possenti, A., Vilela, L., Carvalho, J.E., Antiulcerogenic activity of a crude hydroalcoholic extract and coumarin isolated from Mikania laevigata Schultz (2005) Bip, Phytomedicine, 12, pp. 72-77Lakshimi, V., Singh, N., Shrivastva, S., Mishra, S.K., Dharmani, P., Mishra, V., Palit, G., Gedunian and photogedunin of Xilocarpus granatum show significant antisecretory effects and protect the gastric mucosa of peptic ulcer in rats (2010) Phytomedicine, 17, pp. 569-574Jain, K.S., Shah, A.K., Bariwal, J., Shelke, S.M., Kale, A.P., Jagtapc, J.R., Bhosale, A.V., Recent advances in proton pump inhibitors and management of acid-peptic disorders (2007) Bioorg Med Chem, 15, pp. 1181-1205Martelli, A., Mattlioli, F., Mereto, E., Brambilla, C.G., Sini, D., Bergamaschi, R., Evaluation of omeprazole genotoxicity in a battery of in vitro and in vivo assays (1998) Toxicology, 30, pp. 19-41Wolfef, M.M., Sachs, G., Acid suppression: Optimizing therapy for gastroduodenal ulcer healing, gastrooesophageal disease and stress-related erosive syndrome (2000) Gastroenterology, 118, pp. S9-S31Sairam, K., Rao, C.V., Goel, R.K., Effect of Centella asiatica Linn. on physical and chemical factors induced gastric ulceration and secretion (2001) Indian J Exp Biol, 39, p. 137Goel, R.K., Sairam, K., Antiulcer drugs from indigenous sources with emphasis on Musa sapientum, Tamrabhasna, Asparagus racemosus and (2002) Zingiber Officinale, Ind J Pharmacol, 34, pp. 100-110Indran, M., Mahmood, A., Kuppusamy, U., Protective effect of Carica papaya L leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats (2008) West Indian Med. J, 57, pp. 323-326Mahmood, A., Mariod, F., I-Bayaty, A., Abdel-Wahab, S.I., Anti-ulcerogenic activity of Gynura procumbens leaf extract against experimental-induced gastric lesions in rats (2010) J. Med. Plant Res, 4, pp. 685-691Falcão, H.S., Mariath, I.R., Diniz, M.F.F.M., Batista, L.M., Barbosa filho, J.M., (2008) Plants of the American Continent with Antiulcer Activity, Phytomedicine (Stuttgart), 15, pp. 132-146Giulietti, A.M., Pirani, J.R., Patterns of geographic distribution of some plant species from the Espinhaço Range, Minas Gerais and Bahia, Brazil (1988) Proceedings of a Workshop on Neotropical Distribution Patterns, pp. 39-69. , In: W.R. Heyer, P.E. Vanzolini, eds., Rio de Janeiro: Academia Brasileira de CiênciasGiulietti, A.M., Hensold, N., Padrões de distribuição geográfica dos gêneros de Eriocaulaceae (1990) Acta Botanica Brasilica, 4, pp. 133-158Lazzari, L.R.P., (2000) Redelimitacão E Revisão De Syngonanthus Sect. Eulepis (Bong. Ex Koern.) Ruhland - Eriocaulaceae, , PhD Thesis Universidade de São Paulo, BrazilBate-Smith, E.C., Harborne, J.B.J.B., Quercetagetin and patuletin in (1969) Eriocaulon, Phytochemistry, 8, pp. 1035-1037Vilegas, W., Nehme, C.J., Dokkeddal, A.L., Piacente, S., Rastrelli, L., Pizza, C., Quercetagetin 7-methyl ether glycosides from Paepalanthus vellozioides and Paepalanthus latipes (1999) Phytochemistry, 51, pp. 403-409Mota, K.S.L., Dias, G.E.N., Pinto, M.E.F., Luiz-Ferreira, Â., Monteiro Souza-Brito, A.R., Hiruma Lima, C.A., Barbosa Filho, J.M., Batista, L.M., Flavonoids with Gastroprotective Activity (2009) Molecules, 14, pp. 979-1012Coelho, R.G., Batista, L.M., Santos, L.C., Brito, A.R.M.S., Vilegas, W., Phytochemical study and antiulcerogenic activity of Syngonanthus bisulcatus (Eriocaulaceae) (2006) Braz J Pharm Sci, 42, pp. 413-417Morimoto, Y., Shimohara, K., Oshima, S., Sukayuki, T., Effects of the new anti-ulcer agent KB-5492 on experimental gastric mucosal lesion and gastric mucosal defensive factors, as compared to those of teprenone and cimetidine (1991) Japan J Pharmacol, 57, pp. 495-505Szelenyi, I., Thiemer, K., Distention ulcer as a model for testing of drugs for ulcerogenic side effects (1978) Arch Toxicol, 41, pp. 99-105Senay, S.E., Levine, R.J., Synergism between cold and restraint for rapid production of stress ulcer in rats (1967) Proc. Soc. Exp. Biol. Med, 124, pp. 1221-1223Rainsford, K.D., Gastric Ulcerogenicity of non-steroidal anti-inflamatory drugas in mice with mucosa sensitized by cholinomimetic treatment (1978) Biochem. Pharmacol, 27, pp. 1281-1289Shay, H., Komarov, S.A., Fels, S.S., Meranze, D., Gruenstein, M., Siplet, H., A simple method for the uniform production of gastric ulceration in the rat (1945) Gastroenterol, 5, pp. 43-61Raffatullah, S., Tariq, M., Al-Yahya, M.A., Mossa, J.S., Ageel, A.M., Evaluation of turmeric (Curcuma longa) for gastric and duodenal antiulcer activity in rats (1990) J Ethnopharmacol, 29, pp. 25-34Curtis, G.H., Macnaughton, W.K., Gall, D.G., Wallace, J.L., Intraluminal pH modulates gastric prostaglandin synthesis (1995) Can J Physiol Pharmacol, 73 (130), p. 134Jahovic, N., Erkanli, G., Iseri, S., Arbak, S., Alican, I., Gastric protection by [alpha]-melanocyte-stimulating hormone against ethanol in rats: Involvement of somatostatin (2007) Life Sciences, 80, pp. 1040-1045Abdulla, M.A., Ali, H.M., Ahmed, K.A.A., Noor, S.M., Ismail, S., Evaluation of the anti-ulcer activities of Morus alba extracts in experimentally-induced gastric ulcer in rats (2009) Biomedical Research, 20, pp. 35-39Maity, P., Biswas, K., Chattopadhyay, I., Banerjee, R.K., Bandyopadhyay, U., The use of neem for controlling gastric hyperacidity and ulcer (2009) Phytother Res, 23, pp. 747-755Goswami, M., Kulshreshtha, M., Rao, C.V., Yadav, S., Anti-ulcer potential of Lawsonia inermis L. leaves against gastric ulcers in rats (2011) Journal of Applied Pharmaceutical Science, 1, pp. 69-72Salga, M.S., Ali, H.M., Abdullah, M.A., Abdelwahab, S.I., Hussain, P.D., Hadi, A.H.A., Mechanistic studies of the anti-ulcerogenic activity and acute toxicity evaluation of dichlorido-copper (II)-4-(2-5-bromo-benzylideneamino) ethyl) piperazin-1-ium phenolate complex against ethanol-induced gastric injury in rats (2011) Molecules, 16, pp. 8654-8669Laine, L., Takeuchi, K., Tarnawski, A., Gastric mucosal defense and cytoprotection: Bench to bedside (2008) Gastroenterology, 135, pp. 41-60Kitagawa, H., Fujiwara, M., Osumi, Y., Effect of water-immersion stress on gastric secretion and mucosal blood flow in rats (1979) Gastroenterology, 77, pp. 298-302Das, D., Bandyopadhyay, D., Bhattacharjee, M., Banerjee, R.K., Hydroxyl radical is the major causative factor in stress-induced gastric ulceration (1997) Free Radical Biol. Med, 23, pp. 8-18Rao, C.V., Sairam, K., Goel, R.K., Experimental evaluation of Bacopa monniera on rat gastric ulceration and secretion (2000) Ind. J. Physiol. Pharmacol, 44, pp. 35-41Shian, W.M., Sasaki, I., Kamiyama, Y., Naito, H., Matsuno, S., Miyazawa, T., The role of lipid peroxidation on gastric mucosal lesions induced by water immersion-restraint stress in rats (2000) Surg. Today, 30, pp. 49-53Yasukawa, K., Kasazaki, K., Hyodo, F., Utsumi, H., Non-invasive analysis of reactive oxygen species generated in rats with water immersion restraint induced gastric lesions using in vivo electron spin resonance spectroscopy (2004) Free Radical Res, 38, pp. 147-155Hase, T., Moss, B.J., Microvascular changes of gastric mucosa in development of stress ulcers in rats (1973) Gastroenterology, 65, pp. 224-226Sigthorsson, G., Crane, R., Simon, T., Hoover, M., Quan, H., Bolognese, J., COX-2 inhibition with rofecoxib does not increase intestinal permeability in healthy subjects: A double blind crossover study comparing rofecoxib with placebo and indomethacin (2000) Gut, 47, pp. 527-532Botting, R.M., Inhibitors of cyclooxygenases: Mechanisms, selectivity and uses (2006) J Physiol Pharmacol, 57, pp. 113-124Patrignani, P., Nonsteroidal anti-inflammatory drugs, COX-2 and colorectal cancer (2000) Toxicology Letters, 112-113, pp. 493-498Chiou, S.K., Hodges, A., Hoa, N., Suppression of growth arrest and DNA damage-inducible an expression confers resistance to sulindac and indomethacin-induced gastric mucosal injury (2010) J Pharmacol Exp Ther, 334, pp. 693-702Ishihara, S., Rumi, M.A., Kadowaki, Y., Essential role of MD-2 in TLR4-dependent signaling during Helicobacter pylori-associated gastritis (2004) J Immunol, 173, pp. 1406-1416Magee, D.F., Naruse, S., Pap, A., Comparison of the action of cholinomimetics and pentagastrin on gastric secretion in dogs (1985) Br J Pharmacol, 84, pp. 347-355Peskar, B.M., Maricic, N., Role of prostaglandins in gastroprotection (1998) Digestion Disease Sciences, 43, pp. 23S-29SHiruma-Lima, C.A., Calvo, T.R., Rodrigues, C.M., Andrade, F.D., Vilegas, W., Brito, A.R., Antiulcerogenic activity of Alchornea castaneafolia: Effects on somatostatin, gastrin and prostaglandin (2006) J. Ethnopharmacol, 104, pp. 215-224Rosenvinge, E.C.V., Raufman, J.P., Gastrointestinal peptides and regulation of gastric acid secretion (2010) Curr Opin Endocrinol Diabetes Obes, 17, pp. 40-43Zanatta, F., Gandolfi, R.B., Lemos, M., Ticona, J.C., Gimenez, A., Clasen, B.K., Gastroprotective activity of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora Krause (Rutaceae) (2009) Chem Biol Interact, 180, pp. 312-317Allen, A., Flemströn, G., Gastroduodenal mucus bicarbonate barrier: Protection against acid and pepsin (2005) Am J Physiol Cell Physiol, 288, pp. 1-19Wallace, J.L., Mechanisms of protection and healing: Current knowledge and future research (2001) Am. J. Med, 110, pp. 19S-22SWallace, J.L., Prostaglandins, NSAIDs, and Gastric Mucosal Protection: Why Doesn't the Stomach Digest Itself? (2008) Physiological Reviews, 88, pp. 1547-1565Waisman, Y., Zahavi, I., Marcus, H., Ligumsky, M., Rosenbach, Y., Dinari, G., Sucralfate is protective against indomethacin-induced intestinal ulceration in the rat (1988) Digestion, 41, pp. 78-82Ruppin, H., Person, B., Robert, A., Domschke, W., Gastric cytoprotection in man by prostaglandin E2 (1981) Scand J Gastroenterol, 16, pp. 647-652Takeuchi, K., Aihara, E., Sasaki, Y., Nomura, Y., Ise, F., Involvement of cyclo oxygenase-1, prostaglandin E2 and EP1 receptors in acid-induced HCO3-secretion in stomach (2006) J Physiol Pharmacol, 57, pp. 661-676Brzozowski, T., Konturek, P.C., Konturek, S.J., Brzozowska, I., Pawlik, T., Role of prostaglandins in gastroprotection and gastric adaptation (2005) J. Physiol. Pharmacol, 56, pp. 33-55Adhikary, B., Yadav, S.K., Bandyopadhyay, S.K., Chattopadhyay, S., Epigallocatechin gallate accelerates healing of indomethacin-induced stomach ulcers in mice (2011) Pharmacol Rep, 63, pp. 527-53

Indigofera Suffruticosa Mill As New Source Of Healing Agent: Involvement Of Prostaglandin And Mucus And Heat Shock Proteins

Ethnopharmacological relevance: Indigofera suffruticosa is specie typical of the "Cerrado" or Brazilian savannah; it is a member of the Fabaceae family - in folkmedicine is used for gastric disorders, infection and inflammation. Aim of the study: Ethyl acetate fraction (AcF) and aqueous fraction (AqF) of the methanolic extract of I. suffruticosa leaves were evaluated against acute gastric ulcer. The AcF fraction was selected to assess its activity in ulcer healing and its gastroprotective effects via mucus and gastric secretion. Materials and methods: The gastroprotective action of AcF and AqF fractions were evaluated in a rodent experimental model. The action mechanisms, involvements of the antisecretory action, mucus and prostaglandin production, toxicological and healing activity of the AcF (100 mg/kg, p.o.) were evaluated. We also used histological analysis (HE and PAS) and immunohistochemical (PCNA and HSP-70) assays to evaluate the effects of I. suffruticosa. Results: AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant in 100 mg/kg group compared vehicle. AcF did not interfered with gastric secretion, significantly increased the PGE 2 and mucus production (validated in PAS technique). The gastroprotection was attenuated by pretreatment with N-ethylmaleimide, but not L-NAME. In acid-acetic-induced ulcer model AcF accelerated ulcer healing. Immunohistochemistry analysis showed induction of proliferating cell (PCNA) and heat shock protein (HSP 70). Conclusions: These results showed that AcF acted as gastroprotective agent stimulating prostaglandin, mucus and HSP70. © 2011 Elsevier Ireland Ltd All rights reserved.1371192198Arrieta, J., Benitez, J., Flores, E., Castillo, C., Navarrete, A., Purification of Gastroprotective Triterpenoids from the Stem Bark of Amphipterygium adstringensRole of Prostaglandins, Sulfhydryls, Nitric Oxide and Capsaicin-Sensitive Neurons (2003) Planta Medica, 69 (10), pp. 905-909. , DOI 10.1055/s-2003-45098Behmer, O.A., Tolosa, E.M.C., Freitas Neto, A.G., (1976) Manual de Técnicas Para Histologia Normal e Patológica, pp. 80-195. , Editora da USP, São Paulo, SP, BrazilCalvo, T.R., Cardoso, C.R., Da Silva Moura, A.C., Dos Santos, L.C., Colus, I.M., Vilegas, W., Varanda, E.A., Mutagenic activity of Indigofera truxillensis and I. suffruticosa aerial parts (2009) Evidence-Based Complementary and Alternative Medicine, 20, pp. 1-8Cola-Miranda, M., Barbastefano, V., Hiruma-Lima, C.A., Calvo, T.R., Vilegas, W., Souza Brito, A.R.M., Antiulcerogenic activity of Indigofera truxillensis Kunth (2006) Biota Neotropica, 6, pp. 1-9Curtis, G.H., MacNaughton, W.K., Gall, D.G., Wallace, J.L., Intraluminal pH modulates gastric prostaglandin synthesis (1995) Canadian Journal of Physiology and Pharmacology, 73, pp. 130-134De Sousa Falcão, H., Leite, J.A., Barbosa-Filho, J.M., De Athayde-Filho, P.F., De Oliveira Chaves, M.C., Moura, M.D., Ferreira, A.L., Batista, L.M., Gastric and duodenal antiulcer activity of alkaloids: A review (2008) Molecules, 13, pp. 3198-3223Farias-Silva, E., Cola, M., Calvo, T.R., Barbastefano, V., Ferreira, A.L., Michelatto, D.D.P., De Almeida, A.C.A., Souza Brito, A.R.M., Antioxidant activity of indigo and its preventive effect against ethanol-induced DNA damage in rat gastric mucosa (2007) Planta Medica, 73 (12), pp. 1241-1246. , DOI 10.1055/s-2007-981613Grant, C.M., Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions (2001) Molecular Microbiology, 39 (3), pp. 533-541. , DOI 10.1046/j.1365-2958.2001.02283.xGrob, N.G., Peptic ulcer in twenty-century of America (2004) New Jersey Medicine, 101, pp. 19-28Jung, H.K., Lee, K.E., Chu, S.H., Yi, S.Y., Reactive oxygen species activity, mucosal lipoperoxidation and glutathione in Helicobacter pylori-infected gastric mucosa (2001) Journal of Gastroenterology and Hepatology, 16 (12), pp. 1336-1340. , DOI 10.1046/j.1440-1746.2001.02647.xKimura, M., Goto, S., Ihara, Y., Wada, A., Yahiro, K., Niidome, T., Aoyagi, H., Kondo, T., Impairment of glutathione metabolism in human gastric epithelial cells treated with vacuolating cytotoxin from Helicobacter pylori (2001) Microbial Pathogenesis, 31 (1), pp. 29-36. , DOI 10.1006/mpat.2001.0446Kvietys, P.R., Twohig, B., Danzell, J., Specian, R.D., Ethanol-induced injury to the rat gastric mucosa. Role of neutrophils and xanthine oxidase-derived radicals (1990) Gastroenterology, 98 (4), pp. 909-920Laine, L., Takeuchi, K., Tarnawski, A., Gastric Mucosal Defense and Cytoprotection: Bench to Bedside (2008) Gastroenterology, 135 (1), pp. 41-60. , DOI 10.1053/j.gastro.2008.05.030, PII S0016508508007944Malfertheiner, P., Chan, F.K., McColl, K.E., Peptic ulcer disease (2009) Lancet, 374, pp. 1449-1461Massignani, J., Lemos, M., Maistro, E.L., Schaphauser, H.P., Jorge, R.F., Sousa, J.P., Bastos, J.K., De Andrade, S.F., Antiulcerogenic activity of the essential oil of Baccharis dracunculifolia on different experimental models in rats (2009) Phytotherapy Research, 23, pp. 1355-1360Matos, F.J.A., (1999) Plantas da Medicina Popular Do Nordeste: Propriedades Atribuídas e Confirmadas, p. 78. , Editora UFC FortalezaMoreno, M.I.N., Isla, M.I., Sampietro, A.R., Vattuone, M.A., Comparison of the free radical-scavenging activity of propolis from several regions of Argentina (2000) Journal of Ethnopharmacology, 71 (1-2), pp. 109-114. , DOI 10.1016/S0378-8741(99)00189-0, PII S0378874199001890Morimoto, Y., Shimohara, K., Oshima, S., Sukamoto, T., Effects of the new anti-ulcer agent KB-5492 on experimental gastric mucosal lesions and gastric mucosal defensive factors, as compared to those of teprenone and cimetidine (1991) Japanese Journal of Pharmacology, 57, pp. 495-505Mota, K.S., Dias, G.E., Pinto, M.E., Luiz-Ferreira, A., Souza-Brito, A.R., Hiruma-Lima, C.A., Barbosa-Filho, J.M., Batista, L.M., Flavonoids with gastroprotective activity (2009) Molecules, 14, pp. 979-1012Naryzhny, S.N., Proliferating cell nuclear antigen: A proteomics view (2008) Cellular and Molecular Life Sciences, 65, pp. 3789-3808Okabe, S., Amagase, K., An overview of acetic acid ulcer models: The history and state of the art of peptic ulcer research (2005) Biological and Pharmaceutical Bulletin, 28 (8), pp. 1321-1341. , http://bpb.pharm.or.jp/bpb/200508/b08_1321.pdf, DOI 10.1248/bpb.28.1321Rafatullah, S., Tariq, M., Al-Yahya, M.A., Mossa, J.S., Ageel, A.M., Evaluation of turmeric (Curcuma longa) for gastric and duodenal antiulcer activity in rats (1990) Journal of Ethnopharmacology, 29 (1), pp. 25-34Roig, J.T., (1988) Plantas Medicinales, Aromaticas O Venenosas de Cuba, , Editorial Cientifica-Tecnica, La HavanaRokutan, K., Role of heat shock proteins in gastric mucosal protection (2000) Journal of Gastroenterology and Hepatology, 15, pp. 12-19Schmeda-Hirschmann, G., Yesilada, E., Traditional medicine and gastroprotective crude drugs (2005) Journal of Ethnopharmacology, 100 (1-2), pp. 61-66. , DOI 10.1016/j.jep.2005.06.002, PII S037887410500351X, Perspectives of EthnopharmacologyShay, H., Komarov, S.A., Fels, S.S., Meranze, D., Gruenstein, M., Siplet, H., A simple method for the uniform production of gastric ulceration in the rat (1945) Gastroenterology, 5, pp. 43-61Shichijo, K., Ihara, M., Matsuu, M., Ito, M., Okumura, Y., Sekine, I., Overexpression of heat shock protein 70 in stomach of stress-induced gastric ulcer-resistant rats (2003) Digestive Diseases and Sciences, 48 (2), pp. 340-348. , DOI 10.1023/A:1021939829515Sostres, C., Gargallo, C.J., Arroyo, M.T., Lanas, A., Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Practice and Research (2010) Clinical Gastroenterology, 24, pp. 121-132Szelenyi, I., Thiemer, K., Distention ulcer as a model for testing of drugs for ulcerogenic side effects (1978) Archives of Toxicology, 41 (1), pp. 99-105Takagi, K., Okabe, S., Saziki, R., A new method for the production of chronic gastric ulcer in rats and the effect of several drugs on its healing (1969) Japanese Journal of Pharmacology, 19, pp. 418-426Tarnawski, A., Cellular and molecular mechanisms of gastrointestinal ulcer healing (2005) Digestive Diseases and Sciences, 50, pp. 24-S33Tarnawski, A., Stachura, J., Krause, W.J., Douglass, T.G., Gergely, H., Quality of gastric ulcer healing: A new, emerging concept (1991) Journal of Clinical Gastroenterology, 13, pp. 42-S47Tsukimi, Y., Nakai, H., Itoh, S., Amagase, K., Okabe, S., Involvement of heat shock proteins in the healing of acetic acid-induced gastric ulcers in rats (2001) Journal of Physiology and Pharmacology, 52 (3), pp. 391-406Vacca, L.L., (1985) Laboratory Manual of Histochemistry, pp. 176-224. , Raven Press New YorkVieira, J.R., De Souza, I.A., Do Nascimento, S.C., Leite, S.P., Indigofera suffruticosa: An alternative anticancer therapy (2007) Evidence-Based Complementary and Alternative Medicine, 4, pp. 355-35

Natural Trans-crotonin: The Antiulcerogenic Effect Of Another Diterpene Isolated From The Bark Of Croton Cajucara Benth

The nor-clerodane diterpene trans-crotonin isolated from the bark of Croton cajucara BENTH. was investigated for its ability to prevent the formation of gastric-mucosa ulceration in different experimental models in mice. The results obtained from crotonin were compared with those obtained with another diterpene, DHC (trans-dehydrocrotonin) in the same models. When previously administered (p.o.) at the dose of 100 mg/kg, crotonin, as well as DHC, significantly reduced (p0.05). The results suggest that crotonin presents a significant anti-ulcer effect when assessed in these ulcer-induced models. As with DHC, the antiulcerogenic effects of crotonin are probably related to anti-secretory or/and gastroprotective properties of this substance. In light of results obtained with DHC and natural trans-crotonin in the present study, we concluded that the A-ring of both diterpenes is not directly involved in the antiulcerogenic activity.254452456Di Stasi, L.C., Santos, E.M.C., Moreira Dos Santos, C., Hiruma, C.A., (1989) Plantas Medicinais Da Amazônia, pp. 127-128. , Editora UNESP, São PauloSouza Brito, A.R.M., Nunes, D.S., (1997) Ciência e Cultura, 49, pp. 402-408Souza Brito, A.R.M., Rodríguez, J.A., Hiruma-Lima, C.A., Haun, M., Nunes, D.S., (1998) Planta Med., 64, pp. 126-129Hiruma-Lima, C.A., Spadari-Bratfisch, R.C., Grassi Kassisse, D.M., Souza Brito, A.R.M., (1999) Planta Med., 65, pp. 325-330Rodriguez, J.A., Haun, M., (1999) Pharmacology and Taxicology, 65, pp. 1-5Hiruma-Lima, C.A., Gracioso, J.S., Toma, W., Almeida, A.B.A., Paula, A.C.B., Brasil, D.S.B., Muller, A.H., Souza Brito, A.R.M., (2001) Phytomedicine, 8, pp. 94-100Hiruma-Lima, C.A., Gracioso, J.S., Toma, W., Paula, A.C.B., Almeida, A.B.A., Brasil, D.S.B., Muller, A.H., Souza Brito, A.R.M., (2000) Biol. Pharm. Bull., 23, pp. 1465-1469Olfert, E.D., Cross, B.M., McWilliam, A.A., (1993) Canadian Council on Animal Care, 1, pp. 1-213. , Ottawa, OntarioItokawa, H., Ichihara, Y., Kojima, H., Watanabe, K., Takeya, K., (1989) Phytochemistry, 28, pp. 1667-1669Mizui, T., Doteuchi, M., (1983) Jpn. J. Pharmacol., 33, pp. 939-945Szelenyi, I., Thiemer, K., (1978) Arch. Toxicol., 41, pp. 99-105Rainsford, K.D., (1978) J. Pharm. Pharmacol., 39, pp. 669-672Levine, R.J., (1971) Peptic Ulcer, pp. 92-97. , ed. by Pfeiffer, C. J., Munksgaard, CopenhagenShay, H., Komarov, S.A., Fels, S.S., Meranze, D., Gruenstein, M., Siplet, H., (1945) Gastroenterol., 5, pp. 43-61Bolton, J.P., Palmer, D., Cohen, M., (1978) Digest. Diseases, 23, pp. 359-364Sun, S.B., Matsumoto, T., Yamada, H., (1991) J. Pharm. Pharmacol., 43, pp. 699-704Wallace, J.L., Granger, D.N., (1996) FASEB J., 10, pp. 731-740Weir, D.G., (1988) Br. Med. J., 296, pp. 195-200Lewis, D.A., Hanson, P.J., (1991) Progress in Medicinal Chemistry, pp. 201-231. , ed. by Ellis G. P., West G. B., Elsevier Science Publishers, AmsterdamAlkofahi, A., Atta, A.H., (1999) J. Ethnopharmacology, 67, pp. 341-345Kitazawa, E., Sato, A., Takahashi, H., Kuwano, H., Ogiso, A., (1980) Chem. Pharm. Bull., 28, pp. 227-234Desai, J.K., Parmar, N.S., (1994) Agents Actions, 42, pp. 149-152Sarosiek, J., Slomiany, B.L., Kojima, K., Swierczec, J., Slomiany, A., Konturek, S.J., (1984) J. Appl. Biochem., 5, pp. 429-436Guth, P.H., Paulsen, G., Nagata, H., (1984) Gastroenterol., 87, pp. 1083-1090Szabo, S., (1987) Scand. J. Gastroenterol., 22, pp. 21-28Parnaham, M.J., Brune, K., (1987) Agents Actions, 21, pp. 232-234Murakami, M., Lam, S.K., Inada, M., Miyake, T., (1985) Gastroenterol., 88, pp. 660-665Kitagawa, H., Fujiwara, M., Osumi, Y., (1979) Gastroenterol., 77, pp. 298-302Koo, M.W.L., Ogle, C.W., Cho, C.H., (1986) Pharmacology, 32, pp. 326-334Sato, N., Kawano, S., Tsuji, S., Ogihara, T., Yamada, S., (1995) Scand. J. Gastroenterol., 30, pp. 14-20Whittle, B.J., (1981) Gastroenterol., 80, pp. 94-98Droy-Lefaix, M.T., (1988) Prostaglandins: Biology and Chemistry of Prostaglandins and Related Eicosanoids, pp. 345-360. , ed. by Curtis-Prior P. B., Churchill Livingtone, New YorkWallace, J.L., Whittle, B.J., (1985) Eur. J. Pharmacol., 115, pp. 45-51Bilski, J., Sarosiek, J., Murty, V.L.N., Aono, M., Moriga, M., Slomiany, A., Slomiany, B.L., (1987) Biochem. Pharmacol., 36, pp. 4059-4065Hiruma-Lima, C.A., Gracioso, J.S., Nunes, D.S., Souza Brito, A.R.M., (1999) J. Pharm. Pharmacol., 51, pp. 341-34

Gastroprotective Effects (in Rodents) Of A Flavonoid Rich Fraction Obtained From Syngonanthus Macrolepsis

Objectives Syngonanthus macrolepis, popularly known in Brazil as 'sempre-vivas', is a plant from the family Eriocaulaceae, it is found in the states of Minas Gerais and Bahia. The species contains a variety of constituents, including flavonoids with gastroprotective effect. In this work, a flavonoid-rich fraction (Sm-FRF) obtained from scapes of S. macrolepis was investigated for preventing gastric ulceration in mice and rats. Methods The activity was evaluated in models of induced gastric ulcer (absolute ethanol, stress, non-steroidal anti-inflammatory drugs and pylorus ligation). The cytoprotective mechanisms of the Sm-FRF in relation to sulfhydryl (SH) groups, nitric oxide (NO) and antioxidant enzymes were also evaluated. Key findings The Sm-FRF (100 mg/kg, p.o.) significantly reduced gastric injury in all models, and did not alter gastric juice parameters after pylorus ligation. Conclusions The results indicate significant gastroprotective activity for the Sm-FRF, which probably involves the participation of both SH groups and the antioxidant system. Both are integral parts of the gastrointestinal mucosa's cytoprotective mechanisms against aggressive factors. © 2013 Royal Pharmaceutical Society.663445452Yeomans, N.D., Naesdal, J., Systematic review: Ulcer definition in NSAID ulcer prevention trials (2008) Aliment Pharmacol Ther, 27, pp. 465-472Martin, G.R., Wallace, J.L., Gastrointestinal inflammation: A central component of mucosal defence and repair (2006) Exp Biol Med, 231, pp. 130-137Tamashiro Filho, P., Evaluation of antiulcer activity and mechanism of action of methanol stem bark extract of Lafoensia pacari A. St.-Hil. (Lytraceae) in experimental animals (2012) J Ethnopharmacol, 144, pp. 497-505Bandyopadhyay, U., Gastroprotective effect of Neem (Azadirachta indica) bark extract: Possible involvement of H(+)-K(+)-ATPase inhibition and scavenging of hydroxyl radical (2002) Life Sci, 71, pp. 2845-2865Malfertheiner, P., Peptic ulcer disease (2009) Lancet, 374, pp. 1449-1461Lin, P.C., The efficacy and safety of proton pump inhibitors vs histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among critical care patients: A meta-analysis (2010) Crit Care Med, 38, pp. 1197-1205Bansal, V.K., Goel, R.K., Gastroprotective effect of Acacia nilotica young seedless pod extract: Role of polyphenolic constituents (2012) Asian Pac J Trop Med, 5, pp. 523-528Giulietti, A.M., Pirani, J.R., Patterns of geographic distribution of some plant species from the Espinhaço Range, Minas Gerais and Bahia, Brazil (1988) Proceedings of A Workshop on Neotropical Distribution Patterns, pp. 39-69. , Heyer W.R. Vanzolini P.E. eds. Rio de Janeiro: Academia Brasileira de CiênciasGiulietti, A.M., Hensold, N., Padróes de distribuição geográfica dos gêneros de Eriocaulaceae (1990) Acta Bot Brasil, 4, pp. 133-158Lazzari, L.R.P., (2000) Redelimitacão e Revisão de Syngonanthus Sect. Eulepis (Bong. Ex Koern.), , Ruhland - Eriocaulaceae. PhD Thesis, Universidade de São Paulo, BrazilBate-Smith, E.C., Harborne, J.B., Quercetagetin and patuletin in Eriocaulon (1969) Phytochemistry, 8, pp. 1035-1037Vilegas, W., Quercetagetin 7-methyl ether glycosides from Paepalanthus vellozioides and Paepalanthus latipes (1999) Phytochemistry, 51, pp. 403-409Monteiro, M.V., Topical anti-inflammatory, gastroprotective and antioxidant effects of the essential oil of Lippia sidoides Cham. Leaves (2007) J Ethnopharmacol, 111, pp. 378-382Botelho, M.A., Protective effect of locally applied carvacrol gel on ligature-induced periodontitis in rats: A tapping mode AFM study (2009) Phytother Res, 25, pp. 1439-1448Veras, H.N.H., Topical antiinflammatory activity of essential oil of Lippia sidoides cham: Possible mechanism of action (2013) Phytother Res, 27, pp. 179-185Coelho, R.G., Phytochemical study and antiulcerogenic activity of Syngonanthus bisulcatus (Eriocaulaceae) (2006) Braz J Pharm Sci, 42, pp. 413-417Batista, L.M., Gastric antiulcer activity of Syngonanthus arthrotrichus Silveira (2004) Biol Pharm Bull, 27, pp. 328-332Batista, L.M., Gastroprotective effect of the ethanolic extract and fractions obtained from Syngonanthus bisulcatus Rul (2013) Rec Nat Prod, 7, pp. 35-44Agrawal, P.K., (1989) Carbon 13 NMR of Flavonoids, , Amsterdam: Elsevier(1986) Phytochemical Methods, , Harborne J.B. ed. 3rd edn. London: Champman and HallSzelenyi, I., Thiemer, K., Distention ulcer as a model for testing of drugs for ulcerogenic side effects (1978) Arch Toxicol, 41, pp. 99-105Morimoto, Y., Effects of the new anti-ulcer agent KB-5492 on experimental gastric mucosal lesion and gastric mucosal defensive factors, as compared to those of teprenone and cimetidine (1991) Japan J Pharmacol, 57, pp. 495-505Levine, R.J., A method for rapid production of stress ulcers in rats (1971) Peptic Ulcer, pp. 92-97. , Pfeiffer C.J. ed. Copenhagen: MunksgaardRainsford, K.D., Gastric ulcerogenicity of non-steroidal anti-inflamatory drugas in mice with mucosa sensitized by cholinomimetic treatment (1978) Biochem Pharmacol, 27, pp. 1281-1289Shay, H., A simple method for the uniform production of gastric ulceration in the rat (1945) Gastroenterol, 5, pp. 43-61Matsuda, H., Roles of capsaicin-sensitive sensory nerves, endogenous nitric oxide, sulphydryls, and prostaglandins in gastroprotection by mormodin Ic, an oleanolic acid oligoglycoside, on ethanolinduced gastric mucosal lesion in rats (1999) Life Sci, 65, pp. 27-32Sikiric, P., The influence of a novel pentadecapeptide, BPC 157, on NG-nitro-L-arginine methylester and L-arginine effect on stomach mucosa integrity and blood pressure (1997) Eur J Pharmacol, 332, pp. 23-33Yoshikawa, T., Role of active oxygen, lipid, peroxidation, and antioxidants in the pathogenesis of gastric mucosal injury induced by indomethacin in rats (1993) Gut, 34, pp. 732-737Worthington, D.J., Rosemeyer, M.A., Human glutathione reductase: Purification of the crystalline enzyme from erythrocytes (1974) Eur J Biochem, 48, pp. 167-177Winterbourn, C.C., The estimation of red cell superoxide dismutase activity (1975) J Lab Clin Med, 85, pp. 337-341Zapata-Colindres, J.C., The association of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs in peptic ulcer disease (2006) Can J Gastroenterol, 20, pp. 277-280Lima, G.R.M., Database survey of anti-inflammatory plants in South America: A review (2011) Int J Mol Sci, 12, pp. 2692-2749Lima, G.R.M., Bioactivities of the genus Combretum (Combretaceae): A review (2012) Molecules, 17, pp. 9142-9206Falcão, H.S., Gastric and duodenal antiulcer activity of alkaloids: A review (2008) Molecules, 13, pp. 3198-3223Mota, K.S., Flavonoids with gastroprotective activity (2009) Molecules, 14, pp. 979-1012Jesus, N.Z., Tannins, peptic ulcers and related mechanisms (2012) Int J Mol Sci, 13, pp. 3203-3228Lima, G.R.M., Gastroprotective activity of the ethanolic extract and hexane phase of Combretum duarteanum Cambess. (Combretaceae) (2012) J Nat Med, 67, pp. 492-502Falcão, H.D., Gastroprotective mechanisms of the chloroform and ethyl acetate phases of Praxelis clematidea (Griseb.) R.M.King & H.Robinson (Asteraceae) (2012) J Nat Med, 67, pp. 480-491Sheeba, M.S., Asha, V.V., Effect of Cardiospermum halicacabum on ethanol-induced gastric ulcers in rats (2006) J Ethnopharmacol, 106, pp. 105-110Shaw, S., Effect of ethanol generated free radicals on gastric intrinsic factor and glutathione (1990) Alcohol, 7, pp. 153-157La Casa, C., Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions (2000) J Ethnopharmacol, 71, pp. 45-53Jiang, P., Protective role of metallothionein in stress-induced gastric ulcer in rats (2005) World J Gastroenterol, 11, pp. 2739-2743Konturek, S.J., Healing of chronic gastroduodenal ulcerations by antacids. Role of prostaglandins and epidermal growth factor (1990) Dig Dis Sci, 35, pp. 1121-1129Konturek, P.C., Interaction of Helicobacter pylori (Hp) and non steroidal anti-inflammatory drugs (NSAID) on gastric mucosa and risk of ulcerations (2002) Med Sci Monit, 9, pp. 197-209Toma, W., Modulation of gastrin and epidermal growth factor by pyrrolizidine alkaloids obtained from Senecio brasiliensis in acute and chronic induced gastric ulcers (2004) Can J Physiol Pharmacol, 82, pp. 319-325Bharti, S., Protective effect of Calotropis procera latex extracts on experimentally induced gastric ulcers in rat (2010) J Ethnopharmacol, 127, pp. 440-444Szabo, S., Vattay, P., Experimental gastric and duodenal ulcers. Advances in pathogenesis (1990) Gastroenterol Clin North Am, 19, pp. 67-85Ferreira, M.P., Gastroprotective effect of Cissus sicyoides (Vitaceae): Involvement of microcirculation, endogenous sulfhydryls and nitric oxide (2008) J Ethnopharmacol, 117, pp. 170-174Nagy, L., Protein and non-protein sulfhydryls and disulfides in gastric mucosa and liver after gastrotoxic chemicals and sucralfate: Possible new targets of pharmacologic agents (2007) World J Gastroenterol, 13, pp. 2053-2060Chandranath, S.I., A comparative study on the activity of lansoprazole, omeprazole and PD-136450 on acidified ethanoland indomethacin-induced gastric lesions in the rat (2002) Clin Exp Pharmacol Physiol, 29, pp. 173-180Kanter, M., Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats (2005) World J Gastroenterol, 11, pp. 6662-6666Brzozowski, T., The role of melatonin and L-tryptophan in prevention of acute gastric lesions induced by stress, ethanol, ischemia, and aspirin (1997) J Pineal Res, 23, pp. 79-89El-Missiry, M.A., Protection by metal complexes with SOD-mimetic activity against oxidative gastric injury induced by indomethacin and ethanol in rats (2001) Ann Clin Biochem, 38, pp. 694-700Repetto, M., Protective effect of Artemisia douglasiana Besser extracts in gastric mucosal injury (2003) J Pharm Pharmacol, 55, pp. 551-55