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Hepatic steatosis can cause liver dysfunction and cell injury, on which natural functional factors are expected to be an effective approach for long-term intervention. However, the cellular molecular mechanisms are unclear. Chlorogenic acid is a phenolic compound, which can regulate lipid metabolism and is abundant in burdock root. The aim of this study was to investigate the potential molecular mechanism of the effect of chlorogenic acid from burdock root (ACQA) on steatosis in HepG2 cells. In this study, we found that ACQA reduced the number of lipid droplets and lipid levels in oleic acid-treated HepG2 cells. Molecular mechanistic results showed that ACQA enhanced CPT-1 expression by activating AMPK-related signaling pathways, and the concentrations of Ca2+ and cAMP were increased with the intervention of ACQA. In addition, ACQA enhanced the ß-oxidation of fatty acids, reduced alanine transaminase and aspartate transaminase, and inhibited apoptosis in oleic acid-treated HepG2 cells. Our studies elucidate a novel mechanism that ACQA enhances the ß-oxidation of fatty acids through the AMPK/ACC/CPT-1 pathway to protect against steatosis in HepG2 cells, which provides insight into its molecular mechanism as well as intervention strategies for chlorogenic acid against fatty liver diseases.
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Arctium , Enfermedad del Hígado Graso no Alcohólico , Humanos , Células Hep G2 , Proteínas Quinasas Activadas por AMP/metabolismo , Ácido Clorogénico/farmacología , Ácido Clorogénico/metabolismo , Ácido Oléico/farmacología , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Metabolismo de los Lípidos , Ácidos Grasos/metabolismo , HígadoRESUMEN
BACKGROUND: Fluoxetine, a selective serotonin reuptake inhibitor, has been reported to directly bind with 5-HT2B receptor (5-HT2BR), but the precise mechanisms, whereby fluoxetine confers the anti-depressive actions via 5-HT2BR is not fully understood. Although neuroinflammation-induced A1 astrocytes are involved in neurodegenerative diseases, the role of A1 astrocyte in the pathogenesis and treatment of major depressive disorder (MDD) remains unclear. METHODS: Mice were subjected to chronic mild stress (CMS) for 6 weeks and subsequently treated with fluoxetine for 4 weeks. The depressive-like and anxiety-like behaviors and the activation of A1 reactive astrocyte in hippocampus and cortex of mice were measured. Primary astrocytes were stimulated with A1 cocktail (tumor necrosis factor (TNF)-α, interleukin (IL)-1α and C1q), activated (LPS) microglia-conditioned medium (MCM) or IL-6 for 24 h and the expression of A1-special and A2-special markers were determined using RT-qPCR and western blot. The role of 5-HT2BR in the effects of fluoxetine on A1 reactive astrocyte was measured using 5-HT2BR inhibitor and siRNA in vitro and AAVs in vivo. The functions of downstream signaling Gq protein and ß-arrestins in the effects of fluoxetine on the activation of A1 astrocyte were determined using pharmacological inhibitor and genetic knockout, respectively. RESULTS: In this study, we found that fluoxetine inhibited the activation of A1 reactive astrocyte and reduced the abnormal behaviors in CMS mice, as well as ameliorated A1 astrocyte reactivity under three different stimulators in primary astrocytes. We also showed that astrocytic 5-HT2BR was required in the inhibitory effects of fluoxetine on A1 reactive astrocyte in MDD in vivo and in vitro. We further found that the functions of fluoxetine in the activation of A1 astrocyte were independent of either Gq protein or ß-arrestin1 in vitro. ß-arrestin2 pathway was the downstream signaling of astrocytic 5-HT2BR mediated the inhibitory effects of fluoxetine on A1 astrocyte reactivity in primary astrocytes and CMS mice, as well as the improved roles of fluoxetine in behavioral impairments of CMS mice. CONCLUSIONS: These data demonstrate that fluoxetine restricts reactive A1 astrocyte via astrocytic 5-HT2BR/ß-arrestin2 pathway in a mouse model of MDD and provide a novel therapeutic avenue for MDD.
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Trastorno Depresivo Mayor , Fluoxetina , Animales , Astrocitos/metabolismo , Trastorno Depresivo Mayor/metabolismo , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Ratones , Serotonina/metabolismo , Arrestina beta 2/genética , Arrestina beta 2/metabolismoRESUMEN
The innovative catalyst Fe@B10H14 is designed through Fe doping of the boron cage B10H14 and is employed to catalyze CO2 hydrogenation using a quantum mechanical method. First, the structure of the Fe@B10H14 complex is characterized through calculated 11B NMR chemical shifts and Raman spectra, and the interactions between Fe and the four H atoms of the opening in the cage are analyzed, which show that various iron hydride (Fe-H) characteristics exist. Subsequently, the potential of Fe@B10H14 as a catalyst for the hydrogenative reduction of CO2 in the gas phase is computationally evaluated. We find that an equivalent of Fe@B10H14 can consecutively reduce double CO2 to obtain the double product HCOOH through a two-step reduction, and Fe@B10H12 and Fe@B10H10 are successively obtained. The Fe presents single-atom character in the reduction of CO2, which is different from the common iron(ii) catalyzed CO2 reduction. The calculated total free energy barrier of the first CO2 reduction is only 8.79 kcal mol-1, and that of the second CO2 reduction is 25.71 kcal mol-1. Every reduction reaction undergoes two key transition states TSC-H and TSO-H. Moreover, the transition state of the C-H bond formation TSC-H is the rate-determining step, where the interaction between πC[double bond, length as m-dash]O* and the weak σFe-H bond plays an important role. Furthermore, the hydrogenations of Fe@B10H12 and Fe@B10H10 are investigated, which aim at determining the ability of Fe-H circulation in the Fe doped decaborane complex. We find that the hydrogenation of Fe@B10H10 undergoes a one-step H2-adsorbed transition state TSH-adsorb with an energy barrier of 6.42 kcal mol-1 from Fe@B10H12. Comparing with the hydrogenation of Fe@B10H10, it is slightly more difficult for the hydrogenation of Fe@B10H12, where the rate-determining step is the H2-cleaved transition state TS2H-H with an energy barrier of 17.38 kcal mol-1.
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Low-salt stress germination is an effective way to improve the nutritional composition of food crops. A novel soluble dietary fiber (MS-SDF) was isolated from low-salt stress mung bean sprouts that were exposed to low-salt stress using anion exchange and gel permeation techniques. Structural analysis revealed that MS-SDF was a homogeneous heteropolysaccharide with an average molecular weight of 164.997 KDa. It featured a loose structure and contained the characteristic functional groups typical of polysaccharides. MS-SDF was composed of arabinose, galactose, glucose, and mannose with a molar ratio of 3.95:3.86:82.69:9.02. The structure was mainly composed of â6)-α-D-Glcp-(1â, â5)-α-L-Araf-(1â, and â3,6)-α-D-Glcp-(1â as the main chain. Branched at O-3 position with single ß-D-Manp-(1â as major the side chain. Furthermore, in vitro hypoglycemic assays indicate that MS-SDF exhibits α-glucosidase inhibitory activity, significantly enhancing glucose uptake, glycogen synthesis, and pyruvate kinase activity in insulin-resistant HepG2 cells. Overall, MS-SDF could be used as a promising source of functional hypoglycemic foods.
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Burdock (Arctium lappa L) root is eaten as a vegetable in many countries and used as an ethnomedicine because of its various pharmacological effects. The objective of this study was to investigate the underlying mechanisms of ethanolic extract of root from Arctium lappa L root (ALE) to lose weight and regulate lipid metabolism. The results showed that ALE can regulate lipid metabolism level and inhibit the weight gain of rats induced by the high-sugar and high-fat diet. The contents of triglyceride and cholesterol in the liver of obese rats significantly reduced, and hepatic steatosis was ameliorated. In addition, this study identified that ALE enhanced hepatic fatty acid ß-oxidation and ameliorated hepatic steatosis by activating AMPK/ACC/CPT-1 pathway. These results indicated that ALE has a potential preventive and therapeutic effect on metabolic-associated fatty liver disease and obesity. PRACTICAL APPLICATIONS: Obesity is already a global health problem. Obesity causes accumulation of triglycerides, which leads to hepatic steatosis. Long-term steatosis causes liver damage and metabolic fatty liver disease. Plant-derived functional foods or herbal medicines have better effects on weight loss and liver protection, which are more conducive to long-term use with less toxic side effects. As a medicinal and edible plant material, Arctium lappa L root has the effect in losing weight. Our study showed that ethanolic extract of Arctium lappa L root effectively regulates lipid metabolism and inhibits hepatic steatosis. Arctium lappa L root may be used as a therapeutic drug and functional food raw material for obesity and fatty liver disease.
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Arctium , Enfermedad del Hígado Graso no Alcohólico , Ratas , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Proteínas Quinasas Activadas por AMP/genética , Etanol , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Obesidad/tratamiento farmacológico , TriglicéridosRESUMEN
Blueberries are rich in bioactive anthocyanins, with a high level of malvidin, which is associated with antioxidant benefits that contribute to reducing the risk of diabetes. The objective of this study was to investigate the hypoglycemic and hypolipidemic effects of blueberry anthocyanin extract (BAE), malvidin (Mv), malvidin-3-glucoside (Mv-3-glc), and malvidin-3-galactoside (Mv-3-gal) in both human hepatocarcinoma cell line HepG2 and in a high-fat diet combining streptozotocin-induced diabetic mice. High glucose treatment significantly increased hepatic oxidative stress up to 6-fold and decreased HepG2 cell viability. Pretreatment with BAE, Mv, Mv-3-glc and Mlv-3-gal significantly mitigated these damages by lowering the reactive oxygen species (ROS) by 87, 80, 76, and 91%, and increasing cell viability by 88, 79, 73, and 98%, respectively. These pretreatments also effectively inhibited hyperglycemia and hyperlipidemia, respectively by reducing the expression levels of enzymes participating in gluconeogenesis and lipogenesis and enhancing those involved in glycogenolysis and lipolysis, via adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in HepG2 cells. To determinate the role of AMPK in BAE-induced reaction of glucose and lipid metabolism in vivo, doses of 100 mg/kg (blueberry anthocyanin extracts - low concentration, BAE-L) and 400 mg/kg (blueberry anthocyanin extracts - high concentration, BAE-H) were administrated per day to diabetic mice for 5 weeks. BAE treatments had a significant (P < 0.05) effect on body weight and increased the AMPK activity, achieving the decrease of blood- and urine-glucose, as well as triglyceride and total cholesterol. This research suggested that anthocyanins contributed to the blueberry extract-induced hypoglycemia and hypolipidemia effects in diabetes and BAE could be a promising functional food or medicine for diabetes treatment.
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Arándanos Azules (Planta) , Diabetes Mellitus Experimental , Animales , Antocianinas , Antioxidantes , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Ratones , Extractos Vegetales/farmacologíaRESUMEN
Considerable progress has been made in improving the performance of optoelectronic devices based on hybrid organic-inorganic perovskites of the form ABX3. However, the influences of A-site doping on the structure and dynamics of the inorganic perovskite crystal lattice and, in turn, on the optoelectronic performance of the resulting devices remain poorly understood at an atomic level. This work addresses this issue by combining the results of several experimental characterization methods for three-dimensional MA1-xDMAxPbBr3 perovskite single crystals (MA, methylammonium; DMA, dimethylammonium). The results reveal a two-stage change in lattice with an increase in DMA content, which has completely opposite effects on the optoelectronic performance of the double-cation perovskite. At low DMA concentrations, fast reorientation of incorporated DMA cations strengthens the interaction between MA cations and the lattice without significant lattice distortion, which could suppress lattice fluctuation and thus improve the photovoltaic performance. At high DMA concentrations, the lattice get a severe distortion, leading to poorer photovoltaic performance.
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In recent years, with the discovery and research of lactate-specific receptor HCAR1(hydroxycarboxylic acid receptor 1), lactate is not only as a product of Glycolysis in astrocytes, but also as a signaling molecule which has gradually received attention. Studies have found that lactate can be used as an intercellular signaling molecule involved in synaptic plasticity, and so that peripheral administration of lactate can produce antidepressant effects. Here, we focus on HCAR1 on the most widely distributed astrocytes in the brain, found and verified that lactate could cause Arc/arg3.1 protein overexpression in astrocytes through HCAR1. However, the expression of Arc/arg3.1 does not depend on the Gi protein pathway of HCAR1, and we found that lactate enhanced the expression of Arc/arg3.1 protein through the HCAR1-ß-arrestin2 pathway. In summary, lactate acts on HCAR1 of astrocytes. It enhances the expression of MAPK-dependent Arc through ß-arrestin2, thereby reducing the influx of calcium ions when astrocytes are exposed to glutamate damage, achieving the role of protecting astrocytes and indirectly enhancing the absorption of glutamate by astrocytes. These results also demonstrate that HCAR1 in the brain is a potential therapeutic target in an experimental in vitro model of glutamate damage, which is strongly associated with many neurodegenerative diseases.