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Spatholobi Caulis dispensing granule reduces deep vein thrombus burden through antiinflammation via SIRT1 and Nrf2
Institution:1. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China;2. Guangdong Provincial Key Laboratory of Drug Non-clinical Evaluation and Research, Guangdong Lewwin Pharmaceutical Research Institute Co., Ltd., Guangzhou, Guangdong, 510990, China;3. College of Mathematics and Statistics, Shenzhen University, Shenzhen, Guangdong, 518060, China;1. School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan;2. Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan;3. Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan;4. School of Food Safety, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan;1. College of Animal Science and Technology, Northwest A&F University, Xinong Road 22nd, Yangling, Shaanxi 712100, China;2. College of Chemistry and Pharmacy, Northwest A&F University, Xinong Road 22nd, Yangling, Shaanxi 712100, China
Abstract:BackgroundDeep vein thrombosis (DVT) is a kind of blood stasis syndrome. Spatholobi Caulis (SC) has been widely used for the treatment of blood stasis syndrome in China, but the underlying mechanism remains poorly understood.PurposeThe aim of present study was to investigate the anti-DVT mechanism of Spatholobi Caulis dispensing granule (SCDG).Study design/methodsA rat model of inferior vena cava (IVC) stenosis-induced DVT and a cell model of oxygen-glucose deprivation (OGD) were performed. Rats were orally administered with SCDG solution once daily for seven consecutive days. IVC stenosis-induced DVT was operated on the sixth day. Thrombi were harvested and weighed on the seventh day. Pathological changes were observed by hematoxylin-eosin (HE) staining. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β of serum were analyzed by enzyme-linked immunosorbent assay. C-reactive protein (CRP) was measured with turbidimetric immunoassay. Protein expressions in thrombosed IVCs and/or OGD-stimulated EA. hy926 cells were evaluated by western blot and/or immunofluorescence analyses.ResultsSCDG dramatically decreased thrombus weight. SCDG decreased tissue factor (TF) protein expression, inflammatory cells influxes in thrombosed vein wall and serum levels of inflammatory cytokines and CRP. Further, SCDG up-regulated Sirtuin 1 (SIRT1) protein expression and down-regulated acetylated-NF-κB p65 (Ace-p65) protein expression. Moreover, SCDG up-regulated nuclear factor-erythroid 2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expressions, and down-regulated phosphorylated-NF-κB p65 (p-p65) protein expression. In the OGD cell model, SCDG medicated serum decreased the protein expression of TF. SCDG medicated serum enhanced SIRT1 protein expression and reduced Ace-p65 nuclear protein expression. SCDG medicated serum promoted protein expressions of nuclear Nrf2 and total HO-1, and inhibited translocation of p65. Furthermore, inhibiting SIRT1 and Nrf2 reversed the protective effect of SCDG medicated serum on OGD-induced EA. hy926 cells.ConclusionSCDG may prevent DVT through antiinflammation via SIRT1 and Nrf2.
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