Aqueous Extract of Enantia chlorantha (Annonaceae) Prevents the Delay in Chronic Gastric Ulcer Healing Caused by Indomethacin in Rats

Abstract

Aims: To investigate the ability of Enantia chlorantha aqueous extract to heal acetic acid-induced chronic gastric ulcers and to prevent the delay in chronic ulcer healing induced by indomethacin. Study Design: Random allocation of male rats to groups of five rats each. Place and Duration of Study: Department of Animal Biology and Physiology, Animal Physiology Laboratory (Gastroenterology Research Unit) University of Yaounde 1 and Department of Biomedical Sciences (Pathology Unit), University of Buea between January and April 2015. Methodology: 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. Ulcer healing was delayed by indomethacin administered s.c. at 1 mg/kg once daily for 2 weeks from 5 days after the acid injection. Extract or sucralfate were administered concomitantly. Mucus secretion and oxidative stress parameters (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 82.7% and 88.6% for the 250 and 500 mg/kg doses of extract following 10 day treatment of acetic acid-induced ulcers vs 55.7% and 85.2% for spontaneous healing and Ranititine, respectively. Spontaneous healing (60.9%) was significantly (P<0.01) delayed by indomethacin (22.5% healing rate). Co-administration of extract (250-500 mg/kg) or sucralfate (100 mg/ kg) significantly (P<.001) inhibited the adverse effect of indomethacin, raising healing rates to 76.7%, 82.2% and 85.8%, respectively. Indomethacin significantly depressed gastric mucus production (39.79 mg) but extract and sucralfate restored values to 40.08-55.75 mg and 70.06 mg, respectively. Indomethacin raised MDA levels and decreased antioxidant enzyme levels. These effects were counteracted by E. chlorantha extract. Microscopy showed advanced re-epithelialisation with recovery of ulcer craters due to extract. Conclusion: E. chlorantha accelerates the spontaneous healing of acetic acid-induced chronic gastric ulcers, and prevents the delay in chronic gastric ulcer healing caused by indomethacin. The healing-promoting effect of the extract could be due not only to stimulation of gastric mucus secretion but also to enhanced re-epithelialisation and inhibition of enhanced lipid peroxidation in the ulcerated gastric tissue.