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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 10(8) 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 10(4), 17.3 +/- 4.9 x 10(4) and 8.1 +/- 6.6 x 10(4) cfu/stomach, respectively; and combinations of AM quinolones and omeprazole: 8.0 +/- 5.6 x 10(4), 4.2 +/- 2.5 x 10(4) and 5.5 +/- 2.7 x 10(4) cfu/stomach) compared with the vehicle-treated group (control: 359.9 +/- 180.3 x 10(4) 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.

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