plaunotol and Disease-Models--Animal

Plaunotol, a cytoprotective anti-ulcer agent, has antibacterial activity against Helicobacter pylori. The purpose of the present study was to investigate the effect of plaunotol when combined with clarithromycin or amoxicillin against H. pylori. When combined with clarithromycin, plaunotol showed synergic activity against 11 of 14 strains, and additive activity against the other three strains, by chequerboard titration. When combined with amoxicillin, plaunotol showed additive activity against 10 of 14 strains. No antagonistic effects were seen against any of the strains tested. The interactions between plaunotol and either clarithromycin or amoxicillin were determined by time-kill assay against the Sydney Strain (strain SS1) of H. pylori. The combination of plaunotol with clarithromycin showed synergic activity and with amoxicillin showed additive activity. In a C57BL/6 mouse gastritis model infected with H. pylori SS1, the plaunotol-clarithromycin and plaunotol-amoxicillin combinations both exhibited synergic effects, which allowed the effective dose of clarithromycin to be reduced when co-administered with plaunotol. These results suggest that plaunotol may have a useful role in combination with anti-H. pylori drugs in the treatment of H. pylori-associated diseases.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Clarithromycin; Colony Count, Microbial; Disease Models, Animal; Diterpenes; Drug Synergism; Drug Therapy, Combination; Fatty Alcohols; Helicobacter Infections; Helicobacter pylori; Male; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Stomach

The aim of this study was to assess the effect of plaunotol, an anti-ulcer agent, on trinitrobenzene sulfonic acid (TNB)- and acetic acid-induced colonic lesions in rats. Plaunotol significantly reduced the severity of colonic mucosal lesions induced by TNB at a dose of 600 mg/kg/day. Moreover, plaunotol, at a dose of 600 mg/kg/day, significantly depressed the myeloperoxidase activity of the lesioned area induced by TNB of the rat colon. In the model of colitis induced by acetic acid, plaunotol reduced the area of lesions dose-dependently and significantly at doses of 60, 200 and 600 mg/kg/day as assessed by macroscopic observation. Microscopic observation showed obvious changes by administration of plaunotol such as reduction of epithelial cell necrosis, decreased mucin production and a decreased infiltration of a large number of neutrophils. In conclusion, plaunotol showed a protective effect against colonic lesion formation induced by TNB and acetic acid in rats. This study suggests the possibility that plaunotol may be effective and useful for treatment of inflammatory bowel disease in humans.

Topics: Acetic Acid; Animals; Anti-Ulcer Agents; Colon; Disease Models, Animal; Diterpenes; Dose-Response Relationship, Drug; Fatty Alcohols; Humans; Inflammatory Bowel Diseases; Male; Rats; Rats, Sprague-Dawley; Trinitrobenzenesulfonic Acid

To evaluate the efficacy of a new triple therapy (amoxycillin, metronidazole, plaunotol) in eradicating Helicobacter pylori in a nude mouse model and in humans.. In an animal study we used 215 nude mice infected with H. pylori to assess the ability of single, dual and triple therapy to eradicate H. pylori from the mouse stomach. The number of H. pylori in the mouse stomach and extent of the gastritis was assessed from 1 to 4 weeks after treatment. In a human study, we enrolled 78 H. pylori-positive patients with recurrent peptic ulcer diseases, 29 of whom were given triple therapy (amoxycillin and metronidazole for 1 week and plaunotol for 4 weeks). Patients in the control group (n = 49) were given a histamine H2-receptor antagonist. All patients were assessed 5 and 11 months after completion of therapy.. In the mouse model, both the number of H. pylori and the gastritis score were significantly lower in the triple therapy group than in any other treatment group assessed 1-4 weeks after completion of therapy. In the human study, the triple therapy eradicated H. pylori from the stomachs of 25 out of 29 patients (86%), compared to the control group in which none of the 49 patients were free of H. pylori in the stomach 11 months after completion of therapy. There were no reported side effects with this triple therapy. None of the H. pylori-eradicated patients showed a recurrence of peptic ulcer disease; three of the four patients whose H. pylori was not eradicated by triple therapy showed a peptic ulcer recurrence within the study period, whereas 16 out of 49 patients in the control group had a peptic ulcer recurrence.. This new triple therapy was effective in the eradication H. pylori, had very few side effects and greatly reduced the rate of recurrent peptic ulcers.

Topics: Amoxicillin; Animals; Anti-Ulcer Agents; Antitrichomonal Agents; Bismuth; Colony Count, Microbial; Contraindications; Disease Models, Animal; Diterpenes; Drug Therapy, Combination; Fatty Alcohols; Gastritis; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Metronidazole; Mice; Mice, Inbred BALB C; Mice, Nude; Penicillins; Peptic Ulcer; Recurrence; Severity of Illness Index; Treatment Outcome