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Planta Med 2005; 71(8): 733-738
DOI: 10.1055/s-2005-871286
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Gastroprotective Mechanisms of Indole Alkaloids from Himatanthus lancifolius

Cristiane Hatsuko Baggio1 , Glaucia De Martini Otofuji1 , Wesley Mauricio de Souza2 , Cid Aimbiré de Moraes Santos2 , Luce Maria Brandao Torres3 , Lia Rieck1 , Maria Consuelo de Andrade Marques1 , Sonia Mesia-Vela1
  • 1Department of Pharmacology, Biological Sciences Sector, Universidade Federal of Paraná, Curitiba, Brazil
  • 2Department of Pharmacognosy, Health Sciences Sector, Universidade Federal of Paraná, Curitiba, Brazil
  • 3Department of Physiology, Institute of Botany, Sao Paulo, SP, Brazil
Further Information

Publication History

Received: October 11, 2004

Accepted: April 22, 2005

Publication Date:
11 August 2005 (online)

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Abstract

The indole alkaloids mixture (AlkF) obtained from the barks of Himatanthus lancifolius (Muell. Arg.) Woodson was evaluated for gastroprotective properties in rodents. The AlkF potently protected rats from experimentally induced gastric lesions by ethanol (ED50 = 30 mg/kg, p. o.) and reduced gastric acid hypersecretion induced by pylorus ligature (ED50 = 82 mg/kg, i. d.). Protective effects of the AlkF in the ethanol and hypersecretion models included increase of GSH levels of gastric mucosa indicating activation of GSH-dependent cytoprotective mechanisms. Also, an increase of the antioxidant capacity as measured through glutathione S-transferase activity was observed in the hypersecretory but not in the ulcerative model. Furthermore, the amount of nitric oxide derivatives (NO3 + NO2) in the forestomach was increased while the amount released into the gastric juice during pylorus ligature was decreased by the AlkF suggesting an alteration of NO-related mechanisms. Reduction of gastric acid hypersecretion induced by pylorus ligature seems to correlate with the blockade of H+,K+-ATPase activity as determined in vitro by the capacity of the AlkF mix to decrease the hydrolysis of ATP by the ATPase isolated from dog gastric mucosa (EC50 = 212 µg/mL). Cholinergic mechanisms can be excluded since intestinal transit was not modified with doses up to 100 mg/kg (p. o.). GC-MS investigation of components of the AlkF resulted in the identification of 3 main indole alkaloids, uleine (53 %), its isomer (13 %), demethoxyaspidormine (23.8 %) and traces of at least other five alkaloids. Collectively, the results show the novel gastroprotective properties of the indole AlkF of H. lancifolius through a variety of mechanisms.

Key words

Alkaloids - uleine - demethoxyaspidormine - antiulcer - medicinal plant - Himatanthus

References

  • 1 Coimbra R. Manual de Fitoterapia. 2nd edn Belem; CEJUP 1994: pp 22-3
    Google Scholar
  • 2 Perdue G P, Blomster R N. South-American plants 3. Isolation of fulvoplumierin from Himatanthus sucuuba (M-Arg) Woodson (Apocynaceae).  J Pharm Sci. 1978;  67 1322-3
    PubMedGoogle Scholar
  • 3 Souza C P, Azevedo M LL, Lopes J LC, Sarti J, Santos-Filho D D, Lopes J NC. et al . Molluscicidal activity of natural products.  Ana Acad Brasil Science. 1984;  56 333-8
    PubMedGoogle Scholar
  • 4 Endo Y, Hayashi H, Sato T, Maruno M, Ohta T, Nozoe S. Confluentic acid and 2′-O-methylperlatolic acid, monoamine-oxidase-B inhibitors in a Brazilian plant, Himatanthus sucuuba .  Chem Pharm Bull. 1994;  42 1198-201
    PubMedGoogle Scholar
  • 5 de Miranda A LP, Silva J RA, Rezende C M, Neves J S, Parrini S C, Pinheiro M LB. et al . Anti-inflammatory and analgesic activities of the latex containing triterpenes from H. sucuuba .  Planta Med. 2000;  66 284-6
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Vanderlei M F, Souza-Brito A RM. Spasmodic effects of Himatanthus phagedaenica (Mart) Woodson.  J Braz Chem Soc. 1991;  2 51
    PubMedGoogle Scholar
  • 7 França Jr O O, Santos C AM, Brown R T. Uleine and demethoxyaspidospermine from the barks of Plumeria lancifolia .  Fitoterapia. 2000;  71 208-10
    CrossrefPubMedGoogle Scholar
  • 8 Joule J A, Djerassi C. Alkaloid studies XLIV. Mass spectrometry in structural and stereochemical problems. XLII. Some aspects of the chemistry and mass spectrometry of uleine. J Chem Soc 1964: 2777-90
    Google Scholar
  • 9 Gaskell J, Joule J A. The structure of uleine - relative stereochemistry.  Chem Ind. 1967;  23 1089-90
    PubMedGoogle Scholar
  • 10 Robert A, Nezamis J E, Lancaster C, Hanchar A J. Cytoprotection by prostaglandin in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl and thermal injury.  Gastroenterology. 1979;  77 433-43
    PubMedGoogle Scholar
  • 11 Vela S M, Souccar C, Lima-Landman M TR, Lapa A J. Inhibition of gastric acid secretion by the aqueous extract and purified extracts of Stachytarpheta cayennensis .  Planta Med. 1997;  63 36-9
    PubMedGoogle Scholar
  • 12 Shay H, Komarov S A, Fels S S, Meranze D, Gruenstein M, Siplet H. A simple method for the uniform production of gastric ulceration in rat.  Gastroenterology. 1945;  5 43-61
    PubMedGoogle Scholar
  • 13 Kubo K, Uehara A, Kubota T, Nozu T, Moriya M, Watanabe Y. et al . Effects of ranitidine on gastric vesicles containing H+/K+-adenosine triphosphatase in rats.  Scand J Gastroenterol. 1995;  30 944-51
    CrossrefPubMedGoogle Scholar
  • 14 Murakami S, Arai I, Muramatsu M, Otomos S, Baba K, Kido T. et al . Inhibition of gastric H+/K+-ATPase and acid secretion by cassigarol A: a polyphenol from Cassia garrettiana Craib.  Biochem Pharmacol. 1992;  44 33-7
    CrossrefPubMedGoogle Scholar
  • 15 Fiske C H, Subbarow Y. The colorimetric determination of phosphorus.  J Biol Chem. 1925;  66 375-400
    PubMedGoogle Scholar
  • 16 Jaiswal A K, McBride O W, Adesnik M, Nebert D W. Human dioxin-inducible cytosolic NAD(P)H: menadione oxidoreductase. CDNA sequence and localization of gene to chromosome.  J Biol Chem. 1988;  263 13 572-8
    PubMedGoogle Scholar
  • 17 Habig W H, Pabst M J, Jakoby W B. Glutathione S-transferases: the first enzymatic step in mercapturic acid formation.  J Biol Chem. 1974;  249 7130-9
    PubMedGoogle Scholar
  • 18 Sedlak J, Lindsay R H. Estimation of total protein bound and nonprotein sulfhydril groups in tissues with Ellman’s reagent.  Ann Biochem. 1988;  25 192-205
    PubMedGoogle Scholar
  • 19 Granger D L, Hibbs J B, Perfect J R, Durack D T. Metabolic fate of L-arginine in relation to microbiostatic capability of murine macrophages.  J Clin Invest. 1990;  85 264-73
    PubMedGoogle Scholar
  • 20 Stickney J C, Northup D W. Effect of gastric emptying upon propulsive motility of small intestine in rat.  Exp Biol Med. 1959;  101 582
    PubMedGoogle Scholar
  • 21 Szabo S, Trier J, Brown A, Schnoor J. Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat.  Gastroenterology. 1985;  88 228-36
    PubMedGoogle Scholar
  • 22 Cnubben N HP, Rietjens I MCM, Wortelboer H, van Zanden J, van Bladeren P J. The interplay of glutathione related processes in antioxidant defense.  Environ Toxicol Pharmacol. 2001;  10 141-52
    CrossrefPubMedGoogle Scholar
  • 23 Tzeon-Jye C A, Woan-Fang T B. The roles of glutathione and antioxidant enzymes in menadione-induced oxidative stress.  Toxicology. 2000;  154 75-84
    CrossrefPubMedGoogle Scholar
  • 24 Cadenas E. Antioxidant and prooxidant functions of DT-Diaphorase in quinone metabolism.  Biochem Pharmacol. 1995;  49 127-140
    CrossrefPubMedGoogle Scholar
  • 25 Terano A, Hiraishi H, Ota S, Shiga J, Sugimoto T. Role of superoxide and hydroxyl radicals in rat gastric mucosal injury induced by ethanol.  Gastroenterol Jpn. 1989;  24 488-93
    PubMedGoogle Scholar
  • 26 Szelenyi I, Brune K. Possible role of oxygen free radicals in ethanol-induced gastric mucosal damage in rats.  Dig Dis Sci. 1988;  33 865-71
    CrossrefPubMedGoogle Scholar
  • 27 Pihan G, Regillo B A, Szabo S. Free radicals and lipid peroxidation in ethanol- or aspirin-induced gastric mucosal injury.  Dig Dis Sci. 1987;  32 1395-401
    CrossrefPubMedGoogle Scholar
  • 28 Repetto M, Maria A, Guzman J, Giordano O, Llesuy S. Protective effect of Artemisia douglasiana Besser extracts in gastric mucosal injury.  J Pharm Pharmacol. 2003;  55 551-7
    CrossrefPubMedGoogle Scholar
  • 29 Calatayud S M, Barranchina D, Esplugues J V. Nitric oxide: relation to integrity, injury and healing of the gastric mucosa.  Microsc Res Tech. 2001;  53 325-35
    PubMedGoogle Scholar
  • 30 Whittle B J, Lopez-Belmonte J. Actions and interactions of endothelins, prostacyclin and nitric oxide in the gastric mucosa.  J Physiol Pharmacol. 1993;  44 91-107
    PubMedGoogle Scholar
  • 31 Whittle B J, Lopez-Belmonte J, Moncada S. Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat.  Braz J Pharmacol. 1990;  99 607-11
    PubMedGoogle Scholar
  • 32 Kisakurek M, Leewenberg A JM, Hesse M. Alkaloids: Chemical and Biological Perspective. Pelletier SW, editor New York; John Wiley and Sons 1983: p 17
    Google Scholar
  • 33 Jasztold-Howorko R, Croisy A, Carrez D, Jaroszewicz I, Nasulewicz A, Pelczynska M. et al . Synthesis, structure, and cytostatic properties of new olivacine derivatives.  Arch Pharm. 2004;  337 599-604
    CrossrefPubMedGoogle Scholar
  • 34 Borris R P, Lanki D C, Cordell G A. Studies of the uleine alkaloids I. Carbon 13NMR studies on 21-uleine, 20-epiuleine and (4S)-uleine Nb-oxide.  J Nat Prod. 1983;  46 200-5
    CrossrefPubMedGoogle Scholar

Sonia Mesia-Vela, Ph. D.

Department of Pharmacology

Biological Sciences Sector

Universidade Federal of Paraná

UFPR

Centro Politecnico

Caixa Postal 19031

Jardim das Americas

CEP 81531-990

Curitiba-PR

Brazil

Phone: +55-41-361-1721

Fax: +55-41-266-2042

Email: sm2418@columbia.edu