Purification of Gastroprotective Triterpenoids from the Stem Bark of Amphipterygium adstringens; Role of Prostaglandins, Sulfhydryls, Nitric Oxide and Capsaicin-Sensitive Neurons

Abstract

In this investigation three bioactive compounds, responsible for the gastroprotective property of Amphipterygium adstringens, were purified from an active dichloromethane fraction. These compounds were 3α-hydroxymasticadienonic acid, β-sitosterol and 3-epi-oleanolic acid. The latter was the most active compound (88.8 % of gastroprotection) followed by 3α-hydroxymasticadienoic acid and β-sitosterol (69.8 and 42.5 % of gastroprotection, respectively). Carbenoxolone was used as positive control and it showed 88.4 % of gastroprotection. Masticadienonic acid was also isolated from the active fraction, but it was unable to inhibit the ethanol-induced gastric lesions. The gastroprotection of the methanol extract was completely inhibited by the pretreatment with l-NAME and attenuated by pretreatment with indomethacin and N-ethylmaleimide. These results suggest that endogenous nitric oxide plays an important role in the gastroprotection of A. adstringens methanol extract on ethanol-induced gastric mucosal lesions and that there is partial participation by prostaglandins and endogenous sulfhydryls. The effect of 3α-hydroxymasticadienonic acid was attenuated only by pretreatment with N-ethylmaleimide, indicating that endogenous sulfhydryls (thiols) participate in its gastroprotective mechanism. Capsaicin-sensitive afferent neurons do not participate in the gastroprotection of either the methanol extract or 3α-hydroxymasticadienoic acid.

Amphipterygium adstringens - Julianaceae - ulcer - 3-epi-oleanolic acid - 3α-hydroxymasticadienoic acid - β-sitosterol - nitric oxide - sulfhydryl

References

• 1 Calatayud S, Borrachina M D, Espulgues J V. Nitric oxide: Relation to integrity, injury, and healing of the gastric mucosa.  Microscopy Research and Techniques. 2001;  53 325-35
• 2 Borrelli F, Izzo A A. The plant kingdom as a source of anti-ulcer remedies.  Phytotherapy Research. 2000;  14 581-91
• 3 Navarrete A, Reyes B, Silva A, Sixtox C, Islas V, Estrada E. Evaluación farmacológica de la actividad antiulcerosa de Amphipterygium adstringens (Cuachalalate).  Revista Mexicana de Ciencias Farmacéuticas. 1990;  21 28-32
• 4 Navarrete A, Mata R, Delgado G. Alkylanacardic acids from Amphipterygium adstringens .  Planta Medica. 1989;  55 579
• 5 Olivera A G, Soto M, Martínez M, Terrazas T, Solares F. Phytochemical study of cuachalalate (Amphipterygium adstringens, Shiede ex Shlecht).  Journal of Ethnopharmacology. 1999;  68 109-13
• 6 Navarrete A, Martínez-Uribe L S, Reyes B. Gastroprotective activity of the stem bark of Amphipterygium adstringens in rats.  Phytotherapy Research. 1998;  12 1-4
• 7 Wan B, Gottfried S. Cytoprotective action of carbenoxolone sodium on ethanol-induced gastric lesions in rats and its inhibition by indomethacin.  Journal of Pharmacy and Pharmacology. 1985;  37 739-41
• 8 Robert A. Cytoprotection by prostaglandins.  Gastroenterology. 1979;  77 761-7
• 9 Matsuda H, Li Y, Yoshikawa M. Roles of capsaicin-sensitive sensory nerves, endogenous nitric oxide, sulfhydryls, and prostaglandins in gastroprotection by momordin Ic, an oleanolic acid oligoglycoside, on ethanol-induced gastric mucosal lesions in rats.  Life Sciences. 1999;  65 PL27-32
• 10 Lewis D, Hanson P J. Anti-ulcer drugs of plant origin.  Progress in Medicinal Chemistry. 1991;  28 201-31
• 11 Navarrete A, Trejo-Miranda J L, Reyes-Trejo L J. Principles of root bark of Hippocratea excelsa (Hippocrataceae) with gastroprotective activity.  Journal of Ethnopharmacology. 2002;  79 383-8
• 12 Giner-Larza E M, Máñes S, Giner R M, Recio MC, Prieto J M, Cérda-Nicolás M, Rios J L. Anti-inflammatory triterpenes from Pistacia terebinthus galls.  Planta Medica. 2002;  68 311-5
• 13 Ling W H, Jones P JH. Dietary phytosterols: a review of metabolism, benefits and side effects.  Life Sciences. 1995;  57 195-206
• 14 Awad A B, Fink C S. Phytosterols as anticancer dietary components: evidence and mechanism of action.  Journal of Nutritional Sciences. 2000;  130 2127-30
• 15 Whittle B JR, Lopez-Belmonte J, Moncada S. Regulation of gastric mucosal integrity by endogenous nitric oxide: interaction with prostanoids and sensory neuropeptides in the rat.  British Journal of Pharmacology. 1990;  99 607-11
• 16 Whittle B JR, Lopez-Belmonte J. Action and interaction of endothelins, prostacyclin and nitric oxide in the gastric mucosa.  Journal of Physiology and Pharmacology. 1993;  44 91-107
• 17 Szabo S, Trier J S, Frankel P W. Sulfhydryl compounds may mediate gastric cytoprotection.  Science. 1981;  214 2000-2
• 18 Holzer P, Sametz W. Gastric mucosal protection against ulcerogenic factors in the rat mediated by capsaicin-sensitive efferent neurons.  Gastroenterology. 1986;  91 975-81
• 19 Lamberts R, Creutzfeldt W, Strübert H G, Brunner G, Solcia E. Long-term omeprazole therapy in peptic ulcer disease: gastrin, endocrine cell growth, and gastritis.  Gastroenterology. 1993;  104 1356-70