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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.

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