Gastroprotective Effect of the Mixture of α- and β-Amyrin from Protium heptaphyllum: Role of Capsaicin-Sensitive Primary Afferent Neurons

Abstract

This investigation evaluated the role of capsaicin-sensitive afferent neurons in the gastroprotective effect of α- and β-amyrin, a triterpenoid mixture isolated from Protium heptaphyllum resin. Gastric mucosal damage was induced in mice by intragastric ethanol and assessed by planimetry. Mice pretreated orally with the amyrin mixture (50 and 100 mg/kg) or capsaicin (2.5 and 5 mg/kg), the pungent principle from red hot peppers, showed a significantly lower intensity of ethanol-associated gastric mucosal damage, in relation to vehicle-treated controls. At higher doses both these agents produced either a diminished protection or no significant effect. The maximal gastroprotection that was observed at the dose of 100 mg/kg amyrin mixture was almost abolished in mice with their sensory afferents chemically ablated by a neurotoxic dose of capsaicin, suggesting that the gastroprotective mechanism of α- and β-amyrin mixture involves at least in part the activation of capsaicin-sensitive primary afferent neurons.

References

• 1 Farina C, Pinza M, Pifferi G. Synthesis and antiulcer activity of new derivatives of glycyrrhetic, oleanolic and ursolic acids.  Il Farmaco. 1998;  5 22-32
• 2 Arrieta J, Benitez J, Flores E, Castillo C, Navarete A. Purification of gastroprotective triterpenoids from the stem bark of Amphipterygium adstringens; role of prostaglandins, sulfhydryls, nitric oxide and capsaicin-sensitive neurons.  Planta Med. 2003;  69 905-9
• 3 Siani A C, Ramos M FS, de Lima M O, Santos R, Ferreira F E, Soares E C, Susunaga G S, Guimarães A C, Zoghbi M GB, Henriques M GMO. Evaluation of anti-inflammatory-related activity of essential oils from the leaves and resin of species of Protium .  J Ethnopharmacol. 1999;  66 57-69
• 4 Bandeira P N, Pessoa O DL, Trevisan M TS, Lemos T LG. Metabólitos secundários de Protium heptaphyllum March.  Quim Nova. 2002;  25 1078-80
• 5 Oliveira F A, Vieira-Junior G M, Chaves M H, Almeida F RC, Lima Junior R CP, Santos F A, Rao V SN. Gastroprotective and anti-inflammatory effects of resin from Protium heptaphyllum in mice and rats.  Pharmacol Res. 2004;  49 05-11
• 6 Szolesányi J, Bartó L. Capsaicin-sensitive afferents and their role in gastroprotection: an update.  J Physiol. 2001;  95 181-8
• 7 Park J -S, Choi M -A, Kim B -S, Han I -S, Kurata T, Yu R. Capsaicin protects against ethanol-induced oxidative injury in the gastric mucosa of rats. Life Sci 2000: 3087-93
• 8 Kato S, Aihara E, Nakamura A, Xin H, Matsui H, Kohama K, Takeuchi K. Expression of vanilloid receptors in rat gastric epithelial cells: role in cellular protection.  Biochem Pharmacol. 2003;  66 1115-21
• 9 Olea R SG, Roque N F. Análise de Misturas de Triterpenos por ¹³C NMR.  Quim Nova. 1990;  13 278-81
• 10 Mahato S B, Kundu A P. ¹³C NMR spectra of triterpenoids - A compilation and some salient features.  Phytochemistry. 1994;  37 1517-75
• 11 Robert A, Nezamis J E, Lancaster C, Hanchar A J. Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl and thermal injury.  Gastroenterology. 1979;  77 433-43
• 12 Szabo S, Trier J S, Brown A, Schnoor J, Homan H D, Bradford J C. A quantification method for assessing the extent of experimental erosions and ulcers.  J Pharmacol Meth. 1985;  13 59-66
• 13 Matsuda H, Li Y, Yoshikawa M. Roles of capsaicin-sensitive sensory nerves, endogenous nitric oxide, sulfhydrils, and prostaglandins in gastroprotection by momordin k, an oleanolic acid oligoglycoside, on ethanol-induced gastric mucosal lesions in rats.  Life Sci. 1999;  65 27-32