RESUMO
Atherosclerosis is a major risk factor for type 2 diabetes (T2D) mortality. We aim to investigate the changes in miR-21, miR-122, miR-33a and miR-3064-5p in circulation and the liver of ApoE-/- mice with streptozocin (STZ)-induced T2D. Twenty 5-week-old male ApoE-/- mice were randomly assigned to the control (n = 10) and T2D group (n = 10) and intraperitoneally injected with a citrate buffer and streptozotocin (STZ) (40 mg/kg BW) once a day for three consecutive days. The successfully STZ-induced T2D mice (n = 5) and control mice (n = 5) were then fed with a high-fat diet (HFD) for 34 weeks. Compared to the control mice, ApoE-/- mice with STZ-induced T2D had slower (p < 0.05) growth, increased (p < 0.05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), decreased (p < 0.05) high-density lipoprotein cholesterol (HDL-C) in serum, reduced (p < 0.05) TC and sterol regulatory element-binding protein-2 (Srebp-2), elevated (p < 0.05) ATP-binding-cassette-transporter-A1 (Abca1) in the liver, aggravated (p < 0.05) atherosclerotic lesions in the aorta, downregulated (p < 0.05) miR-21 and miR-33a, and upregulated (p < 0.05) miR-122 and miR-3064-5p in serum and the liver. In addition, the aortic lesions showed a positive correlation with miR-122 (r = 1.000, p = 0.001) and a negative correlation with miR-21 (r = −1.000, p = 0.001) in ApoE-/- mice with T2D. In conclusion, T2D-accelerated atherosclerosis correlates with a reduction in miR-21 and miR-33a and an elevation in miR-122 and miR-3064-5p in circulation and the liver of ApoE-/- mice.
RESUMO
The anti-inflammatory properties of soyasaponins (especially soyasaponins with different chemical structures) have scarcely been investigated. We investigated the inhibitory effects of five structural types of soyasaponins (soyasaponin A(1), A(2), I and soyasapogenol A, B) on the induction of nitric oxide (NO) and inducible NO synthase (iNOS) in murine RAW 264.7 cells activated with lipopolysaccharide (LPS). Soyasaponin A(1), A(2) and I (25-200 µg/mL) dose-dependently inhibited the production of NO and tumor necrosis factor α (TNF-α) in LPS-activated macrophages, whereas soyasapogenol A and B did not. Furthermore, soyasaponin A(1), A(2) and I suppressed the iNOS enzyme activity and down-regulated the iNOS mRNA expression both in a dose-dependent manner. The reporter gene assay revealed that soyasaponin A(1), A(2) and I decreased LPS-induced nuclear factor kappa B (NF-κB) activity. Soyasaponin A(1), A(2) and I exhibit anti-inflammatory properties by suppressing NO production in LPS-stimulated RAW 264.7 cells through attenuation of NF-κB-mediated iNOS expression. It is proposed that the sugar chains present in the structures of soyasaponins are important for their anti-inflammatory activities. These results have important implication for using selected soyasaponins towards the development of effective chemopreventive and anti-inflammatory agents.
Assuntos
Anti-Inflamatórios/química , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Saponinas/química , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular Tumoral , Lipopolissacarídeos/toxicidade , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Saponinas/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This 6-week study was conducted to evaluate the effects of seven different levels of dietary chromium (Cr) (0, 75, 150, 300, 450, 600, and 1 200 ppb Cr) in the form of Cr nanoparticle (CrNano) on growth, body composition, serum hormones and tissue Cr in Sprague-Dawley (SD) rats. Seventy male SD rats (average initial body weight of (83.2+/-4.4) g) were randomly assigned to seven dietary treatments (n=10). At the end of the trial, body composition was assessed via dual energy X-ray absorptiometry (DEXA). All rats were then sacrificed to collect samples of blood, organs and tissues for determination of serum hormones and tissue Cr contents. The results indicated that lean body mass was significantly increased (P<0.05) due to the addition of 300 and 450 ppb Cr from CrNano. Supplementation of 150, 300, 450, and 600 ppb Cr decreased (P<0.05) percent body fat significantly. Average daily gain was increased (P<0.05) by addition of 75, 150, and 300 ppb Cr and feed efficiency was increased (P<0.05) by supplementation of 75, 300, and 450 ppb Cr. Addition of 300 and 450 ppb Cr decreased (P<0.05) the insulin level in serum greatly. Cr contents in liver and kidney were greatly increased (P<0.05) by the addition of Cr as CrNano in the dosage of from 150 ppb to 1 200 ppb. In addition, Supplementation of 300, 450, and 600 ppb Cr significantly increased (P<0.05) Cr content in the hind leg muscle. These results suggest that supplemental CrNano has beneficial effects on growth performance and body composition, and increases tissue Cr concentration in selected muscles.
Assuntos
Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cromo/administração & dosagem , Cromo/farmacocinética , Hormônios/sangue , Nanopartículas/administração & dosagem , Animais , Cromo/química , Relação Dose-Resposta a Droga , Masculino , Nanopartículas/ultraestrutura , Especificidade de Órgãos , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
OBJECTIVE: To establish and assess the Caco-2 cell in vitro absorption model. METHODS: Caco-2 cells were cultured on the millipore filters fixed in Snapwell transport chamber. The cell morphology, transepithelial electrical resistance, mannitol efflux rate and alkaline phosphatase activities were monitored during culture. RESULTS: After 21 days of in vitro culture, formation of tight junction was observed between the cells. The transepithelial electrical resistance reach a relatively stable value of 620-/+47 Omega.cm(2), the mannitol efflux rate was lower than 0.3%.h(-1).cm(-2), and the alkaline phosphatase activity in the apical side was significantly higher than that in the basolateral side. CONCLUSION: The established Caco-2 cell model shows similar morphology to intestinal epithelial cells with formation of polarity, and can be used as an in vitro model for absorption studies.