Pharmacological Profile of Gastric Mucosal Protection by Marmin and Nobiletin from a Traditional Herbal Medicine, Aurantii Fructus Immaturus

We studied the effects of marmin and nobiletin on the experimental acute gastric lesions, gastric transmucosal potential difference (PD) and gastric motor activity in rats and the contractions of isolated guinea pig ileum. Oral administration of marmin and nobiletin inhibited both the appearance of ethanol-induced gastric hemorrhagic lesions dose-dependently in a dose range of 10-50 mg/kg, with ED50 values for marmin and nobiletin being 17.2 and 8.0 mg/kg, respectively. However, marmin and nobiletin had minimal effects on aspirin-induced gastric lesions at a dose of 50 mg/kg, respectively. Marmin and nobiletin had no significant influence on the basal PD. Intragastrical administration of marmin and nobiletin at a dose of 25 mg/kg significantly prevented the PD reduction induced by ethanol. Both marmin and nobiletin given intragastrically at 25 mg/kg significantly inhibited gastric motor activity measured as intraluminal pressure recordings. Marmin and nobiletin exhibited concentration-dependent relaxations of contractions induced by acetylcholine, transmural electrical stimulation and histamine in isolated guinea pig ileum, respectively. These findings suggest that the anti-ulcer effects of marmin and nobiletin are ascribed primarily to the maintenance of the mucosal barrier integrity and inhibition of gastric motor activity and secondarily due to the prevention of the effects of endogenous acetylcholine and histamine.