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1.
Curr Microbiol ; 81(8): 262, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981879

RESUMO

The vast dissemination of resistance to different antibiotics among bacterial pathogens, especially foodborne pathogens, has drawn major research attention. Thus, many attempts have been made to reveal novel alternatives to the current antibiotics. Due to their variable pharmacologically active phytochemicals, plants represent a good solution for this issue. This study investigated the antibacterial potential of Kumquat or Fortunella japonica methanol extract (FJME) against Salmonella typhimurium clinical isolates. Gas chromatography coupled with mass spectrometry (GC/MS) characterized 39 compounds in FJME. Palmitic acid (15.386%) and cis-vaccenic acid (15.012%) are the major active constituents detected by GC/MS. Remarkably, FJME had minimum inhibitory concentrations from 128 to 512 µg/mL in vitro. In addition, a systemic infection model revealed the in vivo antibacterial action of FJME. The antibacterial therapeutic activity of FJME was noticed by improving the histological features of the liver and spleen. Moreover, there was a perceptible lessening (p < 0.05) of the levels of the oxidative stress markers (nitric oxide and malondialdehyde) using ELISA. In addition, the gene expression of the proinflammatory cytokine (interleukin 6) was downregulated. On the other hand, there was an upregulation of the anti-inflammatory cytokine (interleukin 10). Accordingly, future clinical investigations should be done to reveal the potential antibacterial action of FJME on other food pathogens.


Assuntos
Antibacterianos , Frutas , Testes de Sensibilidade Microbiana , Extratos Vegetais , Salmonella typhimurium , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Salmonella typhimurium/efeitos dos fármacos , Antibacterianos/farmacologia , Frutas/microbiologia , Frutas/química , Animais , Camundongos , Infecções por Salmonella/microbiologia , Infecções por Salmonella/tratamento farmacológico
2.
Microb Cell Fact ; 22(1): 83, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37106372

RESUMO

Various factors contribute to the development of the acute inflammation process, like the pro-inflammatory cytokines, certain enzymes as well as oxidative stress mediators. The anti-inflammatory potential of the endophytic fungus Penicillium brefeldianum was explored in carrageenan-induced inflammation in rats. After isolation of the fungus from Acalypha hispida leaves, it was identified by 18S rRNA gene sequencing. Then, its phytochemical profile was elucidated using LC-ESI-MS/MS technique. There was a remarkable decrease in the edema weight in the endophytic fungi-treated group (200 mg/kg). Also, this group had few inflammatory cells and thickened epidermis with underlying moderate collagenosis when stained with haematoxylin and eosin. Besides, immunostaining with monoclonal antibodies of cyclooxygenase-2 and tumor necrosis factor alpha showed a decrease in the positive immune cells in the endophytic fungi treated group (200 mg/kg) in relation to the positive control. Interestingly, the levels of the inflammatory as well as oxidative stress markers, including prostaglandin E2, nitric oxide, and malondialdehyde, which are hallmarks of the inflammatory process, considerably diminished (p < 0.05) in this group. qRT-PCR was utilised to elucidate the impact of the endophytic fungi treatment on the expression of interleukins (IL-1ß and IL-6) genes, which decreased in comparison with the positive control group. Consequently, we can deduce that P. brefeldianum endophytic fungus has a promising anti-inflammatory potential and should be extensively studied on a broader range in the near future.


Assuntos
Penicillium , Espectrometria de Massas em Tandem , Ratos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Compostos Fitoquímicos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
3.
Bioorg Chem ; 140: 106789, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37611530

RESUMO

Adopting the molecular overlay approach, three novel sets of thiazepinopurines with expected cytotoxicity and CDK2 inhibition potential were designed and synthesized. This was accomplished through the heteroannelation of purines, for the first time, with thiazepine. The obtained thiazepinopurines derivatives were assessed for their cytotoxicity toward tumor cells of three different types, HepG2, MCF-7, and PC-3 as well as one normal cell (WI38). Among the studied compounds, 3b and 3c exhibited significant antiproliferative activity against tumor cells presenting IC50 range of 5.52-17.09 µM in comparison with Roscovitine (9.32-13.82 µM). Additionally, both compounds displayed superior selectivity indices (SI = 3.00-7.15) toward tested cancer cells. The 4-chlorophenyl analog 3b has shown the best selectivity index, and hence it has been subjected to additional investigations to determine its proper mechanistic effect. Accordingly, the CDK2 inhibition potential, apoptosis induction, and cell cycle analysis of MCF-7 were evaluated. Results revealed that this analog displayed a potent CDK2 inhibition potential with an IC50 value of 0.219 µM. Findings also showed that 3b was thought to arrest MCF-7 cell cycle at S phase together with apoptosis induction by the increased expression of Bax, Caspase-8, and -9 markers with a concomitant decrease in Bcl-2 expression. Besides, the probable interaction of 3b with CDK2 binding pocket was investigated by molecular docking.


Assuntos
Tiazepinas , Humanos , Simulação de Acoplamento Molecular , Morte Celular , Células MCF-7 , Tiazepinas/farmacologia , Quinase 2 Dependente de Ciclina
4.
Mar Drugs ; 21(9)2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37755072

RESUMO

Currently, there is growing interest in exploring natural bioactive compounds with anti-inflammatory potential to overcome the side effects associated with the well-known synthetic chemicals. Algae are a rich source of bioactive molecules with numerous applications in medicine. Herein, the anti-inflammatory effect of Ulva intestinalis alone or selenium nanoparticles loaded with U. intestinalis (UISeNPs), after being fully characterized analytically, was investigated by a carrageenan-induced inflammation model. The pretreated groups with free U. intestinalis extract (III and IV) and the rats pretreated with UISeNPs (groups V and VI) showed significant increases in the gene expression of Keap1, with fold increases of 1.9, 2.27, 2.4, and 3.32, respectively. Similarly, a remarkable increase in the Nrf2 gene expression, with 2.09-, 2.36-, 2.59-, and 3.7-fold increases, was shown in the same groups, respectively. Additionally, the groups III, IV, V, and VI revealed a significantly increased HO-1 gene expression with a fold increase of 1.48, 1.61, 1.87, and 2.84, respectively. Thus, both U. intestinalis extract and the UISeNPs boost the expression of the cytoprotective/antioxidant pathway Keap1/Nrf2/HO-1, with the UISeNPs having the upper hand over the free extract. In conclusion, U. intestinalis and UISeNPs have proven promising anti-inflammatory activity through mediating different underlying mechanisms.


Assuntos
Nanopartículas , Selênio , Ulva , Animais , Ratos , Selênio/farmacologia , Antioxidantes/farmacologia , Carragenina/toxicidade , Fator 2 Relacionado a NF-E2 , Proteína 1 Associada a ECH Semelhante a Kelch , Edema
5.
Molecules ; 28(15)2023 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-37570884

RESUMO

Rheumatoid arthritis (RA) remains one of the most prevalent autoimmune diseases worldwide. Janus kinase 3 (JAK3) is an essential enzyme for treating autoimmune diseases, including RA. Molecular modeling techniques play a crucial role in the search for new drugs by reducing time delays. In this study, the 3D-QSAR approach is employed to predict new JAK3 inhibitors. Two robust models, both field-based with R2 = 0.93, R = 0.96, and Q2 = 87, and atom-based with R2 = 0.94, R = 0.97, and Q2 = 86, yielded good results by identifying groups that may readily direct their interaction. A reliable pharmacophore model, DHRRR1, was provided in this work to enable the clear characterization of chemical features, leading to the design of 13 inhibitors with their pIC50 values. The DHRRR1 model yielded a validation result with a ROC value of 0.87. Five promising inhibitors were selected for further study based on an ADMET analysis of their pharmacokinetic properties and covalent docking (CovDock). Compared to the FDA-approved drug tofacitinib, the pharmaceutical features, binding affinity and stability of the inhibitors were analyzed through CovDock, 300 ns molecular dynamics simulations, free energy binding calculations and ADMET predictions. The results show that the inhibitors have strong binding affinity, stability and favorable pharmaceutical properties. The newly predicted molecules, as JAK3 inhibitors for the treatment of RA, are promising candidates for use as drugs.


Assuntos
2-Aminopurina , Antirreumáticos , Desenho Assistido por Computador , Desenho de Fármacos , Janus Quinase 3 , Inibidores de Janus Quinases , 2-Aminopurina/análogos & derivados , 2-Aminopurina/farmacologia , Inibidores de Janus Quinases/química , Inibidores de Janus Quinases/farmacologia , Janus Quinase 3/antagonistas & inibidores , Relação Quantitativa Estrutura-Atividade , Piperidinas/química , Piperidinas/farmacologia , Pirimidinas/química , Pirimidinas/farmacologia , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/química , Antirreumáticos/farmacologia , Farmacóforo
6.
Molecules ; 28(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37446770

RESUMO

In this study, we examined the sub-acute toxicity of quercetin and ferulic acid and evaluated their effects on protein, cholesterol, and estrogen levels in vivo. Six groups of female Wistar rats were fed by gavage. The first and second groups represent the positive (Clomiphene citrate 10 mg/kg) and negative (NaCl 0.9%) control groups, while the other groups received quercetin and ferulic acid at doses of 5 and 10 mg/kg/day for 28 days. The sub-acute toxicity was monitored by examining the weights, biochemical parameters (AST, ALT, ALP, urea, and CREA), and histological changes in the kidneys and liver of the treated animals. Furthermore, the in vivo estrogenic effects were studied in terms of the serum and ovarian cholesterol levels, serum estradiol, and uterine proteins. Finally, Docking studies were conducted to evaluate the binding affinity of quercetin and ferulic acid for alpha and beta estrogen receptors. Results showed that both compounds were devoid of any signs of nephrotoxicity or hepatotoxicity. Additionally, quercetin and ferulic acid caused significant estrogenic effects evidenced by an increase of 8.7 to 22.48% in serum estradiol, though to a lesser amount than in the reference drug-treated group (64.21%). Moreover, the two compounds decreased the serum cholesterol levels (12.26-32.75%) as well as the ovarian cholesterol level (11.9% to 41.50%) compared to the negative control. The molecular docking in estrogen alpha and estrogen beta active sites showed high affinity of quercetin (-10.444 kcal/mol for estrogen alpha and -10.662 kcal/mol for estrogen beta) and ferulic acid (-6.377 kcal/mol for estrogen alpha and -6.3 kcal/mol for estrogen beta) to these receptors. This study provides promising insights into the potential use of quercetin as a therapeutic agent for the management of female fertility issues.


Assuntos
Estrogênios , Quercetina , Ratos , Animais , Feminino , Quercetina/farmacologia , Ratos Wistar , Simulação de Acoplamento Molecular , Estrona , Estradiol , Colesterol
7.
Molecules ; 28(5)2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36903587

RESUMO

In the emerging field of nanomedicine, nanoparticles have been widely considered as drug carriers and are now used in various clinically approved products. Therefore, in this study, we synthesized superparamagnetic iron-oxide nanoparticles (SPIONs) via green chemistry, and the SPIONs were further coated with tamoxifen-conjugated bovine serum albumin (BSA-SPIONs-TMX). The BSA-SPIONs-TMX were within the nanometric hydrodynamic size (117 ± 4 nm), with a small poly dispersity index (0.28 ± 0.02) and zeta potential of -30.2 ± 0.09 mV. FTIR, DSC, X-RD, and elemental analysis confirmed that BSA-SPIONs-TMX were successfully prepared. The saturation magnetization (Ms) of BSA-SPIONs-TMX was found to be ~8.31 emu/g, indicating that BSA-SPIONs-TMX possess superparamagnetic properties for theragnostic applications. In addition, BSA-SPIONs-TMX were efficiently internalized into breast cancer cell lines (MCF-7 and T47D) and were effective in reducing cell proliferation of breast cancer cells, with IC50 values of 4.97 ± 0.42 µM and 6.29 ± 0.21 µM in MCF-7 and T47D cells, respectively. Furthermore, an acute toxicity study on rats confirmed that these BSA-SPIONs-TMX are safe for use in drug delivery systems. In conclusion, green synthesized superparamagnetic iron-oxide nanoparticles have the potential to be used as drug delivery carriers and may also have diagnostic applications.


Assuntos
Nanopartículas de Magnetita , Nanopartículas , Neoplasias , Humanos , Ratos , Animais , Nanopartículas de Magnetita/química , Células MCF-7 , Nanopartículas Magnéticas de Óxido de Ferro , Portadores de Fármacos , Nanopartículas/química , Ferro , Óxidos
8.
Molecules ; 29(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38202676

RESUMO

Cannabis is considered (Cannabis sativa L.) a sacred herb in many countries and is vastly employed in traditional medicine to remedy numerous diseases, such as diabetes. This research investigates the chemical composition of the aqueous extracts from Cannabis sativa L. seeds. Furthermore, the impact of these extracts on pancreatic α-amylase and lipase, and intestinal α-glucosidase enzymes is evaluated, as well as their antihyperglycemic effect. Analysis of the chemical composition of the aqueous extract was conducted using high-performance liquid chromatography with a photodiode array detector (HPLC-DAD). In contrast, the ethanol, hexanic, dichloromethane, and aqueous extract compositions have been established. Additionally, the inhibitory effects of ethanolic, dichloromethane, and aqueous extracts on pancreatic α-amylase and lipase, and intestinal α-glucosidase activities were evaluated in vitro and in vivo. The results of HPLC analysis indicate that the most abundant phenolic compound in the aqueous cannabis seed extract is 3-hydroxycinnamic acid, followed by 4-hydroxybenzoic acid and rutin acid. Moreover, administration of ethanolic and aqueous extracts at a dose of 150 mg/Kg significantly suppressed postprandial hyperglycemia compared to the control group; the ethanolic, dichloromethane, and aqueous extracts significantly inhibit pancreatic α-amylase and lipase, and intestinal α-glucosidase in vitro. The pancreatic α-amylase test exhibited an inhibition with IC50 values of 16.36 ± 1.24 µg/mL, 19.33 ± 1.40 µg/mL, 23.53 ± 1.70 µg/mL, and 17.06 ± 9.91 µg/mL for EAq, EDm, EET, and EHx, respectively. EET has the highest inhibitory capacity for intestinal α-glucosidase activity, with an IC50 of 32.23 ± 3.26 µg/mL. The extracts inhibit porcine pancreatic lipase activity, demonstrating their potential as lipase inhibitors. Specifically, at a concentration of 1 mg/mL, the highest inhibition rate (77%) was observed for EDm. To confirm these results, the inhibitory effect of these extracts on enzymes was tested in vivo. The oral intake of aqueous extract markedly reduced starch- and sucrose-induced hyperglycemia in healthy rats. Administration of the ethanolic extract at a specific dose of 150 mg/kg significantly reduced postprandial glycemia compared with the control group. It is, therefore, undeniable that cannabis extracts represent a promising option as a potentially effective treatment for type 2 diabetes.


Assuntos
Cannabis , Diabetes Mellitus Tipo 2 , Alucinógenos , Hiperglicemia , Animais , Ratos , Suínos , Hipoglicemiantes/farmacologia , alfa-Amilases Pancreáticas , alfa-Glucosidases , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cloreto de Metileno , Lipase , Hiperglicemia/tratamento farmacológico , Agonistas de Receptores de Canabinoides , Etanol , Extratos Vegetais/farmacologia
9.
Saudi Pharm J ; 31(9): 101727, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37638219

RESUMO

In the past, curcumin was the go-to medication for diabetes, but recent studies have shown that tetrahydrocurcumin is more effective. The problem is that it's not very soluble in water or very bioavailable. So, our research aims to increase the bioavailability and anti-diabetic efficacy of tetrahydrocurcumin in streptozotocin-induced diabetic rats by synthesizing tetrahydrocurcumin-loaded solid lipid nanoparticles. Box Behnken Design was employed for the optimization of tetrahydrocurcumin-loaded solid lipid nanoparticles (THC-SLNs). The optimal formulation was determined by doing an ANOVA to examine the relationship between the independent variables (drug-to-lipid ratio, surfactant concentration, and co-surfactant concentration) and the dependent variables (particle size, percent entrapment efficiency, and PDI). Particle size, PDI, and entrapment efficiency all showed statistical significance based on F-values and p-values. The optimized batch was prepared using a drug-to-lipid ratio (1:4.16), 1.21% concentration of surfactant, and 0.4775% co-surfactant (observed with a particle size of 147.1 nm, 83.58 ± 0.838 % entrapment efficiency, and 0.265 PDI, and the values were found very close with the predicted ones. As the THC peak vanishes from the DSC thermogram of the improved formulation, this indicates that the drug has been transformed from its crystalline form into its amorphous state. TEM analysis of optimized formulation demonstrated mono-dispersed particles with an average particle size of 145 nm which are closely related to zetasizer's results. In-vitro release study of optimized formulation demonstrated burst release followed by sustained release up to 71.04% throughout 24 hrs. Increased bioavailability of the adjusted THC-SLN was found in an in vivo pharmacokinetics research with 9.47 folds higher AUC(0-t) compared to plain THC-suspension. Additionally, pharmacodynamic experiments of optimized formulation demonstrated a marked decrease in blood glucose level to 63.7% and increased body weight from 195.8 ± 7.223 to 231.2 ± 7.653 on the 28th day of the study and showed a better anti-diabetic effect than plain drug suspension. Results of stability studies revealed that formulation can be stored for longer periods at room temperature. Tetrahydrocurcumin can be effectively administered by SLN for the treatment of diabetes.

10.
Int J Mol Sci ; 23(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36293055

RESUMO

The increasing prevalence of obesity has become a demanding issue in both high-income and low-income countries. Treating obesity is challenging as the treatment options have many limitations. Recently, diet modification has been commonly applied to control or prevent obesity and its risks. In this study, we investigated novel therapeutic approaches using a combination of a potential probiotic source with prebiotics. Forty-eight adult male Sprague-Dawley rats were selected and divided into seven groups (eight rats per group). The first group was fed a high-fat diet, while the second group was a negative control. The other five groups were orally administered with a probiotic, Lactiplantibacillus plantarum (L. plantarum), and potential prebiotics sources (chia seeds, green tea, and chitosan) either individually or in combination for 45 days. We collected blood samples to analyze the biochemical parameters and dissected organs, including the liver, kidney, and pancreas, to evaluate obesity-related injuries. We observed a more significant decrease in the total body weight by combining these approaches than with individual agents. Moreover, treating the obese rats with this combination decreased serum catalase, superoxide dismutase, and liver malondialdehyde levels. A histopathological examination revealed a reduction in obesity-related injuries in the liver, kidney, and pancreas. Further docking studies indicated the potential role of chia seeds and green tea components in modulating obesity and its related problems. Therefore, we suggest that the daily administration of a pre- and probiotic combination may reduce obesity and its related problems.


Assuntos
Quitosana , Hiperlipidemias , Ratos , Masculino , Animais , Chá , Catalase , Quitosana/farmacologia , Quitosana/uso terapêutico , Ratos Sprague-Dawley , Obesidade/tratamento farmacológico , Obesidade/patologia , Dieta Hiperlipídica/efeitos adversos , Sementes , Inflamação/tratamento farmacológico , Superóxido Dismutase , Malondialdeído
11.
Molecules ; 27(13)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35807240

RESUMO

Ethnobotanical studies have reported the traditional medicinal uses of Acacia senegal (L.) Willd. and Argania spinosa (L.) Skeels against kidney stone formation and other chronic kidney diseases. The present work is undertaken to study the litholytic activity and the inhibiting activity of calcium oxalate crystallization by bioactive compounds identified in Argania spinosa (L.) Skeels press-cake (residue of Argan oil) and in Acacia senegal (L.) Willd. The litholytic activity was studied in vitro on cystine and uric acid stones using a porous bag and an Erlenmeyer glass. The study of the inhibiting activity of calcium oxalate crystallization, was based on temporal measurements of the optical density, registered at a 620 nm wavelength for 30 min using an ultraviolet−visible spectrophotometer. The silylation method was performed to identify phytochemicals, followed by gas chromatography coupled with mass spectrophotometry (GC/MS) analysis. The results show significant litholytic activity of Argania Spinosa press-cake hydro-ethanolic extract on uric acid and cystine stones, respectively, with dissolution rates (DR) of 86.38% and 60.42% versus 3.23% and 9.48% for the hydro-ethanolic extract of Acacia senegal exudate. Furthermore, the percentages of nucleation inhibition are 83.78% and 43.77% (p ˂ 0.05) for Argania spinosa and Acacia senegal, respectively. The results point to the detection of 17 phytochemicals in Argania spinosa press-cake extract, the majority of which are phenolic acids and have potent anti-urolithiatic action.


Assuntos
Acacia , Sapotaceae , Oxalato de Cálcio , Cistina , Frutas/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Sapotaceae/química , Senegal , Ácido Úrico/análise
12.
Molecules ; 27(15)2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35956848

RESUMO

Breast cancer is the most common cancer in women, responsible for over half a million deaths in 2020. Almost 75% of FDA-approved drugs are mainly nitrogen- and sulfur-containing heterocyclic compounds, implying the importance of such compounds in drug discovery. Among heterocycles, thiazole-based heterocyclic compounds have demonstrated a broad range of pharmacological activities. In the present study, a novel set of 1,3-thiazole derivatives was designed and synthesized based on the coupling of acetophenone derivatives, and phenacyl bromide was substituted as a key reaction step. The activity of synthesized compounds was screened against the proliferation of two breast cancer cell lines (MCF-7 and MDA-MB-231). Almost all compounds exhibited a considerable antiproliferative activity toward the breast cancer cells as compared to staurosporine, with no significant cytotoxicity toward the epithelial cells. Among the synthesized compounds, compound 4 exhibited the most potent antiproliferative activity, with an IC50 of 5.73 and 12.15 µM toward MCF-7 and MDA-MB-231 cells, respectively, compared to staurosporine (IC50 = 6.77 and 7.03 µM, respectively). Exploring the mechanistic insights responsible for the antiproliferative activity of compound 4 revealed that compound 4 possesses a significant inhibitory activity toward the vascular endothelial growth factor receptor-2 (VEGFR-2) with (IC50 = 0.093 µM) compared to Sorafenib (IC50 = 0.059 µM). Further, compound 4 showed the ability to induce programmed cell death by triggering apoptosis and necrosis in MCF-7 cells and to induce cell cycle arrest on MCF-7 cells at the G1 stage while decreasing the cellular population in the G2/M phase. Finally, detailed in silico molecular docking studies affirmed that this class of compounds possesses a considerable binding affinity toward VEGFR2 proteins. Overall, these results indicate that compound 4 could be a promising lead compound for developing potent anti-breast cancer compounds.


Assuntos
Antineoplásicos , Neoplasias da Mama , Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Estaurosporina/farmacologia , Relação Estrutura-Atividade , Tiazóis/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular
13.
AAPS PharmSciTech ; 23(4): 103, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35381906

RESUMO

Vaccination has produced a great improvement to the global health by decreasing/eradicating many infectious diseases responsible for significant morbidity and mortality. Thanks to vaccines, many infections affecting childhood have been greatly decreased or even eradicated (smallpox, measles, and polio). That is why great efforts are made to achieve mass vaccination against COVID-19. However, developed vaccines face many challenges with regard to their safety and stability. Moreover, needle phobia could prevent a significant proportion of the population from receiving vaccines. In this context, microneedles (MNs) could potentially present a solution to address these challenges. MNs represent single dose administration systems that do not need reconstitution or cold-chain storage. Being self-administered, pain-free, and capable of producing superior immunogenicity makes them a more attractive alternative. This review explores microneedles' types, safety, and efficacy in vaccine delivery. Preclinical and clinical studies for microneedle-based vaccines are discussed and patent examples are included.


Assuntos
COVID-19 , Vacinas , Administração Cutânea , Criança , Sistemas de Liberação de Medicamentos , Humanos , Agulhas , Tecnologia , Vacinação
14.
Saudi Pharm J ; 30(8): 1200-1214, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36164579

RESUMO

Thymus vulgaris, Thymus satureioides, and Thymus zygis are endemic Moroccan species that are intensively used due to their extensive medications and culinary properties. To enhance and preserve these overexploited species, the effect of provenance on the chemical composition of essential oils and antimicrobial activity against human pathogens were studied. Essential oils (EO) obtained by hydrodistillation from the flowering tops of thyme species were analyzed by GC-SM. The determination of minimum inhibitory (MIC), bactericidal (MBC), and fungicide (MFC) concentrations of EO were studied by microplate microdilution. The correlation between the chemical composition of EO and antimicrobial properties were evaluated using R software. The samples studied gave variable yields, ranging from 0.70 ± 0.03% to 4.12 ± 0.21%. The main constituents of Thymus vulgaris harvested from the municipality of El Hammam are carvacrol (68.8%), γ-terpinene (11.5%), and p-cymene (3.9%), while borneol (41.3% and 31.7%) and carvacrol (14.6% and 9.8%) are the most abundant in Thymus satureioides of the communes of Tata and Tigrigra respectively. For Thymus zygis, the results revealed the dominance of carvacrol (51.7% and 57.5%) for the municipalities of Tigrigra and Ain Aghbal, thymol (47.1% and 42.1%) for the municipalities of Bensmim and Timahdite respectively. These chemical profiles have similarities, but also reveal differences from the results given in the literature. In addition, the essential oils most active towards the microorganisms evaluated were those of Thymus vulgaris, followed by Thymus zygis and Thymus satureioides. These EO have very powerful MIC (MIC â©½ 300 µg/ml) against Gram-negative bacteria, and in particular, concerning Enterobacters cloacae, Citrobacter koseri, and Acinetobacter baumannii. Thymus zygis EO is the most active on candidates compared to Thymus vulgaris and Thymus satureioides EO, except Candida dubliniensis which was inhibited by Thymus satureioides EO from the commune of Azrou with a MIC = 18.75 µg/ml. The correlation determined between the major components and MIC showed that phenols have the strongest positive effects on antimicrobial properties, followed by terpenes and non-aromatic alcohols. In addition, different sensitivities of pathogens to chemical families have been observed against Enterobacter cloacae, Citrobacter koseri, Candida parapsilosis, Staphylococcus aureus multiresistant, Pseudomonas aeruginosa, Acinetobacter baumannii, and Aspergillus niger. Our results support the idea that these oils could be very useful in flavoring, food preservation, as well as a source of antimicrobial agents of great power against multidrug-resistant strains.

15.
Environ Toxicol ; 36(1): 105-113, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32865349

RESUMO

While clinical innovation has improved, cancer or malignant growth stays a genuine medical issue and has been perceived as a significant factor in mortality and morbidity. Current work aimed to define the cardiac defensive effects of curcumin nanoparticles (Cur Nps) against EAC induced cardiac toxicity, injury, and alterations in apoptosis, proliferation, and cytokines immunoreactivity. Forty female mice were aimlessly and equally divided into four groups [Gp1, Control; Gp2, Cur NPs; Gp3, Ehrlich ascites carcinoma (EAC); Gp4, Co-treatment of EAC with Cur NPs (Cur NPs + EAC)]. Serum lactate dehydrogenase (LDH), phosphocreatine kinase (CPK), creatine kinase myoglobin (CK-MB), alkaline phosphatase (ALP), glutamic oxaloacetic transaminase (GOT), cholesterol, triglycerides, potassium ions, cardiac injury, P53, vascular endothelial growth factor protein (VEGF), Bax, and tumor necrosis factor alpha (TNFα) expressions were significantly elevated while sodium ions levels were significantly depleted in EAC when compared to control. Co-treatment of EAC with Cur NPs (Cur NPs + EAC) improved these parameters as compared with EAC group. So, our results indicate that; Cur NPs induced protection to the blood and heart tissue during Ehrlich ascites carcinoma.

16.
Pak J Pharm Sci ; 34(1(Supplementary)): 337-343, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34275859

RESUMO

Most clinical investigations about the impact of nanoparticles on cells and tissues show that nanoparticles may enter the human body by means of respiratory tracts. Humans, animals, plants and environments are continually presented to a wide scope of business items containing silver nanoparticles (Ag NPs) in their piece. Ag NPs, utilized in various consumer products as room showers, surface cleaners, wound dressings, food storage containers and many textiles. The current examination planned to explore the defensive role of Avenanthramide-C (Avns) contrary to the lung toxicity initiated by Ag NPs injection in rats. 40 male Wistar rats were separated into 4 groups (Gp1, control; Gp2, Avns; Gp3, Ag NPs; Gp4, Ag NPs+Avns). Current results revealed that; Ag NPs induced a significant depletion in RBCs count, hemoglobin, platelets counts and a significant increase in total WBCs, lung injury, cyclooxygenase-2 (COX2) and TNFα expressions as compared to control. Treatments of Ag NPs with Avenanthramide-C extract (Ag NPs+Avns) improved the lung structure and blood complete pictures as compared to Ag NPs group.


Assuntos
Células Sanguíneas/efeitos dos fármacos , Lesão Pulmonar/patologia , Pulmão/efeitos dos fármacos , Nanopartículas Metálicas/efeitos adversos , Prata/efeitos adversos , ortoaminobenzoatos/farmacologia , Animais , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Contagem de Eritrócitos , Hematócrito , Hemoglobinas/efeitos dos fármacos , Hemoglobinas/metabolismo , Contagem de Leucócitos , Pulmão/patologia , Lesão Pulmonar/induzido quimicamente , Contagem de Plaquetas , Ratos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
17.
Environ Toxicol ; 35(9): 952-960, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32293792

RESUMO

Silver nanoparticles (AgNPs), one of the most well-known nanomaterials, are regularly utilized in everyday consumer products. The present study aimed to investigate the testicular toxicity and oxidative stress by AgNPs and the therapeutic role of the rocket seeds (Eruca sativa) in treatments. Forty male Wistar rats were divided into four equivalent groups (group 1, control; group 2, rocket seeds extract [RS]; group 3, AgNPs; group 4, AgNPs+RS). Our results showed that AgNPs induced a significant decrease in serum total testosterone, FSH (follicle-animating hormone), prolactin and LH (luteinizing hormone), testicular glutathione (GSH), superoxide dismutase (SOD), and glutathione S-transferase (GST). In contrast, a significant increase in testicular DNA, injury, testicular thiobarbituric acid, proliferating cell nuclear antigen, and tumor necrosis factor-α (TNFα) expressions after treatments with AgNPs when contrasted with the control group. Treatments of AgNPs with rocket seeds extract (AgNPs+RS) improved testicular functions and structure. Rocket seeds extract might offer benefits against the toxic nature of AgNPs.


Assuntos
Brassicaceae/química , Nanopartículas Metálicas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Prata/toxicidade , Testículo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Glutationa/metabolismo , Hormônio Luteinizante/sangue , Masculino , Ratos , Ratos Wistar , Sementes/química , Superóxido Dismutase/metabolismo , Testículo/enzimologia , Testículo/metabolismo , Testosterona/sangue
18.
Pak J Pharm Sci ; 33(4(Supplementary)): 1839-1845, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33612468

RESUMO

Hydroxyapatite is bio-ceramic materials with a calcium to phosphorus proportion like to that of normal bone and teeth. The current study meant to examine the cardiac toxicity by hydroxyapatite nanoparticles (HAP NPs) and the protective effect of the rocket seeds in treatments. An aggregate of 40 male Wistar rodents were partitioned into 4 equal groups [Gp1, control; Gp2, rocket seeds extract (RS); Gp3, HAP NPs; Gp4, HAP NPs+RS]. Current results exhibit that; HAP NPs induce a significant increase in myoglobin, LDH (lactate dehydrogenase), CK-MB (creatinine kinase) and CK (creatinine kinase) levels, cardiac thiobarbituric acid-reactive substances (TBARS), injury and P53 expressions. In contrast; a significant reduction in cardiac catalase, reduced glutathione (GSH) and superoxide dismutase (SOD) as compared to control group. Post treatment of rat with HAP NPs and rocket seeds extract (HAP NPs+RS) improved the cardiac functions and structure. Rocket seeds extract may offer advantages against the harmful effects of hydroxyapatite nanoparticles.


Assuntos
Brassicaceae/química , Cardiotoxicidade/tratamento farmacológico , Durapatita/farmacologia , Nanopartículas/administração & dosagem , Extratos Vegetais/farmacologia , Animais , Antioxidantes/farmacologia , Cardiotoxicidade/metabolismo , Catalase/metabolismo , Creatina Quinase/metabolismo , Glutationa/metabolismo , Coração/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/farmacologia
19.
Vet Pathol ; 56(5): 691-702, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30686182

RESUMO

Encephalitis in hamsters, which was induced by equine herpesvirus (EHV)-9, EHV-1 strain Ab4p, and zebra-borne EHV-1, was investigated and compared to assess viral kinetics and identify the progression and severity of neuropathological findings. Hamsters were inoculated with EHV-9, EHV-1 strain Ab4p, and zebra-borne EHV-1 via the nasal route and euthanized at 24, 48, 72, 96, 120, 144, and 168 hours postinoculation (HPI). The inoculated hamsters had mild to severe neurological signs at 60 to 72, 96, and 120 HPI, and the mortality rate was 75%, 0%, and 0% for animals inoculated with EHV-9, EHV-1 strain Ab4p, and zebra-borne EHV-1 viruses, respectively. Inoculated hamsters had varying degrees of rhinitis and lymphoplasmacytic meningoencephalitis, as well as differences in the severity and distribution of cerebral lesions. Furthermore, the cellular distribution of viral antigen depended on the inoculated virus. Neuronal necrosis was widely detected in animals inoculated with EHV-9, while marked perivascular cuffs of infiltrating inflammatory cells and gliosis were detected in animals inoculated with EHV-1 strain Ab4p and zebra-borne EHV-1. In the present study, 3 viruses belonging to the herpesvirus family induced encephalitis after initial propagation in the nasal cavity. These viruses might travel to the brain via the olfactory pathway and/or trigeminal nerve, showing different distributions and severities of neuropathological changes.


Assuntos
Antígenos Virais/isolamento & purificação , Encefalopatias/virologia , Encéfalo/virologia , Infecções por Herpesviridae/patologia , Herpesviridae/classificação , Animais , Encefalopatias/patologia , Cricetinae , Infecções por Herpesviridae/virologia , Masculino , Proteínas Virais
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