The antiulcer effect of aqueous extracts of the leaves of the neem tree was investigated in rats exposed to 2-h cold-restraint stress or given ethanol orally for 1 h. Extracts were administered in doses of 10, 40, or 160 mg leaf/kg body weight, either as single- or five-dose pretreatment regimens. Neem dose-dependently reduced gastric ulcer severity in rats subjected to stress and also decreased ethanol provoked gastric mucosal damage. The extract appeared to prevent mast cell degranulation and to increase the amount of adherent gastric mucus in stressed animals. These effects may explain, at least in part, the mode of the antiulcer action of neem.

The effects of verapamil on gastric wall mucus and ulceration were studied in rats which were restrained and exposed to 4 °C (stress). Stress for 2 h significantly depleted stomach wall mucus and produced marked gastric glandular ulcers. Verapamil pretreatment (2, 4, 8 or 16 mg/kg), injected intraperitoneally 30 min before experimentation, significantly prevented stress-induced mucus depletion and gastric ulceration; however, it did not itself influence stomach wall mucus levels in nonstressed animals. Intragastric administration of carbenoxolone (100 or 200 mg/kg), also given 30 min before stress, exhibited similar actions as verapamil. A 15% solution of N-acetylcysteine (10 ml/kg), given orally, strongly decreased the mucus content in both nonstress and stress conditions; it induced ulcers in nonstressed rats, and worsened stress ulceration. These effects were not reversed by verapamil pretreatment. The influence of multiple-dose pretreatment with verapamil or carbenoxolone on mucus content and ulceration in the gastric glandular mucosa during stress is also discussed. It is concluded that gastric wall mucus depletion is likely to play an important role in stress ulcer formation; the antiulcer action of verapamil could partly be due to the preservation of mucus.

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The role of gastric glandular mucosal leukotriene C₄ in gastric ulceration, produced by restraint at 4 °C (stress) for 2 h in rats, was studied in relation to the ulcer-preventing effects of ethacrynic acid, sulphasalazine and its constituents (sulphapyridine and 5-aminosalicylic acid), AA-861 and ONO-1078. Stress itself significantly raised mucosal leukotriene C4 levels; pretreatment with ethacrynic acid, sulphasalazine, sulphapyridine or AA-861 antagonised these changes and reduced the severity of gastric ulceration. Mucosal mast cell degranulation was prevented by ethacrynic acid, sulphasalazine, 5-aminosalicylic acid, AA-861 or ONO-1078; the mucus-depleting effect of stress was also reversed by all these drugs, except for 5-aminosalicylic acid. The anti-ulcer effect of ethacrynic acid and sulphasalazine appears to be related to their influence on glandular mucosal leukotriene C₄ levels.

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