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1.
Int J Biol Macromol ; 214: 610-616, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-35752341

RESUMEN

The drug resistance is higher among Gram-negative bacteria and demands the usage of strong antibiotics which can in turn result in systemic toxicity. In the treatment of the chronic wounds harboring pathogenic Gram-negative bacteria, the demand for an antimicrobial product that can be topically administered has been on the rise. In an effort to address the above issue, we have developed Colistimethate sodium (a high-end antibiotic) loaded chitosan hydrogel and characterized. The prepared hydrogel is very stable and observed to be bio- and hemo-compatible in nature. The antibacterial activity of the prepared hydrogel was studied against both ATCC (American Type Culture Collection) strains and clinical isolates of Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. The CMS incorporated hydrogel is also capable of inhibiting the biofilm formation. The developed hydrogel can be potentially being used for the treatment of Gram-negative bacterial infected wounds.


Asunto(s)
Quitosano , Colistina , Infecciones por Bacterias Gramnegativas , Infección de Heridas , Antibacterianos , Quitosano/farmacología , Quitosano/uso terapéutico , Colistina/análogos & derivados , Colistina/farmacología , Colistina/uso terapéutico , Escherichia coli , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Pruebas de Sensibilidad Microbiana , Infección de Heridas/tratamiento farmacológico
2.
Colloids Surf B Biointerfaces ; 178: 377-384, 2019 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-30903976

RESUMEN

Staphylococcus aureus is a major pathogen causing skin infections and currently treated with topical antibiotic preparations like bacitracin, triple antibiotic ointment (neomycin, polymixin B, and bacitracin), gentamicin or mupirocin. However, their efficacies are restricted when the infections are caused by drug resistant strains. There is an imperative need for new antibacterial compounds for the management of S. aureus topical infections. Maginfera indica (mango) is reported for its antibacterial efficacy in many traditional plant based medicines. In this study we tested the antibacterial efficacy of the methanol extract of mango leaf against SA113 and S. aureus clinical strains. Mango leaf extract (MLE) was found to be an effective anti-staphylococcal agent, non-mutagenic, and contains phytochemicals such as tannins, saponins, flavanoids, phenols, and coumarins. Further, the mango leaf extract (from stock MLE concentration of 130 mg/ml) containing carbopol hydrogel (MLEC) was prepared and characterized further for biocompatibility, rheological and anti-staphylococcal activities. The antibacterial activity of MLEC hydrogel against S. aureus strains was verified using in vitro and ex vivo porcine skin model. Our results demonstrated MLEC hydrogel formulation may act as superior alternative to currently available topical antiseptic/antibiotic formulations for the treatment of drug resistant staphylococcal infections.


Asunto(s)
Resinas Acrílicas/química , Hidrogeles/química , Mangifera/química , Extractos Vegetales/química , Hojas de la Planta/química , Antibacterianos/química , Antibacterianos/farmacología , Staphylococcus aureus/efectos de los fármacos
4.
Int J Biol Macromol ; 110: 514-521, 2018 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-29155154

RESUMEN

Cissus quadrangularis (CQ) is known as "bone setter" in Ayurvedic Medicine because of its ability to promote fracture healing. Polymers incorporated with CQ at lower concentration have shown to enhance osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. However, for the healing of clinically relevant critical sized bone defects, large amount of CQ would be required. Based on this perception, a herbal fibrous sheet containing high weight percentage of CQ [20,40 and 60wt/wt% in poly (L-lactic acid) (PLLA)] was fabricated through electrospinning. The solution concentration, flow rate, voltage and tip-target distance was optimized to obtain nanofibers. The hydrophobicity of PLLA fibers was reduced through CQ incorporation. There was considerable increase in the adhesion, proliferation and osteogenic differentiation of MSCs on herbal fibers than normal fibers, mainly on P-Q20 and P-CQ40. MSCs were differentiated into osteoblasts without providing any osteogenic supplements in the medium, indicating its osteoinductive capability. The herbal sheet also could promote mineralization when immersed in simulated body fluid for 14days. These studies specify that PLLA nanofibers loaded with 20 and 40wt% of CQ could serve as a potential candidate for bone tissue engineering applications.


Asunto(s)
Diferenciación Celular , Cissus/química , Células Madre Mesenquimatosas/metabolismo , Nanofibras/química , Osteogénesis , Poliésteres/química , Animales , Células Madre Mesenquimatosas/citología , Ratas
5.
Lett Appl Microbiol ; 65(5): 423-430, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28901019

RESUMEN

Mass mortalities of cobia, Rachycentron canadum, sub-adults occurred during August 2013 in cage culture in the Gulf of Mannar, Mandapam Tamil Nadu, India. The epizootic of disease was started with typical classical clinical signs followed by acute mortality. Grossly, severe haemorrhage and congestion were observed in the gastric mucosa. The abdomen was distended with peritoneal fluid. The heart revealed haemopericardium and fibrinous pericardium. Histologically, the gastric mucosa showed severe erosion and necrosis. Haemorrhagic pericarditis and an increased size of the melano macrophage centre (MMC) in the tail kidney were other histopathological changes. Vibrio sp. was isolated from the gastric lesions and heart blood swab of moribund fishes and it was found to be virulent to the cobia fingerlings. After the challenge, the same bacterium could be re-isolated from moribund fingerlings. The 16S ribosomal RNA of the isolate was amplified and blast analysis of the sequence confirmed that the pathogen was Vibrio alginolyticus. The confirmation was also correlated with its cultural, biochemical and pathomorphological changes. This is the second report and the first incidence of epizootics with severe pathological lesions in cultured cobia in India. The study throws light on the pathology of vibriosis. By practising cage farm management measures, occurrences of infection may be prevented. SIGNIFICANCE AND IMPACT OF THE STUDY: The epizootics of vibriosis caused serious economic losses to farmers. Natural blooms of the pathogen can be prevented by sea cage management measures such as, changing the inner net of the cages, changing the location of the cages to relatively clean water (about 50 m apart) from the affected site and providing shade over the cages while the water temperature rises. Supplementation of the feed with immunostimulants and mineral mixture may be practised to improve the immune response against infection. Early diagnosis and sea cage management measures may prevent occurrences of the infection.


Asunto(s)
Enfermedades de los Peces/microbiología , Perciformes/microbiología , Vibriosis/veterinaria , Vibrio alginolyticus/aislamiento & purificación , Animales , India , Riñón/microbiología , Perciformes/crecimiento & desarrollo , Vibriosis/microbiología , Vibrio alginolyticus/genética , Vibrio alginolyticus/patogenicidad , Virulencia
6.
Int J Biol Macromol ; 93(Pt B): 1402-1409, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27041649

RESUMEN

Cartilage degeneration occurs when the catabolic factors overtakes the anabolic factors. The regeneration capability of damaged cartilage is poor due to its hypovascular and hypocellular tissue. Tissue engineering strategies aims in development of a suitable substrate that provide the required physical, chemical and biological cues to the proliferating cells to direct chondrogenesis. A macroporous polymeric blend scaffold of chitin and poly(caprolactone) (PCL) was fabricated by lyophilisation technique and characterized using Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR) and Thermogravimetric/Differential thermal Analysis (TG/DTA). The effect of prolonged release of Transforming growth factor-ß (TGF-ß) was studied by encapsulating it in chondroitin sulphate nanoparticles (nCS) incorporated in chitin-PCL scaffold. Chondroitin sulphate nanoparticles containing TGF-ß (TGF-ß-nCS) was developed by polyelectrolyte crosslinking using chitosan. Characterization of TGF-ß-nCS by Dynamic Light Scattering particle sizer and SEM showed a 230±20nm sized spherical particles. Swelling and degradation studies of the composite scaffold showed its stability. Protein adsorption was enhanced in nanoparticle containing scaffold. The effect of TGF-ß was well addressed by the increased attachment and proliferation of rabbit adipose derived mesenchymal stem cells (rASCs). The chondrogenic potential of rASCs in the presence of TGF-ß releasing composite scaffold showed an increased proteoglycan deposition. These studies highlight the positive effects of chitin-PCL-TGF-ß-nCS scaffold for cartilage regeneration.


Asunto(s)
Portadores de Fármacos/administración & dosificación , Nanopartículas/administración & dosificación , Andamios del Tejido/química , Factor de Crecimiento Transformador beta/administración & dosificación , Tejido Adiposo/citología , Animales , Células Cultivadas , Quitina/química , Condrogénesis , Preparaciones de Acción Retardada/administración & dosificación , Composición de Medicamentos , Evaluación Preclínica de Medicamentos , Femenino , Células Madre Mesenquimatosas , Nanopartículas/química , Nanopartículas/ultraestructura , Poliésteres/química , Porosidad , Unión Proteica , Conejos , Medicina Regenerativa , Propiedades de Superficie , Ingeniería de Tejidos
7.
Colloids Surf B Biointerfaces ; 127: 33-40, 2015 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-25645750

RESUMEN

Salmonella Paratyphi A is a food-borne Gram-negative pathogen and a major public health challenge in the developing world. Upon reaching the intestine, S. Paratyphi A penetrates the intestinal epithelial barrier; and infects phagocytes such as macrophages and dendritic cells. S. Paratyphi A surviving within macrophages is protected from the lethal action of antibiotics due to their poor penetration into the intracellular compartments. Hence we have developed chloramphenicol loaded chondroitin sulfate (CS-Cm Nps) and dextran sulfate (DS-Cm Nps) nanoparticles through ionotropic-gelation method for the intracellular delivery of chloramphenicol. The size of these nanoparticles ranged between 100 and 200 nm in diameter. The encapsulation efficiency of both the nanoparticles was found to be around 65%. Both the nanoparticles are found to be non-hemolytic and non-toxic to fibroblast and epithelial cells. The prepared nanoparticles exhibited sustained release of the drug of up to 40% at pH 5 and 20-25% at pH 7.0 after 168 h. The anti-microbial activities of both nanoparticles were tested under in vitro and ex vivo conditions. The delivery of DS-Cm Nps into the intracellular compartments of the macrophages was 4 fold more compared to the CS-Cm Nps which lead to the enhanced intracellular antimicrobial activity of Ds-Cm Nps. Enhanced anti-microbial activity of Ds-Cm Nps was further confirmed in an ex vivo chicken intestine infection model. Our results showed that Cm loaded DS Nps can be used to treat intracellular Salmonella infections.


Asunto(s)
Cloranfenicol/uso terapéutico , Sulfatos de Condroitina/química , Sulfato de Dextran/química , Espacio Intracelular/microbiología , Nanopartículas/química , Infecciones por Salmonella/tratamiento farmacológico , Animales , Antibacterianos/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular , Cloranfenicol/farmacología , Endocitosis/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Nanopartículas/ultraestructura , Ratas , Espectroscopía Infrarroja por Transformada de Fourier , Resultado del Tratamiento
8.
Biochim Biophys Acta ; 1840(9): 2730-43, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24946270

RESUMEN

BACKGROUND: Evaluation of the combinatorial anticancer effects of curcumin/5-fluorouracil loaded thiolated chitosan nanoparticles (CRC-TCS-NPs/5-FU-TCS-NPs) on colon cancer cells and the analysis of pharmacokinetics and biodistribution of CRC-TCS-NPs/5-FU-TCS-NPs in a mouse model. METHODS: CRC-TCS-NPs/5-FU-TCS-NPs were developed by ionic cross-linking. The in vitro combinatorial anticancer effect of the nanomedicine was proven by different assays. Further the pharmacokinetics and biodistribution analyses were performed in Swiss Albino mouse using HPLC. RESULTS: The 5-FU-TCS-NPs (size: 150±40nm, zeta potential: +48.2±5mV) and CRC-TCS-NPs (size: 150±20nm, zeta potential: +35.7±3mV) were proven to be compatible with blood. The in vitro drug release studies at pH4.5 and 7.4 showed a sustained release profile over a period of 4 days, where both the systems exhibited a higher release in acidic pH. The in vitro combinatorial anticancer effects in colon cancer (HT29) cells using MTT, live/dead, mitochondrial membrane potential and cell cycle analysis measurements confirmed the enhanced anticancer effects (2.5 to 3 fold). The pharmacokinetic studies confirmed the improved plasma concentrations of 5-FU and CRC up to 72h, unlike bare CRC and 5-FU. CONCLUSIONS: To conclude, the combination of 5-FU-TCS-NPs and CRC-TCS-NPs showed enhanced anticancer effects on colon cancer cells in vitro and improved the bioavailability of the drugs in vivo. GENERAL SIGNIFICANCE: The enhanced anticancer effects of combinatorial nanomedicine are advantageous in terms of reduction in the dosage of 5-FU, thereby improving the chemotherapeutic efficacy and patient compliance of colorectal cancer cases.


Asunto(s)
Quitosano , Neoplasias del Colon/tratamiento farmacológico , Curcumina , Fluorouracilo , Nanopartículas , Animales , Disponibilidad Biológica , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Quitosano/farmacocinética , Quitosano/farmacología , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Curcumina/farmacocinética , Curcumina/farmacología , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Fluorouracilo/farmacocinética , Fluorouracilo/farmacología , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones
9.
J Biomed Nanotechnol ; 10(4): 559-70, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24734508

RESUMEN

Silymarin, a clinically proved hepato-protective herbal drug having significant anti-cancerous property towards prostate cancer, is inadequately utilized for cancer therapy due to its hydrophobic nature and poor bioavailability. In this work, we have developed silymarin Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in order to improve the therapeutic efficacy of silymarin towards prostate cancer by single emulsion solvent evaporation technique. The prepared nanoparticles had an encapsulation efficiency of 60% and a loading efficiency of 13%. The silymarin-PLGA NPs (SNPs) characterization, using DLS and SEM analysis revealed its size as less than 300 nm. FT-IR analysis confirmed encapsulation of silymarin by the SNPs, whereas XRD and TGA proved amorphous nature of the SNPs. In vitro drug release study demonstrated a slow and sustained release of encapsulated drug from the SNPs in physiological conditions. The hemocompatibility of the SNPs was established by in vitro hemolysis and coagulation assays. In vitro cell viability studies revealed preferential toxicity of SNPs towards prostate cancer cells (PC-3) compared to normal cells (Vero) in a dose dependant way. Cell uptake studies using confocal microscopy confirmed internalization of the SNPs by PC-3 cells. Furthermore, in vitro cell migration assay showed a concentration and time dependent inhibitory effect of SNPs on PC-3 cell migration. Finally, flow-cytometry based apoptosis assay suggested induction of apoptosis mediated death in PC-3 cells by the SNPs. Overall, the prepared SNPs proved as a promising candidate for prostate cancer therapy.


Asunto(s)
Ácido Láctico/química , Nanocápsulas/administración & dosificación , Ácido Poliglicólico/química , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Silimarina/administración & dosificación , Silimarina/farmacocinética , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Difusión , Humanos , Masculino , Tasa de Depuración Metabólica , Nanocápsulas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Neoplasias de la Próstata/patología , Silimarina/química , Distribución Tisular , Resultado del Tratamiento , Células Vero
10.
J Biomed Nanotechnol ; 10(1): 166-78, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24724508

RESUMEN

In this work, biocompatible and mucoadhesive thiolated chitosan (TCS) was used in the preparation of oral nanoformulation of human parathyroid hormone 1-34 (PTH 1-34) as an alternative patient compliant route in treating osteoporosis. PTH 1-34 loaded thiolated chitosan nanoparticles (TCS-PTH 1-34 NPs) size, morphology and interaction was analysed by DLS, SEM and FTIR respectively. TCS-PTH 1-34 NPs (90-100 nm) with 60% encapsulation efficiency was subjected to an in vitro release in simulated rat body fluids. TCS-PTH 1-34 NP's treated human primary osteoblast cells (HOB) upon PTH 1-34 receptor activation, produced second messenger-cAMP which down stream stimulated, production of bone specific alkaline phosphatase, osteocalcin and even enhanced the intracellular calcium uptake. These data substantiates the anabolic effect and bioactivity of the PTH 1-34 released from the TCS-PTH 1-34 NPs. Bare PTH 1-34 failed to reach the systemic circulation following oral dosage in rats whereas TCS-PTH 1-34 NPs showed an oral bioavailability of 0.075 microg PTH 1-34 throughout 48 h which is indeed a significant improvement in the half life of this peptide. TSC-PTH 1-34 NPs have released an advantageous anabolic dose of the peptide in blood that is suited for the treatment of osteoporosis. NIR image of gastrointestinal transit of ICG conjugated nanoformulation supports and justifies this significant finding. These results cumulatively point out that TCS NPs loaded with PTH 1-34 is efficient in orally delivering the peptide. This route of administration has increased its half life and improved the bioavailability compared to the bare peptide that is delivered systemically for treating osteoporosis.


Asunto(s)
Anabolizantes/administración & dosificación , Anabolizantes/farmacocinética , Quitosano/uso terapéutico , Nanopartículas/uso terapéutico , Osteoblastos/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Hormona Paratiroidea/administración & dosificación , Hormona Paratiroidea/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/farmacocinética , Quitosano/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Nanopartículas/química , Osteoblastos/metabolismo , Osteoporosis/metabolismo , Ratas , Ratas Sprague-Dawley , Compuestos de Sulfhidrilo/química
11.
Pharm Res ; 31(5): 1338-51, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24287625

RESUMEN

PURPOSE: In vitro evaluation of antibacterial and antifungal drugs encapsulated fibrin nanoparticles to prove their potential prospect of using these nanocomponent for effective treatment of microbial infested wounds. METHODS: Surfactant-free oil-in-water emulsification-diffusion method was adopted to encapsulate 1 mg/ml each of antimicrobial drugs (Ciprofloxacin and Fluconazole) in 4 ml of aqueous fibrinogen suspension and subsequent thrombin mediated cross linking to synthesize drug loaded fibrin nanoparticles. RESULTS: Ciprofloxacin loaded fibrin nanoparticles (CFNPs) showed size range of 253 ± 6 nm whereas that of Fluconazole loaded fibrin nanoparticles (FFNPs) was 260 ± 10 nm. Physico chemical characterizations revealed the firm integration of antimicrobial drugs within fibrin nanoparticles. Drug release studies performed at physiological pH 7.4 showed a release of 16% ciprofloxacin and 8% of fluconazole while as the release of ciprofloxacin at alkaline pH 8.5, was 48% and that of fluconazole was 37%. The antimicrobial activity evaluations of both drug loaded systems independently showed good antibacterial activity against Escherichia coli (E.coli), Staphylococcus aureus (S. aureus) and antifungal activity against Candida albicans (C. albicans). The in vitro toxicity of the prepared drug loaded nanoparticles were further analyzed using Human dermal fibroblast cells (HDF) and showed adequate cell viability. CONCLUSION: The efficacies of both CFNPs and FFNPs for sustained delivery of encapsulated anti microbial drugs were evaluated in vitro suggesting its potential use for treating microbial infested wounds (diabetic foot ulcer).


Asunto(s)
Antiinfecciosos/administración & dosificación , Fibrina , Heridas y Lesiones/tratamiento farmacológico , Antiinfecciosos/farmacocinética , Antiinfecciosos/uso terapéutico , Candida albicans/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus aureus/efectos de los fármacos , Heridas y Lesiones/microbiología
12.
Colloids Surf B Biointerfaces ; 106: 109-16, 2013 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-23434699

RESUMEN

In this work, we have developed a nanocomposite scaffold using a mixture of pectin, chitin and nano CaCO3 using the technique of lyophilization, with an intended use towards biomedical applications such as tissue engineering and drug delivery. The prepared composite scaffold was characterized using scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). In addition, swelling, degradation and biomineralization capability of the composite scaffold was evaluated. The developed composite scaffold showed controlled swelling and degradation in comparison with the control scaffold. Cytocompatibility evaluation of the scaffold was tested on NIH3T3, L929 and human dermal fibroblast (HDF) cells, showed negligible toxicity towards cells. Cell attachment and proliferation studies were also conducted using these cells, which showed that cells attached onto the scaffolds and started to proliferate after 48 h of incubation. Further, drug delivery through the scaffold was examined using a bisphosphonate called Fosamax. These results suggest that the developed composite scaffold possess the essential requisites for their application in the fields of tissue engineering and drug delivery.


Asunto(s)
Materiales Biocompatibles , Carbonato de Calcio/química , Quitina/química , Pectinas/química , Ingeniería de Tejidos , Andamios del Tejido , Animales , Línea Celular , Sistemas de Liberación de Medicamentos , Humanos , Ratones , Microscopía Electrónica de Rastreo , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X
13.
Carbohydr Polym ; 92(2): 1561-5, 2013 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-23399189

RESUMEN

In this work, Hemigraphis alternata extract incorporated chitosan scaffold was synthesized and characterized for wound healing. The antibacterial activity of Hemigraphis incorporated chitosan scaffold (HIC) against Escherichia coli and Staphylococcus aureus was evaluated which showed a reduction in total colony forming units by 45-folds toward E. coli and 25-fold against S. aureus respectively. Cell viability studies using Human Dermal Fibroblast cells (HDF) showed 90% viability even at 48 h when compared to the chitosan control. The herbal scaffold made from chitosan was highly haemostatic and antibacterial. The obtained results were in support that the herbal scaffold can be effectively applied for infectious wounds.


Asunto(s)
Acanthaceae/química , Quitosano/química , Quitosano/farmacología , Hidrogeles/química , Extractos Vegetales/química , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/metabolismo , Materiales Biocompatibles/farmacología , Coagulación Sanguínea/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quitosano/metabolismo , Escherichia coli/efectos de los fármacos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Humanos , Activación Plaquetaria/efectos de los fármacos , Porosidad , Staphylococcus aureus/efectos de los fármacos , Agua/química
14.
Food Chem ; 134(3): 1580-4, 2012 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-25005983

RESUMEN

Spices are rich sources of antioxidants due to the presence of phenols and flavonoids. In this study, the DNA protecting activity and inhibition of nicotine-induced cancer cell migration of 9 spices were analysed. Murine fibroblasts (3T3-L1) and human breast cancer (MCF-7) cells were pre-treated with spice extracts and then exposed to H2O2 and nicotine. The comet assay was used to analyse the DNA damage. Among the 9 spices, ginger, at 50 µg/ml protected against 68% of DNA damage in 3T3-L1 cells. Caraway, cumin and fennel showed statistically significant (p<0.05) DNA protecting activity. Treatment of MCF-7 cells with nicotine induced cell migration, whereas pre-treatment with spices reduced this migration. Pepper, long pepper and ginger exhibited a high rate of inhibition of cell migration. The results of this study prove that spices protect DNA and inhibit cancer cell migration.


Asunto(s)
Movimiento Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Peróxido de Hidrógeno/química , Nicotina/efectos adversos , Extractos Vegetales/química , Especias/análisis , Antioxidantes , Ensayo Cometa , Humanos , Estrés Oxidativo , Extractos Vegetales/farmacología
15.
Nat Prod Res ; 23(16): 1499-506, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19844824

RESUMEN

Isodon wightii is a common plant found in the Western Ghats of South India. The ent-kaurene diterpenoid melissoidesin, isolated from the leaves of I. wightii, showed significant cytotoxicity against lung cancer and neuroblastoma cell lines with IC(50) values of 6 and 4.2 microg mL(-1), respectively. The prevention of deoxyribose degradation activity of melissoidesin was significant and the IC(50) value was calculated to be 163.1 microg mL(-1). The anticarcinogenic activity of melissoidesin by comet assay showed significant DNA damage protecting activity in a dose-dependent manner.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/toxicidad , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/toxicidad , Isodon/química , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/uso terapéutico , Línea Celular Tumoral , Células Cultivadas , Ensayo Cometa , Desoxirribosa/metabolismo , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/uso terapéutico , Humanos , India , Neoplasias Pulmonares/tratamiento farmacológico , Linfocitos/efectos de los fármacos , Estructura Molecular , Neuroblastoma/tratamiento farmacológico , Extractos Vegetales/química , Hojas de la Planta/química
16.
Eur J Med Chem ; 44(5): 2307-12, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-18486995

RESUMEN

A novel series of N-Mannich bases of benzimidazole derivatives were synthesized and characterized by (1)H NMR, IR spectral studies and elemental analysis. The compounds were screened for analgesic and anti-inflammatory activity. 1-((Diethylamino)-methyl)-2-styryl benzimidazole 4 at 40mg/kg was found to be equipotent to paracetamol. 1-((Piperidin-1-yl) methyl)-2-styryl-benzimidazole 6 at 40mg/kg was found to be more potent than Diclofenac. Corneal permeability and quantum chemical calculations were performed to correlate the hydrogen bonding ability with permeability and activity. The energies of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were correlated with pharmacological activity. The semi-empirical PM3 calculations (quantum chemical calculations) revealed that E(LUMO) and energy gap DeltaE were capable of accounting for the high in vitro bovine corneal permeability and activity of the compounds.


Asunto(s)
Bencimidazoles/síntesis química , Permeabilidad de la Membrana Celular , Córnea/metabolismo , Bases de Mannich/síntesis química , Analgésicos/síntesis química , Analgésicos/farmacocinética , Animales , Antiinflamatorios/síntesis química , Antiinflamatorios/farmacocinética , Bencimidazoles/farmacocinética , Bovinos , Evaluación Preclínica de Medicamentos , Enlace de Hidrógeno , Bases de Mannich/farmacocinética , Modelos Moleculares
17.
Nat Prod Res ; 22(8): 681-8, 2008 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-18569709

RESUMEN

The ent kaurene diterpenoid, melissoidesin was isolated from the acetone extract of the leaves of Isodon wightii and the structure was designated as 3beta, 11beta, 15beta-trihydroxy-6alpha-acetoxy-ent-kaur-16-ene based on spectral data and previous reports. Melissoidesin isolated from the acetone extract of leaves showed potent antiacetylcholinesterase activity and the IC(50) value was observed as 215 microg mL(-1). DPPH (1, 1-diphenyl-2-picrylhydrazyl) free radical scavenging activity of melissoidesin was significant and the IC(50) value was 138 microg mL(-1). The significant reducing property of the melissoidesin was stronger in high concentration. IC(50) value of melissoidesin on hydroxyl radicals and metal chelation was observed as 99 and 143 microg mL(-1), respectively. The 50% inhibitory concentration of melissoidesin on lipid peroxidation was calculated as 133 microg mL(-1). These findings indicate that ent kaurene diterpenoid, melissoidesin was promising antiacetylcholinesterase and antioxidant which can be used as food and drug preparations.


Asunto(s)
Antioxidantes/aislamiento & purificación , Inhibidores de la Colinesterasa/aislamiento & purificación , Diterpenos de Tipo Kaurano/aislamiento & purificación , Isodon/química , Antioxidantes/química , Inhibidores de la Colinesterasa/química , Diterpenos de Tipo Kaurano/química , Extractos Vegetales/química , Hojas de la Planta/química
18.
Mol Cell Biochem ; 298(1-2): 69-81, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17136482

RESUMEN

A beta vaccination as a therapeutic intervention of Alzheimer's has many challenges, key among them is the regulation of inflammatory processes concomitant with excessive generation of free radicals seen during such interventions. Here we report the beneficial effects of melatonin on inflammation associated with A beta vaccination in the central and peripheral nervous system of mice. Mice were divided into three groups (n=8 in each): control, inflammation (IA), and melatonin-treated (IAM). The brain, liver, and spleen samples were collected after 5 days for quantitative assessment of plasma lipid peroxides (LPO), an oxidative stress marker, and antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (Gpx). IA group mice have shown the elevated concentration of LPO significantly while there was a reduction at antioxidant enzyme levels. In addition, a significant (P<0.05) reduction in neurotransmitters like dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) was also observed in the IA group mice. Nevertheless, their metabolites, such as homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) increased significantly (P<0.05) as compared to control. Samples were further evaluated at microscopic level to examine the neuropathological changes by immunohistochemical methods. Melatonin treatment effectively reversed these above changes and normalized the LPO and antioxidant enzyme levels (P<0.05). Furthermore, melatonin salvaged the brain cells from inflammation. Our Immunohistochemical findings in the samples of melatonin-treated animals (IAM group) indicated diminished expression of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (Nf kappa B) than those observed in the IA group samples. Our results suggest that administration of melatonin protects inflammation associated with A beta vaccination, through its direct and indirect actions and it can be an effective adjuvant in the development of vaccination in immunotherapy for Alzheimer's disease (AD).


Asunto(s)
Péptidos beta-Amiloides/inmunología , Inflamación/tratamiento farmacológico , Melatonina/uso terapéutico , Vacunación/efectos adversos , Adenosina Trifosfatasas/metabolismo , Animales , Antioxidantes/metabolismo , Astrocitos/citología , Astrocitos/metabolismo , Membrana Celular/efectos de los fármacos , Membrana Celular/enzimología , Cromatografía Líquida de Alta Presión , Ensayo de Inmunoadsorción Enzimática , Proteína Ácida Fibrilar de la Glía/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Melatonina/farmacología , Ratones , FN-kappa B/metabolismo , Neocórtex/citología , Neocórtex/efectos de los fármacos , Neurotransmisores/análisis , Especies Reactivas de Oxígeno/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
19.
Free Radic Res ; 39(6): 603-12, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16036338

RESUMEN

The major pathological ramification of Alzheimer's disease (AD) is accumulation of beta-Amyloid (Abeta) peptides in the brain. An emerging therapeutic approach for AD is elimination of excessive Ass peptides and preventing its re-accumulation. Immunization is the most effective strategy in removing preexisting cerebral Abetas and improving the cognitive capacity as shown in transgenic mice model of AD. However, active immunization is associated with adverse effect such as encephalitis with perivascular inflammation and hemorrhage. Details about the mechanistic aspects of propagation of these toxic effects are matter of intense enquiry as this knowledge is essential for the understanding of the AD pathophysiology. The present work aimed to study the oxidative vulnerability in the plasma, liver and brain of the inflammation-induced rats subjected to Ass immunization. Induction of inflammation was performed by subcutaneous injection of 0.5?ml of 2% silver nitrate. Our present result shows that the proinflammatory cytokines such as IL1alpha and TNFalpha are increased significantly in the inflammation-induced, Abeta1-42, Abeta25-35 treated groups and inflammation with Abeta25-35 treated group when compared to control, complete Freund's adjuvant and Abeta35-25 treated groups. These increased proinflammatory cytokines concurrently releases significant amount of free radicals in the astrocytes of respected groups. The present result shows that nitric oxide (NO) level was significantly higher (P<0.001) in plasma, liver and brain of the rat subjected to inflammation, Abeta1-42, Abeta25-35 and inflammation with Abeta25-35 injected groups when compared to control. The increased level of lipid peroxides (LPO) (P<0.001) and decreased antioxidant status (P<0.05) were observed in the plasma, liver and brain of inflammation-induced group when compared to control. Our result shows that significant oxidative vulnerability was observed in the inflammation with Ass treated rats when compared to other groups. Based on our results, we suggest that immunization of AD patients with Ass should be done with caution as the increase in Ass could trigger the brain inflammation in uncontrollable level.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Modelos Animales de Enfermedad , Fragmentos de Péptidos/metabolismo , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/genética , Animales , Ácido Ascórbico/metabolismo , Astrocitos/metabolismo , Encéfalo/metabolismo , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Inflamación/genética , Inflamación/metabolismo , Interleucina-1/metabolismo , Peroxidación de Lípido , Hígado/metabolismo , Óxido Nítrico/metabolismo , Oxidación-Reducción , Fragmentos de Péptidos/genética , Ratas , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
20.
Biomaterials ; 23(14): 2841-7, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12069323

RESUMEN

Collagen, a unique connective tissue protein finds extensive application as biocompatible biomaterial in wound healing, as drug carriers, cosmetics, etc. A study has been undertaken to stabilise Type-I collagen of rat-tail tendon using plant polyphenol (Acacia Mollissima) in the presence of an acrylic polymer. It has been found that collagen fibres pre-treated with acrylic polymer followed by the treatment with Acacia Mollissima exhibited an increase in hydrothermal stability by 25 degrees C. Infrared spectroscopic studies display the changes in the spectral characteristics of native and treated collagen films. Transmission electron microscopic and circular dichroic studies provide an insight into the understanding of the improved stabilisation of collagen, due to treatment with acrylic polymer and plant polyphenols. The study is expected to enhance the biomaterial applications of collagen tissues.


Asunto(s)
Colágeno Tipo I/química , Flavonoides , Mimosa/química , Fenoles/química , Polímeros/química , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/metabolismo , Dicroismo Circular , Colágeno Tipo I/metabolismo , Colágeno Tipo I/ultraestructura , Estructura Molecular , Fenoles/metabolismo , Extractos Vegetales/química , Polímeros/metabolismo , Polifenoles , Ratas , Ratas Sprague-Dawley , Espectroscopía Infrarroja por Transformada de Fourier , Taninos/química , Temperatura
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