State Key Laboratory of Long acting and Targeting Drug Delivery Technologies

Yantai, China

State Key Laboratory of Long acting and Targeting Drug Delivery Technologies

Yantai, China
SEARCH FILTERS
Time filter
Source Type

Jiang W.-L.,Binzhou Medical University | Xu Y.,Binzhou Medical University | Zhang S.-P.,Binzhou Medical University | Zhu H.-B.,State Key Laboratory of Long Acting and Targeting Drug Delivery Technologies | Hou J.,State Key Laboratory of Long Acting and Targeting Drug Delivery Technologies
European Journal of Pharmaceutical Sciences | Year: 2012

There have been several studies of nuclear factor-κB (NF-κB) and high-mobility group box1 (HMGB1) associated with the pathophysiology of cerebral ischemia. Tricin 7-glucoside, a major bioactive compound extracted from Sedum sarmentosum Bunge. The objectives of this study were to determine the effects of Tricin 7-glucoside on a cultured neuronal cell line, SH-SY5Y in vitro and experimental ischemic stroke in vivo. For oxygen-glucose deprivation (OGD) and tumor necrosis factor-α (TNF-α) stimulated SH-SY5Y cell line in vitro, SH-SY5Y cells were incubated with Tricin 7-glucoside. For in vivo experiment, rats were subjected to middle cerebral artery occlusion (MACO) for 1 h, then followed by reperfusion for 23 h. Treatment of SH-SY5Y cells with Tricin 7-glucoside reduced the OGD-induced apoptosis and cytotoxicity, blocked TNF-α-induced NF-κB and IκB-α phosphorylation, and decreased HMGB1 expression. At doses higher than 50 mg/kg, Tricin 7-glucoside produced a significant neuroprotective potential in rats with ischemia and reperfusion (I/R). Tricin 7-glucoside (100 mg/kg) demonstrated significant neuroprotective activity even after delayed administration at 2 h and 4 h after I/R. Tricin 7-glucoside 100 mg/kg attenuated histopathological damage, decreased brain edema, inhibited NF-κB activation and reduced HMGB1 expression. These data show that Tricin 7-glucoside protects brain against I/R injury with a favorable therapeutic time-window by alleviating cerebral I/R injury and attenuating blood-brain barrier (BBB) breakdown, and its protective effects may involve HMGB1 and NF-κB signaling pathway. © 2011 Elsevier B.V. All rights reserved.


Kang Z.-C.,Binzhou Medical University | Jiang W.-L.,Binzhou Medical University | Xu Y.,Binzhou Medical University | Zhu H.-B.,State Key Laboratory of Long acting and Targeting Drug Delivery Technologies | Hou J.,State Key Laboratory of Long acting and Targeting Drug Delivery Technologies
European Journal of Pharmaceutical Sciences | Year: 2012

8-O-acetyl shanzhiside methylester (ND01) was isolated from the leaves of Lamiophlomis rotata (Benth.) Kudo. In this study, we investigated the anti-myocardial ischemia and reperfusion (I/R) injury effects of ND01 in vivo and elucidated the potential mechanism in vitro. The results indicated that ND01 significantly attenuated hypoxia-induced cytotoxicity in a concentration- dependent manner in H9c2 cells. Treatment of H9c2 cells with ND01 9 μM blocked TNF-α-induced nuclear factor kappaB (NF-κB) phosphorylation by blocking High-mobility group box1 (HMGB1) expression. Treatment of rats with ND01 10 mg/kg, (i.v.) protected the animals from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics and reduction of myocardial damage severity. Treatment with ND01 also lowered serum levels of pro-inflammatory factors and reduced High mobility group box-1 protein (HMGB1) and phosphorylated NF-κB expression in ischemic myocardial tissue. Additionally, continuos i.v. of ND01 14 days attenuated cardiac remodeling. These protective effects suggested that ND01 might be due to block of myocardial inflammatory cascades through an HMGB1-dependent NF-κB signaling pathway. © 2012 Elsevier B.V. All rights reserved.


Xu Y.,Binzhou Medical University | Jiang W.-L.,Binzhou Medical University | Zhang S.-P.,Binzhou Medical University | Zhu H.-B.,State Key Laboratory of Long acting and Targeting Drug Delivery Technologies | Hou J.,State Key Laboratory of Long acting and Targeting Drug Delivery Technologies
Basic and Clinical Pharmacology and Toxicology | Year: 2012

Recent studies have demonstrated that nuclear factor-κB (NF-κB) and high-mobility group box 1 (HMGB1) are associated with the pathophysiology of sepsis. The present study was carried out to investigate the effects of protocatechuic aldehyde (PA) on an experimental model of sepsis induced by caecal ligation and puncture (CLP) in rats and to elucidate the potential mechanism in the cultured murine macrophage cell line, RAW264.7 cells. Treatment of RAW 264.7 cells with PA blocked TNF-α-induced NF-κB phosphorylation and decreased HMGB1 expression. Septic rats received doses of 50mg of PA alone or plus Imipenem by intravenous bolus injection into the tail vein. The results showed that PA reduced serum levels of HMGB1 and triggering the receptor expressed on myeloid cells, it attenuated myeloperoxidase in the lung, liver and small intestine, while it up-regulated serum level of IL-10. Meanwhile, PA alone or plus Imipenem reduced CLP-induced lethality in septic rats. These data indicate that the anti-septic effect of PA is mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. The protective effects of PA might block the inflammatory cascades through HMGB1 and NF-κB signalling pathway. Our studies enhance the case for the use of PA in sepsis, and PA therefore seems promising in the treatment of sepsis in human beings. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.


Jiang W.-L.,Binzhou Medical University | Xu Y.,Binzhou Medical University | Zhang S.-P.,Binzhou Medical University | Hou J.,State Key Laboratory of Long acting and Targeting Drug Delivery Technologies | Zhu H.-B.,State Key Laboratory of Long acting and Targeting Drug Delivery Technologies
Basic and Clinical Pharmacology and Toxicology | Year: 2012

Connective tissue growth factor (CTGF) plays a pathogenic role in diabetic nephropathy (DN). Rosmarinic acid (RA) is a naturally occurring phenolic acid. This study was conducted to investigate the efficacy of RA on DN and to elucidate the potential mechanism. High glucose (HG)-stimulated cultured human renal proximal tubular epithelial cells (HK-2) analysed CTGF expression by western blotting, and it was investigated whether extracellular signal-regulated kinase (ERK) signalling pathway was involved. Using streptozotocin (STZ)-induced rat animal models, diabetic rats were randomized to receive intragastric (i.g.) doses of RA. Renal tissue, blood and urine samples were collected to determine biochemical index and analyse protein expression. In vitro study, RA reduced CTGF excretion in HG-induced HK-2 cells through the ERK signalling pathway. In an in vivo study, I.g. of RA 7.5 or 15mg/kg significantly ameliorated renal function and increased body-weight. Meanwhile, RA reduced renal CTGF expression by immunohistochemical staining and reduced serum levels of CTGF. Besides, there were no significant differences in glycaemia levels between the RA groups compared with the STZ-treated group. Furthermore, RA ameliorated renal pathology. These results suggest that RA exerts an early renal protective role to DN. Inhibition of CTGF may be a potential target in DN therapy, which highlights the possibility of using RA in the treatment of DN. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.


Jiang W.-L.,Binzhou Medical University | Jiang W.-L.,State Key Laboratory of Long acting and Targeting Drug Delivery Technologies | Zhang S.-P.,Binzhou Medical University | Hou J.,State Key Laboratory of Long acting and Targeting Drug Delivery Technologies | Zhu H.-B.,State Key Laboratory of Long acting and Targeting Drug Delivery Technologies
Phytomedicine | Year: 2012

Connective tissue growth factor (CTGF) plays a pathogenic role in diabetic nephropathy (DN). Loganin, an iridoid glucoside compound was isolated from Cornus officinalis Sieb. et Zucc. This study was conducted to investigate the efficacy of loganin on DN and to elucidate the potential mechanism. High glucose (HG) stimulated cultured human renal proximal tubular epithelial cells (HK-2) analyzed CTGF expression by Western blotting and investigated whether extracellular signal-regulated kinase (ERK) signaling pathway was involved. Streptozotocin (STZ)-induced experimental DN, randomized to receive intragastric (i.g.) of loganin. Renal tissue, blood and urine samples were collected to determine and analyze. In vitro study, loganin reduced CTGF excretion in HG-induced HK-2 cells through the ERK signaling pathway. In vivo study, I.g. of loganin 5 mg/kg or 10 mg/kg significantly ameliorated renal function and increased body weight. Meanwhile, loganin reduced renal CTGF expression by immunohistochemical staining, reduced serum levels of CTGF. Besides, there were no significant differences in blood sugar levels between the loganin groups compared to the STZ-treated group. Furthermore, loganin ameliorated renal pathology. These results suggested that loganin exerts an early renal protective role to DN. Inhibition of CTGF may be a potential target in DN therapy, which highlights the possibility of using loganin to treat DN. © 2011 Elsevier GmbH. All rights reserved.


Zhang S.,Ocean University of China | Ye L.,State Key Laboratory of Long acting and Targeting Drug Delivery Technologies | Tang X.,Ocean University of China
Journal of Ocean University of China | Year: 2012

Among the 116 actinomycetes collected from marine sediments of the Yellow Sea, 56 grew slowly and appeared after 2-3 weeks of incubation. Among the 56 strains, only 3 required seawater (SW) for growth, and 21 grew well in the medium prepared with SW rather than distilled water (DW), while the remaining 32 grew well either with SW or with DW. Six representatives with different morphological characteristics, including 1 SW-requiring strain and 5 well-growing with SW strains, were selected for phylogenetic analysis based on 16S rRNA gene. Two strains belong to Micrococcaceae and Nocardiopsaceae respectively. The other 4 strains belong to the family of Streptomycetaceae. In the analyzed 6 strains, one was related to Nocardiopsis spp. and the other three were related to Streptomyces spp., representing new taxa. Bioactivity testing of fermentation products from 3 SW-requiring strains and 21 well-growing with SW strains revealed that 17 strains possessed remarkable activities against gram-positive pathogen or/and tumor cells, suggesting that they were prolific resources for natural drug discovery. © 2012 Science Press, Ocean University of China and Springer-Verlag Berlin Heidelberg.


Yu X.,Yantai University | Yao J.-Y.,Yantai University | He J.,State Key Laboratory of Long acting and Targeting Drug Delivery Technologies | Tian J.-W.,Yantai University | Tian J.-W.,State Key Laboratory of Long acting and Targeting Drug Delivery Technologies
Life Sciences | Year: 2015

Aims The aim of the study is to evaluate the neuroprotective effects of continuous dopaminergic stimulation (CDS) by rotigotine-loaded microspheres (RoMS) in a mouse model of MPTP-induced Parkinson's disease (PD) and to elucidate the potential mechanism underlying these effects. Main methods Male C57BL/6 mice were treated either intramuscularly once with RoMS or twice daily for two weeks with rotigotine, and from the 9th day, MPTP (30 mg/kg, i.p.) was injected for the last 5 days. Following treatment, Parkinsonism scores were calculated and oxidative stress-related indicators in the striatum were performed. Neuroinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were detected in the striatum. Expression of apoptosis-related proteins B-cell leukemia/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX) was measured in the striatum by Western blot. Nigral tyrosine hydroxylase (TH)-positive neurons and microglial cell markers, i.e., ionized calcium binding adaptor molecule-1 (Iba-1) and neuronal synaptosomes, were quantified to assess the neuroprotective efficacy of RoMS. Key findings The administration of rotigotine significantly improved the Parkinsonism score, protected dopaminergic neurons with antioxidants, reduced microglial cell activation and the release of neuroinflammatory cytokines, and balanced the expression of Bcl-2 and Bax in MPTP-treated mice. Interestingly, the neuroprotective properties of rotigotine were remarkably amplified by CDS treatment with RoMS. Significance These results suggest that CDS therapy can play a neuroprotective role in an MPTP mouse model. Neuroprotective disease-modifying therapy may have the potential benefits of early treatment by normalizing compensatory mechanisms and may also help to delay dyskinesia in the later stages of PD. © 2015 Elsevier Inc. All rights reserved.

Loading State Key Laboratory of Long acting and Targeting Drug Delivery Technologies collaborators
Loading State Key Laboratory of Long acting and Targeting Drug Delivery Technologies collaborators