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26 April 2014, Volume 4 Issue 2 Previous Issue    Next Issue

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From Curcumin Toward Treatment of Alzheimer’s Disease: Some Thoughts on New Drug Discovery YIN Ming, WANG Ze-jian, ZHAO Wen-juan 2014, 4 (2):  1-7.  Abstract ( 3288 )   PDF (6968KB) ( 1200 )   During the last two decades， the story of vigorous curcumin R&D from activity assay to pre-clinical and clinical trials for Alzheimer’s disease and to final failure represents a chaotic thinking on pharmaceutical drug development. The research goals of pharmacologically involved compounds are usually as follows: to observe and record the activity spectrum of synthesized or isolated molecules; to advance drug candidate development based on activity，pharmacodynamic and pharmacokinetic data; to study the mechanism of action of druggable compound; and to participate in the basic biomedical research with the compound as a tool after the mechanism has been well known. Therefore， to avoid the waste of research resources and time，it is necessary for people to set up a clear goal，compare the chemical structures and exhaustively review the literature before a compound is going to be studied. References | Related Articles | Metrics

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Amelioration of Depression-like Behaviors with Proanthocyanidins in Combination with Piperine HUI Hu, PAN Bo-shi, HUANG Qi-meng, BI Meng-yun, PAN Jian-chun 2014, 4 (2):  8-15.  Abstract ( 3072 )   PDF (6254KB) ( 894 )   Objective: To investigate the effects of different doses (50，25，12.5 mg·kg-1) of Proanthocyanidin (OPC) combined with piperine (5 mg·kg-1) on depression-like behaviors in mice under chronic unpredictable mild stress. Methods: Chronic stress was applied for 21 days. After that, the immobility time of mice in the forced swimming test and tail suspension test were observed respectively. In addition, the HPLC-ECD was used to analyze the concentration of monoamines and their metabolites in the hippocampus and frontal cortex, and Fluorescence spectrophotometry was used to analyze the monoamine oxidase activity in mice brain. Results: Compared with the control group，the stressed group decreased the immobility time in the forced swimming test and tail suspension test ; At the same time, reduced 5-HT and NE levels, but increased the ratio of 5-HIAA/5-HT in the hippocampus and frontal cortex of mice were observed. The OPC (50，25，12.5 mg·kg-1) combined with piperine (5 mg·kg-1) showed a significantly larger effect on these measures. In addition, MAO-A activity in the brain was increased significantly when the mice were exposed to chronic stress, but MAO-B activity was not changed. The combination strategy could significantly decrease MAO-A activity which was raised by chronic stress, while they did not affect the MAO-B activity. Conclusion: Proanthocyanidins in combination with piperine ameliorated depression-like behaviors induced by chronic unpredictable mild stress in mice, which may be partially mediated through the serotonin and noradrenaline systems. References | Related Articles | Metrics

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Effect of Kangnaoye on Expression of VEGF, BDNF, MMP-9 after Cerebral Ischemia Reperfusion in Rats MA Jian-peng, CHANG-Qing, XUE-Qian, ZOU Yu-an 2014, 4 (2):  16-21.  Abstract ( 2197 )   PDF (4942KB) ( 925 )   Objective: To observe the effect of Kangnaoye pretreatment on the expression of vascular endothelial growth factor (VEGF), brain derived neurotrophic factor (BDNF),matrix metalloproteinase-9 (MMP-9) in rats with cerebral ischemia-reperfusion injury, and further to explore the neurovacular unit protective mechanism of Kangnaoye against the injury of cerebral ischemia-reperfusion. Methods: Male Spraque-Dawley rats were randomly divided into: Sham operation group，ischemia-reperfusion group，Kangnaoye 28.6，14.3，7.15 g·kg -1·d-1 dose group (intragastric administration, 7 d). Improved Zea Longa method was used to prepare cerebral ischemia-reperfusion model of rats. Reperfusion after ischemia for 2 h（rats were sacrificed respectively after reperfusion 6 h，12 h，24 h，72 h，7 d）. TTC staining method was used for observing the infarct area of rat brain; Immunohistochemical method was used for observing the expression of VEGF, BDNF, MMP-9 in rats brain tissue. Results: The comparison of the infarct area between the groups 24h after reperfusion ischemic found that the Kny High, Middle dose group significantly decreased the infarct area (P<0.05), along with the unregulated expression of VEGF,BDNF（P<0.01）. The expression of MMP-9 was significantly decreased as compared to model group（P<0.01）. Conclusion: Kangnaoye promoted the expression of VEGF, BDNF in brain tissue, inhibited the expression of MMP-9, decreased the infarct area and protected neurovascular unit against cerebral ischemia reperfusion injury. References | Related Articles | Metrics

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Effect of NMDA Receptor Antagonist Memantine on the Conditioned Fear Memory in Mice XU Chun-hua, HUANG Si-qi, YANG Hua-jia, HUANG Lu-lu, LV Xiu-yi, ZHOU Wen-hua 2014, 4 (2):  22-26.  Abstract ( 2333 )   PDF (3701KB) ( 935 )   NMDA receptor antagonist memantine is selected to examine the effects for the conditioned fear memory on mice. The mice were randomized into normal saline group, low dose group and high dose group. The percentage of mice freezing in different drug interventions was tested. The result showed that memantine dose-dependently affected the long-term and short-term memory of mice differently. However, memantine did not affect the extinction of fear memory. Consequently, memantine could affect the conditioned fear memory of mice and the effect varied according to the drug doses and interventions. References | Related Articles | Metrics

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Animal Models of Alzheimer's Disease: a Review WANG Ying, LIU Yu-gang, ZHANG Dan-shen 2014, 4 (2):  27-38.  Abstract ( 3557 )   PDF (11787KB) ( 976 )   Alzheimer's disease (AD) is one of the neurodegenerative diseases with brain atrophy, extracellular senile plaques and intracellular neurofibrillary tangles. Animal disease models are an indispensible part in the evaluation of potential therapeutics. This review summarized current animal models of AD. A thorough and critical evaluation of current models of AD, and a discussion about their roles in drug discovery and development were included as well. References | Related Articles | Metrics

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Antioxidative and Neuroprotective Effects of Angelica Sinensis Polysaccharide ZHANG Hai-hong, WANG Shu, WANG Jin, ZHANG Ji, HOU Yong 2014, 4 (2):  39-45.  Abstract ( 3020 )   PDF (6444KB) ( 816 )   Angelica Sinensis polysaccharide (ASP) is one of the main ingredients of Angelica sinensis. ASP can remove free radicals in the body and protect the nerve function. This article reviewed the effects of ASP in antioxidant and neuroprotection. References | Related Articles | Metrics

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RGMb/DRAGON Mediated Signaling Pathways LIU Jiang-feng, YANG Bao-xue 2014, 4 (2):  46-54.  Abstract ( 3267 )   PDF (9064KB) ( 859 )   The repulsive guidance molecule (RGM) family includes three members: RGMa, RGMb and RGMc. RGMb has been found in many tissues and organs, such as the nervous system, the reproductive system, the immune system, kidney, lung, muscle, etc. Accumulated evidences show that RGMb is related to embryonic development, immunoregulation, cell-to-cell adhesion, tumorigenesis, tissue repair, and other physiological processes. RGMb-neogenin-Rho signaling pathway and BMP signaling pathway play key roles in RGMb related functional regulation. This article focused on RGMb and reviewed the current knowledge regarding its structure, expression localization, signaling pathway, and physiological/pathophysiological functions. References | Related Articles | Metrics

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Progress in Understanding the Multiple Organ Injury Induced by Cerebral Ischemia-reperfusion ZHAO Wei, WANG Shu, LI Fang-jiang 2014, 4 (2):  55-64.  Abstract ( 2738 )   PDF (8605KB) ( 877 )   Acute ischemic cerebrovascular diseases such as cerebral infarction and cerebral hemorrhage are common and frequently-occurring diseases among the aged people with high mortality rate. After the attack of the ischemic cerebrovascular disease, some organ function would damage and fail, and even worse the occurrence of multiple organs function damage and failure. The failure of various organs causes the aggravation of the original brain lesions, further leading to aggravated multiple organs dysfunction with the emergence of a vicious spiral and even death. Accordingly, it is important to study the prevention and treatment of the multiple organ injury induced by cerebral ischemia-reperfusion. This review focused on the research progress in understanding organ injury such as heart, lung, liver, kidney, gastrointestinal tract, spleen and other organs, hemodynamic changes, and dysfunction of extremities induced by cerebral ischemia-reperfusion. A novel concept on cerebral ischemia-reperfusion was also discussed. References | Related Articles | Metrics