RESUMEN
BACKGROUND: Aging is associated with learning and memory disorder, affecting multiple brain areas, especially the hippocampus. Previous studies have demonstrated trilobatin (TLB), as a natural food additive, can extend the life of Caenorhabditis elegans and exhibit neuroprotection in Alzheimer's disease mice. However, the possible significance of TLB in anti-aging remains elusive. PURPOSE: This study aimed to delve into the physiological mechanism by which TLB ameliorated aging-induced cognitive impairment in senescence-accelerated mouse prone 8 (SAMP8) mice. METHODS: 6-month-old SAMP8 mice were administrated with TLB (5, 10, 20 mg/kg/day, i.g.) for 3 months. The therapeutic effect of TLB on aging-induced cognitive impairment was assessed in mice using behavioral tests and aging score. The gut microbiota composition in fecal samples was analyzed by metagenomic analysis. The protective effects of TLB on blood-brain barrier (BBB) and intestinal barrier were detected by transmission electron microscope, H&E staining and western blot (WB) assay. The inhibitive effects of TLB on inflammation in brain and intestine were assessed using immunofluorescence, WB and ELISA assay. Molecular docking and surface plasma resonance (SPR) assay were utilized to investigate interaction between TLB and sirtuin 2 (SIRT2). RESULTS: Herein, the findings exhibited TLB mitigated aging-induced cognitive impairment, neuron injury and neuroinflammation in hippocampus of aged SAMP8 mice. Moreover, TLB treatment repaired imbalance of gut microbiota in aged SAMP8 mice. Furthermore, TLB alleviated the damage to BBB and intestinal barrier, concomitant with reducing the expression of SIRT2, phosphorylated levels of c-Jun NH2 terminal kinases (JNK) and c-Jun, and expression of MMP9 protein in aged SAMP8 mice. Molecular docking and SPR unveiled TLB combined with SIRT2 and down-regulated SIRT2 protein expression. Mechanistically, the potential mechanism of SIRT2 in TLB that exerted anti-aging effect was validated in vitro. As expected, SIRT2 deficiency attenuated phosphorylated level of JNK in HT22 cells treated with d-galactose. CONCLUSION: These findings reveal, for the first time, SIRT2-mediated brain-gut barriers contribute to aging and aging-related diseases, and TLB can rescue aging-induced cognitive impairment by targeting SIRT2 and restoring gut microbiota disturbance to mediate the brain-gut axis. Overall, this work extends the potential application of TLB as a natural food additive in aging-related diseases.
Asunto(s)
Envejecimiento , Eje Cerebro-Intestino , Disfunción Cognitiva , Microbioma Gastrointestinal , Sirtuina 2 , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Ratones , Envejecimiento/efectos de los fármacos , Sirtuina 2/metabolismo , Masculino , Eje Cerebro-Intestino/efectos de los fármacos , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Simulación del Acoplamiento Molecular , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Modelos Animales de EnfermedadRESUMEN
Ginsenoside Re (GS-Re) is one of the main ingredients of ginseng, a widely known Chinese traditional medicine, and has a variety of beneficial effects, including vasorelaxation, antioxidative, anti-inflammatory, and anticancer properties. The aims of the present study were to observe the effect of GS-Re on balloon injury-induced neointimal hyperplasia in the arteries and to investigate the mechanisms underlying this effect. A rat vascular neointimal hyperplasia model was generated by rubbing the endothelium of the common carotid artery (CCA) with a balloon, and GS-Re (12.5, 25 or 50â¯mg/kg/d) were subsequently continuously administered to the rats by gavage for 14 days. After GS-Re treatment, the vessel lumen of injured vessels showed significant increases in the GS-Re 25.0 and 50.0â¯mg/kg/d (intermediate- and high-dose) groups according to H.E. staining. Additionally, a reduced percentage of proliferating cell nuclear antigen (PCNA)-positive cells and an increased number of SM α-actin-positive cells were detected, and the levels of NO, cyclic guanosine monophosphate (cGMP), and eNOS mRNA as well as the phos-eNOSser1177/eNOS protein ratio were obviously upregulated in the intermediate- and high-dose groups. Moreover, the promotive effects of GS-Re on NO and eNOS expression were blocked by L-NAME treatment to different degrees. These results suggested that GS-Re can suppress balloon injury-induced vascular neointimal hyperplasia by inhibiting VSMC proliferation, which is closely related to the activation of the eNOS/NO/cGMP pathway.
Asunto(s)
Angioplastia de Balón/instrumentación , Traumatismos de las Arterias Carótidas/prevención & control , Arteria Carótida Común/efectos de los fármacos , GMP Cíclico/metabolismo , Ginsenósidos/farmacología , Neointima , Óxido Nítrico Sintasa de Tipo III/metabolismo , Óxido Nítrico/metabolismo , Actinas/metabolismo , Animales , Traumatismos de las Arterias Carótidas/enzimología , Traumatismos de las Arterias Carótidas/etiología , Traumatismos de las Arterias Carótidas/patología , Arteria Carótida Común/enzimología , Arteria Carótida Común/patología , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hiperplasia , Masculino , Óxido Nítrico Sintasa de Tipo III/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratas Sprague-Dawley , Sistemas de Mensajero Secundario/efectos de los fármacosRESUMEN
It has been reported that icariin (ICA) increased contents of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) by improving expression of endothelial nitric oxide synthase (eNOS) and inhibition of phosphodiesterase type 5 (PDE5). In addition, dysfunction of the NO/cGMP pathway may play a crucial role in the pathogenesis of pulmonary hypertension (PH). In this study, the potential protective effects of ICA on PH induced by monocrotaline (MCT, 50 mg/kg) singly subcutaneous injection were investigated and the possible mechanisms involved in NO/cGMP pathway were explored in male Sprague Dawley rats. The results showed that ICA (20, 40, and 80 mg/kg/d) treatment by intragastric administration could significantly ameliorate PH and upregulate the expression of eNOS gene and downregulate the expression of PDE5 gene in MCT-treated rats. Both ICA (40 mg/kg/d) and L-arginine (200 mg/kg/d), a precursor of NO as positive control, notably increased the contents of NO and cGMP in lung tissue homogenate, which were inversed by treatment with (N) G-nitro-L-arginine-methyl ester (L-NAME), a NOS inhibitor, and L-NAME-treatment could also inhibit the protective effects of ICA (40 mg/kg/d) on mean pulmonary artery pressure and artery remodeling and tends to inhibit right ventricle hypertrophy index. In summary, ICA is effective in protecting against MCT-induced PH in rats through enhancement of NO/cGMP signaling pathway in rats.
RESUMEN
OBJECTIVE: To evaluate the correlation between image quality and thoracic diameters, anteroposterior diameter (AP) and right-left diameter (RL) for the optimization of reducing radiation dose in coronary artery imaging with Dual-source CT. METHODS: 118 patients underwent CT coronary artery imaging (CTCA) were divided into two groups (A and B) according to body mass index (BMI). There were 58 patients in group A with BMI values > or = 25 kg/m2 and < 30 kg/m2; and 60 patients in group B with BMI values < 25 kg/m2. Scan parameters: collimation 64 X 0.6 mm, reconstruction slice thickness 0.75 mm, reconstructin interval 0.7 mm, FOV 150-180 mm, the pitch adjusted according to heart rate automatically. CT imagings were obtained with tube voltage 100 kV, tube current 330 mAs (group A) and 100 kV, tube current 220 mAs (group B). The contrast-noise ratio (CNR), signal to noise ratio (SNR), as well as blind correlation test score values were calculated to establish the relationship among BMI, AP, RL and CNR, SNR. RESULTS: RL of five levels in groups of A, B were correlated to CNRa (P < 0.05). In group A and B (except iii, iv level of Group A), AP were associated with CNRa (P < 0.05). In addition to ii, iv level of group A, v level of group B, BMI were associated with CNRa (P < 0.05). The correlation coefficient of CNRa and RL of group A except ii level was greater than that of CNRa and AP. The correlation coefficient of CNRa, SNRa and RL of group B was greater than that of CNRa, SNRa and AP. Except iii level, the correlation coefficient of CNRa, SNRa and AP of group A was greater than that of CNRa, SNRa and BMI. Except ii level, the correlation coefficient of CNRa and AP of group B was greater than that of CNRa and BMI. CONCLUSION: Thoracic diameter of RL can be used as a guider to select the appropriate scan protocol in the coronary imaging acqusition with dual-source CT.