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Li Y, Zhao K, Wu Z, Zheng Y, Yu J, Wu S, Wong VKW, Chen M, Liu W, Zhao S. Discovery of Cinnamic Acid Derivatives as Potent Anti- H. pylori Agents. Molecules 2024; 29:4548. [PMID: 39407478 PMCID: PMC11477721 DOI: 10.3390/molecules29194548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/12/2024] [Accepted: 09/19/2024] [Indexed: 10/20/2024] Open
Abstract
Antibiotics are currently used for the treatment of Helicobacter pylori (H. pylori), which is confirmed to be the major cause of gastric disorders. However, the long-term consumption of antibiotics has already caused antibiotic resistance and side effects in vivo. Therefore, there is an emerging need for searching for safe and effective anti-H. pylori agents. Inspired by the excellent bioactivities of cinnamic acid, a series of cinnamic acid derivatives (compounds 1-30) were synthesized and determined for H. pylori inhibition. The initial screening revealed that compound 23, a 2,4-dinitro cinnamic acid derivative containing 4-methoxyphenol, showed excellent H. pylori inhibition with an MIC value of 4 μM. Further studies indicated that compound 23 showed anti-bacterial activity and had a bactericidal effect on H. pylori due to the destruction of the bacterial structure. Molecular docking analysis revealed that the 2,4-dinitro groups in cinnamic acid moiety formed hydrogen bonding with amino acid residues in an active pocket of H. pylori protein. Interestingly, the ester moiety fitted into the hydrophobic pocket, attaining additional stability to compound 23. Above all, the present study reveals that compound 23 could be considered a promising anti-H. pylori agent to treat H. pylori causing gastritis.
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Affiliation(s)
- Yonglian Li
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China; (Y.L.); (K.Z.); (Z.W.); (Y.Z.); (S.W.)
- School of Eco-Environment Technology, Guangdong Industry Polytechnic University, Guangzhou 510300, China
| | - Kun Zhao
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China; (Y.L.); (K.Z.); (Z.W.); (Y.Z.); (S.W.)
| | - Zhidi Wu
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China; (Y.L.); (K.Z.); (Z.W.); (Y.Z.); (S.W.)
| | - Yujun Zheng
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China; (Y.L.); (K.Z.); (Z.W.); (Y.Z.); (S.W.)
| | - Jialin Yu
- School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China; (J.Y.); (M.C.)
| | - Sikun Wu
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China; (Y.L.); (K.Z.); (Z.W.); (Y.Z.); (S.W.)
| | - Vincent Kam Wai Wong
- Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China;
| | - Min Chen
- School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China; (J.Y.); (M.C.)
| | - Wenfeng Liu
- School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China; (J.Y.); (M.C.)
| | - Suqing Zhao
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China; (Y.L.); (K.Z.); (Z.W.); (Y.Z.); (S.W.)
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A new approach against Helicobacter pylori using plants and its constituents: A review study. Microb Pathog 2022; 168:105594. [PMID: 35605740 DOI: 10.1016/j.micpath.2022.105594] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 05/11/2022] [Accepted: 05/15/2022] [Indexed: 02/07/2023]
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3
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Ghobadi E, Ghanbarimasir Z, Emami S. A review on the structures and biological activities of anti-Helicobacter pylori agents. Eur J Med Chem 2021; 223:113669. [PMID: 34218084 DOI: 10.1016/j.ejmech.2021.113669] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/11/2021] [Accepted: 06/21/2021] [Indexed: 12/19/2022]
Abstract
Helicobacter pylori is one of the main causal risk factor in the generation of chronic gastritis, gastroduodenal ulcers and gastric carcinoma. Thus, the eradication of H. pylori infection is an important way for preventing and managing the gastric diseases. Multiple-therapy with several antibacterial agents is used for the eradication of H. pylori infections; however the increase of resistance to H. pylori strains has resulted in unsatisfactory eradication and unsuccessful treatment. Furthermore, the combination therapy with high dosing leads to the disruption of intestinal microbial flora and undesired side effects. Therefore, the search for new therapeutic agents with high selectivity against H. pylori is a field of current interest. In recent years, diverse compounds originating from natural sources or synthetic drug design programs were evaluated and tried to optimize for applying against H. pylori. In this review, we have described various classes of anti-H. pylori compounds, their structure-activity relationship studies, and mechanism of actions, which could be useful for the development of new drugs for the treatment of H. pylori infections.
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Affiliation(s)
- Elham Ghobadi
- Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Zahra Ghanbarimasir
- Department of Organic Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran
| | - Saeed Emami
- Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
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Nabekura T, Kawasaki T, Kato Y, Kawai K, Fiorito S, Epifano F, Genovese S, Uwai Y. Citrus auraptene induces drug efflux transporter P-glycoprotein expression in human intestinal cells. Food Funct 2020; 11:5017-5023. [PMID: 32530447 DOI: 10.1039/d0fo00315h] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
P-glycoprotein (encoded by MDR1) is a membrane transport protein expressed in the intestine, liver, kidney, placenta, and blood-brain barrier. It excludes various clinically important drugs from cells, such as verapamil, digoxin, tacrolimus, and vinblastine. Therefore, human P-glycoprotein plays important roles in drug absorption, distribution, and excretion. We reported previously that auraptene, a natural compound occurring widely in citrus fruit (e.g., grapefruit), inhibited P-glycoprotein-mediated drug transport. In this study, we investigated the effects of auraptene and other phenylpropanoids on P-glycoprotein expression using human intestinal epithelial LS174T cells and a reporter plasmid expressing 10.2 kbp of the upstream regulatory region of MDR1. Auraptene (7-geranyloxycoumarin), a prenylated coumarin, and several phenylpropanoids, such as 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid, derricidin [2'-hydroxy-4'-(prenyloxy)chalcone], and 3-(4'-geranyloxyphenyl)-propanoic acid, induced MDR1 promoter activity in LS174T cells. Overexpression of the nuclear receptor human pregnane X receptor gene (NR1I2) enhanced auraptene-induced MDR1 activation. Nuclear factor-kappaB inhibitors, Bay11-7082 and JSH-23, repressed MDR1 activation by auraptene. Western blot analyses showed the induction of P-glycoprotein expression in the auraptene-treated LS174T cells. The citrus phytochemical auraptene can induce the drug efflux transporter P-glycoprotein in human intestinal cells, and thus has the potential to cause food-drug interactions.
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Affiliation(s)
- Tomohiro Nabekura
- Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650, Japan.
| | - Tatsuya Kawasaki
- Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650, Japan.
| | - Yu Kato
- Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650, Japan.
| | - Kazuyoshi Kawai
- Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650, Japan.
| | - Serena Fiorito
- Dipartimento di Farmacia, Università "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti Scalo, CH, Italy
| | - Francesco Epifano
- Dipartimento di Farmacia, Università "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti Scalo, CH, Italy
| | - Salvatore Genovese
- Dipartimento di Farmacia, Università "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti Scalo, CH, Italy
| | - Yuichi Uwai
- Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650, Japan.
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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: 28] [Impact Index Per Article: 5.6] [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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Racha S, Wongrattanakamon P, Raiwa A, Jiranusornkul S. Discovery of Novel Potent Small Natural Molecules Able to Enhance Attenuation of the Pathobiology of Gastric Cancer-Associated Helicobacter pylori by Molecular Modeling. Int J Pept Res Ther 2019. [DOI: 10.1007/s10989-018-9737-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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7
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Biomolecular Targets of Oxyprenylated Phenylpropanoids and Polyketides. PROGRESS IN THE CHEMISTRY OF ORGANIC NATURAL PRODUCTS 2019; 108:143-205. [PMID: 30924014 DOI: 10.1007/978-3-030-01099-7_2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Oxyprenylated secondary metabolites (e.g. phenylpropanoids and polyketides) represent a rare class of natural compounds. Over the past two decades, this group of phytochemicals has become a topic of intense research activity by several teams worldwide due to their in vitro and in vivo pharmacological activities, and to their great therapeutic and nutraceutical potential for the chemoprevention of acute and chronic diseases affecting humans. Such investigations have provided evidence that oxyprenylated secondary metabolites are able to interact with several biological targets at different levels accounting for their observed anticarcinogenic, anti-inflammatory, neuroprotective, immunomodulatory, antihypertensive, and metabolic effects. The aim of the present contribution is to provide a detailed survey of the so far reported data on the capacities of selected oxyprenylated phenylpropanoids and polyketides to trigger receptors, enzymes, and other types of cellular factors for which they exhibit a high degree of affinity and therefore evoke specific responses. With respect to the rather small amounts of these compounds available from natural sources, their chemical synthesis is also highlighted.
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Kawasaki T, Takeichi Y, Tomita M, Uwai Y, Epifano F, Fiorito S, Taddeo VA, Genovese S, Nabekura T. Effects of phenylpropanoids on human organic anion transporters hOAT1 and hOAT3. Biochem Biophys Res Commun 2017; 489:375-380. [DOI: 10.1016/j.bbrc.2017.05.121] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Accepted: 05/22/2017] [Indexed: 12/26/2022]
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Barbieri R, Coppo E, Marchese A, Daglia M, Sobarzo-Sánchez E, Nabavi SF, Nabavi SM. Phytochemicals for human disease: An update on plant-derived compounds antibacterial activity. Microbiol Res 2016; 196:44-68. [PMID: 28164790 DOI: 10.1016/j.micres.2016.12.003] [Citation(s) in RCA: 336] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Revised: 12/09/2016] [Accepted: 12/12/2016] [Indexed: 12/11/2022]
Abstract
In recent years, many studies have shown that phytochemicals exert their antibacterial activity through different mechanisms of action, such as damage to the bacterial membrane and suppression of virulence factors, including inhibition of the activity of enzymes and toxins, and bacterial biofilm formation. In this review, we summarise data from the available literature regarding the antibacterial effects of the main phytochemicals belonging to different chemical classes, alkaloids, sulfur-containing phytochemicals, terpenoids, and polyphenols. Some phytochemicals, besides having direct antimicrobial activity, showed an in vitro synergistic effect when tested in combination with conventional antibiotics, modifying antibiotic resistance. Review of the literature showed that phytochemicals represent a possible source of effective, cheap and safe antimicrobial agents, though much work must still be carried out, especially in in vivo conditions to ensure the selection of effective antimicrobial substances with low side and adverse effects.
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Affiliation(s)
| | - Erika Coppo
- Sezione di Microbiologia DISC University of Genoa, Italy
| | - Anna Marchese
- Sezione di Microbiologia DISC-IRCCS San Martino-IST University of Genoa, Italy.
| | - Maria Daglia
- Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Italy
| | - Eduardo Sobarzo-Sánchez
- Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain; Dirección de Investigación, Universidad Central de Chile, Santiago, Chile
| | - Seyed Fazel Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Seyed Mohammad Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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10
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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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da Silva CR, Michel V, Genovese S, Prévost MC, Epifano F, Touati E. Anti-Helicobacter Pylori Activities of Natural Isopentenyloxycinnamyl Derivatives from Boronia Pinnata. Nat Prod Commun 2012. [DOI: 10.1177/1934578x1200701024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
In this study we investigated the anti- Helicobacter pylori activity of four isopentenyloxycinnamyl derivatives from the Australian shrub Boronia pinnata Sm. (Rutaceae), structurally related to boropinic acid: ( E)-3-(4-(3-methylbut-2-enyloxy)-3,5-dimethoxyphenyl)acrylaldehyde (1), boropinol C (2), boropinal (3) and boropinol A (4). In vitro growth of H. pylori strains 26695 and B128 was analyzed in liquid culture with increasing doses of these compounds. Bacterial morphology was visualized by scanning electron microscopy. The in vivo effects of the two most efficient molecules that reduced bacterial growth in vitro, compounds 3 and 4, were investigated on H. pylori gastric colonization in the mouse model. The presence of these compounds in the bacterial cultures led to alterations of bacterial surface and flagella. In vivo, both compounds 3 and 4 at 250 μM reduced significantly the ability of H. pylori to colonize the gastric mucosa of mice, compared with untreated ones. These data indicate that these natural isopentenyloxycinnamyl derivatives related to boropinic acid can be considered as novel antibacterial agents with anti- H. pylori activity.
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Affiliation(s)
- Cécile Ribeiro da Silva
- Unit of Helicobacter Pathogenesis, Institut Pasteur,75724 Paris cedex 15, France
- CNRS-ERL3526, Department of Microbiology, Institut Pasteur,75724 Paris cedex 15, France
| | - Valérie Michel
- Unit of Helicobacter Pathogenesis, Institut Pasteur,75724 Paris cedex 15, France
- CNRS-ERL3526, Department of Microbiology, Institut Pasteur,75724 Paris cedex 15, France
| | - Salvatore Genovese
- Dipartimento di Scienze del Farmaco, Università “G. D'Annunzio”, Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy
| | - Marie-Christine Prévost
- Plateform of Ultrastructurale Microscopy, Institut Pasteur, 25 Rue du Dr Roux, 75724 Paris cedex 15, France
| | - Francesco Epifano
- Dipartimento di Scienze del Farmaco, Università “G. D'Annunzio”, Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy
| | - Eliette Touati
- Unit of Helicobacter Pathogenesis, Institut Pasteur,75724 Paris cedex 15, France
- CNRS-ERL3526, Department of Microbiology, Institut Pasteur,75724 Paris cedex 15, France
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Marquis A, Genovese S, Epifano F, Grenier D. The plant coumarins auraptene and lacinartin as potential multifunctional therapeutic agents for treating periodontal disease. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2012; 12:80. [PMID: 22742512 PMCID: PMC3489859 DOI: 10.1186/1472-6882-12-80] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Accepted: 06/28/2012] [Indexed: 12/16/2022]
Abstract
BACKGROUND Periodontal diseases are bacterial infections leading to chronic inflammation disorders that are frequently observed in adults. In the present study, we evaluated the effect of auraptene and lacinartin, two natural oxyprenylated coumarins, on the growth, adherence properties, and collagenase activity of Porphyromonas gingivalis. We also investigated the capacity of these compounds to reduce cytokine and matrix metalloproteinase (MMP) secretion by lipopolysaccharide (LPS)-stimulated macrophages and to inhibit MMP-9 activity. METHODS Microplate dilution assays were performed to determine the effect of auraptene and lacinartin on P. gingivalis growth as well as biofilm formation stained with crystal violet. Adhesion of FITC-labeled P. gingivalis to oral epithelial cells was monitored by fluorometry. The effects of auraptene and lacinartin on LPS-induced cytokine and MMP secretion by macrophages were determined by immunological assays. Fluorogenic assays were used to evaluate the capacity of the two coumarins to inhibit the activity of P. gingivalis collagenase and MMP-9. RESULTS Only lacinartin completely inhibited P. gingivalis growth in a complex culture medium. However, under iron-limiting conditions, auraptene and lacinartin both inhibited the growth of P. gingivalis. Lacinartin also inhibited biofilm formation by P. gingivalis and promoted biofilm desorption. Both compounds prevented the adherence of P. gingivalis to oral epithelial cells, dose-dependently reduced the secretion of cytokines (IL-8 and TNF-α) and MMP-8 and MMP-9 by LPS-stimulated macrophages, and inhibited MMP-9 activity. Lacinartin also inhibited P. gingivalis collagenase activity. CONCLUSIONS By acting on multiple targets, including pathogenic bacteria, tissue-destructive enzymes, and the host inflammatory response, auraptene and lacinartin may be promising natural compounds for preventing and treating periodontal diseases.
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Bruyère C, Genovese S, Lallemand B, Ionescu-Motatu A, Curini M, Kiss R, Epifano F. Growth inhibitory activities of oxyprenylated and non-prenylated naturally occurring phenylpropanoids in cancer cell lines. Bioorg Med Chem Lett 2011; 21:4174-9. [DOI: 10.1016/j.bmcl.2011.05.089] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2011] [Revised: 05/22/2011] [Accepted: 05/24/2011] [Indexed: 12/26/2022]
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Use of HPLC in the Determination of the Molar Absorptivity of 4′-Geranyloxyferulic Acid and Boropinic Acid. Chromatographia 2011. [DOI: 10.1007/s10337-011-1979-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Menghini L, Leporini L, Tirillini B, Epifano F, Genovese S. Chemical Composition and Inhibitory Activity Against Helicobacter pylori of the Essential Oil of Apium nodiflorum (Apiaceae). J Med Food 2010; 13:228-30. [DOI: 10.1089/jmf.2009.0010] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Affiliation(s)
- Luigi Menghini
- Dipartimento di Scienze del Farmaco, Università “G. D'Annunzio” Chieti-Pescara, Chieti Scalo
| | - Lidia Leporini
- Dipartimento di Scienze del Farmaco, Università “G. D'Annunzio” Chieti-Pescara, Chieti Scalo
| | - Bruno Tirillini
- Istituto di botanica ed Orto Botanico, Università di Urbino, Urbino, Italy
| | - Francesco Epifano
- Dipartimento di Scienze del Farmaco, Università “G. D'Annunzio” Chieti-Pescara, Chieti Scalo
| | - Salvatore Genovese
- Dipartimento di Scienze del Farmaco, Università “G. D'Annunzio” Chieti-Pescara, Chieti Scalo
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Prenyloxyphenylpropanoids as a novel class of anticonvulsive agents. Bioorg Med Chem Lett 2009; 19:5419-22. [PMID: 19679472 DOI: 10.1016/j.bmcl.2009.07.110] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2009] [Revised: 07/22/2009] [Accepted: 07/23/2009] [Indexed: 12/19/2022]
Abstract
In this study, we synthesized some natural and semi-synthetic prenyloxyphenylpropanoids (e.g., acetophenones, benzoic and cinnamic acids, chalcones, and coumarins), and we assessed their in vivo neuroprotective activity, using the mouse maximal electroshock-induced seizure model (MES test). 7-Isopentenyloxycoumarin and (2E)-3-{4-[(3-methylbut-2-enyl)oxy]phenyl}prop-2-enoic acid, administered ip at a dose of 300 mg/kg, suppressed MES-induced seizures in mice in a time- and dose-dependent manner.
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Touati E, Michel V, Correia M, Menghini L, Genovese S, Curini M, Epifano F. Boropinic acid, a novel inhibitor of Helicobacter pylori stomach colonization. J Antimicrob Chemother 2009; 64:210-1. [DOI: 10.1093/jac/dkp136] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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18
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MassimoCurini, Genovese S, Menghini L, Marcotullio MC, Epifano F. Phytochemistry and Pharmacology of Boronia Pinnata Sm. Nat Prod Commun 2008. [DOI: 10.1177/1934578x0800301235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Boronia pinnata Sm. (Rutaceae) is a plant that is widespread in New South Wales (Australia). Although there are no reports about the use of this species in the local ethnomedical traditions, recent investigations led to the characterization of several secondary metabolites, most belonging to the class of prenyloxyphenylpropanoids. Some of the compounds extracted from B. pinnata showed valuable biological properties, such as anti-inflammatory activity and in vitro inhibition of growth of Helicobacter pylori. The aim of this review is to cover what has been reported so far in the literature on the title plant from a phytochemical and pharmacological point of view.
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Affiliation(s)
- MassimoCurini
- Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di Chimica Organica, Università degli Studi di Perugia, Via del Liceo, Perugia, Italy 06123
| | - Salvatore Genovese
- Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di Chimica Organica, Università degli Studi di Perugia, Via del Liceo, Perugia, Italy 06123
| | - Luigi Menghini
- Dipartimento di Scienze del Farmaco, Università “G. D'Annunzio”, Via dei Vestini 31, 66013, Chieti Scalo (CH), Italy 66013
| | - Maria Carla Marcotullio
- Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di Chimica Organica, Università degli Studi di Perugia, Via del Liceo, Perugia, Italy 06123
| | - Francesco Epifano
- Dipartimento di Scienze del Farmaco, Università “G. D'Annunzio”, Via dei Vestini 31, 66013, Chieti Scalo (CH), Italy 66013
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Epifano F, Molinaro G, Genovese S, Ngomba RT, Nicoletti F, Curini M. Neuroprotective effect of prenyloxycoumarins from edible vegetables. Neurosci Lett 2008; 443:57-60. [PMID: 18675882 DOI: 10.1016/j.neulet.2008.07.062] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2008] [Revised: 07/13/2008] [Accepted: 07/18/2008] [Indexed: 12/26/2022]
Abstract
The present study is designed to investigate the effect of some natural prenyloxyphenylpropanoids as neuroprotective agents against NMDA-induced toxicity in mixed cortical cell cultures containing both neurons and astrocytes. Excitotoxicity was induced by exposure of cultures to NMDA (100microM) at room temperature in a HEPES-buffered salt solution followed by incubation at 37 degrees C for the following 24h in MEM-Eagle's supplemented with 15.8mM NaHCO(3) and 25mM glucose. Tested compounds were mixed with NMDA. Neuronal injury was measured in all experiments by examination of cultures with phase-contrast microscopy at 20x, 18-20h after the insult while neuronal damage was quantitatively assessed by counting dead neurons stained with trypan blue and by measuring lactate dehydrogenase (LDH) released in the medium. Results showed that only natural prenyloxyphenylpropanoids containing a coumarin nucleus, namely 7-isopentenyloxycoumarin and auraptene, both found in nature from plants belonging to the genus Citrus and other of the family of Rutaceae, including edible ones, exerted a good dose-dependent manner protective effect against NMDA-induced neurotoxicity in particular at concentrations ranging from 1 to 10microM.
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Affiliation(s)
- Francesco Epifano
- Dipartimento di Scienze del Farmaco, Università G. D'Annunzio, Via dei Vestini 31, 66013 Chieti Scalo, Italy.
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20
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Menghini L, Epifano F, Leporini L, Pagiotti R, Tirillini B. Phytochemical Investigation on Leaf Extract of Cordia salicifolia Cham. J Med Food 2008; 11:193-4. [DOI: 10.1089/jmf.2007.583] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Affiliation(s)
- Luigi Menghini
- Dipartimento di Scienze del Farmaco, University “G. D'Annunzio,” Chieti Scalo, Italy
| | - Francesco Epifano
- Dipartimento di Scienze del Farmaco, University “G. D'Annunzio,” Chieti Scalo, Italy
| | - Lidia Leporini
- Dipartimento di Scienze del Farmaco, University “G. D'Annunzio,” Chieti Scalo, Italy
| | - Rita Pagiotti
- Dipartimento di Biologia Vegetale e Biotecnologie Agroambientali, University of Perugia, Perugia, Italy
| | - Bruno Tirillini
- Istituto di Botanica ed Orto Botanico, University of Urbino, Urbino, Italy
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21
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Bodet C, Epifano F, Genovese S, Curini M, Grenier D. Effects of 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid and its ester derivatives on biofilm formation by two oral pathogens, Porphyromonas gingivalis and Streptococcus mutans. Eur J Med Chem 2007; 43:1612-20. [PMID: 18093697 DOI: 10.1016/j.ejmech.2007.11.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2007] [Revised: 10/10/2007] [Accepted: 11/01/2007] [Indexed: 12/26/2022]
Abstract
The aim of this study was to investigate the effect of 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid, active principle isolated from Acronychia baueri Schott, and its ester derivatives on biofilm formation by two important oral pathogens, Porphyromonas gingivalis and Streptococcus mutans. The parent acid and conjugates with vanillic acid, 2-hydroxynaphthoquinone and guaiacol caused a significant and reproducible inhibition of P. gingivalis biofilm formation. This effect could be related to the ability of the compounds to inhibit bacterial growth. These compounds also efficiently caused a reduction of biofilm formation by S. mutans, a phenomenon not related to growth inhibition. These data suggest that 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid and some of its ester derivatives may have a therapeutic/preventive potential for oral infections.
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Affiliation(s)
- Charles Bodet
- Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Université Laval, Quebec City, Quebec G1K 7P4, Canada
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Epifano F, Curini M, Genovese S, Blaskovich M, Hamilton A, Sebti SM. Prenyloxyphenylpropanoids as novel lead compounds for the selective inhibition of geranylgeranyl transferase I. Bioorg Med Chem Lett 2007; 17:2639-42. [PMID: 17314046 DOI: 10.1016/j.bmcl.2007.01.097] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2006] [Revised: 01/29/2007] [Accepted: 01/30/2007] [Indexed: 11/26/2022]
Abstract
In this study, we synthesized some natural and semisynthetic prenyloxyphenylpropanoids (e.g., coumarins and cinnamic acid derivatives) and we assessed their in vitro inhibitory activity against farnesyl transferase (FTase) and geranylgeranyl transferase I (GGTase I). No compound was an effective inhibitor of FTase, while farnesyloxycinnamic acids were shown to selectively inhibit GGTase I with IC(50) values ranging from 28 to 39 microM.
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Affiliation(s)
- Francesco Epifano
- Dipartimento di Scienze del Farmaco, Via dei Vestini 31, 66013 Chieti Scalo (CH), Italy.
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