South China Center for Innovative Pharmaceuticals

Guangzhou, China

South China Center for Innovative Pharmaceuticals

Guangzhou, China
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Liang Y.,Weifang Medical University | Jiang W.,South China Center for Innovative Pharmaceuticals | Zhang Z.,Peoples Hospital of Shouguang | Yu J.,Weifang Medical University | And 2 more authors.
Biological and Pharmaceutical Bulletin | Year: 2012

Neuropathic pain is a devastating neurological disease that seriously affects patients' quality of life. Despite a high level of incidence, the underlying mechanisms of neuropathic pain are still poorly understood. However, recent evidence supports the prominent role of spinal glial cells in neuropathic pain states. In our laboratory, we observed that najanalgesin, a novel peptide isolated from the venom of Naja naja atra, exerts significant analgesic effects on acute pain in mice and neuropathic pain in rats. The objective of the present study was to determine whether spinal glia are associated with the antinociceptive effect of najanalgesin in an L5 spinal nerve ligation (SNL) rodent model of neuropathic pain. Mechanical allodynia developed after surgery, and hypersensitivity was significantly attenuated by the intrathecal administration of najanalgesin. The inhibitory effect of najanalgesin was significantly (p<0.05) enhanced after pretreatment with fluorocitrate (a glial cell antagonist). In addition, the astrocyte activation was attenuated following najanalgesin treatment in the dorsal horn of neuropathic rats, as assessed by immunohistology and Western blotting. The tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) content of cerebral spinal fluid and cell culture supernatants changed significantly after najanalgesin administration. The results suggest that najanalgesin may exert its anti-allodynic effect by altering astrocyte cell function. © 2012 The Pharmaceutical Society of Japan.

Liu A.,South China University of Technology | Liu A.,Ningbo University | Gonzalez F.J.,U.S. National Institutes of Health | Cheng G.Q.,South China Center for Innovative Pharmaceuticals | Dai R.,South China University of Technology
Chemical Research in Toxicology | Year: 2011

Gemfibrozil is the most myotoxic fibrate drug commonly used for dyslipidemia, but the mechanism is poorly understood. The current study revealed that gemfibrozil inhibits myoblast differentiation through the regulation of intracellular calcium ([Ca2+]i) as revealed in L6 myoblasts by use of laser scan confocal microscopy and flow cytometry using Fluo-4 AM as a probe. Gemfibrozil at 20-400 μM, could regulate [Ca2+]i in L6 cells in a biphasic manner, and sustained reduction was observed when the concentration reached 200 μM. Inhibition of L6 differentiation by gemfibrozil was concentration-dependent with maximal effect noted between 200 and 400 μM, as indicated by creatine kinase activities and the differentiation index, respectively. In differentiating L6 myoblasts, gemfibrozil at concentrations below 400 μM led to no significant signs of apoptosis or cytotoxicity, whereas differentiation, inhibited by 200 μM gemfibrozil, was only partially recovered. A good correlation was noted between gemfibrozil concentrations that regulate [Ca2+]i and inhibit L6 myoblasts differentiation, and both are within the range of total serum concentrations found in the clinic. These data suggest a potential pharmacodynamic effect of gemfibrozil on myogenesis as a warning sign, in addition to the complex pharmacokinetic interactions. It is also noteworthy that mobilization of [Ca2+]i by gemfibrozil may trigger complex biological responses besides myocyte differentiation. Information revealed in this study explores the mechanism of gemfibrozil-induced myotoxicity through the regulation of intracellular calcium. © 2010 American Chemical Society.

Zhang H.-L.,Guangdong Pharmaceutical University | Zhang H.-L.,South China Center for Innovative Pharmaceuticals | Tao Y.,Guangdong Pharmaceutical University | Guo J.,Guangdong Pharmaceutical University | And 2 more authors.
International Immunopharmacology | Year: 2011

The aim of this study was to investigate the hypolipidemic effects of chitosan nanoparticles(CTS-NP) preparations with ionotropic gelation, rotary evaporation, and spray-drying technique. Male SD (Sprague-Dawley) rats were separated into five groups, a normal diet group, a high fat emulsions group, a CTS control group and CTS-NP groups treated with two different doses of CTS-NP. The nanoparticles were spherical in shape and had a smooth surface. The size range of the nanoparticles was between 500 and 1000 nm. The apparent serum lipid and plasma viscosity in CTS-NP group was significantly lower than that in the CTS group, as well as the serum superoxide dismutate (SOD) levels was increased. Although no significant difference in adipose tissue was found among the groups, the rats fed on CTS-NP had lower relative liver weight and body weight when compared with those fed on normal diet. This study was the first report of the effects of CTS-NP in the hyperlipidemia rats, and suggests that the CTS-NP could be used for the treatment of hyperlipidemia. © 2010 Elsevier B.V.

Ji X.,South China Center for Innovative Pharmaceuticals | Feng Y.F.,Guangdong Pharmaceutical University | Rui W.,Guangdong Pharmaceutical University
Proceedings - 2012 International Conference on Biomedical Engineering and Biotechnology, iCBEB 2012 | Year: 2012

A rapid method for the chemical constituents analysis of Chinese herbal Rhizoma Anemarrhenae was developed by using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF MS) in both positive and negative ESI mode. This method could provide good accuracy of molecular weight of each component found in the Rhizoma with relative deviation within 5 ppm. On the basis of the mass spectrometric fragmentation mechanisms, MS/MS data and relevant literatures, the constituents of Rhizoma Anemarrhenae, including 7 xanthones and 43 steroidal saponins, were identified, in which 17 new isomers and 9 components were discriminated in Rhizoma Anemarrhenae for the first time. Meanwhile, the fragmentation behaviors of individual components were discussed in details. © 2012 IEEE.

Yan G.,South China Center for Innovative Pharmaceuticals | Yan G.,Sun Yat Sen University | Zhang G.,BGI Shenzhen | Fang X.,BGI Shenzhen | And 47 more authors.
Nature Biotechnology | Year: 2011

The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies. © 2011 Nature America, Inc. All rights reserved.

Zhang H.,Sun Yat Sen University | Zhu W.,Sun Yat Sen University | Su X.,Sun Yat Sen University | Wu S.,Sun Yat Sen University | And 10 more authors.
Journal of Neuro-Oncology | Year: 2012

Malignant glioma is the most devastating and aggressive tumor in brain, characterized by rapid proliferation and diffuse invasion. Chemotherapy and radiotherapy are the pivotal strategies after surgery; however, high drug resistance of malignant glioma and the blood-brain barrier usually render chemotherapy drugs ineffective. Here, we find that triptolide, a small molecule with high lipid solubility, is capable of inhibiting proliferation and invasion of malignant glioma cells effectively. In both investigated malignant glioma cell lines, triptolide repressed cell proliferation via inducing cell cycle arrest in G0/G1 phase, associated with downregulation of G0/G1 cell cycle regulators cyclin D1, CDK4, and CDK6 followed by reduced phosphorylation of retinoblastoma protein (Rb). In addition, triptolide induced morphological change of C6 cells through downregulation of protein expression of MAP-2 and inhibition of activities of GTPases Cdc42 and Rac1/2/3, thus significantly suppressing migratory and invasive capacity. Moreover, in an in vivo tumor model, triptolide delayed growth of malignant glioma xenografts. These findings suggest an important inhibitory action of triptolide on proliferation and invasion of malignant glioma, and encourage triptolide as a candidate for glioma therapy. © 2012 Springer Science+Business Media, LLC.

Zhang G.-Q.,South China University of Technology | Ni C.,South China University of Technology | Ling F.,South China University of Technology | Qiu W.,South China University of Technology | And 9 more authors.
Tissue Antigens | Year: 2012

Cynomolgus macaques (Macaca fascicularis, Mafa) have emerged as an important animal model for infectious disease and transplantation research. Extensive characterization of their major histocompatibility complex (MHC) polymorphism regions therefore becomes urgently required. In this study, we identified 41 MHC class I A nucleotide sequences in 34 unrelated cynomolgus macaques of Vietnamese origin farmed in Southern China, including eight novel Mafa-A sequences. We found two sequences with perfect identity and six sequences with close similarity to previously defined MHC class I alleles from other populations, especially from Indonesian-origin macaques. We also found three Vietnamese-origin cynomolgus macaque MHC class I sequences for which the predicted protein sequences identical throughout their B and F binding pockets to Mamu-A1*001:01 and Mamu-A3*13:03, respectively. This is important because Mamu-A1*001:01 and Mamu-A3*13:03 are associated with longer survival and lower set-point viral load in simian immunodeficiency virus (SIV)-infected rhesus monkeys. These findings have implications for the evolutionary history of Vietnamese-origin cynomolgus macaque as well as for the use of this model in SIV/SHIV (a virus combining parts of the HIV and SIV genomes) research. © 2012 John Wiley & Sons A/S.

Liu B.,University of Sichuan | Wu J.-M.,University of Sichuan | Li J.,South China Center for Innovative Pharmaceuticals | Liu J.-J.,University of Sichuan | And 4 more authors.
Biochimie | Year: 2010

Polygonatum cyrtonema lectin (PCL), a mannose/sialic acid-binding lectin, has been reported to display remarkable anti-proliferative and apoptosis-inducing activities toward a variety of cancer cells; however, the precise molecular mechanisms by which PCL induces cancer cell death are still elusive. In the current study, we found that PCL could induce apoptosis and autophagy in murine fibrosarcoma L929 cells. Subsequently, we demonstrated that inhibition of Ras could promote L929 cell death, suggesting that Ras-Raf signaling pathway plays the key negative regulator in PCL-induced apoptosis. And, we showed that Ras-Raf signaling pathway was also involved in PCL-induced autophagy as the negative regulator. In addition, we found that class I phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway could play the negative regulator in PCL-induced apoptosis and autophagy. Taken together, these results demonstrate that PCL induces murine fibrosarcoma L929 cell apoptosis and autophagy via blocking Ras-Raf and PI3K-Akt signaling pathways. © 2010 Elsevier Masson SAS. All rights reserved.

Li W.,General Hospital of PLA T | Wang T.,South China University of Technology | Ling F.,South China University of Technology | Zhao H.,General Hospital of PLA T | And 6 more authors.
American Journal of Primatology | Year: 2012

Cynomolgus macaques have been used widely to build a research model of infectious and chronic diseases, as well as in transplantation studies, where disease susceptibility and/or resistance are associated with the major histocompatibility complex (MHC). To better elucidate polymorphisms and genetic differences in the Mafa-DRB locus, and facilitate the experimental use of cynomolgus macaques, we used pool screening combined with cloning and direct sequencing of polymerase chain reaction products to characterize MhcMafa-DRB gene alleles in 153 Vietnamese cynomolgus macaques. We identified 30 Mafa-DRB alleles belonging to 17 allelic lineages, including four novel sequences that had not been documented in earlier reports. The highest frequency allele was Mafa-DRB*W27:04, which was present in 7 of 35 (20%) monkeys. The next most frequent alleles were Mafa-DRB*3:07 and Mafa-DRB*W7:01, which were detected in 5 of 35 (14.3%) and 4 of 35 (11.4%) of the monkeys, respectively. The high-frequency alleles in this Vietnamese population may be high priority targets for additional characterization of immune functions. Only the DRB1*03 and DRB1*10 lineages were also present in humans, whereas the remaining alleles were monkey-specific lineages. We found 25 variable sites by aligning the deduced amino acid sequences of 29 identified alleles. Evolutionary and population analyses based on these sequences showed that human, rhesus, and cynomolgus macaques share several Mhc-DRB lineages and the shared polymorphisms in the DRB region may be attributable to the existence of interbreeding between rhesus and cynomolgus macaques. This information will promote the understanding of MHC diversity and polymorphism in cynomolgus macaques and increase the value of this species as a model for biomedical research. © 2012 Wiley Periodicals, Inc.

Liu M.,Jinan University | Liu W.,Jinan University | Jiang J.,Jinan University | Cheng Q.,South China Center for Innovative Pharmaceuticals | Ren J.-L.,South China Center for Innovative Pharmaceuticals
Chinese Journal of New Drugs | Year: 2011

Objective: To synthesize the resveratrol analogs with more potent anti-oxidative activities. Methods: The A ring of resveratrol was substituted by TMP ring or 4-aminoquinoline ring. The DPPH radical scavenging abilities of the target molecules 9, 12 and intermediate 8, 11 were tested. Results and Conclusion: Two novel resveratrol analogues were synthesized, and their structures were confirmed by MS and 1H-NMR. Compoud 8 possesses more potent DPPH radical scavenging ability than resveratrol at low concentration and holds potent anti-oxidative activity.

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