As well as peptic ulcers, Helicobacter pylori is associated with the development of gastritis, gastric adenocarcinoma and lymphoma, and has been classified as a class I carcinogen in humans (International Agency for Research on Cancer Working Group, 1994). Although the bacteria can be eradicated in up to 90% of patients, side effects, poor compliance and the resistance of the bacteria to antibiotics are common causes of frequent treatment failure. Celery seed extracts (CSE) from a unique source in India has been used as herbal medicine since antiquity and found to have anti-inflammatory and gastroprotective properties (Butters et al., 2004; Whitehouse et al., 2001). This study followed on observations that crude extracts exhibited anti-helicobacter activity (Rainsford & Liu, 2006).CSE was selectively fractionated followed by HPLC. Fractions were collected and bio-assayed against different strains of H. pylori using conventional culture methods. The most potent component that was obtained from HPLC and purified was designated celery seed with anti-Helicobacter activity (CAH). This component has strong bactericidal effects against H. pylori; the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 3.15 mug ml[-1] and 6.25 - 12.5 mug ml[-1], respectively. This compares favourably with the MIC and MBC of tetracycline, which are in the region of 3.15 mug ml[-1]. The isolated compound has highly specific inhibitory effect on H. pylori, since no inhibitory activity was detected against Campylobacter jejuni or Escherichia coli at these levels. The molecular ion of CAH was measured as 384.23 by mass spectrometry, giving the empirical formula as C[24]H[32]O[4]. The MS and NMR data strongly suggest this compound is a phthalide dimer. From radioactive bioassay, CAH inhibits RNA synthesis by 50% of that seen in a negative control in 3 days, while DNA and protein synthesis were unchanged. These suggested that the new compound may be suitable for further investigation as an agent for treating H. pylori infections.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:495479 |
| Date | January 2008 |
| Creators | Zhou, Yong |
| Contributors | Rainsford, Kim ; Smith, Thomas |
| Publisher | Sheffield Hallam University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://shura.shu.ac.uk/20709/ |
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