Mechanism of antiulcer effect of Neem (Azadirachta indica) leaf extract: Effect on H+-K+-ATPase, oxidative damage and apoptosis

被引:39
作者
Chattopadhyay I. [1 ]
Nandi B. [1 ]
Chatterjee R. [1 ]
Biswas K. [1 ]
Bandyopadhyay U. [1 ]
Banerjee R.K. [1 ]
机构
[1] Department of Physiology, Indian Institute of Chemical Biology, Kolkata-700 032
关键词
Apoptosis; Gastric ulcer; H[!sup]+[!/sup]-K [!sup]+[!/sup]-ATPase; Neem (Azadirachta indica) leaf extract; Oxidative damage;
D O I
10.1163/1568560041352257
中图分类号
学科分类号
摘要
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 (•OH) 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 •OH- mediated mucosal DNA damage in vitro by scavenging the •OH. Neem leaf extract, thus, offers antiulcer activity by blocking acid secretion through inhibition of H+-K+-ATPase and by preventing oxidative damage and apoptosis.
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页码:153 / 176
页数:23
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  • [1] Ausubel F.M., Brent R., Kingston R.E., Et al., Current Protocols in Molecular Biology, 1, (1998)
  • [2] Babbs C.F., Steiner N.G., Detection and quantitation of hydroxyl radical using dimethylsulfoxide as molecular probe, Methods Enzymol., 186, pp. 137-147, (1990)
  • [3] Badam L., Joshi S.P., Bedekar S.S., In vitro antiviral activity of Neem (Azadirachta indica, Juss) leaf extract against group B coxsackie viruses, Commun. Dis., 31, pp. 79-90, (1999)
  • [4] Balasenthi L.S., Arivazhagan S., Ramachandram C.R., Et al., Chemopreventive potential of Neem (Azadirachta indica) on 7, 12-dimethylbenzanthracene (DMBA) induced hamster buccal pouch carcinogenesis, J. Ethnopharmacol., 67, pp. 189-195, (1999)
  • [5] Bandyopadhyay D., Biswas K., Bandyopadhyay U., Et al., Melatonin protects against stress-induced gastric lesions by scavenging the hydroxyl radical, J. Pineal Res., 29, pp. 143-151, (2000)
  • [6] Bandyopadhyay U., Bhattacharyya D.K., Chatterjee R., Et al., Localization of gastric peroxidase and its inhibition by mercaptomethylimidazole, an inducer of gastric acid secretion, Biochem. J., 284, pp. 305-312, (1992)
  • [7] Bandyopadhyay U., Biswas K., Chatterjee R., Et al., Gastroprotective effect of Neem (Azadirachta indica) bark extract. Possible involvement of H<sup>+</sup>-K<sup>+</sup>-ATPase inhibition and scavenging of hydroxyl radical, Life Sci., 71, pp. 2845-2865, (2002)
  • [8] Bandyopadhyay U., Chatterjee R., Chakraborty T.K., Et al., Activation of parietal cell by mercaptomethylimidazole - A novel inducer of gastric acid secretion, Biochem. Pharmacol., 54, pp. 241-248, (1997)
  • [9] Banerjee R.K., Das P.K., Bhattacharjee M., Gastric peroxidase and its role in cellular control of gastric acid secretion, Biological Oxidation Systems, 1, pp. 505-513, (1990)
  • [10] Berglindh T., Effect of common inhibitors of gastric acid secretion on secretagogue-induced respiration and aminopyrine accumulation in isolated gastric glands, Biochim. Biophys. Acta, 464, pp. 217-233, (1977)