Indian 10urnal of Experimental Biology Vol. 42, April 2004, pp. 389-397 Effect of Bacopa monniera and Azadirachta indica on gastric ulceration and healing in experimental NIDDM rats M Dorababu, T Prabha. S Priyambada, V K Agrawal, N C Aryya* & R K Goel** Department of Pharmacology and *Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India Received 15 July 2003; revised 17 December 2003 Gastric ulcers were induced in normal/ NIDDM rats by various physical (2 hr cold restraint stress and 4 hr pylorus ligation) and chemical agents (ethanol, 1 ml1200 g, oral, 1 hr before; aspirin, 200 mg/kg, oral, 4 hr) and duodenal ulcers were induced by cysteamine (40 mg/200 g). Ulcer healing activity was studied in gastric ulcers induced by acetic acid (50%) and HCI (0.6 M). The result indicated that in both, normal and NIDDM rats, B. monniera extract (BME, 20-100 mg/kg) did not show any significant effect on blood glucose level, while A. indica (AlE, 250-1000 mg/kg) significantly decreased it. However, both BME (50 mg/kg) and AIE (500 mg/kg) showed significant anti-ulcer and ulcer-healing activities in normal and NIDDM rats. Further, the present results also indicated that the ulcer protective effects of BME was more pronounced in non-diabetic, while that of AlE was more in NIDDM rats. The anti-ulcer and ulcer-healing activities of BME and AlE may be due to their effects on various mucosal offensive and defensive factors, and correction of blood sugar level by AIE may help to have more ulcer protective effect in NIDDM rats. Keywords: Azadirachta indica, 8acopa mOlllliera, Gastric ulceration, Healing, NIDDM, Rat IPC Code: Int. Cl. 7 A61K Diabetes increases the mucosal susceptibility to ul- cerogenic stimuli and predisposition to gastric ulcera- tionl. 2 . Experimental studies indicate that prolonged diabetic conditions have deleterious influences on various functions in the gastrointestinal tract 3 . Recent studies have shown aggravation of gastric mucosal ulcerogenic responses to starvation or stress in insulin dependent diabetic rats 1,4. and impaired healing of gastric lesions in streptozotocin induced insulin de- pendent diabetic rats 5 . Anti-ulcerogenic effect of fresh juice 6 and methanolic extract 7 of Bacopa monniera has been reported earlier in normal rats and, the ac- tivity is expected to be due to augmentation of muco- sal defensive factors rather than on the offensive fac- tors. Neem (Azadirachta indica) has been advocated for the treatment of various disorders like cough, nausea, vomiting, fever, jaundice, gonorrhea. intestinal worm infestation and leprosy in indigenous system of medi- cine 8 and reported to have hypoglycemic 9 and anti- hyperglycemic lO effects and anti-ulcerogenic activ- ity". Numerous reports have indicated that hypogly- cemic and anti-ulcerogenic activity of neem could be due to presence of nimbidine 9 • 11 . **Correspondent author: Fax: 0542-2367568; Email: rkgoel_bhu@yahoo.co.in Peptic ulcer occurs due to imbalance between offen- sive acid-pepsin secretion versus impaired mucosal resistance which includes mucin-bicarbonate secretion, life span of cells. cell proliferation, mucosal blood flow. mucosal glycoproteins, sulfhydryl groups etc. The present work was undertaken with premise that diabetes being a chronic disease would further com- promise, if any, (i) the mucosal defensive factors with concomitant increase in propensity to ulceration in re- sponse to various physical and chemical stimuli; and (ii) the changes induced by diabetes mellitus (OM) can be prevented or cured after using known anti-diabetic and ulcer protective drugs which correct the blood glu- cose levels, promote the mucosal defensive factors or both. Hence, we selected B. monniera and A. indica to evaluate their effects on the susceptibility of NIDDM rat's gastroduodenal mucosa to various ulcerogenic stimuli and on gastric ulcer healing. The results ' were also compared with standard oral hypoglycemic drug glibenclamide (GLC) and anti-ulcer/ulcer protective drugs like ranitidine (RAN) and sucralfate (SFf), on the above ulcer models in both normal and NIDDM rats. Materials and Methods Animals - After approval of the Institutional Ethics Committee, albino rats (CF strain) of either sex