Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling / 中国结合医学杂志

OBJECTIVE@#To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro.@*METHODS@#Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (α-SMA), CD31 and transforming growth factor β (TGF-β)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10 µmol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed.@*RESULTS@#High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I, α-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (P<0.01). Amygdalin down-regulated the expressions of Col-I and α-SMA in JS-1 and LX-2 cells, and TGFβ R1, TGFβ R2 and p-Smad2/3 in LX-2 cells compared to the model group (P<0.05 or P<0.01). Moreover, 1 and 10 µmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group (P<0.05 or P<0.01).@*CONCLUSIONS@#Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-β/Smad signaling pathway, consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.

Análisis Histomorfométrico de la Asociación de Aceite de Oliva y Bisfosfonatos en la Remodelación Ósea Periimplantaria / Histomorphometric Analysis of the Association of Olive Oil and Bisphosphonates on Peri-Implant Bone Remodeling

RESUMEN: Los bisfosfonatos son potentes inhibidores de la resorción ósea. El aceite de oliva (O) presenta propiedades anti-inflamatorias y anti-oxidantes. Estudiar el efecto del tratamiento combinado de alendronato (AL) y pamidronato (PA) por vía subcutánea y de O vía oral sobre la regeneración tisular de cavidades óseas neoformadas.: 54 ratas macho de la línea Wistar, se dividieron en 6 grupos. Grupo control (C), recibieron solución salina vía subcutánea. Grupo (AL) recibió 0,5 mg de AL/Kg de peso corporal de por vía subcutánea. Grupo (PA) recibió de igual manera que el grupo anterior. Grupo (O) fue tratado con aceite de oliva con la dieta, 50 g/ Kg de comida. Grupo (ALO) recibió tratamiento combinado con AL y O. Grupo (PAO) recibió de igual tratamiento. Los sacrificios para la toma de muestras fueron a los 15, 30, 60 y 90 días. Para los estudios histopatológicos los cortes fueron teñidos con HE y observados con microscopía óptica. Los estudios estadísticos se realizaron a través del análisis de la variancia. A los quince días las áreas de los osteocitos del grupo PA se diferencian significativamente sólo respecto al grupo AL. En cuanto a la Densidad trabecular se observa un incremento de tejido óseo en todos los grupos. O mejora cualitativamente la estructura del hueso trabecular y cortical, preservando la mineralización, el tamaño y la estructura de los cristales minerales Esto sugiere que O representa una opción terapéutica prometedora para la prevención y tratamiento de las patologías óseas.

ABSTRACT: Bisphosphonates are potent inhibitors of bone resorption. Olive oil (O) has anti-inflammatory and anti-oxidant properties. To study the effect of combined treatment with alendronate (AL) and pamidronate (PA) subcutaneously or orally, and on tissue regeneration of newly formed bone cavities, we divided 54 male Wistar rats into 6 groups. Control group (C) received saline subcutaneously. Group (AL) received 0.5 mg of AL / kg body weight subcutaneously. Group (PA) received the same as the previous group. (O) was treated with olive oil diet, 50 g / kg of food. Group (ALO) received combined treatment with AL and O. Group (PAO) received the same treatment. The animals were euthanized for sampling at 15, 30, 60 and 90 days. For histopathology sections were stained with HE and observed these with light microscopy. Statistical studies were performed by analysis of variance. Fifteen days osteocytes areas of the PA group were significantly different only for the AL group. As the density increased trabecular bone tissue was observed in all groups. O qualitatively improved the structure of trabecular and cortical bone mineralization while preserving the size and structure of the mineral crystals. This suggests that O represents a promising therapeutic option for prevention and treatment of bone diseases.

Development of nanotechnology-based drug delivery systems with olive vegetable oil for cutaneous application

ABSTRACT Liquid-Crystalline Systems represent active compounds delivery systems that may be able to overcome the physical barrier of the skin, especially represented by the stratum corneum. To obtain these systems, aqueous and oily components are used with surfactants. Of the different association structures in such systems, the liquid-crystalline offer numerous advantages to a topical product. This manuscript presents the development of liquid-crystalline systems consisting, in which the oil component is olive oil, its rheological characterizations, and the location of liquid crystals in its phase map. Cytotoxic effects were evaluated using J-774 mouse macrophages as the cellular model. A phase diagram to mix three components with different proportions was constructed. Two liquid crystalline areas were found with olive oil in different regions in the ternary diagram with two nonionic surfactants, called SLC1 (S1) and SLC2 (S2). These systems showed lamellar liquid crystals that remained stable during the entire analysis time. The systems were also characterized rheologically with pseudoplastic behavior without thixotropy. The texture and bioadhesion assays showed that formulations were similar statistically (p < 0.05), indicating that the increased amount of water in S2 did not interfere with the bioadhesive properties of the systems. In vitro cytotoxic assays showed that formulations did not present cytotoxicity. Olive oil-based systems may be a promising platform for skin delivery of drugs.

RESUMO Os cristais líquidos representam um sistema de liberação de substâncias ativas capazes de vencer a barreira cutânea, representada especialmente pelo estrato córneo. Água, óleo e tensoativos são misturados para se obter esses sistemas. Diferentes estruturas podem ser formadas nesses sistemas, as quais oferecem muitas vantagens para os produtos de uso tópico. Esse trabalho visou ao desenvolvimento de sistemas líquido-cristalinos preparados com óleo de oliva, sua caracterização reológica e a identificação das fases cristalinas no diagrama ternário. Efeitos citotóxicos foram avaliados usando células de rato como modelo celular. Construiu-se um diagrama de fases que mistura três componentes em diferentes proporções. Duas áreas de cristal líquido, denominadas SLC1 (S1) e SLC2 (S2), foram encontradas com óleo de oliva em diferentes regiões no diagrama ternário preparado com dois diferentes tensoativos não-iônicos. Esses sistemas mostraram fase cristalina lamelar, que permaneceu estável durante o tempo estudado. Os sistemas foram também caracterizados reologicamente e apresentaram comportamento pseudoplástico com tixotropia. Os ensaios de textura e bioadesão mostraram que as formulações foram similares (p < 0.05), indicando que o aumento da quantidade de água em S2 não interferiu nas propriedades bioadesivas dos sistemas. Os ensaios de citotoxicidade mostraram que as formulações não foram citotóxicas. Sistemas à base de óleo de oliva são interessantes para a liberação de fármacos na pele.

Reducción de la esteatosis hepática, insulino resistencia y pérdida de la defensa antioxidante en ratones alimentados con dieta alta en grasa suplementados con AGPICL n-3 más aceite de oliva extra virgen / Reduction of hepatic steatosis, insulin resistance and loss of antioxidant defense in high fat diet fed mice suplemented with n-3 LCPUFA more extra virgin olive oil

Non-alcoholic fatty liver disease (NAFLD) is directly associated with insulin resistance and oxidative stress. In NAFLD is established a reduction in n-3 LCPUFA (EPA + DHA) levels and hepatic activity of transcription factor PPAR-alpha. EPA and DHA inhibit lipogenesis and stimulate fatty acid oxidation in the liver. Extra virgin olive oil (EVOO) has important antioxidant properties. This study evaluated the prevention of insulin resistance and prevention of depletion of hepatic antioxidant defense inC57BL/6J mice fed high-fat diet (HFD), supplemented with n-3 LCPUFA plus EVOO. HFD generated insulin resistance and hepatic steatosis, together with significant reduction in i) n-3 LCPUFA hepatic levels, ii) DNA binding activity of PPAR-alpha, iii) activity of antioxidant enzymes (catalase and superoxide dismutase), respect to control group (fed with control diet). Supplementation with n-3 LCPUFA plus EVOO prevent development insulin resistance and attenuate increased of fat in liver (p < 0.05), together with a normalization of i) DNA binding activity of PPAR-á, ii) activity of antioxidant enzymes (catalase and superoxide dismutase) and iii) reducing depletion of n-3 LCPUFA levels in liver tissue, compared to the control group (p < 0.05). Supplementation with n-3 LCPUFA plus EVOO reduced hepatic steatosis and prevent development of insulin resistance, along with preserving the antioxidant defense in liver. Projecting the use of this mixture of AGPICL n-3 plus EVOO as a potential treatment of NAFLD.