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Improving effect of Ginkgolide B on mitochondrial respiration of ischemic neuron after cerebral thrombosis in tree shrews

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Chinese Medical Journal 2007年第17期120卷 1529-1533页

作者： LI Shu-qing ZHANG Ying YANG Li-jun Department of Pathophysiology Kunming Medical CollegeKunming 650031 China

Background It has been known that platelet activating factor receptors （PAFR） may mediate many acute pathological responses and that PAFR antagonist Ginkgolide B （GB） possesses multiple effects, but the actions of GB on PAFR affinity and mitochondrial respiration in the ischemic neuron were unclear until now. This study explored the possible effects of GB on PAFR and the mitochondrial respiration of the neuron in the ischemic microenvironment. Methods Thrombotic cerebral ischemia in tree shrews was induced by a photochemical reaction; changes in the regional cerebral blood flow （rCBF, using ^99rnTc tracer technique ）, the brain water content （specific gravimetric method）, PAFR （3H-labelled PAF assay）, the respiratory control rate （RCR）, the phosphorus-oxygen （P/O） ratio of mitochondrial respiration （Clark oxygen electrode）, mitochonddal permeability transition （MPT） pore, and the mitochondrial ultrastructure in the ischemic neurons were also observed. Data were compared between the two groups （the ischemia group vs the sham group, and the ischemia group vs the GB group）. Results There were high affinity and low affinity sites for PAFR on the tree threws＇ brain cell membranes. The varying-affinity PAFR binding sites, the respiration state Ⅲ, the state Ⅳ, RCR, the P/O ratio of the mitochondria, and the rCBF all decreased markedly （respectively, P〈0.01 and P〈0.05）, but the water content increased （P〈0.01） in the ischemia group after the application of cerebral thrombosis. In tree shrews treated with GB （5 mg/kg i.v.） 6 hours after photochemical reaction, their PAFR binding sites and respiratory state increased markedly. The rCBF gradually increased and the brain edema ameliorated （P〈0.01） at 24h after cerebral ischemia. There were significant differences between the ischemJa group and sham group （P〈0.01）. In GB treated isolated neurons＇ mitochondria, with or without cerebral ischemia, the energy metabolism of the mitochondria had not been changed. Conclusions The activation of the PAFR may play an important

关键词： photochemistry cerebral ischemia mitochondria Ginkgolide tree shrews

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Transcellular transport characteristics of huperzine alone or in combination with Ginkgolide B across Caco-2 and Madin-Darby canine kidney cell monolayer

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Asian Pacific Journal of Tropical Medicine 2014年第11期7卷 889-894页

作者： Wen-Cui Zhao Zhi-Hong Hou Qi Zhang Wei Zheng Pharmacy Department 208th Hospital of PLA. Hospital Office 208th Hospital of PLA. Infirmary 208th Hospital of PLA.

Objective:To study the various processes involved in transcellular transport(TT) of huperzine A alone or in combination with Ginkgolide B in Caco-2 and Madin-Darby canine renal(MDCK)cell monolayer.Methods:The transepithelial passage was assayed in the apical-to-basolateral(AP to BL) direction and opposite direction(BL to AP) in both cell lines.The determination of huperzine A and Ginkgolide B were performed by high performance liquid chromatography(HPLC).The passage rates of huperzine A and Ginkgolide B were calculated.Bi-directional TT(absorption and secretion) were taken in huperzine A and Ginkgolide B in Caco-2 and MDCK cell monolayer.Results:TT absorption and secretion kinetics of huperzine A and Ginkgolide B across two cells existed at the same time.The passage rates of huperzine A were increased significantly with adding different concentrations of Ginkgolide B.Conclusions:The compound preparations of HA in combination with CB for dementia caused by cerebral ischemic have synergistic effects on the pharmacodynamics,and improve the bioavailability through BBB.

关键词： Caco-2 Huperzine A Ginkgolide B Madin-Darby canine renal Transcellular Transport

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Ginkgolide C Stimulates CFTR-mediate Anion Conductance in Distal Colon:Implication for Therapy of Gastrointestinal Diseases

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Chemical Research in Chinese Universities 2009年第6期25卷 909-913页

作者： LIAO Qi MA Xiao-yan WU Fu-ju YANG Li-xiao WANG Shuai Second Teaching Hospital of Jilin University Changchun 130041 P. R. China The Daqing Longnan Hospital Daqing 163453 P. R. China

The effects and the mechanisms of natural compounds Ginkgolides on CFTR-mediate anion transport were investigated. The CFTR-mediate iodide influx rates were studied via a cell-based fluorescence assay done for FRT cells stably transfected by CFTR; transepithelial short-circuit current recordings of FRT cells and rat distal colon mucosa were respectively obtained. Cellular cAMP concentrations were measured via a radioimmunoassay analysis kit. Ginkgolide C dose-dependently increases CFTR-mediate anion transport, whereas Ginkgolide A and B show no effect. The activation is sensitive to CFTR specific activator CFTRinh-172. Ginkgolide C stimulated amiloride and indomethacin pre-treated Cl currents in rat distal colon mucosa. Studies on FRT cells also manifest that Ginkgolide C had additive effect with FSK/IBMX mixture and didn＇t elevate intracellular cAMP concentration, which implies it works through a direct binding mechanism. In conclusion, Ginkgolide C directly stimulates CFTR-mediate anion transport. Ginkgolide C may be a promising drug for the prevention and treatment of CFTR-related diseases such as idiopathic chronic pancreatitis（ICP）, habitual constipation, and kcratoconjunctivitis sicca（KCS）.

关键词： Ginkgolide Cystic fibrosis transmembrane conductance regulator Fluorescence Mucosa

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Ginkgolide K protects cardiomyocytes against ER stress through stimulating ER-associated degradation （ERAD） and autophagy

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中国药理学通报 2015年第B11期31卷 181-182页

作者： WANGShou-bao WANGZhen-zhong FANQi-ru DUGuan-hua WANGXin XIAOWei FacultyofLifeSciences TheUniversityofManchesterManchesterM139NTUK

Aim Endoplasmic reticulum （ER） stress is increasingly recognized as an important contributor to the pathophysiology of many diseases, and therapeutic interventions that target ER stress response emerge as new thera- peutic modalities to treat cardiovascular diseases driven by prolonged ER stress. Ginkgolides K （GK） is a diterpene lactone constituent isolated from the leaves of Ginkgo biloba and has been found to possess potent neuroprotective properties. This study is aimed to investigate the cytoprotective effect of GK in cultured cardiomyocytes subjected to ER stress injury. Neonatal rat cardiomyocytes （NRCMs） were treated with ER stress inducer tunicamycin to mimic the ER stress injury. We demonstrated that GK pre-treatment mitigated ER stress-induced apoptosis in tunicamycin treated NRCMs. We observed that the activation of ER-associated degradation （ERAD） and autophagy were in- volved in the ER stress inhibition exerted by GK. These beneficial effects of GK were nearly abolished by the addi- tion of specific short interfering RNA （siRNA） for IRElα and XBP-1. Therefore, we conclude that GK might be a promising therapeutic agent for ER stress-mediated cardiovascular diseases, and ER-associated degradation （ERAD） and autophagy play a vital role in GK mediated cytoprotection.

关键词： Ginkgolide K ER stress Neonatal rat cardiomyocytes (NRCMs) ER-associated degradation (ERAD) Autophagy

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Influence of Ginkgolide combined with edaravone on the brain function of elderly patients with acute cerebral infarction and its preventive effect on ischemia reperfusion injury

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Journal of Hainan Medical University 2017年第24期23卷 121-125页

作者： Ju-Rong Li Department of Geriatrics Dazhou Central Hospital in Sichuan ProvinceDazhouSichuan Province635000

Objective: To explore the influence of Ginkgolide combined with edaravone on the brain function of elderly patients with acute cerebral infarction and its preventive effect on ischemia reperfusion injury. Methods: A total of 126 patients with acute cerebral infarction who were treated in Dazhou Central Hospital between February 2016 and May 2017 were divided into the control group (n=67) and Ginkgolide group (n=59) according to different therapies. Control group received routine intravenous thrombolysis + edaravone therapy, and Ginkgolide group received routine intravenous thrombolysis + edaravone + Ginkgolide therapy. The differences in brain function and nerve ischemia reperfusion injury extent were compared between the two groups. Results: At T1 and T2, serum nerve function indexes NT-proBNP and NSE levels of Ginkgolide group were lower than those of control group whereas BDNF levels were higher than those of control group;serum inflammatory mediators MCP-1, NF-κB, CRP and TNF-α levels were lower than those of control group;serum apoptosis molecules caspase-3 and Bax levels were lower than those of control group whereas Bcl-2 levels were higher than those of control group. Conclusion: Ginkgolide combined with edaravone therapy on the basis of intravenous thrombolysis can effectively optimize the brain function and alleviate the ischemia reperfusion injury caused by inflammatory response and apoptosisis in elderly patients with acute cerebral infarction.

关键词： Acute cerebral infarction Ginkgolide Edaravone Brain function Ischemia reperfusion injury

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Effects of Ginkgo biloba extract EGb761 on neural differentiation of stem cells offer new hope for neurological disease treatment

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Neural Regeneration Research 2019年第7期14卷 1152-1157页

作者： Chao Ren Yong-Qiang Ji Hong Liu Zhe Wang Jia-Hui Wang Cai-Yi Zhang Li-Na Guan Pei-Yuan Yin Department of Neurology and Suzhou Clinical Research Center of Neurological Disease the Second Affiliated Hospital of Soochow University Department of Neurology Affiliated Yantai Yuhuangding Hospital of Qingdao University Department of Nephrology Affiliated Yantai Yuhuangding Hospital of Qingdao University Department of Clinical Laboratory Affiliated Yantai Yuhuangding Hospital of Qingdao University Department of Central Laboratory Affiliated Yantai Yuhuangding Hospital of Qingdao University Department of Emergency and Rescue Medicine Xuzhou Medical University Department of Neurosurgical Intensive Care Unit the Affiliated Yantai Yuhuangding Hospital of Qingdao University Department of Blood Supply Yantai Center Blood Station

Stem cell transplantation has brought new hope for the treatment of neurological diseases.The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells.Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors,the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located.Accordingly,the optimal microenvironment for inducing stem cell differentiation is a hot topic.EGb761 is extracted from the leaves of the Ginkgo biloba tree.It is used worldwide and is becoming one of the focuses of stem cell research.Studies have shown that EGb761 can antagonize oxygen free radicals,stabilize cell membranes,promote neurogenesis and synaptogenesis,increase the level of brain-derived neurotrophic factors,and replicate the environment required during the differentiation of stem cells into nerve cells.This offers the possibility of using EGb761 to induce the differentiation of stem cells,facilitating stem cell transplantation.To provide a comprehensive reference for the future application of EGb761 in stem cell therapy,we reviewed studies investigating the influence of EGb761 on stem cells.These started with the composition and neuropharmacology of EGb761,and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.

关键词： nerve regeneration Ginkgo biloba extract Ginkgolide B traditional Chinese medicine stem cells induction of differentiation stem cell transplantation synaptic plasticity pharmacological effect neurological diseases nervous systems neural regeneration

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Applying risk management to analytical methods for the desorbing process of ginkgo diterpene lactone meglumine injection

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Chinese Journal of Natural Medicines 2018年第5期16卷 366-374页

作者： XU Fang-Fang BI Yu-An HUANG Wen-Zhe WANG Zhen-Zhong XIAO Wei Nanjing University of Traditional Chinese Medicine Nanjing 210000 China Jiangsu Kanion Pharmaceutical Co. Ltd. Lianyungang 222000 China State Key Laboratory of New-techfor Chinese Medicine Pharmaceutical Process Lianyungang 222001 China

Analysis errors can occur in the desorbing process of ginkgo diterpene lactone meglumine injection(GDMI) by a conventional analysis method, due to several factors, such as easily crystallized samples, solvent volatility, time-consuming sample pre-processing, fixed method, and offline analysis. Based on risk management, near-infrared(NIR) and mid-infrared(MIR) spectroscopy techniques were introduced to solve the above problems with the advantage of timely analysis and non-destructive nature towards samples. The objective of the present study was to identify the feasibility of using NIR or MIR spectroscopy techniques to increase the analysis accuracy of samples from the desorbing process of GDMI. Quantitative models of NIR and MIR were established based on partial least square method and the performances were calculated. Compared to NIR model, MIR model showed greater accuracy and applicability for the analysis of the GDMI desorbing solutions. The relative errors of the concentrations of Ginkgolide A(GA) and Ginkgolide B(GB) were 2.40% and 2.89%, respectively, which were less than 5.00%. The research demonstrated the potential of the MIR spectroscopy technique for the rapid and non-destructive quantitative analysis of the concentrations of GA and GB.

关键词： Risk management Near-infrared Mid-infrared Desorbing process Ginkgolide A Ginkgolide B

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银杏二萜内酯有效部位(GA,GB,GK)配伍活性研究

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中国中药杂志 2018年第7期43卷 1410-1415页

作者：张红罗燕平曹泽彧张新庄曹亮王振中萧伟江苏康缘药业股份有限公司江苏连云港222001 中药制药过程新技术国家重点实验室江苏连云港222001

研究银杏二萜内酯（Ginkgolide）A,B,K（GA,GB,GK）最佳活性配伍。比较化合物GA,GB,GK单用,两两配伍及三者配伍对PAF诱导的血小板聚集活性及大鼠脑缺血再灌注模型（tMCAO）的影响。GA,GB,GK不同配伍均可明显降低血小板活化因子（platele... 详细信息

研究银杏二萜内酯（Ginkgolide）A,B,K（GA,GB,GK）最佳活性配伍。比较化合物GA,GB,GK单用,两两配伍及三者配伍对PAF诱导的血小板聚集活性及大鼠脑缺血再灌注模型（tMCAO）的影响。GA,GB,GK不同配伍均可明显降低血小板活化因子（platelet-activating,PAF）诱导的血小板聚集的最大聚集率,其中三者联用抑制率最高;GA,GB,GK不同配伍对大鼠tMCAO模型的神经功能,脑梗死体积和脑水肿有不同程度的减轻,其作用强弱为三者组合大于两两配伍及单用。GA,GB,GK三者联用抗血小板聚集及改善tMCAO大鼠引起的神经损伤的作用最强。

关键词： Ginkgolide A Ginkgolide B Ginkgolide K 血小板活化因子血小板聚集 tMCAO神经损伤

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