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JAC Advance Access published online on September 6, 2002
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkf159
© 2002 by The British Society for Antimicrobial Chemotherapy
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© 2002 The British Society for Antimicrobial Chemotherapy

Original Paper

In vivo action of novel alkyl methyl quinolone alkaloids against Helicobacter pylori

Kazunari Tominaga 1*, Kazuhide Higuchi 1, Norio Hamasaki 1, Masaki Hamaguchi 1, Takashi Takashima 1, Tetsuya Tanigawa 1, Toshio Watanabe 1, Yasuhiro Fujiwara 1, Yasuhiro Tezuka 2, Takema Nagaoka 2, Shigetoshi Kadota 2, Eiji Ishii 3, Kazuo Kobayashi 4, Tetsuo Arakawa 1

1 Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585
2 Research Institute for Traditional Sino-Japanese Medicines, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama 930-0194
3 Department of Health and Epidemiology, Osaka City Institute of Public Health and Environmental Sciences, 8-34 Tohjo-cho, Tennoji-ku, Osaka 543-0026, Japan
4 Department of Host Defense, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585

* Corresponding author. E-mail: tomy{at}med.osaka-cu.ac.jp.

Received 14 February 2002 ; revised 6 June 2002 ; accepted 21 June 2002

Abstract

Previously purified and isolated compounds of novel alkyl methyl quinolone alkaloids (AM quinolones) from Gosyuyu (Wu-Chu-Yu), a Chinese herbal medicine, have a strong and highly selective antibacterial activity against Helicobacter pylori in vitro. To clarify the antibacterial mechanism(s) of AM quinolones, we examined the effects of AM quinolones on respiration of H. pylori in vitro. One week after treatment with AM quinolones alone (2, 10 or 20 mg/kg/day, orally) or combinations of AM quinolones and omeprazole (30 mg/kg/day) for H. pylori (1 x 108 cfu)-infected Mongolian gerbils, we checked viable H. pylori and myeloperoxidase (MPO) activity in the gastric tissues. AM quinolones decreased the number of H. pylori and inhibited H. pylori respiration in a dose-dependent manner. AM quinolones decreased the number of viable H. pylori (AM quinolones alone: 46.0 ± 22.6 x 104, 17.3 ± 4.9 x 104 and 8.1 ± 6.6 x 104 cfu/stomach, respectively; and combinations of AM quinolones and omeprazole: 8.0 ± 5.6 x 104, 4.2 ± 2.5 x 104 and 5.5 ± 2.7 x 104 cfu/stomach) compared with the vehicle-treated group (control: 359.9 ± 180.3 x 104 cfu/stomach). AM quinolones significantly decreased MPO activity of H. pylori-inoculated gastric tissues. These findings suggest that AM quinolones have a potent antibacterial effect against H. pylori through respiratory inhibition, and reduced bacterial growth in vivo. AM quinolones might be novel therapeutic agents for H. pylori eradication.

Keywords: H. pylori, alkyl methyl quinolones, eradication, respiration
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