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1.
Nutr Res Pract ; 18(3): 345-356, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38854468

RESUMO

BACKGROUND/OBJECTIVES: Okra seed is a rich source of various nutritional and bioactive constituents, but its mechanism of action is still unclear. The aim of this study was to evaluated the effects on glucose uptake and serum lipid profiles of unsaponifiable matter (USM) from okra seed in adipocytes and diabetic animal models. MATERIALS/METHODS: USM was prepared from okra seed powder by saponification. The contents of phytosterols and vitamin E in USM were measured. 3T3-L1 preadipocytes were cultured for 6 days with different concentrations of USM (0-200 µg/mL). The diabetic rats were administered with or without USM for 5 wk. RESULTS: In the USM, the contents of phytosterols and vitamin E were 394.13 mg/g USM and 31.16 mg/g USM, respectively. USM showed no cytotoxicity and led to an approximately 1.4-fold increase in glucose uptake in 3T3-L1 adipocytes. The treatment of USM also increased the expressions of peroxisome proliferator-activated receptor-γ and glucose transporter-4 in a dose-dependent manner in adipocytes. The body weight change was not significantly different in all diabetic rats. However, blood glucose and the weights of liver and adipose tissues were significantly reduced compared to those in the control diabetic rats. Treatment with USM decreased the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol compared to the control group. The USM group also showed significantly decreased atherogenic indices and cardiac risk factors. CONCLUSION: These results suggest that USM from okra seed improves the hypoglycemic and hypolipidemic effects in diabetic rats, and provides valuable information for improving the functional properties of okra seed.

2.
Front Nutr ; 11: 1409309, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933882

RESUMO

Lignans are phytoestrogens found in various forms such as glycosides, ester-linked oligomers, and aglycones in a variety of foods, including soy products, legumes, grains, nuts, vegetables, and fruits. This study aimed to optimize the extraction of lignans from cereal grains using response surface methodology (RSM). Lignans, including secoisolariciresinol (Seco), matairesinol (Mat), pinoresinol (Pin), lariciresinol (Lar), and syringaresinol (Syr), were quantified using high-performance liquid chromatography-tandem mass spectrometry. A Box-Behnken design was employed to determine the optimal values for three extraction parameters: temperature (X1: 20°C-60°C), methanol concentration (X2: 60%-100%), and extraction time (X3: 30-90 min). The highest lignan contents were obtained at X1 = 44.24°C, X2 = 84.64%, and X3 = 53.63 min. To apply these experimental conditions to the actual experiment, the optimal conditions were slightly adjusted to X1 = 40°C, X2 = 80%, and X3 = 60 min. The predicted results closely matched the experimental results obtained using the modified optimal extraction conditions. The highest lignan content found in barley sprouts (85.930 µg/100 g), however, most grains exhibited relatively low concentrations of lignans. These findings provide valuable insights into the lignan content of grains and contribute to the generation of reliable data in this field.

3.
Prev Nutr Food Sci ; 29(1): 40-46, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38576882

RESUMO

This study investigated the protective effects of cereal grains on alcohol-induced hepatocyte damage. Cereal grains were extracted with methanol, and their radical scavenging properties and total phenolic contents were examined. Black rice extract exhibited the highest total polyphenol content and radical scavenging capacity. Treatment with sorghum extract increased the viability of cells exposed to alcohol by up to 81.6%. All cereal grain extracts decreased reactive oxygen species and malondialdehyde production and glutathione depletion in HepG2 cells exposed to ethanol. In particular, black rice and sorghum extracts exhibited greater antioxidant effects than other cereal grains. Treatment with black rice extract increased the levels of alanine aminotransferase and aspartate aminotransferase of alcohol-exposed cells to control levels. Overall, black rice extract showed a greater protective effect compared with other cereal grains against alcohol exposure in HepG2 cells and could improve alcohol-induced liver problems.

4.
Antioxidants (Basel) ; 13(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38671930

RESUMO

We comparatively evaluated the antioxidant properties of key triterpenes from Centella asiatica, including asiatic acid (AA), asiaticoside, madecassic acid, and madecassoside, in several cell types, including skin fibroblasts, macrophages, hepatocytes, and endothelial cells, under conditions promoting oxidative stress. AA conferred the highest viability on Hs68 cells exposed to ultraviolet B (UVB) irradiation. Triterpene pretreatment attenuated the UVB-induced generation of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as the UVB-induced depletion of glutathione (GSH) in skin fibroblasts. AA most potently inhibited UVB-induced MMP generation, resulting in increased intracellular collagen levels. Pretreatment with triterpenes, particularly AA, significantly improved cell viability and attenuated TBHP-induced levels of ROS, alanine aminotransferase, and aspartate aminotransferase in HepG2 cells. Triterpenes attenuated ROS levels and reduced MDA and GSH expression in EA.hy926 cells. In RAW264.7 macrophages, production of nitric oxide, tumor necrosis factor-α, and interleukin-6 (indicators of LPS-induced oxidative damage) was significantly reduced by treatment with any of the triterpenes. Statistical analyses of triterpene biological activities using principal component analysis and hierarchical clustering revealed that AA exerted the greatest overall influence and showed remarkable activity in Hs68 and HepG2 cells.

5.
Animals (Basel) ; 14(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38338113

RESUMO

In animal farming, timely estrus detection and prediction of the best moment for insemination is crucial. Traditional sow estrus detection depends on the expertise of a farm attendant which can be inconsistent, time-consuming, and labor-intensive. Attempts and trials in developing and implementing technological tools to detect estrus have been explored by researchers. The objective of this review is to assess the automatic methods of estrus recognition in operation for sows and point out their strong and weak points to assist in developing new and improved detection systems. Real-time methods using body and vulvar temperature, posture recognition, and activity measurements show higher precision. Incorporating artificial intelligence with multiple estrus-related parameters is expected to enhance accuracy. Further development of new systems relies mostly upon the improved algorithm and accurate data provided. Future systems should be designed to minimize the misclassification rate, so better detection is achieved.

6.
Foods ; 12(21)2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37959135

RESUMO

Unsaponifiable matter (USM) from wheat bran, a by-product obtained from wheat milling, is abundant in health-promoting compounds such as phytosterols, tocopherols, policosanols, and alkylresorcinols. This study aimed to examine the effects of USM from the wheat bran of normal and waxy type wheat, Saekeumkang (SKK) and Shinmichal (SMC), on hepatic lipid accumulation in free fatty acid (FFA)-induced hepatocytes and to investigate the cellular mechanism. The total phytochemical contents were 46.562 g/100 g USM and 38.130 g/100 g USM from SKK and SMC, respectively. FFA treatment increased intracellular lipid accumulation by approximately 260% compared to the control group; however, treatment with USM from SKK and SMC significantly attenuated lipid accumulation in the hepatocytes in a dose-dependent manner. Moreover, USM downregulated the expression of lipogenic factors such as fatty acid synthase and sterol regulatory-element-binding protein 1c by approximately 40% compared to the FFA treatment group. Treatment with USM promoted lipolysis and positively regulated the expression of the proteins involved in ß-oxidation, including peroxisome proliferator-activated receptor α and its downstream protein, carnitine palmitoyltransferase 1A. Moreover, the blockade of AMPK activation significantly abolished the inhibitory effects of USM on hepatic lipid accumulation. These results indicated that the USM from both SKK and SMC can alleviate lipid accumulation in hepatocytes in an AMPK-dependent manner. Therefore, USM from wheat bran may be useful as a therapeutic intervention for treating metabolic-dysfunction-associated fatty liver disease.

7.
Animals (Basel) ; 13(19)2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37835754

RESUMO

The late gestation period is crucial for fetal growth and development, impacting swine enterprises' profitability. Various nutritional strategies have been explored to enhance reproductive performance in sows, but findings regarding birth weight and litter size have been inconsistent. This study investigated the effects of increased feeding allowance during the late gestation period on the reproductive performance and farrowing behavior of primiparous and multiparous sows. A total of 28 sows (Landrace × Yorkshire) were used in this experiment, and fed 2.50 kg/d or 3.50 kg/d from 84 days of gestation until farrowing. Farrowing behavior was monitored using a DeepEyesTM M3SEN camera. The data were analyzed using the 2 × 2 factorial within Statistical Analysis System (SAS, 2011, Version 9.3) software. The results indicated that regardless of the parity number, sows fed a high diet exhibited a numerical increase in the total number of born piglets and a significant increase in milk yield (p = 0.014) and piglet birthweight (p = 0.023). Backfat thickness loss was significantly higher in sows with a 2.50 kg feeding allowance (p = 0.022), and the total number of piglets born, live births, and litter size were numerically higher in sows fed 3.50 kg per day. Moreover, stillborn piglets, mortality rate, and re-estrus days were numerically lower in sows with a high feeding allowance. The diet and parity did not individually affect the average duration of farrowing and farrowing intervals. However, the duration of postural changes in sows after farrowing was significantly reduced (p = 0.012). The principal component analysis revealed 81.40% and 80.70% differences upon partial least-squares discriminant analysis. Therefore, increasing feeding allowance during the late gestation period, regardless of parity, could positively influence sows' reproductive performance and piglets' growth performance during the lactation phase.

8.
Animals (Basel) ; 13(11)2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37889795

RESUMO

Porcine respiratory disease complex is an economically important disease in the swine industry. Early detection of the disease is crucial for immediate response to the disease at the farm level to prevent and minimize the potential damage that it may cause. In this paper, recent studies on the application of artificial intelligence (AI) in the early detection and monitoring of respiratory disease in swine have been reviewed. Most of the studies used coughing sounds as a feature of respiratory disease. The performance of different models and the methodologies used for cough recognition using AI were reviewed and compared. An AI technology available in the market was also reviewed. The device uses audio technology that can monitor and evaluate the herd's respiratory health status through cough-sound recognition and quantification. The device also has temperature and humidity sensors to monitor environmental conditions. It has an alarm system based on variations in coughing patterns and abrupt temperature changes. However, some limitations of the existing technology were identified. Substantial effort must be exerted to surmount the limitations to have a smarter AI technology for monitoring respiratory health status in swine.

9.
Int J Mol Sci ; 24(16)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37629185

RESUMO

Neovascular age-related macular degeneration (nAMD) is the primary disastrous retinal disease that leads to blindness in the elderly population. In the early 2000s, nAMD resulted in irreversible vision loss and blindness with no available treatment options. However, there have been breakthrough advances in the drug development of anti-angiogenic biological agents over the last two decades. The primary target molecule for treating nAMD is the vascular endothelial growth factor (VEGF), and there are currently several anti-VEGF drugs such as bevacizumab, ranibizumab, and aflibercept, which have made nAMD more manageable than before, thus preventing vision loss. Nevertheless, it should be noted that these anti-VEGF drugs for nAMD treatment are not effective in more than half of the patients, and even those who initially gain visual improvements lose their vision over time, along with potential deterioration in the geography of atrophy. As a result, there have been continuous endeavors to improve anti-VEGF agents through better efficacy, fewer doses, expanded intervals, and additional targets. This review describes past and current anti-VEGF therapeutics used to treat nAMD and outlines future directions to improve the effectiveness and safety of anti-VEGF agents.


Assuntos
Cegueira , Degeneração Macular , Humanos , Idoso , Fatores de Crescimento do Endotélio Vascular , Bevacizumab , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Degeneração Macular/tratamento farmacológico
10.
Antioxidants (Basel) ; 12(8)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37627645

RESUMO

The aim of this study was to investigate the effects of different cooking methods on the hepatoprotective effects of purple sweet potatoes against alcohol-induced damage in HepG2 cells. Purple sweet potatoes (Ipomeoea batatas L. Danjami) were subjected to different cooking methods, including steaming, roasting, and microwaving. Steaming resulted in a higher cytoprotective effect against alcohol damage than the other cooking methods. Additionally, the highest inhibition of glutathione depletion and production of reactive oxygen species against alcohol-induced stress were observed in raw and/or steamed purple sweet potatoes. Compared to roasted and/or microwaved samples, steamed samples significantly increased the expression of NADPH quinone oxidoreductase 1, heme oxygenase 1, and gamma glutamate-cysteine ligase in alcohol-stimulated HepG2 cells via the activation of nuclear factor erythroid 2-related factor 2. Moreover, ten anthocyanins were detected in the raw samples, whereas five, two, and two anthocyanins were found in the steamed, roasted, and microwaved samples, respectively. Taken together, steaming purple sweet potatoes could be an effective cooking method to protect hepatocytes against alcohol consumption. These results provide useful information for improving the bioactive properties of purple sweet potatoes using different cooking methods.

11.
Animals (Basel) ; 12(20)2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36290245

RESUMO

This experiment evaluated the performance of a combined geothermal heat pump and solar system (GHPS). A GHPS heating system was installed at a pig house and a comparative study was carried out between the environmentally friendly renewable energy source (GHPS) and the traditional heating method using fossil fuels. The impact of both heating systems on production performance, housing environment, noxious gas emission, and energy efficiency were evaluated along with the GHPS system performance parameters such as the coefficient of performance (COP), inlet and outlet water temperature and efficiency of solar collector. The average temperature inside the pig house was significantly higher (p < 0.05) in the GHPS heating system. Similarly, the outflow temperature was increased significantly (p < 0.05) than the inflow temperature. The results of COP and efficiency of the solar system also indicated that the GHPS is an efficient heating system. The electricity consumption and carbon dioxide gas concentration were also reduced (p < 0.05) in the GHPS system. This study also predicts electricity consumption using an artificial intelligence (AI)-based model. The results showed that the proposed model justifies all the acceptance criteria in terms of the correlation coefficient, root mean square value and mean absolute error. The results of our experiment show that the GHPS system can be installed at a pig house for sustainable swine production as a renewable energy source.

12.
Theranostics ; 12(14): 6380-6394, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36168637

RESUMO

Rationale: [18F]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) has been widely used as an imaging technique to measure interscapular brown adipose tissue (iBAT) activity. However, it is challenging to obtain iBAT-specific images using [18F]FDG-PET because increased uptake of [18F]FDG is observed in tumors, muscle, and inflamed tissues. Uncoupling protein 1 (UCP1) in the mitochondrial membrane, a well-known molecular marker of BAT, has been proposed as a useful BAT imaging marker. Recently, the UCP1 ThermoMouse was developed as a reporter mouse for monitoring UCP1 expression and investigating BAT activation. In addition, Translocator protein-18 kDa (TSPO) located in the outer mitochondrial membrane is also overexpressed in BAT, suggesting that TSPO-targeting PET has potential for iBAT imaging. However, there are no studies monitoring BAT using TSPO-targeting PET probes in the UCP1 ThermoMouse. Moreover, the non-invasive Cerenkov luminescence imaging (CLI) using Cerenkov radiation from the PET probe has been proposed as an alternative option for PET as it is less expensive and user-friendly. Therefore, we selected [18F]fm-PBR28-d 2 as a TSPO-targeting PET probe for iBAT imaging to evaluate the usefulness of CLI in the UCP1 ThermoMouse. Methods: UCP1 ThermoMouse was used to monitor UCP1 expression. Western blotting and immunohistochemistry were performed to measure the level of protein expression. [18F]fm-PBR28-d 2 and [18F]FDG were used as radioactive probes for iBAT imaging. PET images were acquired with SimPET, and optical images were acquired with IVIS 100. Results: UCP1 ThermoMouse showed that UCP1 and TSPO expressions were correlated in iBAT. In both PET and CLI, the TSPO-targeting probe [18F]fm-PBR28-d 2 was superior to [18F]FDG for acquiring iBAT images. The high molar activity of the probe was essential for CLI and PET imaging. We tested the feasibility of TSPO-targeting probe under cold exposure by imaging with TSPO-PET/CLI. Both signals of iBAT were clearly increased after cold stimulation. Under prolonged isoflurane anesthesia, TSPO-targeting images showed higher signals from iBAT in the short-term than in long-term groups. Conclusion: We demonstrated that TSPO-PET/CLI reflected UCP1 expression in iBAT imaging better than [18F]FDG-PET/CLI under the various conditions. Considering convenience and cost, TSPO-CLI could be used as an alternative TSPO-PET technique for iBAT imaging.


Assuntos
Fluordesoxiglucose F18 , Isoflurano , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/metabolismo , Animais , Fluordesoxiglucose F18/metabolismo , Isoflurano/metabolismo , Luminescência , Camundongos , Tomografia por Emissão de Pósitrons/métodos , Proteína Desacopladora 1/metabolismo
13.
Int J Mol Sci ; 23(16)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36012530

RESUMO

Immune checkpoint inhibitors (ICIs) are widely used in cancer immunotherapy, requiring effective methods for response monitoring. This study evaluated changes in 18F-2-fluoro-2-deoxy-D-glucose (FDG) and 18F-fluorothymidine (FLT) uptake by tumors following ICI treatment as potential imaging biomarkers in mice. Tumor uptakes of 18F-FDG and 18F-FLT were measured and compared between the ICI treatment and control groups. A combined imaging index of glucose-thymidine uptake ratio (GTR) was defined and compared between groups. In the ICI treatment group, tumor growth was effectively inhibited, and higher proportions of immune cells were observed. In the early phase, 18F-FDG uptake was higher in the treatment group, whereas 18F-FLT uptake was not different. There was no difference in 18F-FDG uptake between the two groups in the late phase. However, 18F-FLT uptake of the control group was markedly increased compared with the ICI treatment group. GTR was consistently higher in the ICI treatment group in the early and late phases. After ICI treatment, changes in tumor cell proliferation were observed with 18F-FLT, whereas 18F-FDG showed altered metabolism in both tumor and immune cells. A combination of 18F-FLT and 18F-FDG PET, such as GTR, is expected to serve as a potentially effective imaging biomarker for monitoring ICI treatment.


Assuntos
Fluordesoxiglucose F18 , Neoplasias , Animais , Biomarcadores , Didesoxinucleosídeos , Fluordesoxiglucose F18/uso terapêutico , Glucose/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Timidina/farmacologia
14.
Nucl Med Biol ; 114-115: 135-142, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35501237

RESUMO

INTRODUCTION: Claudin-3 (CLDN3), a tight junction protein, regulates cell-to-cell interactions in epithelial or endothelial cell sheets. During tumorigenesis, epithelial cells are transformed, and tumor cells proliferate through out-of-plane division, resulting in external exposure of CLDN3. Since alterations of CLDN3 expression are associated with cancer progression and higher CLDN3 expression is observed in most ovarian cancers, we tested the feasibility of using a CLDN3-specific antibody as a novel imaging tracer. MATERIALS AND METHODS: After reducing the CLDN3-specific antibodies to expose the -SH groups, click chemistry was used to conjugate the radioactive isotope 111In or the fluorescent protein FNR648. Human ovarian cancer OVCAR-3 and glioblastoma U87MG cells were used as CLDN3-positive and -negative cells. Flow cytometry was used to determine the CLDN3 IgG1 monoclonal antibody binding to both cell lines. OVCAR-3 cells were injected subcutaneously into mice to establish a xenograft model. 111In-labeled CLDN3 antibodies (370 kBq/50 µL) were administered intravenously into mice. After 24 h, organs, including tumors, were excised and measured with a γ-counter. Images were acquired with the IVIS optical imaging system and SPECT/CT. RESULTS: The labeling efficiency of NOTA-111In and antibody-NOTA-111In was 98.52% and 100%, respectively. FNR648-labeled CLDN3 antibody bound to the cell surface of OVCAR-3 and U87MG with 83.4% and 5.7% specificity, respectively. In OVCAR-3 tumor xenografted mice, CLDN3 IgG1 antibody showed a 2.5-fold higher tumor uptake (20.4 ± 7.4% ID/g) than human IgG1 (8.8 ± 2.6% ID/g) at 24 h post injection. The CLDN3 antibody fluorescence signal in the tumor peaked at 24 h post injection. CONCLUSION: We have successfully conjugated a radioisotope and a fluorescent protein with CLDN3-specific antibodies and verified the specific binding of labeled antibodies to OVCAR-3 tumors in a mouse model. Our data suggested that CLDN3-specific human monoclonal antibodies could be used as a useful theranostic tracer.


Assuntos
Neoplasias Ovarianas , Humanos , Animais , Camundongos , Feminino , Claudina-3 , Neoplasias Ovarianas/patologia , Anticorpos Monoclonais , Apoptose , Linhagem Celular Tumoral , Imunoglobulina G
15.
Biomed Pharmacother ; 145: 112245, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34772578

RESUMO

Cathepsin S (CTSS), a lysosomal protease, belongs to a family of cysteine cathepsin proteases that promote degradation of damaged proteins in the endolysosomal pathway. Aberrant CTSS expression and regulation are associated with the pathogenesis of several diseases, including lung diseases. CTSS overexpression causes a variety of pathological processes, including pulmonary fibrosis, with increased CTSS secretion and accelerated extracellular matrix remodeling. Compared to many other cysteine cathepsin family members, CTSS has unique features that it presents limited tissue expression and retains its enzymatic activity at a neutral pH, suggesting its decisive involvement in disease microenvironments. In this review, we investigated the role of CTSS in lung disease, exploring recent studies that have indicated that CTSS mediates fibrosis in unique ways, along with its structure, substrates, and distinct regulation. We also outlined examples of CTSS inhibitors in clinical and preclinical development and proposed CTSS as a potential therapeutic target for pulmonary fibrosis.


Assuntos
Catepsinas/antagonistas & inibidores , Fibrose Pulmonar/tratamento farmacológico , Animais , Catepsinas/metabolismo , Desenvolvimento de Medicamentos , Matriz Extracelular/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Terapia de Alvo Molecular , Fibrose Pulmonar/fisiopatologia
16.
Foods ; 12(1)2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36613388

RESUMO

We examined the effect of chrysoeriol on adipogenesis and lipolysis and elucidated the underlying molecular mechanisms. Chrysoeriol inhibited fat deposition in adipocytes. Treatment with chrysoeriol suppressed the expression of peroxisome proliferator-activated receptor γ, fatty acid synthase, fatty acid-binding protein, CCAAT/enhancer-binding proteins (C/EBP) α, C/EBPß, and sterol regulatory element-binding protein-1. In addition, chrysoeriol significantly elevated the activation of 5'-adenosine monophosphate-activated protein kinase. Moreover, chrysoeriol increased free glycerol and fatty acid levels and promoted lipolysis in adipocytes. Overexpression of adipose triglyceride lipase and hormone-sensitive lipase by chrysoeriol led to increased lipolysis in 3T3-L1 adipocytes. Taken together, chrysoeriol showed anti-adipogenic and lipolytic properties in adipocytes.

17.
Xenobiotica ; 51(7): 811-817, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33949288

RESUMO

Esculetin is the main active ingredient isolated from Artemisia montana (Nakai) Pamp. and Euphorbia lathyris L. The present study investigated the oral bioavailability and pharmacokinetics of esculetin in rats, following intravenous and oral administration.Twenty Sprague-Dawley rats were randomly assigned to receive 10 mg/kg of esculetin either by the intravenous or oral route. Plasma concentrations of esculetin were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using non-compartmental analysis as well as a compartmental modelling approach using WinNonlinTM and ADAPT 5 software, respectively.According to non-compartmental analysis, the mean oral bioavailability of esculetin was 19%. Mean ± standard deviation values of esculetin half-life, steady-state volume of distribution and clearance, following intravenous dosing, were 2.08 ± 0.46 h, 1.81 ± 0.52 L/kg and 1.27 ± 0.26 L/h/kg, respectively. As indicated by compartmental modelling, a two-compartment pharmacokinetic model with first-order absorption and elimination rate constants of 0.98 ± 0.18 h-1 and 2.47 ± 0.28 h-1, respectively, sufficiently described the plasma concentration-time curve of esculetin.Improving our understanding of the pharmacokinetic properties of esculetin could help with future development of herbal medicine products with appropriate bioactivity.


Assuntos
Disponibilidade Biológica , Administração Intravenosa , Administração Oral , Animais , Meia-Vida , Injeções Intravenosas , Ratos , Ratos Sprague-Dawley , Umbeliferonas
18.
Bioengineering (Basel) ; 8(4)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805342

RESUMO

Dolastatin derivatives, represented by monomethylauristatin E (MMAE), have been translated in clinic with a form of antibody-drug conjugate; however, their potential in nanoparticle systems has not been well established due to the potential risk of immature release of extremely high cytotoxic dolastatin drugs during blood circulation. Herein, we rationally propose monomethylauristatin F (MMAF), a dolastatin-derived, loaded nanoparticle system composed of bombesin (BBN)-tethered ROS-responsive micelle system (BBN-PEG-PPADT) to achieve efficient anticancer therapy with targeted and efficient delivery of MMAF. The developed MMAF-loaded BBN-PEG-PPADT micelles (MMAF@BBN-PEG-PPADT) exhibited improved cellular uptake via interactions between BBN and gastrin-releasing peptide receptors on the cancer cells and the intracellular burst release of MMAF, owing to the ROS-responsive disruption, which allowed the efficient anticancer effects of MMAF in vitro. This study suggests the potential of nanoparticle systems in the delivery of dolastatin drugs.

19.
Antioxidants (Basel) ; 10(3)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800272

RESUMO

Ginseng seeds are rich in phytosterols, ginsenosides, and fatty acids, and can therefore be used in skincare to delay the aging process. Ginseng seed embryo (GSE) and ginseng seed coat (GSC) were separated from ginseng seeds (Panax ginseng Meyer). This study evaluated the protective activity and underlying mechanism of GSE and GSC on UVB irradiation-induced skin photoaging using Hs68 cells. Their bioactive compounds, including phytosterols, ginsenosides, tocopherols, tocotrienols, and fatty acids were determined by HPLC and GC. The levels of reactive oxygen species, matrix metalloproteinases (MMPs), and collagen levels were measured in human dermal fibroblast cell line, Hs68 cells. The antioxidant capacity and contents of total polyphenols and flavonoids were higher in GSC than those in GSE. Linoleic acid was the major fatty acid in both GSE and GSC. GSE and GSC treatment alleviated UVB-induced increase of reactive oxygen species (ROS), matrix metalloproteinase (MMP)-1, and MMP-3, resulting in reduced collagen degradation. Increased UVB-mediated phosphorylation of mitogen activated protein kinase (MAPK) and activator protein-1 (AP-1) was inhibited by GSE and GSC treatment. Moreover, GSE and GSC effectively upregulated transforming growth factor-ß (TGF-ß) 1 levels. It was found that ginseng seeds regulate the expression of TGF-ß/Smad and MAPK/AP-1 pathways. Ginseng seeds contain various bioactive compounds and have protective activity against UVB-induced skin photoaging. Therefore, ginseng seeds have the potential for use in cosmeceutical preparations.

20.
J Food Biochem ; 45(4): e13639, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33533516

RESUMO

In this study, the cytoprotective effect of gamma-aminobutyric acid (GABA) via inducing phase II enzymes in C2C12 myoblasts was evaluated. The highest concentration of GABA (100 µM) significantly increased the cell viability by approximately 90% in hydrogen peroxide-induced C2C12 cells. The treatment with GABA (100 µM) effectively decreased the glutathione (GSH) depletion and the activities of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). And, reactive oxygen species (ROS) levels were effectively reduced by about 50% in GABA-treated cells. In addition, the protein expression of phase II enzymes, such as NADPH:quinone oxidoreductase 1 and heme oxygenase-1 was significantly increased by GABA treatment. Moreover, GABA treatment increased the nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression in the nucleus of C2C12 myoblasts. Altogether, the results in this study indicate that GABA possesses the cytoprotective effects against oxidative insults by regulating the GSH levels, CAT and SOD activities, ROS scavenging activities, and expression of phase II enzymes through the activation of Nrf2 in C2C12 cells. Hence, this study suggests that the GABA supplementation could be effective in alleviating oxidative stress-induced muscle damage. PRACTICAL APPLICATIONS: GABA exists in the germ and bran layers of rice and is well-known as the inhibitory neurotransmitter in the central nervous system. GABA also has various health beneficial effects, such as preventing chronic alcohol-related diseases and lowering blood pressure. The present study shows the cytoprotective effect of GABA against oxidative stress in C2C12 myoblasts, and suggests that GABA has great potential as a functional food ingredient for attenuating oxidative stress-induced muscle damage.


Assuntos
Heme Oxigenase-1 , Estresse Oxidativo , Heme Oxigenase-1/genética , Mioblastos/metabolismo , Regulação para Cima , Ácido gama-Aminobutírico/farmacologia
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