Dorababu M, Joshi M C, Bhawani G, Kumar M Mohan, Chaturvedi Aditi, Goel R K
Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005.
Indian J Physiol Pharmacol. 2006 Jul-Sep;50(3):241-9.
Standardized aqueous extract of Neem (Azadirachta indica) leaves (AIE) has been reported to show both ulcer protective and ulcer healing effects in normal as well as in diabetic rats. To study the mechanism of its ulcer protective/healing actions, effects of AIE (500 mg/ kg) was studied on various parameters of offensive acid-pepsin secretion in 4 hr pylorus ligation, pentagastrin (PENTA, 5 microg/kg/hr)-stimulated acid secretion and gastric mucosal proton pump activity and defensive mucin secretion including life span of gastric mucosal cells in rats. AIE was found to inhibit acid-pepsin secretion in 4 hr pylorus ligated rats. Continuous infusion of PENTA significantly increased the acid secretion after 30 to 180 min or in the total 3 hr acid secretion in rat stomach perfusate while, AIE pretreatment significantly decreased them. AIE inhibited the rat gastric mucosal proton pump activity and the effect was comparable with that of omeprazole (OMZ). Further, AIE did not show any effect on mucin secretion though it enhanced life span of mucosal cells as evidenced by a decrease in cell shedding in the gastric juice. Thus, our present data suggest that the ulcer protective activity of AIE may be due to its anti-secretary and proton pump inhibitory activity rather than on defensive mucin secretion. Further, acute as well as sub acute toxicity studies have indicated no mortality with 2.5 g/kg dose of AIE in mice and no significant alterations in body or tissues weight, food and water intake, haematological profile and various liver and kidney function tests in rats when treated for 28 days with 1 g/kg dose of AIE.
据报道,印楝(Azadirachta indica)叶的标准化水提取物(AIE)在正常大鼠和糖尿病大鼠中均显示出溃疡保护和溃疡愈合作用。为了研究其溃疡保护/愈合作用的机制,研究了AIE(500毫克/千克)对4小时幽门结扎大鼠胃酸-胃蛋白酶分泌、五肽胃泌素(PENTA,5微克/千克/小时)刺激的胃酸分泌、胃黏膜质子泵活性以及防御性黏液分泌等各种参数的影响,包括大鼠胃黏膜细胞的寿命。发现AIE可抑制4小时幽门结扎大鼠的胃酸-胃蛋白酶分泌。持续输注PENTA可使大鼠胃灌流液在30至180分钟后或总3小时胃酸分泌显著增加,而AIE预处理可使其显著降低。AIE抑制大鼠胃黏膜质子泵活性,其效果与奥美拉唑(OMZ)相当。此外,AIE对黏液分泌没有任何影响,尽管它通过减少胃液中细胞脱落证明可延长黏膜细胞寿命。因此,我们目前的数据表明,AIE的溃疡保护活性可能归因于其抗分泌和质子泵抑制活性,而不是对防御性黏液分泌的作用。此外,急性和亚急性毒性研究表明,小鼠给予2.5克/千克剂量的AIE没有死亡,大鼠用1克/千克剂量的AIE治疗28天后,体重、组织重量、食物和水摄入量、血液学指标以及各种肝肾功能测试均无显著变化。