Antiulcerogenic activity of the hydroalcoholic extract of leaves of Annona muricata Linnaeus in mice

Abstract

Annona muricata Linnaeus, popularly known as "graviola" and also called soursop, is a species typical of countries with a tropical climate, and it is used in folk medicine as an anticancer, analgesic and antispasmodic agent. The aim of the present study was to validate the gastroprotective activity of the hydroalcoholic extract of the leaves of A. muricata (HEAM) and to investigate the underlying mechanisms of action for this effect. Gastric lesions were induced in mice by absolute ethanol, acidified ethanol or indomethacin. Before, the animals were pretreated with saline, omeprazole or HEAM orally at doses of 50-400 mg/kg. To determine the mechanism of action of the extract, we investigated, using specific inhibitors, the involvement of nitric oxide (NO), prostaglandins (PGEs), ATP-dependent K⁺ channels and α2-noradrenergic receptors. HEAM showed significant antiulcer activity against lesions induced by absolute ethanol, acidified ethanol or indomethacin, which was mediated by endogenous gastric prostaglandins.

Keywords: Annona; Medicinal plants; Peptic ulcer; Phytotherapy.

Figure 1

Effect of oral administration of HEAM on gastric lesions induced by absolute ethanol in mice. (A) Macroscopic appearance of the stomach mucosa: control group (a); groups treated with omeprazole (b), 50 mg/kg HEAM (c), 100 mg/kg HEAM (d), 200 mg/kg HEAM (e) and 400 mg/kg HEAM (f). (B) Quantification of ulcerated area expressed in%. ^***p < 0.001, compared with lesion control (CL).

Figure 2

Effect of oral administration of HEAM on gastric lesions induced by acidified ethanol in mice. (A) Macroscopic appearance of the stomach mucosa: control group (a); groups treated with omeprazole (b), 50 mg/kg HEAM (c), 100 mg/kg HEAM (d), 200 mg/kg HEAM (e) and 400 mg/kg HEAM (f). (B) Quantification of ulcerated area expressed in%. ^ap < 0.001 vs lesion control (CL). ^bp < 0.01 vs CL and ^cp < 0.05 vs omeprazole group.

Figure 3

Effect of oral administration of HEAM on indomethacin-induced gastric lesions in mice. (A) Macroscopic appearance of the stomach mucosa: control group (a); groups treated with omeprazole (b), 50 mg/kg HEAM (c), 100 mg/kg HEAM (d), 200 mg/kg HEAM (e) and 400 mg/kg HEAM (f). (B) Quantification of ulcerated area expressed in%. ^***p < 0.001 compared with lesion control (CL).

Figure 4

Role of nitric oxide (NO) in the gastroprotective effect of HEAM in mice model of gastric lesions induced by absolute ethanol. (A) Macroscopic appearance of the stomach mucosa: control group (a); groups treated with l-NAME (b), l-arginine (c), 200 mg/kg HEAM + l-NAME (d), 200 mg/kg HEAM + l-arginine (e) and 200 mg/kg HEAM (f). (B) Quantification of ulcerated area expressed in%. ^ap < 0.001 vs the lesion control (CL), ^bp < 0.001 vs l-NAME and ^cp < 0.01 vs control.

Figure 5

Role of prostaglandins in the gastroprotective effect of HEAM in mice model of gastric lesions induced by absolute ethanol. (A) Macroscopic appearance of the stomach mucosa: control group (a); groups treated with indomethacin (b), misoprostol (c), 200 mg/kg HEAM + indomethacin (d), 200 mg/kg HEAM + misoprostol (e) and 200 mg/kg HEAM (f). (B) Quantification of ulcerated area expressed in%. ^ap < 0.001 vs lesion control (CL), ^bp < 0.01 vs CL, ^cp < 0.01 vs indomethacin, ^dp < 0.001 vs indomethacin in combination with HEAM.

Figure 6

Role of α2-noradrenergic receptors in the gastroprotective effect of HEAM in mice model of gastric lesions induced by absolute ethanol. (A) Macroscopic appearance of the stomach mucosa: control group (a); groups treated with yohimbine (b), 200 mg/kg HEAM + yohimbine (c) and 200 mg/kg HEAM (d). (B) Quantification of ulcerated area expressed in%. ^ap < 0.001 vs lesion control (CL), ^bp < 0.001 vs yohimbine.

Figure 7

Role of ATP-dependent K+ channels in the gastroprotective effect of HEAM in mice model of gastric lesions induced by absolute ethanol. (A) Macroscopic appearance of the stomach mucosa: control group (a); groups treated with glibenclamide (b), 200 mg/kg HEAM + glibenclamide (c) and 200 mg/kg HEAM (d). (B) Quantification of ulcerated area expressed in%. ^ap < 0.001 vs lesion control (CL), ^bp < 0.001 vs glibenclamide.

Figure 8

Role of capsaicin-associated receptor in the gastroprotective effect of HEAM in mice model of gastric lesions induced by absolute ethanol. (A) Macroscopic appearance of the stomach mucosa: control group (a); groups treated with 0.2 mg/kg capsaicin (b), 4 mg/kg capsaicin (c), 200 mg/kg HEAM + 0.2 mg/kg capsaicin (d), 200 mg/kg HEAM + 4 mg/kg capsaicin (e) and 200 mg/kg HEAM (f). (B) Quantification of ulcerated area expressed in%. ^***p < 0.001 vs lesion control (CL).

Figure 9

The role of intestinal motility in the gastroprotective effect of HEAM in mice model of gastric lesions induced by absolute ethanol. Control group; groups treated with 0.01 mg/kg atropine; 200 mg/kg HEAM. Quantification of ulcerated area expressed in%. ^*p < 0.05 vs control (C).