Abstract
The aim of the present study was to determine the potential gastroprotective effects of Brazilian medicinal plants that are extensively used as gastroprotective agents. The extracts prepared from Achillea millefolium, Himatanthus lancifolius, Maytenus ilicifolia and Pfaffia glomerata were tested against models of gastric injury, acid secretion and gastrointestinal motility. All extracts showed antiulcer effect with variable potency and different mechanisms of action. The inhibitory dose 50% (ID50) for the aqueous extract of A. millefolium was 900 mg/kg (per os; p.o.) when tested against gastric lesions induced by indomethacin or ethanol. No activity was observed against lesions induced by stress. The ID50 for the alkaloid-rich fraction of H. lancifolius in the model of gastric lesions induced by ethanol was 30 mg/kg (p.o.). No activity was observed against lesions induced by indomethacin or stress. The ID50 for the flavonoid-rich fraction of M. ilicifolia was 25 mg/kg (intraperitoneally; i.p.) against gastric lesions induced by ethanol and 4 mg/kg (i.p.) when indomethacin was used as lesive agent. Oral administration of M. ilicifolia did not reproduce these results. The ethanolic extract of P. glomerata protected rodents from gastric ulcers with an ID50 of 314, 866 and 908 mg/kg (p.o.) after induction of gastric lesions by ethanol, indomethacin and stress, respectively. In the pylorus ligature model, the ID50 (mg/kg) for reduction of gastric acid secretion by the extract of A. millefolium, H. lancifolius and M. ilicifolia was >2000 mg/kg (intraduodenally; i.d.), 82 mg/kg (i.d.) and 7 mg/kg (i.p.), respectively. The extract of P. glomerata did not alter the hypersecretion induced by the pylorus ligature. Chemical examination and bio-guided purification of the active fractions allowed identification of the chemical type or the active principle of these plants. Uleine (66%) and yohimbine (24%) were isolated from the most active fraction of H. lancifolius, with uleine showing a threefold more potent ID50 (10.4 mg/kg, p.o.) than the alkaloid-rich fraction of origin. Caryophyllene oxide (31%) was separated from the hexane fraction of A. millefolium but the amounts were not enough for in vivo experiments. A mixture of flavonoids was found in the active fractions of M. ilicifolia and P. glomerata. Galactitol (25%), catechin (2%) and epicatechin (3.1%) were identified in M. ilicifolia. To study the mechanisms of action of these plants, assays were performed in vitro. The activity of gastric H+, K+-ATPase was inhibited by the hexanic fraction of A. millefolium, uleine from H. lancifolius and a flavonoids mixture of M. ilicifolia with inhibitory concentration 50% (IC50) of 121, 197 and 41 mg/ml, respectively. The extracts of A. millefolium, H. lancifolius and P. glomerata did not alter the intestinal motility of the animals, indicating no alteration of cholinergic effects. Maytenus ilicifolia presented a 2.8-fold higher potency to inhibit intestinal transit (ID50=31 mg/kg) than to inhibit gastrointestinal emptying. Collectively, the results indicate that all these Brazilian medicinal plants have a potential therapeutic use as gastroprotective agents.