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1.
Chem Biol Interact ; 347: 109599, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34343525

RESUMO

BACKGROUND: Geraniol, a natural monoterpene, is a component of many plant essential oils. It contains many medicinal and pharmacological properties. Doxorubicin is an anticancer drug; however, its clinical usage is limited due to its cumulative and dose-dependent cardiotoxicity. This study investigates geraniol as a protective agent against doxorubicin-induced cardiotoxicity and explores possible underlying mechanisms of action. METHODS: Male Sprague-Dawley rats were allocated into five groups. Groups 1 and 2 were administered saline and geraniol 200 mg/kg/day/orally, respectively, for 15 days. Group 3 was administered intraperitoneal doxorubicin (5 mg/kg/IP on the 5th, 10th and 15th days to achieve a cumulative dose of 15 mg/kg) to induce cardiotoxicity. The fourth and fifth groups were treated with either geraniol 100 mg/kg or 200 mg/kg orally and doxorubicin to equal the doxorubicin dose administered to Group 3. RESULTS: Treatment with geraniol significantly ameliorated cardiac damage and restored serum cardiac injury marker levels in doxorubicin treated animals. Geraniol upregulated Nrf2 and HO-1 expression, elevated total antioxidant capacity, decreased the nuclear accumulation of kappa-light-chain enhancer of activated B cells (NF-κB), decreased the phosphorylation and degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), suppressed tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin-18 (IL-18) levels, and restored the levels of Bax and caspase-3 and 9 in heart tissue. CONCLUSION: Geraniol may function as a potential activator of nuclear factor erythroid 2-related factor 2 (Nrf2), which subsequently improves Nrf2-dependent antioxidative signaling, diminishes apoptosis and subdues the inflammatory response. The downstream result is protection of the heart from doxorubicin-induced cardiotoxicity.


Assuntos
Monoterpenos Acíclicos/uso terapêutico , Cardiotônicos/uso terapêutico , Cardiotoxicidade/tratamento farmacológico , Cymbopogon/química , Doxorrubicina/toxicidade , Transdução de Sinais/efeitos dos fármacos , Animais , Cardiotoxicidade/patologia , Eletrocardiografia/efeitos dos fármacos , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Heme Oxigenase (Desciclizante)/metabolismo , Masculino , Mitocôndrias/efeitos dos fármacos , Miocárdio/patologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley
2.
Colloids Surf B Biointerfaces ; 206: 111935, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34252691

RESUMO

Silver nanoparticles (AgNPs) could be employed in the combat against COVID-19, yet are associated with toxicities. In this study, biogenic and biocompatible AgNPs using the agro-waste, non-edible Hibiscus sabdariffa stem were synthesized. Under optimized reaction conditions, synthesized green AgNPs were crystalline, face cubic centered, spherical with a diameter of around 17 nm and a surface charge of -20 mV. Their murine lethal dose 50 (LD50) was 4 folds higher than the chemical AgNPs. Furthermore, they were more murine hepato- and nephro-tolerated than chemical counterparts due to activation of Nrf-2 and HO-1 pathway. They exerted an apoptotic anti-ovarian cancer activity with IC50 value 6 times more than the normal cell line. Being functionalized with polydopamine and conjugated to either moxifloxacin or gatifloxacin, the conjugates exerted an augmented antibiofilm activity against Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii biofilms that was significantly higher than antibiotic alone or functionalized AgNPs suggesting a synergistic activity. In conclusion, this study introduced a facile one-pot synthesis of biogenic and biocompatible AgNPs with preferential anti-cancer activity and could be utilized as antibiotic delivery system for a successful eradication of Gram-negative biofilms.


Assuntos
Antibacterianos , Nanopartículas Metálicas , Prata , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Química Verde , Hibiscus , Indóis , Camundongos , Testes de Sensibilidade Microbiana , Polímeros , Prata/farmacologia
3.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200144

RESUMO

Natural products have been extensively used for treating a wide variety of disorders. In recent times, Brucine (BRU) as one of the natural medications extracted from seeds of nux vomica, was investigated for its anticancer activity. As far as we know, this is the first study on BRU anticancer activity against skin cancer. Thus, the rational of this work was implemented to develop, optimize and characterize the anticancer activity of BRU loaded ethosomal gel. Basically, thin film hydration method was used to formulate BRU ethosomal preparations, by means of Central composite design (CCD), which were operated to construct (32) factorial design. Two independent variables were designated (phospholipid percentage and ethanol percentage) with three responses (vesicular size, encapsulation efficiency and flux). Based on the desirability function, one formula was selected and incorporated into HPMC gel base to develop BRU loaded ethosomal gel. The fabricated gel was assessed for all physical characterization. In-vitro release investigation, ex-vivo permeation and MTT calorimetric assay were performed. BRU loaded ethosomal gel exhibited acceptable values for the characterization parameters which stand proper for topical application. In-vitro release investigation was efficiently prolonged for 6 h. The flux from BRU loaded ethosome was enhanced screening optimum SSTF value. Finally, in-vitro cytotoxicity study proved that BRU loaded ethosomal gel significantly improved the anticancer activity of the drug against A375 human melanoma cell lines. Substantially, the investigation proposed a strong motivation for further study of the lately developed BRU loaded ethosomal gel as a prospective therapeutic strategy for melanoma treatment.


Assuntos
Etanol/química , Géis/química , Pele/efeitos dos fármacos , Estricnina/análogos & derivados , Administração Cutânea , Animais , Géis/administração & dosagem , Masculino , Fosfolipídeos/química , Ratos , Ratos Wistar , Absorção Cutânea/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Estricnina/administração & dosagem , Estricnina/química
4.
Braz J Microbiol ; 52(2): 627-638, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33686563

RESUMO

BACKGROUND: Serratia marcescens becomes an apparent nosocomial pathogen and causes a variety of infections. S. marcescens possess various virulence factors that are regulated by intercellular communication system quorum sensing (QS). Targeting bacterial virulence is a proposed strategy to overcome bacterial resistance. Sitagliptin anti-QS activity has been demonstrated previously and we aimed in this study to investigate the effects of antidiabetic drugs vildagliptin and metformin compared to sitagliptin on S. marcescens pathogenesis. METHODS: We assessed the effects of tested drugs in subinhibitory concentrations phenotypically on the virulence factors and genotypically on the virulence encoding genes' expressions. The protection of tested drugs on S. marcescens pathogenesis was performed in vivo. Molecular docking study has been conducted to evaluate the interference capabilities of tested drugs to the SmaR QS receptor. RESULTS: Vildagliptin reduced the expression of virulence encoding genes but did not show in vitro or in vivo anti-virulence activities. Metformin reduced the expression of virulence encoding genes and inhibited bacterial virulence in vitro but did not show in vivo protection. Sitagliptin significantly inhibited virulence factors in vitro, reduced the expression of virulence factors and protected mice from S. marcescens. Docking study revealed that sitagliptin is more active than metformin and fully binds to SmaR receptor, whereas vildagliptin had single interaction to SmaR. CONCLUSION: The downregulation of virulence genes was not enough to show anti-virulence activities. Hindering of QS receptors may play a crucial role in diminishing bacterial virulence.


Assuntos
Antibacterianos/farmacologia , Reposicionamento de Medicamentos , Hipoglicemiantes/farmacologia , Infecções por Serratia/tratamento farmacológico , Serratia marcescens/efeitos dos fármacos , Animais , Antibacterianos/química , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Feminino , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Hipoglicemiantes/química , Metformina/química , Metformina/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Infecções por Serratia/microbiologia , Serratia marcescens/genética , Serratia marcescens/patogenicidade , Serratia marcescens/fisiologia , Vildagliptina/química , Vildagliptina/farmacologia , Virulência/efeitos dos fármacos , Fatores de Virulência/química , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
6.
Polymers (Basel) ; 13(4)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672981

RESUMO

BACKGROUND: Curcumin (Cur) possesses a variety of beneficial pharmacological properties including antioxidant, antimicrobial, anti-cancer and anti-inflammatory activities. Nevertheless, the low aqueous solubility and subsequent poor bioavailability greatly limits its effectiveness. Besides, the role of myrrh oil as an essential oil in treating inflammatory disorders has been recently demonstrated. The objective of the current investigation is to enhance Cur efficacy via developing Cur nanoemulgel, which helps to improve its solubility and permeability, for transdermal delivery. METHODS: The formulated preparations (Cur gel, emulgel and nanoemulgel) were evaluated for their physical appearance, spreadability, viscosity, particle size, in vitro release and ex vivo drug permeation studies. The in vivo anti-inflammatory activity was estimated using the carrageenan-induced rat hind paw edema method. RESULTS: The formulated Cur-loaded preparations exhibited good physical characteristics that were in the acceptable range of transdermal preparations. The release of Cur from gel, emulgel and nanoemulgel after 12 h was 72.17 ± 3.76, 51.93 ± 3.81 and 62.0 ± 3.9%, respectively. Skin permeation of Cur was significantly (p < 0.05) improved when formulated into nanoemulgel since it showed the best steady state transdermal flux (SSTF) value (108.6 ± 3.8 µg/cm2·h) with the highest enhancement ratio (ER) (7.1 ± 0.2). In vivo anti-inflammatory studies proved that Cur-loaded nanoemulgel displayed the lowest percent of swelling (26.6% after 12 h). CONCLUSIONS: The obtained data confirmed the potential of the nanoemulgel dosage form and established the synergism of myrrh oil and Cur as an advanced anti-inflammatory drug.

7.
Trop Doct ; 51(1): 40-44, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33050839

RESUMO

Coagulase-negative staphylococci (CoNS) are frequently isolated from wound infections. There are limited data examining the prevalence of methicillin-resistant CoNS (MRCoNS) among Egyptian patients after surgery. Thus, we studied 208 hospitalised patients, who had skin and soft tissue infections (SSTIs) due to various causes. Samples were cultured for isolation and identification of CoNS and isolates were screened for susceptibility against 23 different antimicrobials. Out of 241 Staphylococcal isolates, 114 (47.3%) were CoNS. The prevalence of MRCoNS among surgical site infection, diabetic foot, abscess, and burn patients was 13.4%, 11.5%, 15.6%, and 10.3%, respectively. The lowest resistance of the 27 identified MRCoNS isolates was to vancomycin, amikacin and gatifloxacin (7% each). We conclude that CoNS isolates are major pathogens associated with wound infections at our institution and MRCoNS probably poses a substantial threat for patients in Egypt, though most MRCoNS isolates demonstrated susceptibility to vancomycin.


Assuntos
Coagulase/deficiência , Resistência a Meticilina , Infecções Estafilocócicas/microbiologia , Staphylococcus/isolamento & purificação , Infecção da Ferida Cirúrgica/microbiologia , Antibacterianos/farmacologia , Egito/epidemiologia , Humanos , Resistência a Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Prevalência , Infecções Estafilocócicas/epidemiologia , Staphylococcus/efeitos dos fármacos , Staphylococcus/enzimologia , Infecção da Ferida Cirúrgica/epidemiologia
8.
Nanomaterials (Basel) ; 10(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33008104

RESUMO

The purpose of this study was to fabricate biostable inorganic silver nanoparticles (AgNPs) using fresh peel (aqueous) extract of Benincasa hispida. A fast, robust, and eco-friendly approach was used for the synthesis of AgNPs, where bioactive components of peel extract of B. hispida acted as reducing and stabilizing agents. Synthesized AgNPs were characterized using a UV-Vis spectrophotometer, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and electron microscopy. The synthesized nanoparticles exhibited maximum absorption at 418 nm under the typical AgNPs surface plasmon resonance band range. They depicted a mean size of 26 ± 2 nm with a spherical shape. Their therapeutic prospective was determined by evaluating their antimicrobial and anticancer potential. The bio-synthesized silver nanoparticles exhibited strong antimicrobial activity with minimum inhibitory concentration (MIC 50) values of 14.5, 8.6, 6.063, and 13.4 µg/mL against Staphylococcus aureus (ATCC 25923), Micrococcus luteus (ATCC 14593), Escherichia coli (ATCC 25922), and Klebsiella pneumonia (ATCC 13883), respectively. The biosynthesized AgNPs showed potent in vitro cytotoxicity against human cervical cancer cell line with a half maximal inhibitory concentration (IC50) value of 0.066 µg/mL; however, no cytotoxic effect was observed on normal human primary osteoblasts cell line. This study explored B. hispida extract and confirmed its effectiveness as a promising source in producing AgNPs that could be employed for several therapeutic applications.

9.
Naunyn Schmiedebergs Arch Pharmacol ; 392(12): 1591-1604, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31367864

RESUMO

Hepatocellular carcinoma (HCC) is characterized by bad prognosis and is the second most common reason for cancer-linked mortality. Treatment with sorafenib (SRF) alone increases patient survival by only a few months. A causal link has been determined between angiotensin II (Ang-II) and HCC. However, the mechanisms underlying the tumorigenic effects of Ang-II remain to be elucidated. N-Nitrosodiethylamine was utilized to examine the effects of telmisartan (TEL) (15 mg/kg), SRF (30 mg/kg), and a combination of these two agents on HCC mice. Downregulation of NF-кBP65 mRNA expression and inhibition of the phosphorylation-induced activation of both ERK1/2 and NF-кB P65 were implicated in the anti-tumor effects of TEL and SRF. Consequent regression of malignant changes and improvements in liver function associated with reduced levels of AFP, TNF-α, and TGF-ß1 were also confirmed. Anti-proliferative, anti-metastatic, and anti-angiogenic effects of treatment were indicated by reduced hepatic cyclin D1 mRNA expression, reduced MMP-2 levels, and reduced VEGF levels, respectively. TEL, but not SRF, demonstrated agonistic activity for PPARγ receptors, as evidenced by increased PPARγ DNA binding activity, upregulation of CD36, and HO-1 mRNA expression followed by increased liver antioxidant capacity. Both TEL and SRF inhibited TAK1 phosphorylation-induced activation, indicating that TAK1 might act as a central mediator in the interaction between ERK1/2 and NF-кB. TEL, by modulating the ERK1/2, TAK1, and NF-кB signaling axis in the context of PPARγ agonistic activity, exerted anti-tumor effects and increased tumor sensitivity to SRF. Therefore, TEL is an encouraging agent for further clinical trials regarding the management of HCC.


Assuntos
Anti-Hipertensivos/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Telmisartan/uso terapêutico , Animais , Anti-Hipertensivos/farmacologia , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Dietilnitrosamina , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , MAP Quinase Quinase Quinases/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , PPAR gama/metabolismo , Telmisartan/farmacologia , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
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