E Se tea extract ameliorates CCl4 induced liver fibrosis via regulating Nrf2/NF-κB/TGF-ß1/Smad pathway.

BACKGROUND: Liver fibrosis is a crucial progress to deteriorate liver disease. E Se tea (ES) is an ethnic herbal tea in China that has various biological activities for human beings. However, the traditional application on the treatment of liver disease is not studied. PURPOSE: This study is firstly performed to explore the chemical constituents of ES extract together with its anti-hepatic fibrosis effect and potential mechanism on CCl4 treated mice. STUDY DESIGN AND METHODS: The chemical constituents of ethanol-aqueous extract from ES (ESE) were analyzed by UPLC-ESI-MS/MS. The anti-hepatic fibrosis effect of ESE was determined by measuring ALT and AST activities, antioxidative indexes, inflammatory cytokines and collagen protein levels on CCl4 treated mice. Moreover, H&E, Masson staining and immunohistochemical analysis were performed for evaluating the protective effect of ESE on histopathological changes of liver tissues. RESULTS: UHPLCHRESI-MS/MS analysis showed that the ESE was rich in flavonoids such as phlorizin, phloretin, quercetin and hyperoside. ESE could significantly reduce the plasma AST and ALT activities. The cytokines (IL-6, TNF-α, IL-1ß) expressions were inhibited after ESE administration via suppressing NF-κB pathway. In addition, ESE could decrease MDA accumulation for alleviating CCl4 induced liver oxidative stress via regulating Nrf2 pathway to promote the expressions of antioxidant enzymes (SOD, HO-1, CAT and NQO1). Moreover, ESE could inhibit the expressions of TGF-ß1, Smad2, α-SMA, and collagens Ⅰ and III proteins, thereby effectively alleviate the liver fibrosis. CONCLUSION: This study demonstrated that ESE could alleviate liver fibrosis through enhancing antioxidant and anti-inflammatory abilities by Nrf2/NF-κB pathway and reducing deposition of liver fibrosis via suppressing TGF-ß/Smad pathway.

Rice Bran as an Alternative Feedstuff in Broiler Nutrition and Impact of Liposorb® and Vitamin E-Se on Sustainability of Performance, Carcass Traits, Blood Biochemistry, and Antioxidant Indices.

The impact of dietary rice bran with or without feed additives on the performance, carcasses, and blood profiles of chickens was examined. A total of 245 unsexed one-week-old broiler chicks were divided into seven groups, with seven replications of five chicks each. The treatments were: (1) control, (2) 5% rice bran, (3) 5% rice bran + 0.5 g/kg of Liposorb®, (4) 5% rice bran + 1 g/kg of vitamin E-Se, (5) 10% rice bran, (6) 10% rice bran + 0.5 g/kg Liposorb®, and (7) 10% rice bran + 1 g/kg of vitamin E-selenium. Considering the entire experimental period, it did not affect the in vivo performance of the broilers. However, all the experimental diets decreased dressing % compared with the control (p < 0.01) and the worst values were obtained for the 10% RB groups (75.7, 75.9, and 75.8%, respectively, for 10%RB, 10%RB + Liposorb, and 10%RB + Vit. E-Se groups). All the experimental diets decreased (p < 0.01) the albumin/globulin ratio due to an increased level of serum globulins. Differences in lipid profiles, antioxidants, and immunity parameters in plasma were not related to dietary treatments. In conclusion, the use of rice bran up to 10% in diets had no harmful effect on the overall growth performance of the broilers from 1 to 5 weeks of age. Still, carcass characteristics were negatively affected, except for heart percentage. In addition, the supplementation of Liposorb® or vitamin E-Se to rice bran diets did not recover these harmful effects. Thus, rice bran could be utilized at 10% in broiler diets when growth performance was considered; further research is required.

Effects of Injectable Administration of Dexamethasone Alone or in Combination with Vitamin E/Se in Newborn Low Birth Weight Piglets.

Increasing litter size may lead to low-birth-weight piglets (LBW) and further negative long-term effects. This study aimed to evaluate the effects of intramuscular administration (IM) of dexamethasone (Dexa) alone or in combination with vitamin E/Se on LBW piglets during the early postnatal period. The study included a total of 100 LBW piglets that were divided into 5 groups (20 LBW piglets per group) and treated with IM Dexa alone or in combination with vitamin E/Se (Vit E/Se) after birth as follows: (a) Group A-Cont: Control group, (b) Group B-Dexa1: Dexa on D1 (1st day of life), (c) Group C-Dexa3: Dexa on D1, D2, D3 (D2: 2nd day of life, D3: 3rd day of life), (d) Group D-Dexa + VitE/S1: Dexa + Vit E/Se on D1, and (e) Group E-Dexa + VitE/S3: Dexa + Vit E/Se (IM) on D1, D2, D3. Body weight (BW) and the Average Daily Weight Gain (ADWG) were recorded for all piglets on days 1, 7, 14, and 25, and vitality score (VS) was recorded on days 1, 2, 3, 4, and 14. A significant increase in BW and ADWG in Group E-Dexa + VitE/S3 and a significant reduction in Group C-Dexa3 were noticed in comparison to other groups. VS in groups Group B-Dexa1 and Group C-Dexa3 were significantly lower in comparison to other groups. Furthermore, piglets of Group C-Dexa3 had a significantly higher frequency of clinical findings compared to other groups. In conclusion, the administration of Dexa and vitamin E/Se combined after the birth of LBW piglets for 1-3 days has beneficial effects on their growth and survival scores.

Protective effects of E Se tea extracts against alcoholic fatty liver disease induced by high fat/alcohol diet: In vivo biological evaluation and molecular docking study.

BACKGROUND: With the development of economy and increased workload, chronic a high-fat/alcohol diet intake may lead to alcoholic fatty liver disease (AFLD), which is considered as a crucial health problem worldwide. E Se tea is produced of the leaves and leaf buds of Malus toringoides (Rehd.) Hughes in Tibet and has human health benefits with anti-hyperglycemia, hypertension, and hyperlipidemia effects. PURPOSE: The objective of this work was to investigate the protective effect of aqueous-ethanol and hot-water extracts of E Se tea against chronic high-fat/alcohol diet induced AFLD rats. METHODS: Firstly, to determine the chemical profiling of E Se tea extracts, UHPLC-ESI-HRMS analysis was conducted. Secondly, Sprague-Dawley male rats were used to establish the AFLD animal model by feeding with high-fat/alcohol diet. The animals were treated with E Se tea extracts for 12 weeks. Serum parameters were determined, histologic sections were prepared, and activities of enzymes related to inflammatory response and lipid metabolism imbalance were analyzed. The underlying mechanisms of E Se tea extracts alleviating AFLD were analyzed by immunofluorescence staining and Western blotting analysis. Lastly, key targets of 11-MT against AFLD were verified through molecular docking. RESULTS: In this study, seven main compounds were confirmed or tentatively identified in E Se tea extracts by UHPLC-ESI-HRMS. The results revealed that both the extracts could reverse histopathological steatotic alternation of the liver and reduced the activity of liver damage markers (ALT, AST). E Se tea extracts mitigated oxidative stress by inhibiting CYP2E1 protein and lipid peroxidation parameters (MDA), but enhancing the endogenous antioxidants (CAT, GSH, SOD). Moreover, E Se tea extracts ameliorated inflammation by restraining the activation of NF-κB, consequently releasing the expression of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, COX-2 and iNOS). Subsequently, E Se tea extracts reduced hepatocyte apoptosis by increasing capase-9, caspase-3 and Bax protein expression but decreasing Bcl-2 protein expression. Furthermore, E Se tea extracts improved metabolism imbalance by stimulating AMPK/SREBP1/FAS and PPAR-α/CPT1 signaling pathway by regulating lipid metabolism parameters (TC, TG, HDL-C, LHD-C). Furthermore, molecular docking results indicated that 7 chemical constituents of E Se tea extracts had strong docking affinity with 4 key target proteins (AMPK, PPAR-α, NF-кB and Caspase-9). CONCLUSION: E Se tea ameliorated AFLD through ameliorating inflammatory response, apoptosis, and lipid metabolism imbalance.

Effect of Tibetan medicine E-se on insulin resistance in KK-Ay mice with spontaneous type 2 diabetes / 中国药理学通报

Aim To evaluate the effect of E-se extract on insulin resistance in KK-Ay mice with spontaneous type 2 diabetes anrl explore its mechanism.Methods Ten C57/6J mice were assigned to a normal control group.Fifty KK-Ay model mice were randomly divided into model group, positive control group ( rosiglita- zone, 2.67 mg • kg 1 ), and low- ( 0.75 g • kg 1 ) , medium- ( 1.50 g • kg 1 ) , and high-dose ( 3.00 g • kg ') E-se groups, with 10 mice in each group.All mice were measured for body weight and fasting blood glucose weekly, insulin tolerance on the 32nd day, and insulin after the last administration on the 35th day, and the insulin resistance/sensitivity indexes were calculated.The pancreas was stained by hematoxylin- eosin ( HE ).Islet cell apoptosis was detected by TUNEL staining.Glucagon-like peptide-1 ( GLP-1 ) was detected by immunohistochemistry.Results j j Compared with the model group, the E-se groups showed reduced body weight, fasting blood glucose, serum insulin concentration, and insulin resistance in¬dex, elevated insulin sensitivity index, decreased le¬sion grading score of pancreatic tissues and apoptosis percentage of islet cells, and increased content of GLP- 1 protein in pancreatic tissues.Conclusions E-se ex¬tract can improve insulin resistance by reducing serum insulin level, inhibiting islet cell apoptosis, and in¬creasing the sensitivity of the body to insulin.

Safety evaluation and hypolipidemic effect of aqueous-ethanol and hot-water extracts from E Se tea in rats.

E Se tea, processed by the fresh leaves of Malus toringoides (Rehd.) Hughes, is a traditional herbal tea with various human benefits. The present study was aimed to evaluate the toxicity and hypolipidemic effect of aqueous-ethanol extract (EE) and hot-water extract (WE) from E Se tea. Eight main chemical constituents in EE and WE were respectively identified and quantified by UHPLC-HRMS/MS. EE is rich in TPC and TFC, while WE had higher TPS content. Both EE and WE exhibited strong antioxidant activity with no significant difference. The acute toxicity study revealed that the LD50 values were higher than 5000 mg/kg, while both WE and EE had no significant adverse effect in rats by subacute toxicity assay. However, the triglyceride (TG) content in experiment groups (male) and highest doses groups (female) significantly decreased. Furthermore, the hypolipidemic effect of WE and EE were performed on high fat diet induced hyperlipidemic rats. The result exhibited that either WE or EE could effectively regulate lipid droplet accumulation in liver, and reduce the adipocyte size. These results demonstrated that these two extracts from E Se tea could be regarded as a potential functional dietary supplement in preventing and treating diet induced metabolic diseases.

A transformação didático-pedagógica da ginástica para as crianças pelo "brincar e se-movimentar" / The didactic-pedagogical transformation of gymnastics for children by the "play and self-moving" / La transformación didáctica-pedagógica de la gimnasia con niños por el "jugar y moverse"

O objetivo do ensaio é refletir e problematizar o "brincar e se-movimentar" na ginástica como possibilidade pedagógica de uma Educação Física centrada no sujeito, perspectivando a ampliação do campo existencial. Considerando que o agir humano é carregado de intencionalidade e conexão entre corpo-mundo, defende-se uma ginástica que fomente a realização de experiências corporais por meio da resolução de problemas e da participação das crianças nas aulas com autonomia, criatividade e liberdade, permitindo-lhes constituir sentidos outros naquilo que fazem, pensam e sentem, dialogando com o mundo numa aventura saudável que as convida para se desenvolver no decurso de infinitas possibilidades de ação.

The present text discusses theoretical and philosophical elements based on "play and move" as a pedagogical possibility of a subject-centered Physical Education, with a view to expanding the existential field. The goal is to expand knowledge about gymnastics practice that presupposes awakening new meanings and meanings of children, recognizing that human action weaves relationships of meanings to and with the world, through experiences that refer to the meanings attributed by the being that moves. Considering that human action is loaded with intentionality and connection between body and world, a gymnastics is defended that fosters the realization of body experiences through problem solving and the participation of children in classes with autonomy, creativity and freedom, allowing constitute them other senses in what they do, think and feel, dialoguing with the world in a healthy adventure that invites them to develop in the course of infinite possibilities of action.

El presente texto discute elementos teóricos y filosóficos basados en "jugar y moverse" como una posibilidad pedagógica de una Educación Física centrada en el tema, con miras a expandir el campo existencial. El objetivo es ampliar el conocimiento sobre la práctica de gimnasia que presupone despertar nuevos significados y significados de los niños, reconociendo que la acción humana entrelaza las relaciones de significados con y con el mundo, a través de experiencias que se refieren a los significados atribuidos por el ser que se mueve. Teniendo en cuenta que la acción humana está cargada de intencionalidad y conexión entre el cuerpo y el mundo, se defiende una gimnasia que fomenta la realización de experiencias corporales a través de la resolución de problemas y la participación de los niños en clases con autonomía, creatividad y libertad, permitiendo Los constituyen otros sentidos en lo que hacen, piensan y sienten, dialogando con el mundo en una sana aventura que los invita a desarrollarse en el curso de infinitas posibilidades de acción.

UHPLC-ESI-HRMS/MS analysis on phenolic compositions of different E Se tea extracts and their antioxidant and cytoprotective activities.

E Se tea, prepared from the leaves of Malus toringoides (Rehd.) Hughes, is a traditional beverage, but there is little known about its chemical substances. This paper is aimed to investigate the chemical composition, antioxidant, and cytoprotective activities of the extract and fractions from E Se tea. Sixteen compounds were characterized by UHPLC-ESI-HRMS/MS. Phloridzin was the main compound, especially in ethyl acetate fraction (EAF). Moreover, EAF had the highest total phenolic and flavonoid contents with 197.54 ± 7.52 mg gallic acid equivalents/g extract and 85.94 ± 5.39 mg rutin equivalents/g extract, respectively, and exhibited the strongest antioxidant capacity (DPPH: IC50 = 54.91 ± 3.38 µg/mL; ABTS: IC50 = 98.08 ± 6.92 µg/mL). Different fractions of E Se tea, especially EAF, significantly inhibited intracellular ROS generation, reduced cell apoptosis, and decreased oxidative stress damage in H2O2-induced HepG-2 cells. Therefore, the obtained results highlight that E Se tea is a promising source for functional beverage or nutritional foods.

Pharmacokinetics, bioavailability, excretion, and metabolic analysis of Schisanlactone E, a bioactive ingredient from Kadsura heteroclita (Roxb) Craib, in rats by UHPLC-MS/MS and UHPLC-Q-Orbitrap HRMS.

Schisanlactone E (SE) is a bioactive ingredient extracted from the stem of Kadsura heteroclita (Roxb) Craib. SE has various pharmacological activity such as anti-tumor and anti-leukemia effects. However, its absorption, distribution, metabolism, and excretion have rarely been examined. In this study, new quali-quantitative analytical methods were developed for metabolic and pharmacokinetic studies of SE in rats. A UHPLC-MS/MS method was developed to determine SE in rat plasma, urine, and feces. Samples were precipitated with methanol and analyzed in multiple reaction monitoring mode. The established method was validated and applied to the pharmacokinetics, bioavailability, and excretion analysis of SE after oral (6 mg/kg) or intravenous (2 mg/kg) administration. The absolute oral bioavailability of SE was approximately 79.3%. After oral administration, SE was mainly excreted via feces with a rate of 41.7% for 48 h. SE could not be detected in urine. Furthermore, a UHPLC-Q-Orbitrap HRMS method was developed for the metabolite screening of SE in rat plasma, urine, and feces. Metabolites were extracted by solid phase extraction and analyzed with full MS/dd-MS2 scan mode. As a result, 15 metabolites including 11 phase I and 4 phase II metabolites were identified by a three-step analytical strategy. The carboxyl group, the five membered ring, and the six membered α,ß-unsaturated lactone ring of SE could be predicted as the main metabolic sites. This study provides comprehensive insights into the pharmacokinetic and metabolic profiles of SE, and would be valuable for future development and utilization of SE and Kadsura heteroclita.

Bifenthrin exerts proatherogenic effects via arterial accumulation of native and oxidized LDL in rats: the beneficial role of vitamin E and selenium.

The purpose of this study was to investigate, for the first time, the effects of Bifenthrin (Bif) chronic exposure on plasmatic and aortic lipid parameters disturbance and their pro-atherogenic possibility in Wistar rats. The ameliorative role of vitamin E (Vit E) and selenium (Se) were also targeted. Thus, rats were treated by gastric gavage with combination of Vit E (100 mg/kg/bw) and Se (0.25 mg/kg/bw) in alone and co-treated groups for 90 days. Apart from control and Vit E-Se groups, all the groups were subjected to Bif (3 mg/kg, via gavage) toxicity. Results showed that Bif increased markedly plasmatic and aortic total cholesterol, LDL-cholesterol, native LDL-apoB-100, and oxidized-LDL, compared to the control. Moreover, Bif treatment significantly increased the plasmatic levels of the pro-inflammatory cytokines TNF-α, IL-2, and IL-6. In addition, the densitometric quantification of protein bands showed that the amount of hepatic native LDL-receptor protein decreased significantly in the intoxicated rats compared to the control group. The expression of arterial LDL receptors (LDLRs) and scavenger receptors (CD36) was amplified owing to Bif toxicity. This harmful effect was confirmed by histological study using Oil-Red-O staining. Owing to their antioxidant capacities, Vit E and Se have maintained all the changes in plasma and aorta lipids and prevented the pro-atherogenic effect observed in Bif-treated animals.

Educação e sensibilidade: o brincar e o se-movimentar da criança pequena na escola / Education and sensitivity: the play and move yourself the child in school / Educación y sensibilidad: el jugar y el "movimiento" del niño pequeño en la escuela

Este estudo teve como objetivo central investigar como o brincar e o se-movimentar são proporcionados no espaço escolar e de que maneira eles contribuem para a educação da sensibilidade da criança pequena. Foi desenvolvido um estudo de caso que envolveu duas escolas municipais da cidade de Capinzal, SC; uma localizada no interior do município e a outra na cidade. Foi selecionada uma turma de crianças entre 4 e 6 anos de idade em cada escola, que totalizaram 40 crianças. Constatou-se que o brincar e o se-movimentar nas escolas estudadas acontecem muitas vezes por intermédio do controle dos professores, sempre com o intuito de promover uma competição e de chegar a um resultado final. Portanto, nas escolas investigadas, o incentivo à construção de situações que possibilitem o desenvolvimento da sensibilidade recebe pouca importância, o que compromete significativamente a educação da sensibilidade dessas crianças e limita o poder de criação.

Thus, this study had as main objective to investigate about the ways as the play and the move yourself are proposed in the school environment and how they contribute for the sensibility education to the child. First, it was developed a theorical research about the subjets and the fundamental authors, that suply the base for the second part of the study. This other step was an empirical study that involved two municipal schools from the city of Capinzal, SC; one located in the countryside and the other one downtown. It was chosen a class of chuildren from 4 to 6 years old in each school, that totaling 40 children. Therefore, in the investigated schools, the stimulus to situations construction that enable the sensibility development receives little importance, what commits meaningly the sensibility education of these children and limits the creation' power.

Este estudio tuvo como objetivo central investigar cómo el juego y el movimiento se proporcionan en el espacio escolar y de qué manera contribuyen a la educación de la sensibilidad del niño pequeño. Se desarrolló un estudio de caso que involucró dos escuelas municipales de la ciudad de Capinzal, SC; una ubicada en el interior del municipio y la otra en la ciudad. Se seleccionó una clase de niños entre 4 y 6 años de edad en cada escuela, que totalizaron 40 niños. Se constató que el jugar y el mudanza en las escuelas estudiadas ocurren muchas veces por intermedio del control de los profesores, siempre con el propósito de promover una competición y de llegar a un resultado final. Por lo tanto, en las escuelas investigadas, el incentivo a la construcción de situaciones que posibiliten el desarrollo de la sensibilidad recibe poca importancia, lo que compromete significativamente la educación de la sensibilidad de esos niños y limita el poder de creación.

Chemical constituents from aqueous extract of Carthamus tinctorius / 中国药学杂志

OBJECTIVE: To study the chemical constituents of the aqueous extract of Carthamus tinctorius. METHODS: Compounds were isolated by a combination of various chromatographic techniques including column chromatography on macroporous resin and Sephadex LH-20 and reversed-phase HPLC. Their structures were elucidated by physiochemical properties and spectral analysis. RESULTS: Twelve compounds were isolated and identified as (2E, SE)-12R-tetradecadiene-4, 6-diyne-1, 12, 14-triol (1), (8Z)-decaene-4, 6-diyn-1-O-β-2)-glucopyranoside (2), (SE)-decaene-4, 6-diyn-1-O-β-D-glucopyranoside (3), (2S)-4′, 5, 6, 7-tetrahydroxy-flavavone 6-O-β-D-glucoside (4), p-hydroxybenzoic acid (5), 3-hydroxy-4-methoxybenzoic acid (6), dihydrophaseic acid methyl ester-3-O-β-Z)-glucoside (7), dihydrophaseic acid methyl ester (8), 4-hydroxy benzaldehyde (9), N, N′-dicoumaroyl-putrescine (10), 4-(4′,-hydroxyphenyl)but-3-en-2-one (11) and 4-hydroxyacetophenone (12). CONCLUSION: Compounds 1, 3-4, 6, 8, and 10 are isolated from this plant for the first time. The absolute configuration and C-NMR data of compound 1 are for the first time reported.