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Mechanism of Action of Multi–Potent Ulcer Blockers in In Vitro and In Vivo Models

Srikanta, B. M. (2010) Mechanism of Action of Multi–Potent Ulcer Blockers in In Vitro and In Vivo Models. PhD thesis, University of Mysore.

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Abstract

Ulcer is a common global problem with increasing incidence and prevalence. Worldwide 14.5 million people have ulcers with a mortality of 4.08 million. The increasing incidence and prevalence of ulcers have been attributed to several factors encountered during day-to-day life, such as stress, exposure to bacterial infection, use of non-steroidal anti-inflammatory drugs (NSAIDs) etc. Ulcers are resulted from excess secretion of hydrochloric acid from gastric parietal cells via activation of H+, K+ -ATPase enzyme, which releases H+ into the lumen of the stomach leading to acidity. Released acid act on gastric mucosa leading to loss of mucosal damage and hence impaired mucosal protection. Gastric lesions thus develop due to loss of the delicate balance between gastroprotective and aggressive factors. Reduction in gastric mucin, enhanced the secretion of gastric and susceptibility to Helicobacter pylori infection adding to the severity of the disease. Sustainable efforts and constant research in the area lead to the development of several drugs that can act at multi-steps during ulcer pathogenicity such as proton pump blockers (Lansoprazole, Omeprazole), histamine receptor blockers (Ranitidine, Cimitidine, Famotidine) and H. pylori inhibitors (Amoxicillin, Erythromycin, Metronidazole). However, majority of them have been documented to pose problems of adverse effects. In the light of the above, it was pertinent to study natural products from dietary sources as potential antiulcer compounds. In the current thesis therefore dietary components have been explored as a potential effective and safer antiulcer compounds. Series of commonly used dietary sources were examined for inhibition of H+, K+ -ATPase, inhibition of H. pylori growth and antioxidant activity. The Antiulcer index (AUI) was calculated based on the results. Highest AUI sources – Swallow root (Decalepis hamiltonii) and Black cumin (Nigella Sativa) were selected for further studies. Pectic polysaccharide Abstract v and one of the abundant Swallow root components (2-hydroxy-4-methoxy benzaldehyde) was examined for anti-H. pylori, ulcer preventive or ulcer healing properties. Structure - function analysis of pectic polysaccharides of Swallow root (SRPP) and Black cumin (BCPP) revealed that galacturonan; either arabino or rhamnogalacturonan may be responsible for the antiulcer activity. The in vivo efficacy of these indicated that they are potent in inhibiting 73 to 85% of either swim/ethanol stress induced ulcers. Besides, 80 to 90% ulcer healing together with normalization of H+, K+ - ATPase, oxidative stress, antioxidant levels were also observed. Further, the selected components were also effective against multi-steps of H. pylori induced pathogenicity such as colonization on gastric mucin, invasion and cytotoxicity. Overall, the current study for the first time provided evidence for the ability of dietary pectic polysaccharides to elicit the signaling cascade of ulcer prevention and healing including the multi-step inhibition of potential ulcer pathogenic steps as indicated in scheme 1. Outcome of this study thus may result in the potential use of dietary compounds as better gastroprotective compounds that are safer with no side effects. Further, the ability of these dietary factors in eliciting the signaling cascade of ulcer healing process is quite intriguing and throws insights into the use of such compounds for designing of gastroprotective nutraceutical for gastric ulcer patients.

Item Type: Thesis (PhD)
Uncontrolled Keywords: Ulcer, natural products, dietary sources
Subjects: 600 Technology > 01 Medical sciences > 09 Human Physiology
600 Technology > 08 Food technology > 18 Processed foods > 01 Dietary Fiber
Divisions: Dept. of Biochemistry
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 15 May 2012 04:23
Last Modified: 15 May 2012 10:00
URI: http://ir.cftri.com/id/eprint/10742

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