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Mi Aung W, Songkro S, Songkharak S, Kaewnopparat N, Wungsintaweekul J. Preparation, characterization, and antibacterial activity of plaunotol and plaunoi extracts complexed with hydroxypropyl-β-cyclodextrin. Saudi Pharm J 2022; 30:679-692. [PMID: 35812138 PMCID: PMC9257859 DOI: 10.1016/j.jsps.2022.04.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 04/01/2022] [Indexed: 11/03/2022] Open
Abstract
Croton stellatopilosus (Plaunoi) leaves accumulate several diterpenes and possess various pharmacological activities. The present study aimed to prepare, characterize and assess the antibacterial activity of inclusion complexes prepared by mixing plaunotol (PL) or plaunoi extract (PE) with cyclodextrins (CD), including α-CD, β-CD, γ-CD, and hydroxypropyl-β-cyclodextrin (HP-β-CD). The inclusion complexes were characterized using SEM, XRD, DSC, and FT-IR and evaluated for aqueous solubility and thermal stability. The PL and PE lyophilized complexes with HP-β-CD were further evaluated for their antibacterial activity against acne-causing bacteria. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of PL, PE, and the inclusion complexes evaluated using the agar dilution method revealed that the MIC and MBC values of the inclusion complexes were lower than those of PL or PE alone. Interestingly, the complexes had a synergistic activity with clindamycin after testing with checkerboard assay. The hydrogel containing the inclusion complex and clindamycin were assessed for antibacterial activity using the agar well diffusion method. The results indicated that the hydrogels showed significant inhibition of bacterial growth. In conclusion, the prepared solid dispersion of PL or PE with HP-β-CD could enhance antibacterial activity by increasing the drug solubility. The hydrogels containing PL or PE complex and clindamycin could be considered as a candidate for the treatment of acne vulgaris.
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Baker DA. Plants against Helicobacter pylori to combat resistance: An ethnopharmacological review. ACTA ACUST UNITED AC 2020; 26:e00470. [PMID: 32477900 PMCID: PMC7248673 DOI: 10.1016/j.btre.2020.e00470] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 03/02/2020] [Accepted: 05/12/2020] [Indexed: 12/22/2022]
Abstract
Worldwide, Helicobacter pylori (H. pylori) is regarded as the major etiological agent of peptic ulcer and gastric carcinoma. Claiming about 50 percent of the world population is infected with H. pylori while therapies for its eradication have failed because of many reasons including the acquired resistance against its antibiotics. Hence, the need to find new anti-H.pylori medications has become a hotspot with the urge of searching for alternative, more potent and safer inhibitors. In the recent drug technology scenario, medicinal plants are suggested as repositories for novel synthetic substances. Hitherto, is considered as ecofriendly, simple, more secure, easy, quick, and less toxic traditional treatment technique. This review is to highlight the anti-H. pylori medicinal plants, secondary metabolites and their mode of action with the aim of documenting such plants before they are effected by cultures and traditions that is expected as necessity.
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Affiliation(s)
- Doha Abou Baker
- Medicinal and Aromatic Plants Dept., Pharmaceutical and Drug Industries Division, National Research Centre, Cairo, Egypt
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Wang YC. Medicinal plant activity on Helicobacter pylori related diseases. World J Gastroenterol 2014; 20:10368-10382. [PMID: 25132753 PMCID: PMC4130844 DOI: 10.3748/wjg.v20.i30.10368] [Citation(s) in RCA: 103] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Revised: 01/17/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori eradication and H. pylori induced related gastric disease prevention.
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Thombre NA, Gide PS. Floating-bioadhesive gastroretentiveCaesalpinia pulcherrima-based beads of amoxicillin trihydrate forHelicobacter pylorieradication. Drug Deliv 2014; 23:405-19. [DOI: 10.3109/10717544.2014.916766] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Khovidhunkit SOP, Yingsaman N, Chairachvit K, Surarit R, Fuangtharnthip P, Petsom A. In vitro study of the effects of plaunotol on oral cell proliferation and wound healing. JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH 2011; 13:149-159. [PMID: 21279879 DOI: 10.1080/10286020.2010.546790] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
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.
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Hirata Y, Yukawa T, Kashihara N, Nakao Y, Hiyama T. Nickel-Catalyzed Carbocyanation of Alkynes with Allyl Cyanides. J Am Chem Soc 2009; 131:10964-73. [DOI: 10.1021/ja901374v] [Citation(s) in RCA: 114] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Yasuhiro Hirata
- Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan
| | - Tomoya Yukawa
- Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan
| | - Natsuko Kashihara
- Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan
| | - Yoshiaki Nakao
- Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan
| | - Tamejiro Hiyama
- Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan
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Jodlowski TZ, Lam S, Ashby CR. Emerging therapies for the treatment of Helicobacter pylori infections. Ann Pharmacother 2008; 42:1621-39. [PMID: 18845620 DOI: 10.1345/aph.1l234] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE To describe emerging therapies, such as levofloxacin, moxifloxacin, rifabutin, rifaximin, tinidazole, doxycycline, minocycline, lactoferrin, and plaunotol for the eradication of Helicobacter pylori infection. DATA SOURCES Relevant information was identified through a search of MEDLINE (1966-July 2008), PubMed (1955-July 2008), American Search Premier (1975-July 2008), International Pharmaceutical Abstracts (1960-2008), Science Citation Index Expanded (1996-2008), Cochrane Databases (publications archived until July 2008), and various tertiary sources using the terms Helicobacter pylori, fluoroquinolones, levofloxacin, moxifloxacin, rifabutin, rifaximin, lactoferrin, plaunotol, tinidazole, doxycycline, minocycline, faropenem, new treatments, refractory, and salvage alone or in combination. STUDY SELECTION AND DATA EXTRACTION Relevant information was identified and selected based on clinical relevance and value of information. In vitro and in vivo data were included if available. DATA SYNTHESIS Data exist supporting the use of levofloxacin or rifabutin as salvage therapies for H. pylori infection. Levofloxacin triple therapy has been recommended in the current treatment guideline, but more data are needed, especially from studies conducted in the US. A rifabutin-based regimen is better tolerated than conventional quadruple therapy, but its use is limited due to cost, hematologic adverse effects, drug interactions, and predicted development of resistance. Tinidazole appears to be an option, particularly as sequential therapy when combined with other agents; however, its use is limited by the high prevalence of nitroimidazole-resistant H. pylori strains in the US. Moxifloxacin data are limited. Data supporting the use of rifaximin, doxycycline, and minocycline are lacking or do not show benefit of these drugs over standard treatments. CONCLUSIONS H. pylori infection remains one of the most significant infections worldwide, and treatment failure rate with the current standard therapy continues to rise. Other treatment options should be explored to meet the emerging challenge.
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Affiliation(s)
- Tomasz Z Jodlowski
- College of Pharmacy and Allied Health Professions, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
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Holton J, Besset C, Youinou P, Vaira D. Emerging therapeutic targets in the eradication of Helicobacter pylori. ACTA ACUST UNITED AC 2005. [DOI: 10.1517/14728222.2.2.107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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Abstract
The isoprenoid biosynthetic pathway is the source of a wide array of products. The pathway has been highly conserved throughout evolution, and isoprenoids are some of the most ancient biomolecules ever identified, playing key roles in many life forms. In this review we focus on C-10 mono-, C-15 sesqui-, and C-20 diterpenes. Evidence for interconversion between the pathway intermediates farnesyl pyrophosphate and geranylgeranyl pyrophosphate and their respective metabolites is examined. The diverse functions of these molecules are discussed in detail, including their ability to regulate expression of the beta-HMG-CoA reductase and Ras-related proteins. Additional topics include the mechanisms underlying the apoptotic effects of select isoprenoids, antiulcer activities, and the disposition and degradation of isoprenoids in the environment. Finally, the significance of pharmacological manipulation of the isoprenoid pathway and clinical correlations are discussed.
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Affiliation(s)
- Sarah A Holstein
- Departments of Internal Medicine and Pharmacology, University of Iowa, Iowa City, Iowa 52242, USA
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Chemistry and Biological Activities of Isoprenylated Flavonoids from Medicinal Plants (Moraceous Plants and Glycyrrhiza Species). BIOACTIVE NATURAL PRODUCTS (PART I) 2003. [DOI: 10.1016/s1572-5995(03)80142-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T. Anti-Helicobacter pylori flavonoids from licorice extract. Life Sci 2002; 71:1449-63. [PMID: 12127165 DOI: 10.1016/s0024-3205(02)01864-7] [Citation(s) in RCA: 245] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Licorice is the most used crude drug in Kampo medicines (traditional Chinese medicines modified in Japan). The extract of the medicinal plant is also used as the basis of anti-ulcer medicines for treatment of peptic ulcer. Among the chemical constituents of the plant, glabridin and glabrene (components of Glycyrrhiza glabra), licochalcone A (G. inflata), licoricidin and licoisoflavone B (G. uralensis) exhibited inhibitory activity against the growth of Helicobacter pylori in vitro. These flavonoids also showed anti-H. pylori activity against a clarithromycin (CLAR) and amoxicillin (AMOX)-resistant strain. We also investigated the methanol extract of G. uralensis. From the extract, three new isoflavonoids (3-arylcoumarin, pterocarpan, and isoflavan) with a pyran ring, gancaonols A[bond]C, were isolated together with 15 known flavonoids. Among these compounds, vestitol, licoricone, 1-methoxyphaseollidin and gancaonol C exhibited anti-H. pylori activity against the CLAR and AMOX-resistant strain as well as four CLAR (AMOX)-sensitive strains. Glycyrin, formononetin, isolicoflavonol, glyasperin D, 6,8-diprenylorobol, gancaonin I, dihydrolicoisoflavone A, and gancaonol B possessed weaker anti-H. pylori activity. These compounds may be useful chemopreventive agents for peptic ulcer or gastric cancer in H. pylori-infected individuals.
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Affiliation(s)
- Toshio Fukai
- Department of Physico-chemical Analysis, School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
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Horii T, Mase K, Suzuki Y, Kimura T, Ohta M, Maekawa M, Kanno T, Kobayashi M. Antibacterial activities of beta-lactamase inhibitors associated with morphological changes of cell wall in Helicobacter pylori. Helicobacter 2002; 7:39-45. [PMID: 11886472 DOI: 10.1046/j.1523-5378.2002.00054.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Recent study has demonstrated that beta-lactamase inhibitors including clavulanate, sulbactam and tazobactam have an vitro antibacterial effect on Helicobacter pylori. Here we describe the relationship between viability and cell profiles of H. pylori exposed to beta-lactamase inhibitors and some antibiotics in a short-time course. MATERIALS AND METHODS The antibacterial effects of beta-lactamase inhibitors including clavulanate, sulbactam and tazobactam on the bacterial viability of and morphological changes in H. pylori ATCC43504 were examined. RESULTS The beta-lactamase inhibitors such as clavulanate and sulbactam alone decreased the viable counts of H. pylori, depending on the antibiotic concentrations. Exposure to these beta-lactamase inhibitors resulted in morphological changes of cell shape, cell-wall disintegration and cell lysis. Among these beta-lactamase inhibitors, clavulanate was the most active, causing a decrease in viable counts and morphological changes such as short filamentous to sphaeroplast formation and lysis. One x minimum inhibitory concentration (MIC) of amoxicillin plus 1 x MIC of clavulanate decreased viable counts effectively compared with 1 x MIC of amoxicillin or 1 x MIC of clavulanate alone, and induced morphological changes of cell shape and cell wall. CONCLUSION Our results suggest that the beta-lactamase inhibitors alone have concentration-dependent antibacterial activities against H. pylori and affect the morphology of the cell shape and the cell wall in vitro.
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Affiliation(s)
- Toshinobu Horii
- Department of Laboratory Medicine, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Hamamatsu 431--3192, Japan
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Tago K, Minami E, Masuda K, Akiyama T, Kogen H. Synthesis of plaunotol derivatives and their antibacterial activities against Helicobacter pylori. Bioorg Med Chem 2001; 9:1781-91. [PMID: 11425580 DOI: 10.1016/s0968-0896(01)00080-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Plaunotol, a known antiulcer drug, has antibacterial activities against Helicobacter pylori. Plaunotol thiourea derivatives 2--4 and diol derivatives 6--10 were designed in search for a compound with high antibacterial activities. Thiourea derivatives 2--4 were synthesized regioselectively using our effective synthetic route for plaunotol (1), and diol derivatives 6--10 were also synthesized. Their antibacterial activities against H. pylori are described and we found that the most potent antibacterial agent was C1-thiourea derivative 2c.
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Affiliation(s)
- K Tago
- Exploratory Chemistry Research Laboratories, Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
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Yoshiyama H, Nakamura H, Okamoto T, Okita K, Nakazawa T. A novel in vitro effect of the mucosal protective agent sofalcone--inhibition of chemotactic motility in Helicobacter pylori. Aliment Pharmacol Ther 2000; 14 Suppl 1:230-6. [PMID: 10807429 DOI: 10.1046/j.1365-2036.2000.014s1230.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Motility of Helicobacter pylori is essential for colonization. H. pylori has been shown to exhibit chemotactic activity toward urea and sodium and bicarbonate ions, which are secreted from the gastric epithelia. The importance of urease activity for chemotactic motility of H. pylori in a viscous environment has also been shown. Consequently, application of drugs inhibiting chemotactic motility has been proposed as a strategy for H. pylori eradication. This inhibitory effect can be evaluated through assay of chemotaxis and swarming. MATERIALS AND METHODS H. pylori CPY3401 and ATCC43504 were grown on brucella agar plates/broth supplemented with 3% horse serum under microaerobic conditions (N2, 85%; O2, 5%; CO2, 10%). For motility assay, H. pylori cells grown on brucella-serum agar were stabbed into motility agar containing 0.35% refined agar in brucella-serum broth and the swarming zone was measured. For the chemotaxis assay, cells were suspended in 10 mM potassium phosphate buffer, pH 7.0, with 3% polyvinyl-pyrrolidone and assayed as described previously. Bacterial swimming in the fluid environment was observed under dark-field microscopy. RESULTS Numbers of bacteria attracted toward 1 microM flurofamide were reduced with increasing concentrations of sofalcone (0.2-222 microM). In addition, the size of the swarming zone was reduced in motility agar containing 22 and 222 microM sofalcone. On the other hand, 22 microM sofalcone did not inhibit bacterial growth on day 3. Bacterial swimming speed in brucella broth was slower in the presence of 22 and 222 microM sofalcone than in its absence. CONCLUSION Sofalcone was found to inhibit chemotactic motility of H. pylori. This drug may be useful for inhibiting the bacterium's ability to colonize the human stomach.
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Affiliation(s)
- H Yoshiyama
- Department of Microbiology, Yamaguchi University School of Medicine, Ube, Japan
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Takagi A, Koga Y, Aiba Y, Kabir AM, Watanabe S, Ohta-Tada U, Osaki T, Kamiya S, Miwa T. Plaunotol suppresses interleukin-8 secretion induced by Helicobacter pylori: therapeutic effect of plaunotol on H. pylori infection. J Gastroenterol Hepatol 2000; 15:374-380. [PMID: 10824880 DOI: 10.1046/j.1440-1746.2000.02168.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND It has been suggested that gastric mucosal injury induced by Helicobacter pylori infection is mediated by interleukin-8 (IL-8). METHODS 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. RESULTS 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. CONCLUSIONS These findings suggest that plaunotol has a therapeutic effect on gastritis induced by H. pylori.
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Affiliation(s)
- A Takagi
- Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
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Hojo M, Miwa H, Kikuchi S, Sato N. Do mucosal defensive agents improve the cure rate when used with dual or triple therapy regimens for eradicating Helicobacter pylori infection? Aliment Pharmacol Ther 2000; 14:193-201. [PMID: 10651660 DOI: 10.1046/j.1365-2036.2000.00692.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Some of mucosal defensive agents have anti-Helicobacter pylori activities. However, their effectiveness in eradicating H. pylori infection has not been evaluated. AIM To assess the additive effect of mucosal defensive agents in eradication regimens using statistical analysis. METHODS Pertinent studies were retrieved using the Medline and the Igaku-chuo-zasshi databases in Japan, reference and congress abstract lists. Studies in which regimens consisted of dual or triple therapy with mucosal defensive agents and without them, were selected from the retrieved studies. Eradication rates were extracted from studies according to intention-to-treat analysis. We evaluated the efficacies of mucosal defensive agents by pooled relative risk of eradication rates and its 95% confidence intervals (95% CI), which were calculated by Mantel-Haenszel method. Heterogeneity among the studies in treatment effect was evaluated by a chi2-test. RESULTS In dual therapy regimens, mucosal defensive agents demonstrated significant additive effects (pooled relative risk 1.41; 95% CI: 1.24-1.61). In triple therapy regimens, these agents did not provide significant additive effect. The clinical usefulness of specific agents could not be established, when each agent was analysed independently. CONCLUSIONS Mucosal defensive agents improve the cure rate when used with existing dual therapy regimens for eradicating H. pylori infection.
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Affiliation(s)
- M Hojo
- Department of Gastroenterology, Juntendo University, School of Medicine, Tokyo, Japan
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Ishikawa H, Ito H, Higaki M, Higaki M, Matsumoto Y, Kamimura T, Katsura Y, Tomishi T, Inoue Y, Takasugi H, Tomoi M, Krakowka S, Yoshida K. FR145715, a novel histamine H2 receptor antagonist, with specific anti-Helicobacter pylori activities. Eur J Pharmacol 1999; 378:299-310. [PMID: 10493106 DOI: 10.1016/s0014-2999(99)00466-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The pharmacological profile of N-[3-[2-[N'-(2-methoxyethyl)guanidino]thiazol-4yl]benzyl-ace tamide (FR145715), a novel histamine H2 receptor antagonist, was examined in both in vitro and in vivo models using experimental animals in comparison with ranitidine. In isolated guinea-pig atria, FR145715 antagonized the effect of histamine on heart rate with approximately three times more potent activity than ranitidine. In in vivo experiments, intraduodenal FR145715 dose-dependently inhibited spontaneous gastric acid secretion in rats (Shay's rats), with a ED50 value of 18.4 mg/kg, which was comparable to that of ranitidine (30.5 mg/kg). FR145715 also inhibited histamine-stimulated acid secretion in stomach-perfused anaesthetized rats (Schild's rats), when given intravenously and intraduodenally with ED50 values of 0.59 and 2.72 mg/kg, respectively. Ranitidine displayed more potent activity having respective ED50 values of 0.10 and 0.17 mg/kg. In Heidenhain pouch dogs, intravenous and oral FR145715 dose-dependently inhibited gastrin-stimulated acid secretion with respective ED50 values of 0.12 and 0.32 mg/kg, which were similar to those of ranitidine (0.09 and 0.33 mg/kg). In gastric ulcer models, FR145715 dose-dependently inhibited water immersion restraint stress- and acidified aspirin-induced gastric lesions with ED50 values of 3.2 and 15.1 mg/kg (p.o.), respectively. The comparative compound, ranitidine, also showed beneficial effects on stress-induced gastric ulcers with an ED50 value of 1.5 mg/kg (p.o.). However, it failed to inhibit acidified aspirin-induced gastric ulcers. FR145715 inhibited HCl-induced gastric lesions in rats, while pre-treatment with indomethacin abolished its beneficial effects, suggesting that FR145715 has a so-called cytoprotective effect which is dependent on endogenous prostaglandin production. In addition to its atypical profile as a histamine H2 receptor antagonist, FR145715 exhibited strong anti-microbial activities against strains of Helicobacter pylori (H. pylori) with a mean minimal inhibitory concentration value of 0.32 microg/ml. Moreover, FR145715 showed no anti-microbial effects on 25 other bacteria examined. In addition, in vivo experiments using gnotobiotic piglets infected with H. pylori, FR145715 (16 mg/kg, t.i.d.) completely eliminated the organism with reduced intensity of inflammation, when treated orally for 10 days. These data demonstrate that FR145715 is a novel histamine H2 receptor antagonist having potent and selective anti-H. pylori activities as well as cytoprotective properties. The present data suggest that FR145715 might be useful for the patients suffering from ulcer relapse, since the drug might be able to eradicate H. pylori in the stomach, which is considered a key factor to cause ulcer recurrence in humans.
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Affiliation(s)
- H Ishikawa
- Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical, Osaka, Japan
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Kogen H, Tago K, Arai M, Minami E, Masuda K, Akiyama T. A highly stereoselective synthesis of plaunotol and its thiourea derivatives as potent antibacterial agents against Helicobacter pylori. Bioorg Med Chem Lett 1999; 9:1347-50. [PMID: 10360733 DOI: 10.1016/s0960-894x(99)00203-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Practical and highly stereoselective synthesis of diterpene alcohol, plaunotol (1) and its thiourea derivatives 2a, 3a and 4a, via Z-selective Wittig reaction between alpha-acetal ketone 5 and phosphonium salt 6 and their antibacterial activity against Helicobacter pylori are described.
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Affiliation(s)
- H Kogen
- Exploratory Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan
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20
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Makino M, Koga T, Ito K, Kawada H, Tabata K. Delayed healing of chronic gastric ulcer after Helicobacter pylori infection in mice. J Pharm Pharmacol 1998; 50:943-8. [PMID: 9751461 DOI: 10.1111/j.2042-7158.1998.tb04012.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
It has been suggested that there is a close relationship between Helicobacter pylori and the onset or recurrence of gastroduodenal disease. The aim of this study was to examine the effect of H. pylori on the healing of chronic gastric ulcers induced in mice. H. pylori administered to nude mice delayed the healing of experimental acetic acid-induced gastric ulcers. Histological examination showed the occurrence of high densities of H. pylori on the surface of epithelial cells and in the ulcerated area. Repeated administration of amoxicillin (10 mgkg(-1) daily for 5 days) eradicated H. pylori and increased the rate of healing of gastric ulcers in H. pylori-infected mice, but metronidazole, which also eradicated the organisms, did not significantly affect the rate of healing. In conclusion, H. pylori-infection delayed the healing of gastric ulcers induced by the serosal application of acetic acid in mice, possibly by aggravation or prolongation of the mucosal inflammation. Amoxicillin eradicated H. pylori and promoted gastric ulcer healing in mice infected with H. pylori.
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Affiliation(s)
- M Makino
- Pharmacology and Molecular Biology Research Laboratories, Sankyo Co. Ltd, Tokyo, Japan
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21
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Kono K, Tatara I, Takeda S, Arakawa K, Shirotani T, Okada M, Hara Y. Antibacterial Activity of Epigallocatechin Gallate Against Helicobacter Pylori: Synergistic Effect with Plaunotol. J Infect Chemother 1997. [DOI: 10.1007/bf02491509] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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22
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Tamura H, Tokushima H, Murakawa M, Matsumura O, Itoyama S, Sekine S, Hirose H, Mitarai T, Isoda K. Eradication of Helicobacter pylori in patients with end-stage renal disease under dialysis treatment. Am J Kidney Dis 1997; 29:86-90. [PMID: 9002534 DOI: 10.1016/s0272-6386(97)90012-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The efficacy and safety of combination therapy with amoxicillin, lansoprazole, and plaunotol for the eradication of Helicobacter pylori in patients on dialysis were evaluated. The study subjects comprised 15 dialysis patients in whom H pylori had been found in the gastric mucosa. The patients were given 500 mg amoxicillin once a day for 3 weeks, 30 mg lansoprazole once a day for 8 weeks, and 80 mg plaunotol three times a day for 24 weeks. Endoscopy was performed on entry and at 4 and 24 weeks after cessation of amoxicillin. The concentrations of serum gastrin and gastric juice ammonia also were measured. Fourteen patients completed the treatment protocol, one having dropped out because of nausea and diarrhea. H pylori was eradicated in 11 of the 14 patients 4 weeks after the end of amoxicillin therapy (eradication rate, 78.6%). All but one patient was free of H pylori 24 weeks after the amoxicillin was discontinued. Patients who became negative for H pylori had significantly decreased serum gastrin and gastric juice ammonia concentrations. Our findings indicate that a combination of amoxicillin, lansoprazole, and plaunotol can be used to eradicate H pylori in patients on dialysis.
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Affiliation(s)
- H Tamura
- Fourth Department of Internal Medicine, Saitama Medical Center, Kawagoe, Japan
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23
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Synthesis of a piperidinomethylthiophene derivative as H2-antagonist with inhibitory activity against Helicobacter pylori. Bioorg Med Chem Lett 1996. [DOI: 10.1016/0960-894x(96)00313-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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