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[PMID]:29342216
[Au] Autor:Narayanaswamy VP; Giatpaiboon SA; Uhrig J; Orwin P; Wiesmann W; Baker SM; Townsend SM
[Ad] Endereço:Synedgen, Inc., Claremont, California, United States of America.
[Ti] Título:In Vitro activity of novel glycopolymer against clinical isolates of multidrug-resistant Staphylococcus aureus.
[So] Source:PLoS One;13(1):e0191522, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The incidence of multidrug-resistant (MDR) organisms, including methicillin-resistant Staphylococcus aureus (MRSA), is a serious threat to public health. Progress in developing new therapeutics is being outpaced by antibiotic resistance development, and alternative agents that rapidly permeabilize bacteria hold tremendous potential for treating MDR infections. A new class of glycopolymers includes polycationic poly-N (acetyl, arginyl) glucosamine (PAAG) is under development as an alternative to traditional antibiotic strategies to treat MRSA infections. This study demonstrates the antibacterial activity of PAAG against clinical isolates of methicillin and mupirocin-resistant Staphylococcus aureus. Multidrug-resistant S. aureus was rapidly killed by PAAG, which completely eradicated 88% (15/17) of all tested strains (6-log reduction in CFU) in ≤ 12-hours at doses that are non-toxic to mammalian cells. PAAG also sensitized all the clinical MRSA strains (17/17) to oxacillin as demonstrated by the observed reduction in the oxacillin MIC to below the antibiotic resistance breakpoint. The effect of PAAG and standard antibiotics including vancomycin, oxacillin, mupirocin and bacitracin on MRSA permeability was studied by measuring propidium iodide (PI) uptake by bacterial cells. Antimicrobial resistance studies showed that S. aureus developed resistance to PAAG at a rate slower than to mupirocin but similar to bacitracin. PAAG was observed to resensitize drug-resistant S. aureus strains sampled from passage 13 and 20 of the multi-passage resistance study, reducing MICs of mupirocin and bacitracin below their clinical sensitivity breakpoints. This class of bacterial permeabilizing glycopolymers may provide a new tool in the battle against multidrug-resistant bacteria.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Glucosamina/análogos & derivados
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Polímeros/farmacologia
Polissacarídeos/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/química
Farmacorresistência Bacteriana Múltipla
Glucosamina/química
Glucosamina/farmacologia
Glicosídeos
Seres Humanos
Técnicas In Vitro
Resistência a Meticilina
Staphylococcus aureus Resistente à Meticilina/isolamento & purificação
Staphylococcus aureus Resistente à Meticilina/metabolismo
Testes de Sensibilidade Microbiana
Mupirocina/farmacologia
Permeabilidade/efeitos dos fármacos
Polímeros/química
Polissacarídeos/química
Propídio/farmacocinética
Infecções Estafilocócicas/tratamento farmacológico
Infecções Estafilocócicas/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Glycosides); 0 (Polymers); 0 (Polysaccharides); 0 (pinocembrin 7-O-apiosyl(1-5)apiosyl(1-2)glucopyranoside); 0 (poly-N (acetyl, arginyl)glucosamine); 36015-30-2 (Propidium); D0GX863OA5 (Mupirocin); N08U5BOQ1K (Glucosamine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191522


  2 / 15276 MEDLINE  
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[PMID]:29276981
[Au] Autor:Tao JH; Zhao M; Jiang S; Pu XL; Wei XY
[Ad] Endereço:School of Pharmacy, Nantong University, Nantong 226001, PR China.
[Ti] Título:Comparative metabolism of two major compounds in Fructus Corni extracts by gut microflora from normal and chronic nephropathy rats in vitro by UPLC-Q-TOF/MS.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1073:170-176, 2018 Jan 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Herbal medicines are widely used as therapeutic products in many countries. Fructus Corni, a traditional herb medicine, has been clinically used to cure chronic nephropathy for thousands of years. It could be converted by gut microflora in vivo to shape its pharmacological profiles. Thus, metabolic profiles of major active constituents in Fructus Corni extracts by gut microflora from rats in healthy and nephropathy state were firstly investigated in vitro by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) in this study. According to the features of protonated ions, five metabolites (M1, M2, M3, M5 and M6) were found and preliminarily authenticated. Intestinal bacteria were capable of converting N0 (loganin) to its aglycone M1 (loganetin). The latter was further hydrogenated to the corresponding M2 (hydrogenated loganetin) and subsequently to M3 (hydrogenated and demethylated loganetin) by demethylation; While M5 (demethylated morronisid aglycone) and M6 (dehydroxylated morronisid aglycone) were identified as the two metabolites of N4 (morronisid) through demethylation and dehydroxylation. Gut microflora from healthy and nephropathy rats could degrade loganin and morronisid to the above metabolites. However, healthy rat intestinal bacteria showed more powerful degradation and much more amounts of M1 and M6 were obtained in their samples. Additionally, this work demonstrated that UPLC-Q-TOF/MS approach connected with MetaboLynx™ analysis software was rapid and reliable for screening and authentication of natural product metabolites.
[Mh] Termos MeSH primário: Cornus/química
Microbioma Gastrointestinal/fisiologia
Glicosídeos
Iridoides
Insuficiência Renal Crônica/metabolismo
[Mh] Termos MeSH secundário: Animais
Cromatografia Líquida de Alta Pressão/métodos
Glicosídeos/análise
Glicosídeos/metabolismo
Iridoides/análise
Iridoides/metabolismo
Espectrometria de Massas/métodos
Extratos Vegetais/química
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycosides); 0 (Iridoids); 0 (Plant Extracts); 0 (morroniside); H7WJ16Q93C (loganin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171226
[St] Status:MEDLINE


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[PMID]:28554232
[Au] Autor:Guo T; Tan SB; Wang Y; Chang J
[Ad] Endereço:a School of Life Science and Engineering , Lanzhou University of Technology , Lanzhou , China.
[Ti] Título:Two new monoterpenoid glycosides from the fresh rhizome of Tongling White Ginger (Zingiber officinale).
[So] Source:Nat Prod Res;32(1):71-76, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Two new monoterpenoid glycosides, trans-1,8-cineole-3,6-dihydroxy-3-O-ß-D-glucopyranoside (1), and 5,9-dihydroxy borneol 2-O-ß-D-glucopyranoside (2), together with four known monoterpenoid glycosides (3-6), were isolated from the water-soluble constituents of the fresh rhizome of Tongling White Ginger (Zingiber officinale). Their structures were decisively elucidated by spectroscopic analysis. In vitro tests for antimicrobial activity showed that compounds 1 and 3 possess significant activity against two Gram-positive organisms, Staphylococcus aureus and Staphylococcus epidermidis.
[Mh] Termos MeSH primário: Antibacterianos/química
Gengibre/química
Glicosídeos/química
Monoterpenos/química
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Glicosídeos/farmacologia
Espectroscopia de Ressonância Magnética
Testes de Sensibilidade Microbiana
Estrutura Molecular
Monoterpenos/farmacologia
Rizoma/química
Solubilidade
Espectrometria de Massas por Ionização por Electrospray
Staphylococcus aureus/efeitos dos fármacos
Staphylococcus epidermidis/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Glycosides); 0 (Monoterpenes)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1333994


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[PMID]:28637122
[Au] Autor:Wang ZG; Mi J; Wang XR; Huo YY; Peng YJ; Zhang HM; Gao Y; Zhang HL
[Ad] Endereço:a Department of Pharmaceutical Analysis , Heilongjiang University of Chinese Medicine , Harbin , China.
[Ti] Título:A new cinnamic acid glycoside from roots of Heracleum dissectum.
[So] Source:Nat Prod Res;32(2):133-140, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:From the roots of Heracleum dissectum Lebb., one new cinnamic acid glycoside derivative named dissectumoside (1), together with eight known compounds including three phenolics, three phenolic glycosides and two phenylpropanoic glycoside were isolated using various chromatographic methods. Among them compound 2-9 was isolated from the plant for the first time. Their structures were elucidated and identified on the basis of their physicochemical properties and by extensive analyses of NMR spectroscopy and high-resolution mass spectrometry. The results of triglyceride accumulation screening in 3T3-L1 cells showed that compounds 1, 5 and 9 exhibited significantly accelerating activities of adipogenesis in adipocytes.
[Mh] Termos MeSH primário: Cinamatos/isolamento & purificação
Glicosídeos/isolamento & purificação
Heracleum/química
Extratos Vegetais/química
[Mh] Termos MeSH secundário: Células 3T3-L1
Adipócitos/efeitos dos fármacos
Adipogenia/efeitos dos fármacos
Animais
Glicosídeos Cardíacos
Cinamatos/química
Glicosídeos/química
Camundongos
Fenóis/química
Raízes de Plantas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cardiac Glycosides); 0 (Cinnamates); 0 (Glycosides); 0 (Phenols); 0 (Plant Extracts); U14A832J8D (cinnamic acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1340285


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[PMID]:28627258
[Au] Autor:Manjunath BN; Shenvi S; Raja A; Reddy GC
[Ad] Endereço:a Chemical Sciences Division , Vittal Mallya Scientific Research Foundation , Bangalore , India.
[Ti] Título:New water soluble glycosides of 11-keto-ß-boswellic acid: A paradigm.
[So] Source:Nat Prod Res;32(2):154-161, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Though several glycosides of various triterpenes are known, but surprisingly no boswellic acid glycosides are reported so far. With a view to make water soluble boswellic acids, prepared glycosides of 11-keto boswellic acid for the first time. Naturally occurring boswellic acids which are anti-inflammatory agents are lipophylic in nature and thus, become a limiting factor in terms of their bioavailability. Among boswellic acids, 11-keto-ß-boswellic acid is found to exhibit superior biological activity and hence successfully prepared its glucosyl and maltosyl derivatives viz., 11-keto-ß-boswellic acid-24-O-ß-D-glucopyranoside (9) and 11-keto-ß-boswellic acid-24-O-α-D-glucopyranosyl-(1 â†’ 4)-ß-D-glucopyranoside (15) which are water soluble. Both these compounds are soluble in water to the extent of 10% (w/w) which is very significant.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacocinética
Glicosídeos/farmacocinética
Triterpenos/síntese química
[Mh] Termos MeSH secundário: Anti-Inflamatórios/síntese química
Anti-Inflamatórios/química
Disponibilidade Biológica
Boswellia/química
Glicosídeos/síntese química
Glicosídeos/química
Solubilidade
Triterpenos/química
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (11-keto-boswellic acid); 0 (Anti-Inflammatory Agents); 0 (Glycosides); 0 (Triterpenes); 059QF0KO0R (Water); 631-69-6 (boswellic acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1342084


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[PMID]:29329000
[Au] Autor:Li XS; Ren YC; Bao YZ; Liu J; Zhang XK; Zhang YW; Sun XL; Yao XS; Tang JS
[Ad] Endereço:Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
[Ti] Título:Synthesis of C -Neoglycosides of digoxigenin and their anticancer activities.
[So] Source:Eur J Med Chem;145:252-262, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Cardiac glycosides exhibit significant anticancer effects and the glycosyl substitution at C position of digoxigenin is pivotal for their biological activity. In order to study the structure-activity relationship (SAR) of cardiac glycosides toward cancers and explore more potent anticancer agents, a series of C -O-neoglycosides and C -MeON-neoglycosides of digoxigenin were synthesized by the Koenigs-Knorr and neoglycosylation method, respectively. In addition, digoxigenin bisdigitoxoside and monodigitoxoside were prepared from digoxin by sodium periodate (NaIO ) oxidation and 6-aminocaproic acid hydrolysis. The SAR analysis revealed that C -O-neoglycosides of digoxigenin exhibited stronger cytotoxicity and induction of Nur77 expression of tumor cells than C -MeON-neoglycosides. Also, 3ß-O-glycosides exhibited stronger anticancer effects than 3α-O-glycosides. Among them, 3ß-O-(ß-l-fucopyranosyl)-digoxigenin (3i) showed the highest activity on induction of Nur77 expression and translocation from the nucleus to cytoplasm, leading to cancer cell apoptosis.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Digoxigenina/farmacologia
Glicosídeos/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Proliferação Celular/efeitos dos fármacos
Digoxigenina/síntese química
Digoxigenina/química
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Glicosídeos/síntese química
Glicosídeos/química
Seres Humanos
Estrutura Molecular
Relação Estrutura-Atividade
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Glycosides); NQ1SX9LNAU (Digoxigenin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE


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[PMID]:27776018
[Au] Autor:Vartanian A; Baryshnikova M; Burova O; Afanasyeva D; Misyurin V; Belyаvsky A; Shprakh Z
[Ad] Endereço:Department of Experimental Diagnosis and Therapy of Tumors, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.
[Ti] Título:Inhibitor of vasculogenic mimicry restores sensitivity of resistant melanoma cells to DNA-damaging agents.
[So] Source:Melanoma Res;27(1):8-16, 2017 Feb.
[Is] ISSN:1473-5636
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The increasing incidence of melanoma makes this cancer an important public health problem. Therapeutic resistance is still a major obstacle to the therapy of patients with metastatic melanomas. The aim of this study was to develop the melanoma cell line resistant to DNA-alkylating agents and to elucidate the mechanisms involved in acquired drug resistance. We established a unique melanoma subline Mel MeR resistant to DNA-alkylating drug aranoza by continuous stepwise selection of the Mel Me/WT cell line with increasing concentrations of this drug. Mel MeR cells were also cross-resistant to streptozotocin or cisplatin. Here, we show that aranoza-resistant melanoma cells modulate the ABC transporter activity, upregulate the expression of PRAME, adopt a vascular-related phenotype and engage in vasculogenic mimicry. LCS1269, a vasculogenic mimicry low-molecular-weight inhibitor, reverses the sensitivity of resistant melanoma cells to DNA-damaging agents. In this study, we provide experimental evidence that LCS1269 might be considered as a new potential anticancer agent capable of overcoming multidrug resistance for DNA-damaging agents in melanoma.
[Mh] Termos MeSH primário: Antineoplásicos Alquilantes/farmacologia
Carbazóis/farmacologia
Linhagem Celular Tumoral
Resistência a Medicamentos Antineoplásicos
Glicosídeos/farmacologia
Melanoma/tratamento farmacológico
Melanoma/metabolismo
Metilnitrosoureia/análogos & derivados
Neovascularização Patológica/prevenção & controle
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Antígenos de Neoplasias/genética
Apoptose/efeitos dos fármacos
Antígeno CD24/metabolismo
Resistência a Medicamentos Antineoplásicos/genética
Endoglina/metabolismo
Corantes Fluorescentes/metabolismo
Expressão Gênica/efeitos dos fármacos
Seres Humanos
Receptores de Hialuronatos/metabolismo
Molécula 1 de Adesão Intercelular/metabolismo
Masculino
Melanoma/irrigação sanguínea
Melanoma/genética
Metilnitrosoureia/farmacologia
Meia-Idade
Proteínas de Neoplasias/genética
Células-Tronco Neoplásicas/metabolismo
Proteínas Nucleares/genética
Fenótipo
Fosfoproteínas Fosfatases/genética
Proteínas Proto-Oncogênicas c-kit/metabolismo
Rodamina 123/metabolismo
Tetraspanina 30/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCB5 protein, human); 0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Antigens, Neoplasm); 0 (Antineoplastic Agents, Alkylating); 0 (CD24 Antigen); 0 (CD24 protein, human); 0 (CD44 protein, human); 0 (CD63 protein, human); 0 (Carbazoles); 0 (ENG protein, human); 0 (Endoglin); 0 (Fluorescent Dyes); 0 (GAGE1 protein, human); 0 (Glycosides); 0 (Hyaluronan Receptors); 0 (LCS1269); 0 (Neoplasm Proteins); 0 (Nuclear Proteins); 0 (PRAME protein, human); 0 (Tetraspanin 30); 0 (aranoza); 126547-89-5 (Intercellular Adhesion Molecule-1); 1N3CZ14C5O (Rhodamine 123); 684-93-5 (Methylnitrosourea); EC 2.7.10.1 (Proto-Oncogene Proteins c-kit); EC 3.1.3.16 (CTDSP1 protein, human); EC 3.1.3.16 (Phosphoprotein Phosphatases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1097/CMR.0000000000000308


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[PMID]:29341893
[Au] Autor:Khan H; Amin S; Patel S
[Ad] Endereço:Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan. Electronic address: hkdr2006@gmail.com.
[Ti] Título:Targeting BDNF modulation by plant glycosides as a novel therapeutic strategy in the treatment of depression.
[So] Source:Life Sci;196:18-27, 2018 Mar 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Current therapies in clinical practice face strong criticism regarding their efficacy, and side effects, which forced the neuro-researchers to discover novel agents with different mechanistic insights. Glycosides are naturally-occurring plant secondary metabolites with significant medicinal potential and clinical scope as antidepressant. The aim of this review is to focus on the antidepressant effects of glycosides in preclinical studies, with an emphasis on the possible mechanisms. The literature search revealed that only a few phytoglycosides have been evaluated for their relevance in depression alleviation. Through preclinical tests, it has come forth that the efficacy is mediated by the modulation of brain-derived neurotrophic factor (BDFN) in the hippocampus, that is known for promoting synaptic efficacy, neuronal connectivity and neuroplasticity. Thus, attempting the upregulation of BDNF expression by plant glycosides can be a novel therapeutic strategy for the treatment of depression. The outcome of this review can stimulate neuroscientists to evaluate plant-derived glycosides for the treatment of depression, as these structurally-complex and diverse molecules, might usher in a new paradigm in the treatment of depression, with a better efficacy and tolerability.
[Mh] Termos MeSH primário: Antidepressivos/uso terapêutico
Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos
Depressão/tratamento farmacológico
Depressão/metabolismo
Glicosídeos/uso terapêutico
Fitoterapia
Plantas/química
[Mh] Termos MeSH secundário: Animais
Antidepressivos/efeitos adversos
Antidepressivos/farmacologia
Fator Neurotrófico Derivado do Encéfalo/metabolismo
Glicosídeos/efeitos adversos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Brain-Derived Neurotrophic Factor); 0 (Glycosides); 0 (brain-derived neurotrophic factor, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


  9 / 15276 MEDLINE  
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[PMID]:29210311
[Au] Autor:Currò D
[Ad] Endereço:a Istituto di Farmacologia , Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli , Roma , Italia.
[Ti] Título:The role of gut microbiota in the modulation of drug action: a focus on some clinically significant issues.
[So] Source:Expert Rev Clin Pharmacol;11(2):171-183, 2018 Feb.
[Is] ISSN:1751-2441
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: A healthy gut microbiota is necessary for the normal operation of several body functions, including gastrointestinal sensitivity and motility, lipid and glucid metabolism, immune surveillance, and host behavior. In addition, intestinal bacteria contribute to determining the pharmacological properties of several drugs by producing different drug metabolizing enzymes. Areas covered: Four enzymatic processes are discussed: prodrug activation; drug inactivation; drug deconjugation; and hydrolysis of natural glycosides with further metabolism of released aglycones. For each of these processes, a literature search has been undertaken on certain paradigmatic examples that have significant clinical implications: aminosalicylates and anthranoid laxatives; digoxin; irinotecan and non-steroidal anti-inflammatory drugs (NSAIDs); rutin, diosmin, and baicalin. Expert commentary: The modulation of certain reactions catalyzed by gut bacterial enzymes may offer new opportunities to improve the clinical efficacy of drugs such as aminosalicylates, and natural glycosides by increasing their metabolic transformation, and of digoxin by reducing its inactivation, or to decrease the lower intestinal toxicity of irinotecan, and NSAIDs by inhibiting the hydrolytic cleavage of their conjugates. Randomized clinical trials are awaited to clarify whether new intervention strategies may modulate these processes and provide clinical benefits such as improved therapeutic outcomes and drug safety profiles.
[Mh] Termos MeSH primário: Microbioma Gastrointestinal
Trato Gastrointestinal/metabolismo
Preparações Farmacêuticas/metabolismo
[Mh] Termos MeSH secundário: Animais
Trato Gastrointestinal/microbiologia
Glicosídeos/metabolismo
Seres Humanos
Preparações Farmacêuticas/administração & dosagem
Pró-Fármacos
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Glycosides); 0 (Pharmaceutical Preparations); 0 (Prodrugs)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1080/17512433.2018.1414598


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[PMID]:29342179
[Au] Autor:Ohyama Y; Ito J; Kitano VJ; Shimada J; Hakeda Y
[Ad] Endereço:Division of Oral Anatomy, Meikai University School of Dentistry, Sakado, Saitama, Japan.
[Ti] Título:The polymethoxy flavonoid sudachitin suppresses inflammatory bone destruction by directly inhibiting osteoclastogenesis due to reduced ROS production and MAPK activation in osteoclast precursors.
[So] Source:PLoS One;13(1):e0191192, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inflammatory bone diseases, including rheumatoid arthritis, periodontitis and peri-implantitis, are associated not only with the production of inflammatory cytokines but also with local oxidative status, which is defined by intracellular reactive oxygen species (ROS). Osteoclast differentiation has been reported to be related to increased intracellular ROS levels in osteoclast lineage cells. Sudachitin, which is a polymethoxyflavone derived from Citrus sudachi, possesses antioxidant properties and regulates various functions in mammalian cells. However, the effects of sudachitin on inflammatory bone destruction and osteoclastogenesis remain unknown. In calvaria inflamed by a local lipopolysaccharide (LPS) injection, inflammation-induced bone destruction and the accompanying elevated expression of osteoclastogenesis-related genes were reduced by the co-administration of sudachitin and LPS. Moreover, sudachitin inhibited osteoclast formation in cultures of isolated osteoblasts and osteoclast precursors. However, sudachitin rather increased the expression of receptor activator of NF-κB ligand (RANKL), which is an important molecule triggering osteoclast differentiation, and the mRNA ratio of RANKL/osteoprotegerin that is a decoy receptor for RANKL, in the isolated osteoblasts, suggesting the presence of additional target cells. When osteoclast formation was induced from osteoclast precursors derived from bone marrow cells in the presence of soluble RANKL and macrophage colony-stimulating factor, sudachitin inhibited osteoclastogenesis without influencing cell viability. Consistently, the expression of osteoclast differentiation-related molecules including c-fos, NFATc1, cathepsin K and osteoclast fusion proteins such as DC-STAMP and Atp6v0d2 was reduced by sudachitin. In addition, sudachitin decreased activation of MAPKs such as Erk and JNK and the ROS production evoked by RANKL in osteoclast lineage cells. Our findings suggest that sudachitin is a useful agent for the treatment of anti-inflammatory bone destruction.
[Mh] Termos MeSH primário: Flavonoides/farmacologia
Glicosídeos/farmacologia
Osteoclastos/efeitos dos fármacos
Osteoclastos/metabolismo
Osteogênese/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Conservadores da Densidade Óssea/farmacologia
Reabsorção Óssea/metabolismo
Reabsorção Óssea/patologia
Reabsorção Óssea/prevenção & controle
Diferenciação Celular/efeitos dos fármacos
Linhagem da Célula
Técnicas de Cocultura
Lipopolissacarídeos/toxicidade
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Osteíte/metabolismo
Osteíte/patologia
Osteíte/prevenção & controle
Osteoclastos/citologia
Osteogênese/fisiologia
Espécies Reativas de Oxigênio/metabolismo
Células-Tronco/citologia
Células-Tronco/efeitos dos fármacos
Células-Tronco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bone Density Conservation Agents); 0 (Flavonoids); 0 (Glycosides); 0 (Lipopolysaccharides); 0 (Reactive Oxygen Species); 0 (sudachitin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191192



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