plaunotol and Stomach-Ulcer

We investigated the eradication and recurrence rate of Helicobacter pylori-infected gastric ulcer patients by combination therapies. Eighty-six H. pylori-positive gastric ulcer patients were assigned randomly to one of seven groups: I, omeprazole 20 mg (n = 9); II, lansoprazole (LPZ) 30 mg (n = 16); III, LPZ 30 mg plus plaunotol 480 mg (n = 13); IV, LPZ 30 mg plus ecabet sodium 2 g (n = 11); V, LPZ 30 mg plus clarithromycin 600 mg (the first 2 weeks; n = 11); VI, LPZ 30 mg plus plaunotol 480 mg plus clarithromycin 600 mg (the first 2 weeks; n = 13); and VII, LPZ 30 mg plus ecabet sodium 2 g plus amoxicillin 1,500 mg (the first 2 weeks; n = 13). All therapy was for 8 weeks except where otherwise noted. H. pylori eradication rates as diagnosed by culture, histology, urease test, and [13C]urea breath test 4 weeks after stopping therapy were 0, 0, 8, 45, 6, 46, and 62%, respectively, in groups I-VII. No patient achieving H. pylori eradication suffered recurrence. The combination therapies with proton pump inhibitors in addition to antibiotics and antiulcer agents are safe and effective in H. pylori eradication.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Abietanes; Adult; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Diterpenes; Fatty Alcohols; Female; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Penicillins; Proton Pump Inhibitors; Recurrence; Stomach Ulcer

To investigate the effect of plaunotol in combination with proton-pump inhibitors on Helicobacter pylori eradication in patients with gastric ulcer.. We studied 65 H. pylori-positive gastric ulcer patients. They were randomly assigned to five treatment groups: omeprazole (group I, n = 8), lansoprazole (group II, n = 13), lansoprazole+plaunotol (group III, n = 12), lansoprazole+clarithromycin (group IV, n = 16) and lansoprazole+plaunotol+clarithromycin (group V, n = 16). Ulcer status was diagnosed by endoscopy and H. pylori status by culture, histology, a urease test and a urea breath test at baseline, and after 8 and 12 weeks. The clearance and eradication rates were compared in each group.. The healing rates in groups I-V were 100, 92, 100, 100 and 100%, respectively; clearance rates were 0, 23, 42, 50 and 75%, respectively; and eradication rates were 0, 0, 8, 38 and 69%, respectively.. Combination therapy with plaunotol is efficacious for the eradication of H. pylori in gastric ulcer patients.

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Biopsy; Clarithromycin; Colony Count, Microbial; Diterpenes; Drug Therapy, Combination; Fatty Alcohols; Gastric Mucosa; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Ulcer

The goals of this study were to assess the effectiveness of a new triple therapy consisting of amoxicillin and metronidazole with plaunotol in the eradication of Helicobacter pylori infection in humans, and to determine whether this treatment regimen reduces the rate of recurrence of gastric ulcer in patients infected with H. pylori, without instituting maintenance therapy with H2-receptor antagonists.. Thirty patients with active gastric ulcer who were infected with H. pylori were first treated with omeprazole until scarring occurred. Patients then received plaunotol for 4 wk, with amoxicillin and metronidazole for 7 days.. This triple therapy resulted in the safe eradication of H. pylori in 26 (86.7%) of 30 patients, with no recurrence of ulcer seen during a 12-month follow-up period in patients who tested negative for the presence of H. pylori. In addition, histological inflammatory changes improved in these patients. Of the four patients with persistent H. pylori infection, in three (75%), ulcers recurred.. This new triple therapy was very effective in eradicating H. pylori in infected patients and in reducing the rate of recurrence of gastric ulcer in these patients.

Topics: Amoxicillin; Anti-Ulcer Agents; Diterpenes; Drug Therapy, Combination; Fatty Alcohols; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Recurrence; Stomach Ulcer

Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer properties, has been commercially isolated from leaves of Croton stellatopilosus Ohba. This Thai medicinal plant was traditionally used in the form of crude extracts, suggesting that it is possible to administer these plaunotol-containing extracts without toxicity. To confirm its safety, the oral toxicity of a partially purified plaunotol extract (PPE) was evaluated in vivo. The PPE was simply prepared by 95% ethanol reflux extraction followed by hexane partition. The obtained extract was analyzed and found to contain 43% w/w of plaunotol and another compound, likely a fatty acid-plaunotol conjugate that is considered a major impurity. Oral administration of PPE to ICR mice and Wistar rats was conducted to evaluate acute and chronic toxicity of the plaunotol extract, respectively. The acute toxicity study demonstrated that PPE was practically nontoxic based on its high median lethal dose value (LD₅₀ = 10.25 g/kg). The chronic toxicity studies also showed the absence of mortality and clinical symptoms in all rats treated with 11-1,100 mg/kg/day of PPE during a 6-month period. Histopathological and hematological analyses revealed that altered liver and kidney function and increased blood platelet number, but only at the high doses (550-1,100 mg/kg/day). These results suggest that PPE is potentially safe for further development as a therapeutic agent in humans.

Topics: Animals; Croton; Diterpenes; Drugs, Chinese Herbal; Fatty Alcohols; Humans; Kidney; Liver; Mice; Plant Extracts; Plant Leaves; Plants, Medicinal; Rats; Stomach Ulcer

Plaunotol is an acyclic diterpene alcohol extracted from a medicinal plant called plau-noi, Croton stellatopilosus Ohba, and has been widely used for the treatment of gastric ulcers in Japan. The aim of this study was to examine the effects of plaunotol on human gingival fibroblasts (HGFs) and human oral keratinocytes (HOKs). To assess the cytotoxic effect, HGFs and HOKs were treated with plaunotol. Subsequently, the morphology of cells was recorded and cells were subjected to MTT assay. To investigate cell proliferation effect, cells were treated with plaunotol and counted with a haemocytometer. To determine wound healing effect, the number of cells repopulated into the wounded areas in monolayer culture and in fibroblast-populated collagen lattice (FPCL) was measured. The results showed that 10 and 1 μg/ml (33 and 3.3 μmol/l) plaunotol induced toxicity in HGFs and HOKs, respectively. However, 0.1 μg/ml (0.33 μmol/l) plaunotol promoted HGF proliferation and wound healing in monolayer and FPCL models. In contrast, 0.1 μg/ml plaunotol could not induce HOK proliferation nor in vitro wound healing using monolayer culture, but it induced wound healing in a modified FPCL model. Our data suggested that plaunotol could promote oral cell proliferation and wound healing in vitro and may have an implication on oral wound healing.

Topics: Cell Proliferation; Croton; Diterpenes; Fatty Alcohols; Fibroblasts; Humans; Keratinocytes; Plants, Medicinal; Stomach Ulcer; Wound Healing

It has been suggested that gastric mucosal injury induced by Helicobacter pylori infection is mediated by interleukin-8 (IL-8).. We studied the effect of plaunotol, a drug extracted from the Plau-noi tree of Thailand, and reported it to be effective in the treatment of ulcers, of IL-8 secretion induced by H. pylori and of the inhibitory adhesion activity of the bacterium to gastric epithelial cells. Moreover, the therapeutic effect of plaunotol on H. pylori infection was assessed by using the gnotobiotic murine model.. Plaunotol inhibited the growth of H. pylori (1.5 x 10(4) c.f.u./mL) at high doses (24-48 microg/mL), but not at low doses (3-6 microg/mL). Interleukin-8 secretion induced by H. pylori was inhibited by coculture with plaunotol in a dose-dependent manner. The adhesion of H. pylori to MKN45 cells was also suppressed by coculture with plaunotol in a dose-dependent manner. An in vivo study showed that plaunotol improved histological gastritis and decreased the H. pylori antibody titre.. These findings suggest that plaunotol has a therapeutic effect on gastritis induced by H. pylori.

Topics: Administration, Oral; Animals; Anti-Ulcer Agents; Antibodies, Bacterial; Bacterial Adhesion; Diterpenes; Dose-Response Relationship, Drug; Epithelial Cells; Fatty Alcohols; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Immunoassay; Interleukin-8; Male; Mice; Mice, Inbred BALB C; Rabbits; Stomach Neoplasms; Stomach Ulcer; Tumor Cells, Cultured

The use of H2-blockers in the treatment of patients with peptic ulcer has become popular. However, this treatment has adverse cardiovascular effects. The aim of this study was to investigate proarrhythmic rhythm and autonomic nervous activity by analyzing heart rate variability in patients treated with omeprazole, ranitidine, and plaunotol. Nineteen patients (mean age 67.5 +/- 2.7 years) with active gastric ulcer were treated with omeprazole (20 mg/day) for 8 weeks, then ranitidine (300 mg/day) for the next 4 months, and finally plaunotol (240 mg/day). At each stage of the treatment, Holter electrocardiography was performed, and heart rate variability and arrhythmias analyzed. Heart rate variability yielded power in the low- (0.04-0.15 Hz) and high-frequency components (0.15-0.4 Hz). Although both ranitidine and omeprazole induced little change in cardiac rhythm, the high-frequency power was higher (10.3 +/- 0.8 vs 8.6 +/- 0.6 ms, P < 0.05) and the ratio of low-to-high frequency power was lower (1.41 +/-0.10 vs 1.59 +/- 0.09. P < 0.05) during ranitidine than during plaunotol treatment. Cosinor analysis of heart rate variability revealed a decreased amplitude of low-frequency power during omeprazole compared with during ranitidine and plaunotol treatment. Ranitidine modulated high-frequency power which may be related to the adverse cardiovascular effects of H2-blocker.

Topics: Aged; Analysis of Variance; Anti-Ulcer Agents; Arrhythmias, Cardiac; Circadian Rhythm; Diterpenes; Electrocardiography; Fatty Alcohols; Female; Heart Rate; Histamine H2 Antagonists; Humans; Male; Omeprazole; Ranitidine; Stomach Ulcer

Plaunatol, an anti-ulcer drug, increases prostaglandin content in gastric tissue but its effect on radical-mediated gastric damage or activity against reactive oxygen species is unknown. We examined the effects of oral administration of plaunotol (Kelnac) on the acute gastric mucosal lesion and its progression to ulcer lesion induced by ischaemia-reperfusion in rats. Plaunotol (30 and 100 mg kg-1, 15 min before ischaemia) significantly reduced the total erosion area observed immediately after ischaemia-reperfusion. When plaunotol (30 and 100 mg kg-1, once a day) was administrated orally 60 min after reperfusion, it prevented the progression from erosion to ulcer. At 72 h after ischaemia-reperfusion, the total area of ulcers lesions was significantly reduced compared with that without plaunotol administration. Furthermore, treatment with plaunotol (100 mg kg-1) significantly increased prostaglandin E2 content in gastric tissues of both acute gastric mucosal lesion and gastric ulcer lesion. In in-vitro experiments, plaunotol (1-3 mg mL-1) reduced the superoxide radicals generated by leucocytes, but not by xanthine oxidase. These results indicate that plaunotol has protective effects on both the onset of acute gastric mucosal injury and its progression to ulcer lesion induced by ischaemia-reperfusion. Both effects of plaunotol on increase in prostaglandin content in gastric tissues and inhibition of superoxide radical from leucocytes may play important roles on the protection against gastric mucosal injury.

Topics: Animals; Anti-Ulcer Agents; Dinoprostone; Diterpenes; Fatty Alcohols; Gastric Mucosa; Humans; In Vitro Techniques; Leukocytes; Male; Rats; Rats, Wistar; Reperfusion Injury; Stomach Ulcer; Superoxides; Xanthine Oxidase