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Jiang G.,Anhui University | Wu H.,Anhui University | Hu Y.,Anhui Medical University | Li J.,Anhui University | And 2 more authors.
Cellular and Molecular Neurobiology | Year: 2014

Previous research demonstrated that glutamate induces neuronal injury partially by increasing intracellular Ca2+ concentrations ([Ca 2+]i), and inducing oxidative stress, leading to a neurodegenerative disorder. However, the mechanism of glutamate-induced injury remains elusive. Gastrodin, a major active component of the traditional herbal agent Gastrodia elata (GE) Blume, has been recognized as a potential neuroprotective drug. In the current study, a classical injury model based on glutamate-induced cell death of rat pheochromocytoma (PC12) cells was used to investigate the neuroprotective effect of gastrodin, and its potential mechanisms involved. In this paper, the presence of gastrodin inhibits glutamate-induced oxidative stress as measured by the formation of reactive oxygen species (ROS), the level of malondialdehyde (MDA), mitochondrial membrane potential (MMP), and superoxide dismutase (SOD); gastrodin also prevents glutamate-induced [Ca2+]i influx, blocks the activation of the calmodulin-dependent kinase II (CaMKII) and the apoptosis signaling-regulating kinase-1 (ASK-1), inhibits phosphorylation of p38 mitogen-activated kinase (MAPK). Additionally, gastrodin blocked the expression of p53 phosphorylation, caspase-3 and cytochrome C, reduced bax/bcl-2 ratio induced by glutamate in PC12 cells. All these findings indicate that gastrodin protects PC12 cells from the apoptosis induced by glutamate through a new mechanism of the CaMKII/ASK-1/p38 MAPK/p53-signaling pathway. © 2014 Springer Science+Business Media New York. Source

Jiang G.,Anhui University | Hu Y.,Anhui Medical University | Peng C.,Anhui University | Li Q.,Anhui University | Li Q.,Anqing Medical and Pharmaceutical College
Neurochemistry International | Year: 2014

Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine Gastrodia elata (GE) Blume, has been known to display antioxidant activity. The present study aimed to investigate the protective effects of gastrodin on 1-methyl-4-phenylpyridinium (MPP +)-induced oxidative cytotoxicity in human dopaminergic SH-SY5Y cells and the underlying mechanism for this neuroprotection. Results indicate that pre-treatment with gastrodin for 1 h significantly reduced the MPP +-induced viability loss, apoptotic rate and attenuated MPP +-mediated ROS production. In addition, gastrodin inhibited MPP +-induced lowered membrane potential, decreased Bcl-2/Bax ratio. Moreover, we have revealed the gastrodin increased Nrf2 nuclear translocation, which is upstream of heme oxygenase-1 (HO-1) expression and for the first time revealed gastrodin could increased antioxidant enzyme HO-1 expression in concentration-dependent and time-dependent manners. HO-1 siRNA transfection was employed, and confirmed gastrodin could active the expression of HO-1. And the increase in HO-1 expression was correlated with the protective effect of gastrodin against MPP+-induced injury. Because the inhibitor of HO-1 activity, ZnPP reversed the protective effect of gastrodin against MPP +-induced cell death. We also demonstrated that the specific p38 MAPK inhibitor, SB203580, concentration-dependently blocked on gastrodin-induced HO-1 expression, and meanwhile SB203580 reversed the protective effect of gastrodin against MPP+-induced cell death. Taken together, these findings suggest that gastrodin can induce HO-1 expression through activation of p38 MAPK/Nrf2 signaling pathway, thereby protecting the SH-SY5Y cells from MPP+-induced oxidative cell death. Thus our study indicates that gastrodin has a partial cytoprotective role in dopaminergic cell culture systems and could be of importance for the treatment of PD and other oxidative stress-related diseases. © 2014 Elsevier Ltd. All rights reserved. Source

Cao L.-L.,Anhui Medical University | Cao L.-L.,Huainan Union University | Li W.-Z.,Anhui Medical University | Si X.-L.,Anhui Medical University | And 3 more authors.
Zhongguo Zhongyao Zazhi | Year: 2013

Objective: To study the protective effect of astragaloside IV (AS IV) on H2O2 induced human mesangial cells (HMC), and further explore its molecular mechanism. Method: The cultured mesangial cells were divided into 5 groups: the normal control group, the H2O2 model group, the AS IV (12.5, 100 nmol · L-1) group and the Tempol (1 × 105 nmol · L-1) group. The MTT method was used to observe cell viability. Hoechst 33258 staining was used to observe the HMC apoptosis and DHE staining was used to detect the generation of reactive oxygen species (ROS). The flow cytometry was used to detect the changes in cell cycle. Western blot was used to detect the expression of Cyclin D1, CyclinA, p38, and T-p38. Result: H2O2 (1 × 105, 2 × 105, 3 × 105, and 4 × 10 nmol · L-1) could induce HMC oxidative stress injury, with significant decrease in the cell survival rate. AS IV (100 nmol · L-1) could significantly inhibit HMC oxidative stress injury induced by H2O2(3 × 10 nmol · L-1), increase the survival rate of HMC cells, inhibit cell apoptosis, and decrease intracellular ROS production. AS IV could also increase the expression of Cyclin D1, recover normal cell proliferation, and decrease the expression of p38. Conclusion: AS IV can protect H2O2induced oxidative stress injury in mesangial cells. Its mechanisms may be related to inhibiting the p38/MAPK signaling pathway, increasing the expression of Cyclin D1 and decreasing the intracellular ROS oxidative stress injury. Source

Chen M.,Anhui Medical University | Chen M.,Anhui University of Traditional Chinese Medicine | Chen Z.-W.,Anhui Medical University | Long Z.-J.,Anhui University of Traditional Chinese Medicine | And 3 more authors.
Chinese Journal of Integrative Medicine | Year: 2015

Methods: Thirty-two 16-week-old spontaneously hypertensive rats were randomly divided into four groups (8 in each group): model group (placebo), positive control group (27 mg/kg of Captopril Tablets), Sapindus saponins groups (27 mg/kg and 108 mg/kg, respectively). Another 8 healthy Wistar-Kyoto strain (WKY) rats were used as the normal group. The animals were treated for 8 weeks. Blood pressure of rats was determined by non-invasive blood pressure meter (BP-6). Furthermore, the contents of angiotensin II (Ang II) in plasma and myocardial tissue were determined by enzyme-linked immunosorbent assay (ELISA), the gene expression of receptor angiotensin type 1 (AT1R) in aorta was determined by quantitative realtime polymerase chain reaction (qRT-PCR). The protein expression of transforming growth factor-β1 (TGF-β1) and AT1R in heart was determined by immunohistochemical staining. The protein expression of p-phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK) was determined by Western blotting. The contents of interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF) in serum were determined by radioimmunoassay. And the histopathological and morphological changes of aorta and heart tissue samples were assessed semi-quantitatively by hematoxylin-eosin (HE) or Masson staining.Objectives: To investigate the protective effects of Sapindus saponins in spontaneously hypertensive rats, and the possible cellular and molecular mechanisms.Results: Thirty minutes after single or continuous treatment, systolic blood pressure (SBP) was reduced significantly in Sapindus saponins groups. And the contents of AngII, IL-1, IL-6 and TNF-α in serum, the expression of AT1R mRNA, p-p38MAPK and TGF-β1 were significantly suppressed dose-dependently (P<0.05 or P<0.01). With the Sapindus saponins treatment, compared with those of the model group, the cardiac and aortic pathological changes were ameliorated significantly.Conclusions: Our findings suggest that Sapindus saponins might have protective effects in spontaneously hypertensive rats, the cellular and molecular mechanisms of which might be relevant to the regulation of inflammatory responses mediated by p-p38MAPK signal pathway based on activated Ang II and AT1R. © 2013, Chinese Association of the Integration of Traditional and Western Medicine and Springer-Verlag Berlin Heidelberg. Source

Zhang L.,Anhui University | Guo L.,Anhui University | Ding J.,Anqing Medical and Pharmaceutical College | Lu Y.,Anhui University | And 2 more authors.
Bulletin of the Korean Chemical Society | Year: 2015

In order to develop the application of the natural polysaccharide lentinan (LNT) and decrease the side effects of doxorubicin, we successfully synthesized a novel folate-modified maleilated lentinan-doxorubicin (FA-M. LNT-DOX) polymer and used it for tumor-targeted drug delivery. The release efficiency and cytotoxicity of the prodrugs were evaluated in vitro. Although DOX release from FA-M.LNT-DOX was quite slow in a neutral buffer, it was particularly fast in an acidic solution with a pH of 5.0. Compared with DOX, FA-M. LNT-DOX showed higher cytotoxicity in HeLa cells and significantly lower cytotoxicity in normal cells. These results suggested that FA-M.LNT-DOX could be considered as a potential drug delivery candidate for folate receptor-positive cancer therapy. © 2015 Korean Chemical Society & Wiley-VCH Verlag GmbH & Co. KGaA. Source

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