Abstract

AQUEOUS STEM-BARK EXTRACT OF KHAYA GRANDIFOLIOLA (MELIACEAE) PREVENTS THE DELAY IN CHRONIC ACETIC GASTRIC ULCER HEALING CAUSED BY COMBINED ACTION OF INDOMETHACIN AND HISTAMINE-INDUCED HYPERSECRETION IN RATS

Essama Mbida Désirée Sandrine, Enow-Orock Enonchong George, Mezui Christophe, Nkwengoua Zondegoumba Ernestine, Barthelemy Nyasse and Tan Paul Vernyuy*

ABSTRACT

Aims: We evaluated the ability of K. grandifoliola stem-bark aqueous extract to heal acetic acid-induced chronic gastric ulcers and to prevent the delay in chronic ulcer healing induced by indomethacin and Histamine-induced hypersecretion. Methods: Gastric ulcers were produced 5 days after submucosal injection of 30% acetic acid (0.05 ml) at the lesser curvature of rat stomachs corpus. The extract (250 and 500 mg/kg) was administered p.o. during 10 days. After, the rats were sacrificed. The same protocol was repeated but with slight modifications where ulcer healing was delayed by indomethacin administered (s.c., at 1 mg/kg) once daily for 2 weeks from 5 days after the acetic acid injection. Extract or sucralfate were administered concomitantly. 30 minutes after the last gavage of extract, hypersecretion was induced by pylorus ligation followed by injection of Histamine (2.5 mg/kg s.c) 1 h after pylorus ligature. The animals were sacrified after 4 hours. Mucus secretion and oxidative stress parameters like superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT)) were measured, and macroscopic and histological assessment of ulcer healing was done. Results: Ulcer healing rates were 99.47% and 99.67 % for the 250 and 500 mg/kg doses of extract following 10 day treatment of acetic acid-induced ulcers vs 41.50 % and 95.74 % for spontaneous healing and Ranititine, respectively. Spontaneous healing (41.50 %) was significantly (P < 0.001) delayed by Indomethacin (with association of pylorus ligation and Histamine s.c) at the end of 14 day to 22.53 % healing rate. Co-administration of extract (250-500 mg/kg) or sucralfate (50 mg/ kg) significantly (P<.001) inhibited the adverse effect of indomethacin, raising healing rates to 94.02 %, 99.52 % and 88.96 %, respectively. Indomethacin significantly depressed gastric mucus production (39.80 mg) but extract (250-500 mg/kg) and Sucralfate (50 mg/ kg) significantly (P < 0.001) restored values to 77.20, 78.00 and 72.03 mg, respectively. Indomethacin also raised MDA concentration and decreased antioxidant enzyme levels. These effects were significantly (P < 0.001) counteracted by K. grandifoliola extract with an increase of levels of SOD and GSH, and decrease of MDA levels. Microscopy showed advanced re-epithelialisation with recovery of ulcer craters due to extract. Conclusion: K. grandifoliola stem-bark aqueous extract accelerates the spontaneous healing of acetic acid-induced chronic gastric ulcers, and prevents the delay in chronic gastric ulcer healing caused by indomethacin/histamine-induced hyperacidity. Ulcer healing effects of the extract are attributed to enhanced mucus production and the antioxidant properties which may likely be associated with the high presence of flavonoids and polyphenols.

Keywords: Khaya grandifoliola, chronic gastric ulcer, delayed healing, hypersecretion, antioxidant.