Mechanism of antiulcer effect of Neem (Azadirachta indica) leaf extract: effect on H+-K+-ATPase, oxidative damage and apoptosis
Mechanism of antiulcer effect of Neem (Azadirachta indica) leaf extract: effect on H+-K+-ATPase, oxidative damage and apoptosis
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DOI：
10.1163/1568560041352257
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发表时间：
2004-01-01
影响因子：
5.8
通讯作者：
Banerjee, Ranajit K.
中科院分区：
文献类型：
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作者：
Chattopadhyay, Ishita;Nandi, Bithi;Banerjee, Ranajit K.
从胃酸分泌、氧化损伤和细胞凋亡等方面探讨印楝叶水提物阻断大鼠胃溃疡的作用机制。该提取物呈剂量依赖性地抑制束缚冷应激、吲哚美辛和乙醇引起的胃损伤。在应激性溃疡模型中，它比雷尼替丁更有效，但不如奥美拉唑有效。它还剂量依赖性地阻断幽门结扎和巯基甲基咪唑诱导的酸分泌。在幽门结扎模型中，它的效果不如奥美拉唑，但与雷尼替丁一样有效。在体外以浓度依赖性方式抑制H+-K+-ATP酶活性，从而抑制胃酸分泌。氧化膜损伤的羟基自由基（cntdotOH）作为衡量在应激性溃疡的脂质过氧化反应显着阻止叶提取物。应激诱导的凋亡DNA片段化也受到保护。该提取物还通过清除cntdotOH在体外防止cntdotOH介导的粘膜DNA损伤。因此，印楝叶提取物通过抑制H+-K+-ATP酶阻断酸分泌并通过防止氧化损伤和细胞凋亡来提供抗溃疡活性。
The mechanism of the antiulcer effect of Neem leaf aqueous extract to block gastric lesions in rat has been studied with emphasis on acid secretion, oxidative damage and apoptosis. The extract dose-dependently inhibits gastric lesions induced by restraint-cold stress, indomethacin and ethanol. In stress ulcer model, it is more effective than ranitidine but less effective than omeprazole. It also dose-dependently blocks pylorus ligation and mercaptomethylimidazole-induced acid secretion. In the pylorus-ligation model, it is less effective than omeprazole but as effective as ranitidine. It inhibits H+-K+-ATPase activity in vitro in concentration-dependent manner to inhibit acid secretion. Oxidative membrane damage by hydroxyl radical (cntdotOH) as measured by lipid peroxidation in stress ulcer is significantly blocked by leaf extract. Stress-induced apoptotic DNA fragmentation is also protected. The extract also prevents cntdotOH-mediated mucosal DNA damage in vitro by scavenging the cntdotOH. Neem leaf extract, thus, offers antiulcer activity by blocking acid secretion through inhibition of H+-K+-ATPase and by preventing oxidative damage and apoptosis.