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1.
Microb Pathog ; 135: 103612, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31252064

RESUMO

Emergence of antibiotic resistant bacteria has necessitated the drive to explore competent antimicrobial agents or to develop novel formulations to treat infections including Aeromonas hydrophila. The present study investigates the synergistic antibacterial effects of citrus flavonoid rutin and florfenicol (FF) against A. hydrophila in vitro and in vivo. Rutin is extracted and purified from Citrus sinensis peel through preparative HPLC and characterized through TLC, GC-MS and 1H and 13C NMR analyses. Though rutin did not display significant antibacterial activity, it modulated FF activity resulting in four-fold reduction in the MIC value for FF. The anti-biofilm potential of synergistic association of rutin and FF was validated by protein analysis, quantification of exopolysaccharide (EPS) and microscopy studies using sub-MIC doses. Besides antibacterial action, in vivo studies showed that Rutin/FF combination enhanced host immunity by improving blood cell count, anti-protease, and lysozyme activities as well as decreased the oxidative stress and the pathological changes of tilapia Oreochromis niloticus against A. hydrophila infection. No significant DNA damages or clastogenic effects were detected in tilapia challenged with A. hydrophila under Rutin/FF treatment. It is shown that an acute-phase Lipopolysaccharide binding protein (LBP) enhances the innate host defence against bacterial challenge. Semi quantitative RT-PCR and western blot results revealed the significant increase of LBP in the supernatant of tilapia monocytes/macrophages challenged with A. hydrophila upon treatment. The study findings substantiate that the combination of natural molecules with antibiotics may open up possibilities to treat MDR strains.


Assuntos
Aeromonas hydrophila/efeitos dos fármacos , Doenças dos Peixes/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/veterinária , Rutina/farmacologia , Rutina/uso terapêutico , Tianfenicol/análogos & derivados , Aeromonas hydrophila/crescimento & desenvolvimento , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Citrus sinensis/química , Dano ao DNA/efeitos dos fármacos , Modelos Animais de Doenças , Combinação de Medicamentos , Sinergismo Farmacológico , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Doenças dos Peixes/patologia , Pesqueiros , Imunidade/efeitos dos fármacos , Imunomodulação , Índia , Testes de Sensibilidade Microbiana , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rutina/imunologia , Tianfenicol/imunologia , Tianfenicol/farmacologia , Tianfenicol/uso terapêutico , Tilápia/microbiologia , Virulência/efeitos dos fármacos
2.
Mater Sci Eng C Mater Biol Appl ; 94: 56-64, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30423741

RESUMO

Drug delivery using synthetic mesoporous nanomaterials, including porous silicon, has been extensively used to ameliorate the constraints currently experienced with conventional chemotherapy. Owing to the amazing potential, the silica based nanomaterials have been used widely. Nevertheless, synthetic nanomaterial involves high cost, lack of scalability, and the use of toxic substances limits its utilization. These issues can be overcome by the use of nature generated nanoscale materials, such as diatoms would serve as a boon for pharmaceutical industries. In this study we investigate the use of a mesoporous, biodegradable nanomaterial obtained from the natural silica found in the diatom species Amphora subtropica (AMPS) for drug delivery applications. AMPS cultures cleaned and chemically treated to obtain Amphora frustules (exoskeleton) (AF), followed by surface functionalization with chitosan (Chi). Results of our experiments demonstrate high drug loading, strong luminescence, biodegradable and biocompatible nature of the doxorubicin tethered diatom. Further, toxicity studies employing immortalized lung cancer cell line (A549) indicates sustained drug delivery and less toxic compared to the free doxorubicin (DOX), suggesting AF could be an excellent substitute for synthetic nanomaterials used in drug delivery applications.


Assuntos
Antineoplásicos/farmacologia , Quitosana/química , Diatomáceas/química , Sistemas de Liberação de Medicamentos , Dióxido de Silício/química , Células A549 , Morte Celular/efeitos dos fármacos , Humanos , Teste de Materiais , Microalgas/isolamento & purificação , Filogenia , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Propriedades de Superfície
3.
Biomed Pharmacother ; 109: 1181-1195, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551368

RESUMO

Recent studies on flavonoids forming complexes with macromolecules attract researchers due to their enhanced bioavailability as well as chemo-preventive efficacy. In this study, a flavonoid rutin (Ru) is non-covalently complexed with fucoidan (Fu) using the functional groups to obtain a therapeutic polymeric complex overcoming the limitations of bioavailability of rutin. The prepared novel rutin-fucoidan (Ru-Fu) complex is characterized for spectroscopic features, particle size and distribution analysis by DLS. It is shown that the complex displayed the nanostructural features that are different from that of the usual rutin-fucoidan mixture. The studies on drug release profiles at different pH (5.5, 6.8 and 7.4) show that the sustained release of compounds from complex occurs preferentially at the desired endosomal pH (5.5). Further, the chemopreventive potential of Ru-Fu complex is investigated against HeLa cells by cellular apoptotic assays and flow cytometric analysis. It showed that the complex is able to disrupt cell cycle regulation and has the ability to induce cellular apoptosis via nuclear fragmentation, ROS generation and mitochondrial potential loss. In vitro cell viability assay with Ru-Fu complex shows that the complex is biocompatible on normal cells. The hemolysis assay also reveals that the complex does not release hemoglobin from human red blood cells (RBCs). Thus, the study is envisaged to open up interests for developing such formulations against cervical cancer and other cancers.


Assuntos
Apoptose/efeitos dos fármacos , Polissacarídeos/farmacologia , Rutina/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Disponibilidade Biológica , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Flavonoides/farmacologia , Células HeLa , Humanos , Mitocôndrias/efeitos dos fármacos , Fitoterapia/métodos
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