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    [Effect of different injections of Chinese herbal medicine on stress hormones and immune cell factors in patients of type 2 diabetes mellitus complicated with acute cerebral infarction]. Chen J,Ma Y,Liang H Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine OBJECTIVE:To investigate the effect and clinical significance of different injections of Chinese herbal medicine on stress hormones and immune cell factors in treating patients of type 2 diabetes mellitus complicated with acute cerebral infarction. METHODS:Patients were divided into three groups, treated with Defibrase injection (DI, n = 32), Acanthopanax injection (AI, n = 20) and Ginaton injection (GI, n = 12) respectively. Parameters, including corticotropin-releasing hormone (CRH), adrenocoticortropic hormone (ACTH), cortisol (CS), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) were determined using RIA in patients before and after treatment. The changes of parameters were analyzed and compared with those of healthy subjects for control. RESULTS:(1) Levels of all the above-mentioned parameters in all the three treated groups were higher than those in the healthy control group (P < 0.01); (2) All parameters were reduced after treatment in the three treated groups and the optimal effect was shown in the DI group (P < 0.01). CONCLUSION:The beneficial action of the three injections is closely related with the levels of stress hormones and immune cell factors, therefore, to monitor dynamically the changes of CRH, ACTH, CS, TNF alpha and IL-6 is of important significance in evaluation of therapeutic effect and elucidation of the pharmacology of Chinese herbal medicine.
    [Study on the mechanism of Alzheimer disease-related gene presenilin-1]. Peng Dan-tao,Xu Xian-hao,Feng Ying,Peng Le Zhonghua nei ke za zhi OBJECTIVE:To study the pathogenic mechanism of Alzheimer disease-related gene presenilin-1 (PS-1) mutation causing AD. METHODS:Four neural cells, including SY5Y cell, transgenic cells harboring PS-1 mutation, wild-type PS-1 and lipofectin were measured for neuronal Ca(2+) homeostasis and cell apoptosis. Intracellular calcium antagonist and antioxidant, such as Ginaton and nimodipine, were used in cultured neural cell and neuronal Ca(2+) level and cell apoptosis were examined. RESULTS:Elevation of intracellular calcium level and cell apoptosis induced by amyloid beta-peptide (Abeta) were enhanced in PS-1 mutation cell, as compared with others cells (P < 0.01). Intracellular calcium antagonist and antioxidant could inhibit apoptosis and decrease intracellular calcium level for PS-1 mutation (P > 0.05). There was significant correlation between the percentage of apoptosis and intracellular calcium level for PS-1 mutation. CONCLUSIONS:The pathogenic mechanism of PS-1 gene mutation causing AD was PS-1 mutation enhancing apoptosis by intracellular calcium overload. Intracellular calcium blocker and antioxidant could decrease intracellular calcium overload and inhibit apoptosis.
    Effects of Ginkgo biloba extract on lipid peroxidation and apoptosis after spinal cord ischemia/reperfusion in rabbits. Fan Li-Hong,Wang Kun-Zheng,Cheng Bin Chinese journal of traumatology = Zhonghua chuang shang za zhi OBJECTIVE:To study the effects of Ginkgo biloba extract (GBE) on lipid peroxidation and apoptosis after spinal cord ischemia/reperfusion (I/R) in rabbits. METHODS:Spinal cord I/R injury model was established according to the description of Erten et al. A total of 27 New Zealand white rabbits were divided into three groups randomly: a sham group (9 rabbits treated with sham operation but without aortic occlusion), a model group (9 rabbits treated with aortic occlusion and volume-matched saline), and a GBE group (9 rabbits treated with aortic occlusion and Ginaton (100 mg/kg) injected 30 minutes before aortic clamping and at the onset of reperfusion). The neurological outcomes were evaluated at 24 and 48 hours after reperfusion, respectively. The spinal cord malondialdehyde (MDA) level, superoxide dismutase (SOD) were then detected. Neural cell apoptosis was determined by terminal deoxynucleotidyl t-ransferase (TdT)-mediated dUTP-fluorescence nick end labeling (TUNEL) method and the expression of bcl-2 and bax were examined histologically in the spinal cord with immunohistochemistry. RESULTS:I/R produced a significant decrease in neurological scoring. The motor scores of the GBE group were significantly higher than those of the model group at 24 and 48 hours after reperfusion (P<0.05). Compared with the model group, GBE ameliorated the down-regulation of SOD and produced a significant reduction of the MDA level (P<0.01). The positive cells for TUNEL in the model group were much more than those of the GBE group (P<0.01). The bcl-2 was up-regulated after I/R, especially in the GBE group (P<0.01). The up-regulation of bax was greatly diminished by GBE (P<0.01). CONCLUSIONS:GBE has protective effects against spinal cord I/R injury, and the mechanism may be that it can scavenge oxygen free radicals and inhibit the apoptosis of neural cells.
    Ginkgo biloba extract improves coronary blood flow in healthy elderly adults: role of endothelium-dependent vasodilation. Wu Yuzhou,Li Shuqin,Cui Wei,Zu Xiuguang,Du Jun,Wang Fengfei Phytomedicine : international journal of phytotherapy and phytopharmacology Advancing age decreases endothelial function; accordingly, it alters the physiological regulation of coronary blood flow. Ginkgo biloba extract (GBE) has well-documented anti-ageing effects. However, little is yet known about the pharmacological actions of GBE on endothelial dysfunction and coronary blood flow in healthy elderly adults. We designed the study to test the effects of GBE on distal left anterior descending coronary artery (LAD) blood flow and endothelium-dependent brachial artery flow-mediated dilation (FMD) in healthy elderly adults. Sixty healthy elderly adults were randomly assigned to either GBE or control groups. LAD blood flow and brachial artery FMD were measured non-invasively using high-resolution ultrasound before and after intravenous administration of GBE or saline. GBE significantly increased LAD blood flow in maximal diastolic peak velocity (MDPV), maximal systolic peak velocity (MSPV) and diastolic time velocity integral (DTVI) compared with the placebo group (19.16+/-13.91% vs. 0.30+/-2.55%, 17.76+/-14.56% vs. 0.53+/-2.32%, and 21.73+/-16.13% vs. 0.81+/-2.33%, MDPV, MSPV, and DTVI improvement from baseline, respectively, p<0.01). Brachial artery FMD was also increased by 56.03% (from 7.21+/-2.52% to 11.28+/-3.95%, p<0.01). A linear correlation was found between the percentage change in MDPV, MSPV, or DTVI of LAD blood flow and the percentage change in brachial artery FMD following treatment with GBE (r=0.538, 0.366, or 0.573, respectively, p<0.01, p<0.05, or p<0.01). Our data demonstrate that GBE treatment in healthy elderly adults leads to the increase of LAD blood flow in MDPV, MSPV and DTVI, and the increased response might relate to the improved endothelium-dependent vasodilatory capacity. This study implies an important future therapeutic strategy of using GBE to counteract the detrimental effects of ageing. 10.1016/j.phymed.2007.12.002
    [The clinical treatment experience of low-middle frequency sudden sensorineural hearing loss with steroid combined with dehydrant in 82 cases]. Qu Y T,Zhang H P,Chen H Y,Guo M L Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery The aim of this study is to explore the treatment of low-middle frequency sudden sensorineural hearing loss with steroid combined with dehydrant.Eighty-two patients with diagnosis of low-middle frequency sudden sensorineural hearing loss were selected;All patients were randomly divided into systemic steroid therapy group and steroid combined with dehydrant therapy group.All patients received Alprostadil,Ginaton and Mecobalamin.Intravenous steroids was given in systemic steroid therapy group,while intravenous steroids and dehydrant were given in steroid combined with dehydrant therapy group.Finally,the results were collected and analyzed.The total effective rate was 92.31% in systemic steroid therapy group,and 93.02% in steroid combined with dehydrant therapy group.There is no significant difference between the twogroups(<0.05).The average time of hearting recovery was (7.03±1.22)days in systemic steroid therapy group,while(6.17±1.15)days in steroid combined with dehydrant therapy group,and significant difference was detected between the two difierent treatments(<0.05).The treatment of low-middle frequency sudden sensorineural hearing loss with steroid combined with dehydrant can achieve a favorable prognosis,and may shorten the treatment time. 10.13201/j.issn.1001-1781.2016.16.016
    [Effects of active components group of Xiaoxuming decoction on brain mitochondria in cerebral ischemia/reperfusion rats during early recovery period]. Du Xiao,Lu Chang,He Xiao-Li,Du Guan-Hua Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica To observe the effect of active components group of Xiaoxuming decoction (XXMD) on brain mitochondria in cerebral ischemia/reperfusion rats during early recovery period, and study its protective mechanism for nerves in cerebral ischemia/reperfusion rats during early recovery period. Cerebral ischemia model of middle cerebral artery occlusion in rats was established by suture method, and reperfusion was conducted 2 h later. The degree of cerebral ischemia in rats was evaluated by using Zea-Longa's standard grading method, and the model rats were randomly divided into model group, Xiaoxuming decoction active components low, medium and high dose groups and positive drug Ginaton group, with sham operated rats as control group. Gradient centrifugation was used to extract the mitochondria from rat brain after 5 days of drug administration. Then the mitochondrial respiratory function was measured by Clark oxygen electrode method; mitochondrial membrane potential and the mitochondrial reactive oxygen species(ROS) level were detected by fluorescence probe methods; and the activity of mitochondrial succinodehydrogenase (SDH) and the content of ATP in the ischemic region of MCAO rats were measured by spectrophotometric method. The results showed that as compared with the model group, XXMD could significantly improve mitochondrial respiratory activity, increase the activity of SDH, reduce the level of ROS, increase mitochondrial membrane potential and obviously promote the synthesis of ATP in brain tissues. The results indicated that XXMD active components group could alleviate the energy metabolism disorders, protect brain mitochondrial damage and improve mitochondrial function in MCAO rats, which may be the mechanism of its neuroprotection activity. 10.19540/j.cnki.cjcmm.2017.0095
    [Protective effects of Ginkgo Terpene Lactones Meglumine Injection on focal cerebral ischemia in rats]. Luo Yan-Ping,Zhang Hong,Hu Han-Fei,Cao Ze-Yu,Zhang Xin-Zhuang,Cao Liang,Wang Zhen-Zhong,Xiao Wei Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica To investigate the protective effects of ginkgo diterpene lactone meglumine injection (GDLMI) on cerebral focal ischemia reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats, and explore its possible mechanism. One hundred and forty male SD rats were randomly divided into sham operation group, model group, ginkgo biloba extract injection (Ginaton, 1.0 mL•kg⁻¹) group, nimodipine (0.4 mg•kg⁻¹) group, and GDLMI (5.2, 2.6, 1.3 mg•kg⁻¹) groups; All of rats received corresponding drugs by tail vein injection 4 days before operation (normal saline in model group and sham operation group). Except the sham operation group, the cerebral ischemic stroke model was established by MCAO method in right brain of the other rats. After 3 h of ischemia, all the animals received intravenous administration again. The neurobehavioral scores of rats after ischemia-reperfusion were evaluated and the infarct rate of brain tissue was observed by TTC staining. The super oxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and lactic acid (LA) contents in brain tissue homogenate and the concentration of Ca2+, glutamate (Glu) and aspartate (Asp), creatine phosphate kinase (CK-BB) and lactate dehydrogenase (LDH) content changes in cerebrospinal fluid were measured. As compared with the sham operation group, the cerebral infarction rate was increased significantly in the model group; the content of MDA and LA in the homogenate of brain tissue was increased, and the content of GSH and SOD was decreased; in cerebrospinal fluid, Ca2+ concentration was decreased, and the content of Glu and Asp, CK-BB and LDH increased significantly. As compared with the model group, the high and medium dose GDLMI groups can significantly reduce the cerebral infarction rate and improve the symptoms of neurological impairment; increase SOD and GSH activity, reduce MDA and LA content in serum; increase Ca2+ concentration in cerebrospinal fluid and decrease the content of neurotransmitter Glu and Asp as well as CK-BB and LDH. GDLMI could obviously improve neurologic impairment in model rats, and the mechanism may be related to recovering the blood brain barrier, scavenging free radicals, decreasing free Ca2+ inflow into the cells and the content of excitatory amino acid in cerebrospinal fluid to improve its protective effect on cerebral ischemia. 10.19540/j.cnki.cjcmm.2017.0209
    Intervention effect of total flavonoids of ilex pubesceus on tolerant rat models under cerebral anoxia. Kang Le,Miao Mingsan Saudi journal of biological sciences To observe the intervention effect of total flavonoid of ilex pubesceus on animal models of cerebral ischemic tolerance. A rat model of global-focal cerebral ischemic tolerance was established by blocking bilateral common carotid artery blood flow and occluding left middle cerebral artery using thread-occlusion method. After the first operation, the Ginaton group and large-dosage, medium-dosage and small-dosage groups of total flavonoid of ilex pubesceus were given intragastric administration of corresponding drugs. The sham-operated group, pretreatment model group and ischemia-reperfusion group were given intragastric administration of the same volume of normal saline, 1 time a day, and administrated for 4d. At 24 h after the second operation, the neurological deficit was assessed, the whole blood viscosity, plasma viscosity, iNOS activity as well as NO level, IL-1β content and TNF-α content in the brain tissue of the rats were determined, and the morphological changes of brain tissue of the rats were observed by HE staining. All the rat models of cerebral ischemic tolerance were established successfully. The total flavonoid of ilex pubesceus can obviously or significantly reduce the neurological deficit score, whole blood viscosity and plasma viscosity, obviously or significantly increase the NO level in the brain tissue of the rats, and significantly reduce the pathological damage of brain tissue of the rats. But compared with the ischemia-reperfusion group, the total flavonoid of ilex pubesceus can significantly or obviously increase the iNOS activity, IL-1β content and TNF-α content in the brain tissue of the rats. 10.1016/j.sjbs.2017.11.030
    [Therapeutic effects of postauricularinjection of lidocaine in tinnitus]. Huang Y,Fu M Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery To observe clinical efficacy of postauricular injection of lidocaine for subjective tinnitus and explore the clinical effective method in the treatment of tinnitus. METHOD:Eighty patients with tinnitus as their first complaint were included in our study. They were randomly divided into four groups, each with 20 cases.They were treated with oral ginaton and mecobalamin tablets,and at the same time with postauricular injection of lidocaine at different doses (Group A, 2% lidocaine 3 ml; Group B, 2% lidocaine 2 ml+physiological saline 1 ml;Group C, 2% lidocaine 1 ml+physiological saline 2 ml; Group D, physiological saline 3 ml). TEQ scores were evaluated and compared before treatment, at the end of treatment, and one month after treatment.At the end of treatment, the clinical effiCIency rates of four groups were 80%,70%,65% and 25% respectively. One month after treatment, the clinical effiCIency rates of four groups were 80%, 55%, 45% and 0% respectively. There were significant differences among four groups by chi square test (<0.05).Patients' TEQ scores of the four groups after treatment were analyzed and compared by one-way ANOVA. TEQ scores of Group A,B and C were lower than Group D(<0.05). TEQ scores of Group A were lower than Group C(<0.05).TEQ scores at the end of treatment and one month after treatment were analyzed by paired t-test. Group B and C had higher TEQ scores one month after treatment(<0.05).The total effective rate at the end of treatment for acute, subacute and chronic tinnitus patients was 79.31%, 70.83% and 42.86% respectively. The total effective rate of one month after treatment was 75.86%, 45.83% and 42.86%, respectively. The results of chi square test showed that the total effective rate of acute tinnitus patients was significantly higher than that of subacute and chronic tinnitus in one month after treatment (<0.05). CONCLUSION:Postauricular injection of lidocaine is effective for simple subjective tinnitus, and the dose and concentration of lidocaine affect the efficacy and durability. Postauricular injection of lidocaine for the treatment of subjective tinnitus is a therapeutic method worthy of further research and popularization. 10.13201/j.issn.1001-1781.2018.15.004
    Effect of acetazolamide and gingko biloba on the human pulmonary vascular response to an acute altitude ascent. Ke Tao,Wang Jiye,Swenson Erik R,Zhang Xiangnan,Hu Yunlong,Chen Yaoming,Liu Mingchao,Zhang Wenbin,Zhao Feng,Shen Xuefeng,Yang Qun,Chen Jingyuan,Luo Wenjing High altitude medicine & biology Acetazolamide and gingko biloba are the two most investigated drugs for the prevention of acute mountain sickness (AMS). Evidence suggests that they may also reduce pulmonary artery systolic pressure (PASP). To investigate whether these two drugs for AMS prevention also reduce PASP with rapid airlift ascent to high altitude, a randomized controlled trial was conducted on 28 healthy young men with acetazolamide (125 mg bid), gingko biloba (120 mg bid), or placebo for 3 days prior to airlift ascent (397 m) and for the first 3 days at high altitude (3658 m). PASP, AMS, arterial oxygen saturation (Sao2), mean arterial pressure (MAP), heart rate (HR), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF) were assessed both at 397 m and 3658 m. HR, PEF, and PASP increased with altitude exposure (p<0.05), and SaO2 decreased (p<0.05). PASP with acetazolamide (mean at 3658 m, 26.2 mm Hg; incremental change, 4.7 mm Hg, 95% CI., 2.6-6.9 mm Hg) was lower than that with ginkgo biloba (mean at 3658 m, 33.7 mm Hg, p=0.001; incremental change, 13.1 mm Hg, 95%CI., 9.6-16.5 mm Hg, p=0.002), and with placebo (mean at 3658 m, 34.7 mm Hg, p<0.001; 14.4 mm Hg, 95% CI., 8.8-20.0 mm Hg, p=0.001). The data show that a low prophylactic dosage of acetazolamide, but not gingko biloba, mitigates the early increase of PASP in a quick ascent profile. 10.1089/ham.2012.1099
    Effects of total saponins from Trillium tschonoskii rhizome on grey and white matter injury evaluated by quantitative multiparametric MRI in a rat model of ischemic stroke. Li Manzhong,Ouyang Junyao,Zhang Yi,Cheng Brian Chi Yan,Zhan Yu,Yang Le,Zou Haiyan,Zhao Hui Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Trillium tschonoskii rhizome (TTR), a medicinal herb, has been traditionally used to treat traumatic brain injury and headache in China. Although the potential neuroprotective efficacy of TTR has gained increasing interest, the pharmacological mechanism remains unclear. Steroid saponins are the main bioactive components of the herb. AIM OF THE STUDY:To investigate the protective and repair-promoting effects of the total saponins from TTR (TSTT) on grey and white matter damages in a rat model of middle cerebral artery occlusion (MCAO) using magnetic resonance imaging (MRI) assay. MATERIALS AND METHODS:Ischemic stroke was induced by MCAO. TSTT and Ginaton (positive control) were administered orally to rats 6h after stroke and daily thereafter. After 15 days of treatment, the survival rate of each group was calculated. We then conducted neurological deficit scores and beam walking test to access the neurological function after ischemic stroke. Subsequently, T2-weighted imaging (T2WI) and T2 relaxometry mapping were performed to measure infarct volume and grey and white matter integrity, respectively. Moreover, diffusion tensor imaging (DTI) was carried out to evaluate the grey and white matter microstructural damage. Additionally, arterial spin labelling (ASL) - cerebral blood flow (CBF) and magnetic resonance angiography (MRA) images provided dynamic information about vascular hemodynamic dysfunction after ischemic stroke. Finally, haematoxylin and eosin (HE) staining was carried out to evaluate the stroke-induced pathological changes in the brain. RESULTS:The survival rate and neurological behavioural outcomes (Bederson scores and beam walking tests) were markedly ameliorated by TSTT (65mg/kg) treatment within 15 days after ischemic stroke. Moreover, T2WI and T2 relaxometry mapping showed that TSTT (65mg/kg) significantly reduced infarct volume and attenuated grey and white matter injury, respectively, which was confirmed by histopathological evaluation of brain tissue. The results obtained from DTI showed that TSTT (65mg/kg) not only significantly alleviated axonal damage and demyelination, but also promoted axonal remodelling and re-myelination. In addition, TSTT treatment also enhanced vascular signal density and increased CBF in rats after MCAO. CONCLUSION:Our results suggested the potential protective and repair-promoting effects of TSTT on grey and white matter from damage induced by ischemia. This study provides a modern pharmacological basis for the application of TSTT in managing ischemic stroke. 10.1016/j.jep.2018.01.006
    Embolic retinal and choroidal vascular occlusion after peribulbar triamcinolone injection: A case report. Li Gang,Xu Dongdong,Hu Zhirou,Li Hui Medicine RATIONALE:Retinal and choroidal vascular occlusion is a vision-threatening complication of therapeutic injections in the facial region. The early identification and early treatment are necessary to reduce the risk of harm to the patient. PATIENT CONCERNS:We report an extremely rare case of embolic retinal and choroidal vascular occlusion after peribulbar triamcinolone injection in a patient with thyroid-associated ophthalmopathy. DIAGNOSES:Central retinal artery occlusion. INTERVENTIONS:First, we performed a fundus examination in the patient. Triamcinolone embolus was observed in both retinal and choroidal vessels. Anterior chamber paracentesis and ocular massage combined with venous injections of alprostadil and Ginaton as well as an acupoint injection of compound anisodine were performed immediately. Sublingual glyceryl trinitrate and intraocular pressure-lowering drugs were also administered. Fundus autofluorescence, optical coherence tomography-angiography, fundus fluorescein angiography (FFA), and indocyanine green angiography (ICGA) were also conducted to evaluate the patient's condition. OUTCOMES:One month after the onset of the situation, the triamcinolone embolus had disappeared. The retinal edema and retinal blood perfusion were also improved. The patient's visual acuity had recovered from inexact light perception to 0.02. LESSONS:Embolic retinal and choroidal vascular occlusion is vision-threatening disease. Measures such as careful aspiration before injecting in the facial region must be taken to avoid such complications. 10.1097/MD.0000000000010467
    Sudden sensorineural hearing loss (SSHL) following a local anesthetic dental procedure. Wang Yi,Cao Jun-Kai,Yang Hui-Xin,Feng Jin,Zhou Qi-You,Ji Fei Journal of otology Acute sensorineural hearing loss is an uncommon phenomenon in dentistry. We describe the case of a 79-year-old male who presented with acute sensorineural hearing loss occurring 2 days after a tooth extraction procedure under local anesthesia. Possible mechanisms are discussed. He was treated with vasodilators (Ginaton and Alprostadil Injection) and Mecobalamin injection with benefit. High dose oral steroids (1 mg/kg) and low molecular weight dextran were used. 10.1016/j.joto.2019.04.003
    Qishen Granule alleviates endoplasmic reticulum stress-induced myocardial apoptosis through IRE-1-CRYAB pathway in myocardial ischemia. Zhang Qian,Shi Jun,Guo Dongqing,Wang Qiyan,Yang Xiaomin,Lu Wenji,Sun Xiaoqian,He Hao,Li Ning,Wang Yong,Li Chun,Wang Wei Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Qishen Granule (QSG) is a prevailing traditional Chinese medicine formula that displays impressive cardiovascular protection in clinical. However, underlying mechanisms by which QSG alleviates endoplasmic reticulum (ER) stress-induced apoptosis in myocardial ischemia still remain unknown. AIM OF THE STUDY:This study aims to elucidate whether QSG ameliorates ER stress-induced myocardial apoptosis to protect against myocardial ischemia via inositol requiring enzyme 1 (IRE-1)-αBcrystallin (CRYAB) signaling pathway. MATERIALS AND METHODS:Left anterior descending (LAD) ligation induced-ischemic heart model and oxygen-glucose deprivation-reperfusion (OGD/R)-induced H9C2 cells injury model were established to clarify the effects and potential mechanism of QSG. Ethanol extracts of QSG (2.352 g/kg) were orally administered for four weeks and Ginaton Tablets (100 mg/kg) was selected as a positive group in vivo. In vitro, QSG (800 μg/ml) or STF080310 (an inhibitor of IRE-1, 10 μM) was co-cultured under OGD/R in H9C2 cells. Inhibition of IRE-1 was conducted in H9C2 cells to further confirm the exact mechanism. Finally, to define the active components of anti-cardiomyocyte apoptosis in QSG which absorbed into the blood, we furtherly used the OGD/R-induced cardiomyocyte apoptosis model to evaluate the effects. RESULTS:QSG treatment improved cardiac function, ameliorated inflammatory cell infiltration and myocardial apoptosis. Similar effects were revalidated in OGD/R-induced H9C2 injury model. Western blots demonstrated QSG exerted anti-apoptotic effects by regulating apoptosis-related proteins, including increasing Bcl-2 and caspase 3/12, reducing the expressions of Bax and cleaved-caspase 3/12. Mechanistically, the IRE-1-CRYAB signaling pathway was significantly activated by QSG. Co-treatment with STF080310, the IRE-1 specific inhibitor significantly compromised the protective effects of QSG in vitro. Especially, the active components of QSG including Formononetin, Tanshinone IIA, Tanshinone I, Cryptotanshinon and Harpagoside showed significantly anti-apoptosis effects. CONCLUSION:QSG protected against ER stress-induced myocardial apoptosis via the IRE-1-CRYAB pathway, which is proposed as a promising therapeutic target for myocardial ischemia. 10.1016/j.jep.2020.112573
    Houshiheisan promotes angiogenesis via HIF-1α/VEGF and SDF-1/CXCR4 pathways: in vivo and in vitro. Xiang Yangyang,Yao Xiaoquan,Wang Xuan,Zhao Hui,Zou Haiyan,Wang Lei,Zhang Qiu-Xia Bioscience reports RATIONALE:Houshiheisan (HSHS), a classic prescription in traditional Chinese medicine (TCM), has remarkable efficacy in the treatment of ischemic stroke. OBJECTIVE:To investigate the pro-angiogenic effect and molecular mechanism of HSHS for stroke recovery. METHODS AND RESULTS:The rat permanent middle cerebral artery occlusion (pMCAO) model was constructed by suture method, HSHS (5.25 or 10.5 g/kg) and Ginaton (28 mg/kg) treatment was intragastrically administrated at 6 h after modeling which remained for 7 consecutive days. Pathological evaluation conducted by Hematoxylin-Eosin (HE) staining and the results showed that HSHS alleviated blood vessel edema, reduced the damage to blood vessels and neurons in the ischemic areas. Immunostaining, quantitative real-time fluorescence PCR results showed that HSHS up-regulated pro-angiogenic factors including platelet endothelial cell adhesion molecule-1 (cluster of differentiation 31 (CD31)), vascular endothelial growth factor (VEGF), vascular endothelial growth factor A (VEGFA), VEGF receptor 2 (VEGFR2), angiopoietin-1 (Ang-1), while down-regulated angiopoietin-2 (Ang-2), stromal cell derived factor-1 (SDF-1), and cxc chemokine receptor 4 (CXCR4) expression in infarct rat cortex, and similar results were obtained in subsequent Western blot experiment. Furthermore, CCK8 assay and transwell migration assay were performed to assess cell proliferation, migration, and tube formation. The medicated serum (MS) of HSHS appeared to have beneficial effects for immortalized human umbilical vein cells (Im-HUVECs) on proliferation and migration after persistence hypoxia. Western blot analysis revealed that the expression of hypoxia inducible factor-1α (HIF-1α), VEGFA, Ang-1, Ang-2, and CXCR4 were significantly up-regulated while Ang-2 was down-regulated by HSHS MS treatment compared with vehicle group in vitro. CONCLUSION:The present study suggests a novel application of HSHS as an effective angiogenic formula for stroke recovery. 10.1042/BSR20191006
    [The effect of antioxidant on optimation of blood preservation]. Liu Jing-Han,Han Wei,Lai Feng-Lei,Yu Yang,Li Rui,Ouyang Xi-Lin Zhongguo shi yan xue ye xue za zhi In order to optimize the preservation of blood, 3 kinds of antioxidant were selected and each of them can be injected directly into vein, then the optimal dose of these antioxidants was chosen using statistical method; ISMC (injectio salvia miltiorrhizae composita), ginaton and the combination of ISMC and ginaton were added into blood as optimal dose, some references as ATP, EI and so on were observed during blood preservation. The results showed that all of the three kinds of antioxidants increased ATP, EI and decreased FHb during blood preservation. It is concluded that both of ISMC and ginaton can effectively optimize the preservation of blood and combination of ISMC and ginaton can produce additive effect.
    Therapeutic effects of JLX001 on cerebral ischemia through inhibiting platelet activation and thrombus formation in rats. Yan Yun-Yi,Ao Lu-Yao,Zhou Lin,Li Cheng-Yuan,Fang Wei-Rong,Shen Wei-Yang,Liang Bing-Wen,Zhu Xiong,Li Yun-Man Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (3β,5α,16α,20S)-4,4,14-trimethyl-3,20-bis(methylamino)-9,19-cyclopregnan-16-ol-dihydrochloride (JLX001), a derivative of cyclovirobuxine D (CVB-D), is a novel compound from synthesis. This study aims to confirm the therapeutic effect of JLX001 on cerebral ischemia and researchits antiplatelet and antithrombosis activities via thromboxane (TXA)/phospholipase C-β-3(PLCβ3)/protein kinase C (PKC) pathway suppression. The therapeutic effects of JLX001 was evaluated by infarct sizes, brain edema and neurological scores in Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO). Brain TXA and prostacyclin (PGI) were measured by enzyme-linked immunosorbentassay (ELISA). P-PLCβ3and activated PKC were detected by immunohistochemical method. Adenosine diphosphate (ADP) or 9, 11-dieoxy-11α, 9α-epoxymethanoeprostaglandin F2α (U46619) was used as platelet agonist in the in vivo and in vitro platelet aggregation experiments. Clotting time and bleeding time were determined. Besides, two whole-animal experiments including arteriovenous shunt thrombosis and pulmonary thromboembolism model were conducted. Results showed that JLX001 treatment markedly alleviated cerebral infarcts, edema, and neurological scores in permanent middle cerebral artery occlusion (pMCAO) rats. Brain TXA level, p-PLCβ3and activated PKC were decreased, while PGIlevel had no significant change. Besides, JLX001 inhibited platelet aggregation induced by ADP or U46619 and exhibited anti-coagulation effects with a minor bleeding risk. In the two whole-animal experiments, JLX001 inhibited thrombus formation. In summary, JLX001 attenuates cerebral ischemia injury and the underlying mechanisms relate to inhibiting platelet activation and thrombus formation via TXA/PLCβ3/PKC pathway suppression. 10.1016/j.biopha.2018.07.023
    [Effects of extract of Ginkgo biloba on magnetic resonance imaging and electroencephalography in patients with delayed encephalopathy after acute carbon monoxide poisoning]. Xiao Q M,Qi H N,Wang W Z,Gao X,Zhu B Y,Liu Y J,Li W,Ma G Y,Wang P,Meng F Z,Gao X F Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases To observe the effects of extract of Ginkgo biloba (Ginaton) on magnetic resonance imaging (MRI) and electroencephalography (EEG) in patients with delayed encephalopathy after acute carbon monoxide poisoning. The 84 patients with delayed encephalopathy after acute carbon monoxide poisoning treated in our hospital from Jan. 2011 to Apr. 2016 were randomly divied into therapy group and observation group. The therapy group received routine treatments of hyperbaric oxygen, cure cerebral edema and promote brain cell metabolism, and observation group was given intravenous injection (intravenous drip) Ginaton 70 mg (adding 0.9% sodium chloride injection 250 ml) , once a day, 2 weeks for one therapeutic course. The changes of MRI and EEG before and after treatment between therapy group and observation group were observed. In the observation group, the white matter and globus pallidus lesions of 14 d after treatment were smaller than those in the treatment group, and the abnormal signal intensity was decreased. At 14 days after treatment the improvement of EEG in observation group were better than therapy group (<0.05) . Early treatment of extract of Ginkgo biloba (Ginaton) in delayed encephalopathy after acute carbon monoxide poisoning can effectively improve lesion and signal on MRI and abnormal rate on EEG. It has a certain therapeutic effect in clinical. 10.3760/cma.j.issn.1001-9391.2017.02.017
    Efficacy of Osthole in Management of Hypoperfused Retina. Du Ran,Meng Zhao-Yang,Wang Jia-Lin,Wang Yan-Ling Journal of ophthalmology Purpose:To determine the effect of osthole on the retina in a chronic cerebral hypoperfusion (CCH) rat model and to investigate its therapeutic activity. Methods:Seventy-two rats were randomly allocated into 6 groups. CCH was induced by permanent bilateral common carotid artery occlusion (BCCAO) in five groups. Sham surgery was performed without occlusion of the artery in the sixth group (control group). Animals were administered with saline (model group), osthole (osthole-IG group), aspirin (aspirin group), or ginaton (ginaton group); the osthole-PI group was performed with peribulbar injection of osthole. Four rats in each group were sacrificed every 5 days after drug administration, and histopathology along with morphology of retina were observed. Fundus fluorescein angiography was performed before the animals were sacrificed at day 15. Retinal Akt, NF-B, Bax, and Bcl-2 levels were assessed using immunohistochemistry, immunofluorescence, and reverse-transcription PCR; retinal injury was assessed using TUNEL in situ; retinal levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. Results:Fundus fluorescein angiography revealed the retinal vascular diameter in the osthole-IG group rats to be wider than that in the model, osthole-PI, aspirin, or ginaton group rats. Histological analysis of retinal tissue revealed an increase in retinal thickness in all treatment groups, and significant improvement was noticed in the osthole-IG group. TUNEL staining revealed fewer apoptotic cells in the osthole-IG and osthole-PI groups than in the other groups. For immunohistochemistry results, in the osthole-IG group, levels of NF-B and Akt were lower than those in the other treated groups, while levels of the ratio Bcl-2/Bax were higher. Levels of MDA were lower and levels of SOD were higher in the osthole-IG group than in the other groups. Conclusions:Osthole protects the retina from ischemia injury secondary to CCH induced by BCCAO, mainly through anti-inflammatory, antioxidant, and antiapoptotic effects. 10.1155/2018/6178347
    Persimmon leaf flavonoid promotes brain ischemic tolerance. Miao Mingsan,Zhang Xuexia,Bai Ming,Wang Linan Neural regeneration research Persimmon leaf flavonoid has been shown to enhance brain ischemic tolerance in mice, but its mechanism of action remains unclear. The bilateral common carotid arteries were occluded using a micro clip to block blood flow for 10 minutes. After 10 minutes of ischemic preconditioning, 200, 100, and 50 mg/kg persimmon leaf flavonoid or 20 mg/kg ginaton was intragastrically administered per day for 5 days. At 1 hour after the final administration, ischemia/reperfusion models were estab-lished by blocking the middle cerebral artery for 2 hours. At 24 hours after model establishment, compared with cerebral ischemic rats without ischemic preconditioning or drug intervention, plasma endothelin, thrombomodulin and von Willebrand factor levels significantly decreased and intercel-lular adhesion molecule-1 expression markedly reduced in brain tissue from rats with ischemic pre-conditioning. Simultaneously, brain tissue injury reduced. Ischemic preconditioning combined with drug exposure noticeably improved the effects of the above-mentioned indices, and the effects of 200 mg/kg persimmon leaf flavonoid were similar to 20 mg/kg ginaton treatment. These results indicate that ischemic preconditioning produces tolerance to recurrent severe cerebral ischemia. However, persimmon leaf flavonoid can elevate ischemic tolerance by reducing inflammatory reactions and vascular endothelial injury. High-dose persimmon leaf flavonoid showed an identical effect to ginaton. 10.3969/j.issn.1673-5374.2013.28.004
    Influence of extract of Ginkgo biloba leaves tablets on the aquaporin-1 expression in isolated lung ischemia reperfusion. Li Xiang-Nan,Yang Ji-Yao,Pan Xue,Zhao Song,Zhang Chun-Yang,Zhu Deng-Yan,Wang Peng Chinese medical journal BACKGROUND:The extract of Ginkgo biloba leaves tablets, ginaton, is widely used in treating ischemic cerebrovascular disease in the clinic. This study aimed to investigate the expression of aquaporin-1 (AQP-1) in rat lung with ischemia/reperfusion injury after pretreatment with ginaton, and whether the pretreatment with ginaton reduces the acute lung injury caused by ischemia/reperfusion injury. METHODS:Adult Wistar rats were divided into two groups. Some rats were used as donors (n = 20), the others as recipients (n = 20). Left lungs of donor rats were used for the isolated lung reperfusion model, which perfused only with low potassium dextran (LPD) solution as group A (n = 10); the others were pretreated with ginaton before reperfusion as group C (n = 10). Right lung of donor rat without any treatment was used as a control group (group B and group D, n = 10 for each group). After the model was established, the expression of AQP-1 in the lung tissues was examined by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction. RESULTS:Immunohistochemical examination revealed that AQP-1 was expressed in endothelia. Immunoblotting demonstrated that the relative gray values of AQP-1 protein in groups A and C were 0.65±0.06, 0.88±0.11, respectively. The relative gray values of the mRNA expression in groups A and C were 0.30±0.08, 0.49±0.11, respectively. The expression of AQP-1 protein and mRNA in group C was significantly higher than in group A (P < 0. 05). CONCLUSION:The pretreatment with ginaton can reduce the acute lung injury caused by ischemia/reperfusion.
    BDNF/PI3K/Akt and Nogo-A/RhoA/ROCK signaling pathways contribute to neurorestorative effect of Houshiheisan against cerebral ischemia injury in rats. Chang Jiahui,Yao Xiaoquan,Zou Haiyan,Wang Lei,Lu Yue,Zhang Qiuxia,Zhao Hui Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Houshiheisan (HSHS), a classic traditional medicine prescription, has notable effects on patients with stroke AIM OF THE STUDY: To investigate the neurorestorative effects of HSHS on ischemic stroke and explore its mode of action. MATERIALS AND METHODS:Focal cerebral ischemia models were induced by permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley (SD) rats were randomly divided into 5 experimental groups: sham vehicle, ischemia vehicle, pMCAO+HSHS at 5.1, 10.2g/kg, and pMCAO+Ginaton 0.028g/kg. HSHS or Ginaton was administrated 6h after pMCAO onset. Neurological function was assessed and then rats were sacrificed 7 days after MCAO. Cerebral ischemic injury was evaluated by hematoxylin and eosin (HE) staining and Neuronal nuclear antigen (NeuN) immunofluorescence analysis. The levels of BDNF were detected by enzyme linked immunosorbent assay (ELISA), and the expression levels of PI3K/Akt and Nogo-A/RhoA/ROCK2 signaling pathway were detected by western blot and quantitative real-time PCR (qRT-PCR). RESULTS:Compared with those results of pMCAO group, HSHS 5.1 and HSHS 10.2 groups markedly improved neurological function, alleviated pathological damage, promoted the neuronal survival, increased the expression of BDNF, PI3K, Akt, in protein and mRNA, decreased the expression of Nogo-A, NgR, RhoA and ROCK2 in protein and mRNA 7 days after pMCAO. CONCLUSIONS:The findings demonstrate that HSHS had significant therapeutic effects on ischemic stroke and it perhaps worked through the activation of BDNF/PI3K/Akt and down-regulation of Nogo-A/RhoA/ROCK signaling pathways. 10.1016/j.jep.2016.11.005
    [Effect of Ginkgo biloba extract preconditioning on discordant cardiac xenografts]. Huang Xue-shan,Liu Xuan,Chen Dao-zhong Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine OBJECTIVE:To investigate the effect of ginkgo biloba extract (ginaton) preconditioning on discordant cardiac xenografts from guinea pig to rat, and explore its mechanism. METHODS:Cervical cardiac transplantation model was established in the rats,which were divided into 4 groups Group 1 (cobra venom factor ( CVF) pretreatment, n = 10]; Group 2 (CVF + ginaton, n = 5) ; Group 3 Ccyclosporine (CsA); Group 4 (CVF + CsA + ginaton, n = 8]. The survival time and histopathology after xenograft were observed and expressions of intercellular adhesion molecule-1 (ICAM-1) heme oxygenase-1 (HO-1) CD68 and CD57 were detected. RESULTS:Pathologic manifestion of grafts showed changes of acute vascular rejection (AVR) in all groups. The mean survival time after car diac xenograft was 41 hrs in Group 1, 68 hrs in Group 2, 55 hrs in Group 3 and 74 hrs in Group 4. Expression of intercellular adhesion molecule-1 (ICAM-1 ) decreased after ginaton preconditioning (P < 0. 05). CD68 and CD57 expressions were down-regulated, HO-1 expression was up-regulated, as well as the apoptotic index (Al) reduced significantly after ginaton with cyclosporine A preconditioning. CONCLUSION:Ginaton preconditioning can prolong the survival time after discordant xenograft, and significantly alleviate pathological lesion from acute xenograft vascular rejection combined with cyclosporine A.
    [Effect of ginkgo biloba extract on plasma vascular endothelial growth factor during peri-operative period of cardiac surgery]. Deng Yun-kun,Wei Fang,An Bang-quan Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine OBJECTIVE:To investigate the effect and clinical value of ginkgo biloba extract (Ginaton) on the plasma vascular endothelial growth factor (VEGF) in patients during peri-operative period of cardiac surgery. METHODS:Twenty patients scheduled to receive cardiac operation were randomly assigned to 2 groups by a digital table. For the 10 patients in the control group, the cardiopulmonary bypass (CPB) was established in routine and received cold (4 degrees C) St. Thomas' cardioplegia perfusion (15 mL/kg) via aortic root after ascending aorta blocking, as for the 10 patients in the Ginaton group, the same was done but with 0.5 mg/kg of Ginaton added to the cardioplegia perfusion. Plasma VEGF contents were detected by ELISA at different time points, i.e., before and after anesthesia induction (T1, T2), after aorta intubation (T3), 0.5 h after aorta clamping (T4), 0.5 h after aorta declamping (T5), immediate after terminating the operation (T6), 6 h after operation (T7), and 24 h after operation (T8). RESULTS:In the control group, VEGF level began to rise at T, and reached the peak at T7(P < 0.01), while in the Ginaton group, it reached the peak early at T, (P < 0.01), and began to drop at T (P < 0.01). CONCLUSION:Ginaton could induce the production of VEGF, which may be one of the mechanisms for its myocardial protection.
    [Multi-center clinical study on the treatment of the low-middle frequency sudden hearing loss]. Zheng Yi-qing,Ou Yong-kang,Xu Yao-dong,Zhang Xue-yuan,Sun Jian-jun,Liu Yang,Lin Yong-sheng,Diao Ming-fang,Chen Dong-lan, Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery OBJECTIVE:To investigate and compare the short-term outcome of patients with low-middle frequency sudden deafness treated with alone or combination treatment. METHODS:From August 2007 to October 2011, 205 patients with the diagnosis of low-middle frequency sudden deafness who were from 33 different clinical centers were recruited. All patients were followed up for four weeks from the initial examination. Patients were treated with steroid , Ginaton, batroxobin respectively, or Ginaton and steroid combination treatment. RESULTS:The total effective rate was 90.73%. In Ginaton group, the total effective rate was 87.27%, 89.19% in steroid group, 87.80% in batroxobin group, and 95.83% in Ginaton and steroid group. Considering the total effective rate, there was no statistical difference between four groups (χ(2) = 7.98, P = 0.54). The clinical cure rate for steroid alone was 81.01%, Ginaton alone 76.36%, batroxobin alone 68.29%, and Ginaton and steroid combination treatment 80.56%. There were no clinically significant differences between the different treatments (P > 0.05). CONCLUSIONS:The low-middle frequency sudden deafness tends to have a relatively favorable prognosis. The steroid played a good effect in the treatment. But different treatments either improving the microcirculation of inner ear or alleviating edema blood has undifferentiated results. Therefore the combination therapy may be more effective.
    [Protective effect of Ginaton on rat liver microcirculation disturbance following liver xenotransplantation]. Zhang Q,Rui X,Cai D Zhonghua yi xue za zhi OBJECTIVE:To study the effect of Ginaton on liver microcirculation disturbance following liver xenotransplantation in rats. METHODS:Ginaton was injected intravenously to recipients at a dosage of 14 mg/kg before graftng liver of guinea pigs. The portal blood flow (PBF) was measured by Doppler ultrasound at 0, 30 and 60 minutes after transplantation, and the pathologic changes of liver and heart were observed. RESULTS:The reperfusion status of control group was poor and leukocyte infiltration appeared in the center of lobute following transplantation and myocardial cells were impaired. Significant reduction in PBF was found in rats following transplantation. Ginaton pretreatment distinctly ameliorated PBF. The speed of PBF was closely correlated with the pathologic changes following transplantation. CONCLUSION:In the process of liver transplantation, ischemia reperfusion damage may lead to xenoheptic microcirculaton disturbance. Ginaton could improve the xenoheptic microcirculation and reduce ischemic reperfusion damage.
    [The effects of ginaton on cochlear microcirculation]. Chen Min,Kong Weijia Lin chuang er bi yan hou ke za zhi = Journal of clinical otorhinolaryngology OBJECTIVE:This study was undertaken to investigate the effects of Ginaton, a kind of extract of gingko biloba with vasoactive, on cochlear blood flow, and to provide the experimental basis for the clinical drug usage. METHOD:Ninety-six guinea pigs were divided into two groups at random, 56 for intravenous infusion (i.v.) group, and 40 for round window membrane (RWM) application group. According to the preliminary results, i.v. group had five subgroups: control, 2.8 mg/kg, 3.5 mg/kg, 3.85 mg/kg, 4.2 mg/kg. RWM group had four sub-groups: control, 3.5 g/L, 0.35 g/L, 0.035 g/L. Ginaton and vehicle were infused through the cervical vein by micropump in 5 minutes. In RWM group, 2 microliters vehicle were dropped into RWM. Cochlear microcirculation was monitored by laser doppler flowmeter (LDF), and mean arterial blood pressure (MABP), which transferred by force transducers and preamplifier, were simultaneously recorded at the computer. RESULT:Cochlear blood flow (CBF) decreased 4.95% and CMBC decreased 6.32% in 3.5 g/L RWM group, and in 0.35 g/L RWM group, these two figures decreased individually 4.75%, 7.61%. In control and 2.8 mg/kg group cochlear microcirculation and MABP had no significant changes. In other i.v. groups, CBF increased 4.53%, 5.21%, 6.65% after 3.5 mg/kg, 3.85 mg/kg, 4.2 mg/kg drugs had been infused, and dosage-effect relation existed. Only in 3.85 mg/kg group, MABP decreased 8.69%. CONCLUSION:Ginaton could improve CBF in a limited dosage range, and this increase showed dose-dependent relation. The mechanism that Ginaton affected the cochlear microcirculation was different because of the way of drug usage.
    [Multi-center study on the treatment for intermediate and high-frequency sudden sensorineural hearing loss]. Wang Ming-ming,Fan Zhao-min,Luo Jian-fen,Hou Zhi-qiang,Ai Yu,Wang Hai-bo,Xu Min,Zhu Kang,Hou Jin,Li Wen-yan, Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery OBJECTIVE:To analyze the therapeutic effect of treatment for intermediate and high-frequency sudden sensorineural hearing loss (SSNHL). METHODS:A prospective clinical multicentre research was conducted using international standardized approach of clinical research. SSNHL Cases with intermediate and high-frequency hearing loss, that accepted no medication from onset of hearing loss within two weeks duration and ages ranged between 18 and 65, were collected. All patients were treated by one of four treatments plans chosen by unified random table. RESULTS:141 patients with intermediate and high-frequency SSNHL were recruited in the research. Twenty subjects were treated with lidocaine, 21 cases with lidocaine and hormone, 40 cases with Ginaton, and 60 cases with Ginaton and hormone. 42 out of 141 (29.79%) patients were total recovery, 24 (17.02%)achieved excellent recovery, 27 (19.15%)achieved partial recovery, and 48 (34.04%) were ineffective. The total effective rate was 65.96%. In lidocaine group, the total effective rate was 55.00%, 66.67% in lidocaine and hormone group, 67.50% in Ginaton group, and 68.33% in Ginaton and hormone group. Considering the total effective rate, there was no statistical difference between four groups (P > 0.05). However, the recovery rate in Ginaton group was significant difference comparing with that in lidocaine group (P = 0.0496). 119 had concomitant symptom of tinnitus, and the tinnitus was improved in patients of 81.51%. With regard to total effective rate of tinnitus in four treatment groups, it was 57.89% (11/19) in lidocaine group, 100.00% (18/18) in lidocaine and hormone group, 88.57% (31/35) in Ginaton group, 78.72% (37/47) in Ginaton and hormone group. There was significant ascendancy in lidocaine and hormone group versus that in lidocaine group (P = 0.002) and Ginaton and hormone group (P = 0.029). And the difference between lidocaine and Ginaton groups was statistical significance (χ(2) = 6.705, P < 0.05). In 43 patients with muffled symptom in aural region, 90.70% was partial recovery. There was no statistical difference between each groups (χ(2) = 5.97,P = 0.74). There were 17 with dizziness or vertigo improved in all cases. Another 10 patients accompanied other complaints all improved. CONCLUSIONS:for the treat of intermediate and high-frequency SSNHL, the therapeutic effect in hearing has no significantly different between single and combined drug therapies. Considering the recovery rate, there is an obvious advantage in Ginaton group compared with lidocaine group. Tinnitus is the major concomitant symptom in intermediate and high-frequency SSNHL, and lidocaine and hormone therapy should be used.
    [Effects of Ginkgo biloba extract (ginaton) on mRNA expression of bcl-2 and bcl-xL in myocardium of patients underwent hypothermic cardiopulmonary bypass]. Deng Yun-kun,Wei Fang,Li Yong-nian Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine OBJECTIVE:To investigate the effects of Ginkgo biloba extract (Ginaton) on bcl-2 and bcl-xL mRNA expression in the myocardium of patients underwent hypothermic cardiopulmonary bypass (CPB). METHODS:Thirty congenital heart disease patients were randomly assigned to 2 groups, the control group and the treated group. Patients in both groups received St. Thomas' cardioplegic solution via radix aortae, while Ginaton (0.5 mg/kg) was added in the treated group. Cardiac surgery was started after complete heart arrest. Myocardium was taken before the aorta ascendens was unblocked and mRNA expression of bcl-2 and bcl-xL in the ventricular tissue was detected by RT-PCR. RESULTS:The gene expressions of bcl-2 and bcl-xL were significantly higher in the treated group than those in the control group (P < 0.05). CONCLUSION:Ginaton could promote the mRNA expressions of the antiapoptotic gene bcl-2 and bcl-xL in myocardium of patients underwent CI'PB.
    [Protective effects of ginaton against ischemia-reperfusion injury on the autograft after lung autotransplantation: experiment with rabbits]. Xu He-yun,Chen Shu-ping,Jin Tao,Wen Xiao-hong,An Xiao-xia,Xu Ming Zhonghua yi xue za zhi OBJECTIVE:To investigate the effects of ginaton against ischemia-reperfusion injury on the autograft after lung autotransplantation. METHODS:Models of lung autotransplantation were established in 18 New Zealand rabbits were established. The 18 rabbits were randomly divided into 3 equal groups: group of simple ischemia-reperfusion (group I/R), undergoing ischemia by blocking the left pulmonary artery for 2 h and then re-perfusion for 90 min; group with perfusion of low potassium dextran solution (group LPD), undergoing perfusion of LSD solution before ischemia; and group with treatment of ginaton (group LPD + E), undergoing intravenous injection of ginaton 15 min before ischemia. Arterial blood samples were collected before ischemia, and 15, 60, and 90 min after re-perfusion to examine the alveolar oxygen pressure (PaO2). Serum tumor necrosis factor-alpha (TNF-alpha) was monitored before ischemia, and 30, 60, and 90 min after re-perfusion. Then the left lungs were taken out to undergo detection of dry/wet ratio (D/W), pathological examination, and contents of myeloperoxidase (MPO) and the malondialdehyde (MDA) in the lung tissues. RESULTS:(1) The PaO2 decreased significantly after reperfusion in all groups. And the PaO2 values at different time points of Group LPD + E were all significantly higher than those of Group I/R (all P < 0.01), however, there were no significant differences between Group LPD and Group LPD + E. (2) The TNF-alpha level after reperfusion increased in Group I/R and Group LPD, while in Group LPD + E it increased only 60 min and 90 min after the reperfusion. The TNF-alpha levels after reperfusion at all time points of Group LPD + E were all significantly lower than those of the other 2 groups (all P < 0.05). (3) The MPO and MDA levels at all time points after re-perfusion of Group LPD + E were all significantly lower than those of the other 2 groups (all P < 0.01). (4) The value of D/W ratio of Group LPD + E was significantly higher than those of the other 2 groups (both P < 0.01). (5) Pathological examination showed that the lung tissue lesion of Group I/R was severe. Interstitial inflammatory cell infiltration, intra-alveolar inflammatory cell aggregation, exudation and even hemorrhage could be observed. The pathological lesion of Group LPD + E was mild, no significant inflammatory cell infiltration or exudation was observed. CONCLUSION:Ginaton provides a protective effect against ischemia-reperfusion injury on the autograft after lung autotransplantation. The mechanism may be related with antioxidation, inhibition of neutrophil aggregation, and TNF-releasing.
    [Effects of Ginaton on the markers of myocardial injury during cardiopulmonary bypass]. Deng Yun-kun,Wei Fang,An Bang-quan Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine OBJECTIVE:To evaluate the effects of Ginaton (Ginkgo biloba leaf extract) on the myocardial injury markers (MIMs) during cardiopulmonary bypass (CPB). METHODS:Forty patients with congenital heart diseases, scheduled to take atrial septum or ventricular septum repairing operation, were randomly divided into the Ginaton group and the control group, 20 cases in each group. Patients in both groups received St. Thomas' cardioplegic perfusion via radix aortae, while Ginaton (0.5 mg/kg) was added into the perfusion for the Ginton group. Cardiac surgery were started after complete heart arrest. Central venous blood was obtained before and at 0, 6th, 12th, 24th and 48th hour after operation for detection of serum C reaction protein (CRP) by immunoturbidimetry, as well as creation kinase-MB isoenzyme (CK-MB), cardiac troponin T (cTnT) and cardiac troponin I (cTnI) with enzyme-linked immunosorbent assay (ELISA). RESULTS:There was no difference in serum concentration of CRP, CK-MB, cTnT and cTnI between the two groups before operation (P > 0.05). These indexes increased immediately after operation in both groups ( P < 0.05). They reached the peak value 12 hrs after CPB and reduced to normal level 48 hrs post-operation in the control group, with the value significantly higher than that in the Ginaton group at all the corresponding time points (P < 0.05, or P < 0.01). CONCLUSION:Perfusion with Ginaton during CPB could significantly decrease the release of MIMs and improve post-CPB cardiac function recovery, exerting favorable myocardium-protective effects.
    [Brain protective effects of ginkgo biloba leaf extract (ginaton) in patients undergoing hypothermic cardiopulmonary bypass]. Deng Yun-kun,Wei Fang,Zhang Da-guo Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine OBJECTIVE:To investigate the brain protective effects of Ginkgo biloba leaf extract (Ginaton) in patients who underwent hypothermic cardiopulmonary bypass (CPB). METHODS:Sixty patients with rheumatic heart disease of ASA grade II-III, who were scheduled for mitral valve replacement with intravenous anaesthesia, were randomly assigned to two groups, the Ginaton group (30 patients) treated with Ginaton 1 mg/kg by intravenous dripping before open heart for CPB, and the control group (30 patients) with normal saline instead. Blood was synchronously collected from arteriae radialis and vena jugularis interna at 5 time points, namely, before CPB (T1), nasopharyngeal temperature (lowered to 30-31 degrees C) stabilized stage (T2), nasopharyngeal temperature restoration (36 degrees C) stage (T3), 30 min after CPB (T4) and 3 after CPB (Ts) for determining blood gas, lactate acid concentration, activity of superoxide dismutase (SOD) and malonaldehyde (MDA) content. And the oxygen content in artery (CaO2) and jugular vein (CjvO2), the difference of oxygen contents in arterial and jugular vein (Ca-jvO2), the cerebral oxygen extraction ratio (ERO2) as well as the arteriojugular lactate difference (ADVL) were calculated. RESULTS:After the beginning of CPB, as compared with those in the control group, in the Ginaton group, the reduction of Ca-jvO2 and ERO2 was significantly higher (P < 0.05 or P < 0.01) and the increase of lactate acid, ADVL and MDA were significantly lower, and with a remarkably higher SOD activity (P < 0.01). CONCLUSION:Ginaton could improve cerebral oxygen supply, promote SOD activity to inhibit production of free radicals in patients undergoing CPB, and thus shows an evident protective effect in the brain.
    Protective effect of a standardized Ginkgo extract (ginaton) on renal ischemia/reperfusion injury via suppressing the activation of JNK signal pathway. Wang Yan,Pei Dong-Sheng,Ji Huai-Xue,Xing Shu-Hua Phytomedicine : international journal of phytotherapy and phytopharmacology A new standardized Ginkgo extract (ginaton) destined for i.v. injection was investigated in rats for its protective effect on renal ischemia/reperfusion injury. We report on the elucidation of the downstream mechanism of action of JNK on the renal ischemia/reperfusion injury, which can be explained as the decrease in JNK phosphorylation at 20 min and c-Jun phosphorylation (Ser63/73) at 3h after renal ischemia. At the same time, ginaton attenuated the increased expression of FasL at 3h and caspase3 immunoreactivity at 6h after renal ischemia. Furthermore, ginaton significantly decreased renal epithelial tubular cell apoptosis induced by renal ischemia/reperfusion, alleviating renal ischemia/reperfusion injury. These results cumulatively indicate that ginaton could suppress the JNK-c-Jun-FasL-caspase3 signaling cascade, protecting renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis, which implies that antioxidants may be a potential and effective agent for prevention of the ischemic/reperfusion injury through the suppression extrinsic apoptotic signal pathway induced by JNK signal pathway. 10.1016/j.phymed.2008.09.003
    Comparative pharmacokinetics of a proliposome formulation of Ginkgo biloba extract and Ginaton in rats by a sensitive ultra performance liquid chromatography-tandem mass spectrometry method. Zheng Bin,Xing Gaoyang,Bi Ye,Yan Guodong,Wang Jing,Cheng Yingkun,Liu Yan,Ashraf Muhammad Aqeel,Xie Jing Saudi journal of biological sciences As a novel oral drug delivery system, proliposome was applied to improve the solubility of active components of Ginkgo biloba extract (GbE). There are currently few reports focusing on the pharmacokinetic characteristics of proliposome of GbE (GbP). A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of active components of GbP and a commercial tablet product (Ginaton) in rat plasma was developed and successfully validated. The method was applied to the comparative pharmacokinetic evaluation of GbP and Ginaton in rat plasma. The results indicated that GbP has a significant effect on absorption, elimination and bioavailability of flavonoids and terpenoid lactones in comparison with Ginaton. The obtained results would be helpful for evaluating the absorption mechanism in the gastrointestinal tract in pharmacokinetic level and guiding the development of the novel oral drug delivery system. 10.1016/j.sjbs.2015.08.009
    [Erythrocyte protective effects of ginaton in patients undergoing hypothermic cardiopulmonary bypass]. Deng Yun-kun,Wei Fang,Zhang Da-guo Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine OBJECTIVE:To investigate the erythrocyte protective effects of Ginaton, a ginkgo biloba extract, in patients undergoing hypothermic cardiopulmonary bypass (CPB). METHODS:Sixty patients, who suffered from rheumatic heart disease of ASA grade II-III and scheduled for mitral valve replacement with intravenous anesthesia, were randomly assigned to two groups equally, the Ginaton group and the control group. They were administered with Ginaton 1 mg/kg and saline respectively via intravenous dripping before open heart surgery before beginning CPB. Blood samples were taken from radial artery at different time points, i.e., before CPB (T1), nasopharyngeal temperature (30-31 degrees C) stabilized stage (T2), nasopharyngeal temperature restoration (36 degrees C) stage (T3), 30 min after CPB (T4) and 3 h after CPB (T5), for determination of malondialdehyde (MDA) and superoxide dismutase (SOD) levels in plasma and erythrocyte (P-MDA, E-MDA, P-SOD and E-SOD), as well as the Na+ -K+ -ATPase and Ca+ -Mg2+ -ATPase activities in erythrocytes. RESULTS:As compared with those at T1, in the control group, P-MDA, E-MDA, and E-SOD at T2-T5 and E-SOD at T2 were higher, but E-SOD at T3-T5 were lower (P < 0.01); while in the Ginaton group P-MDA, E-MDA, and E-SOD at T3-T4 were higher (P < 0.05 or P < 0.01). As compared with those in the control group, the levels of P-MDA and E-MDA at T2-T5 were significantly lower, and E-SOD at T3-T5 were higher (P < 0.05 or P < 0.01). Activities of Na+ -K+ -ATPase and Ca+ -Mg2+ -ATPase significantly increased at T2 and gradually decreased after then in both groups (P < 0.05 or P < 0.01), but those at T2-T5 were significantly higher in Ginaton group than in control group (P < 0.05 or P < 0.01). CONCLUSION:Ginaton displays an erythrocyte protecting effect by way of alleviating the lipid peroxidation in erythrocytes' membrane.
    [Synergic effect of alprostadil injection and ginaton in treating sudden deafness]. Jiang Jiping,Wang Shuyun,Tong Kang Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery OBJECTIVE:To explore synergic effect of Alprostadil injection and ginaton in treating sudden deafness. METHOD:ninety one patients with sudden deafness were divided into group A, group B and group C at random; 33 ears of group A were treated with 70 mg ginaton by vein, 30 ears of group B were treated with 10 microg Alprostadil injection by vein, 31 ears of group C were treated with 10 microg Alprostadil injection and ginaton by vein,once a day, the time of treatment is 14 days. RESULT:the effective rate of group A is 60.61%, the effective rate of group B is 60.00%, the effective rate of group C is 87.09% the treating effect was significantly different in the group A and C (P < 0.05), it was significantly different in the group B and C (P < 0.05)). CONCLUSION:It is effective for Alprostadil injection and ginaton to treat sudden deafness, and it has significantly Synergic effect in treating sudden deafness with Alprostadil injection and ginaton.
    Protective effects of ginaton on vascular endothelial cells injured by angiotensin II and hypoxia in vitro. Han Lei,Li Minggao Vascular and endovascular surgery The objective of this study was to explore the protective effect and possible mechanism of Ginkgo biloba extract (Ginaton) on human vascular endothelial cells (VECs) injured by angiotensin II (Ang-II) and hypoxia. The human aortic VECs were divided into different groups to observe the changes in endothelin (ET), intracellular calcium concentration ([Ca(2+)]i), and mitochondrial membrane potential (MMP). The results showed that Ginaton had inhibited ET secretion induced by hypoxia and Ang-II (P < .01); the protective effects of mid (10 mg/mL) and low concentrations (5 mg/mL) of Ginaton was obviously higher than that of the high concentration (25 mg/mL); [Ca(2+)]i increased and MMP decreased significantly in both the hypoxia and the Ang-II groups (P < .01); however, the changes in [Ca(2+)]i and MMP could be meliorated by Ginaton. This study suggested that Ginaton could effectively protect VECs against injury, and lower dose would be used clinically rather than the higher dose for obtaining better results. 10.1177/1538574413486361
    Protection of vascular endothelial cells injured by angiotensin II and hypoxia in vitro by Ginkgo biloba (Ginaton). Han Lei,Li Minggao Vascular and endovascular surgery The objective of this study was to explore the protective effect and the possible mechanism of Ginkgo biloba extract (Ginaton) on human vascular endothelial cells (VECs) injured by angiotensin II (Ang-II) and hypoxia. The human aortic VECs were divided into different groups to observe the changes in endothelin (ET), calcium concentration ([Ca(2+)]i), and mitochondrial membrane potential (MMP). The results showed that Ginaton had inhibited ET secretion induced by hypoxia and Ang-II (P < .01). the protection offered by Ginaton at mid (10 mg/mL) and low (5 mg/mL) concentrations was obviously better than that offered at high concentration (25 mg/mL). The [Ca(2+)]i increased and MMP decreased significantly in both hypoxia group and Ang-II group (P < .01); however, the changes in [Ca(2+)]i and MMP could be meliorated by Ginaton. This study suggested that Ginaton could effectively protect VECs against injury, and the dose used clinically would rather be low than too high for getting better results. 10.1177/1538574413497106
    [Effects of Ginaton on nitric oxide and nitric oxide synthase in patients with delayed encephalopathy after carbon monoxide poisoning]. Wang W Z,Qi H N,Xiao Q M,Gao X,Zhu B Y,Li J,Liu Y J,Li W,Ma G Y,Wang P Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases To observe the effects of Ginaton on blood nitric oxide (NO) and nitric oxide synthase (NOS) in patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). A total of 116 patients with DEACMP who were treated in Emergency Department of Harrison International Peace Hospital Affiliated to Hebei Medical University from January 2012 to April 2016 were enrolled and ran-domly divided into control group and treatment group using a random number table, with 58 patients in each group. The patients in the control group were given conventional treatment including hyperbaric oxygen, preven-tion and treatment of cerebral edema, and promotion of brain cell metabolism, and those in the treatment group were given Ginaton in addition to the conventional treatment. The course of treatment was 2 weeks for both groups. The levels of neuron-specific enolase (NSE) , NO, NOS, and inducible nitric oxide synthase (iNOS) were measured before treatment and at 2 weeks after treatment, and the change in Mini-Mental State Examina-tion (MMSE) score and clinical outcome were observed in both groups. The correlation between the blood NO level on admission and the MMSE score was analyzed. There was a significant difference in the overall response rate between the treatment group and the control group (81.03% 62.07%, χ(2) = 5.124, =0.024). Be-fore treatment, there were no significant differences in the levels of NO and NSE, the activity of NOS and iN-OS, and MMSE score between the two groups (>0.05). After treatment, both groups showed reductions in the levels of NO and NSE and the activity of NOS and iNOS, but the treatment group had significantly greater reduc-tions compared with the control group (<0.05). Both groups showed a significant increase in the MMSE score after treatment, while the treatment group had a significantly greater increase compared with the control group (<0.05). In the patients with DEACMP, the blood NO level on admission was negatively correlated with the MMSE score (=-0.268, =0.004). In the treatment of patients with DEACMP, Ginaton can effectively reduce the levels of NO and NSE and the activity of NOS and iNOS, increase the MMSE score, and promote the recovery of neurological function. 10.3760/cma.j.issn.1001-9391.2017.01.007
    Gingko biloba extract (Ginaton) ameliorates dextran sulfate sodium (DSS)-induced acute experimental colitis in mice via reducing IL-6/STAT3 and IL-23/IL-17. Sun Yan,Lin Lian-Jie,Lin Yan,Sang Li-Xuan,Jiang Min,Zheng Chang-Qing International journal of clinical and experimental medicine This study explored the underlying mechanism of Gingko biloba extract (Ginaton) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice. 40 male C57BL/6 mice were randomly divided into four groups: normal control group, Ginaton group, Ginaton treatment group, and DSS group. After 7 days administration, mice were sacrificed and colons were collected for H-E staining, immunohistochemistry, real-time PCR and Western blot. By observing clinical disease activity and histological damage, we assessed the effect of Ginaton on DSS-induced acute experimental colitis in mice and observed the effect of Ginaton on normal mice. We also explored the specific mechanism of Ginaton on DSS-induced acute experimental colitis in mice through examining the expression of inflammatory related mediators (gp130, STAT3, p-STAT3, ROR-γt) and cytokines (IL-6, IL-17, IL-23). Ginaton-treated DSS mice showed significant improvement over untreated DSS mice. Specifically, Ginaton improved clinical disease activity (DAI score, weight closs, colon shortening, and bloody stool) and histological damage, and reduced the expression of inflammatory-related mediators (p-STAT3, gp130, ROR-γt) and cytokines (IL-6, IL-17, IL-23). In addition, clinical disease activity, histological damage, the expression of inflammatory related mediators (STAT3, p-STAT3, gp130, ROR-t) and cytokines (IL-6, IL-17, IL-23) in mice of Ginaton group were similar to normal control group. In conclusion, Ginaton ameliorates DSS-induced acute experimental colitis in mice by reducing IL-17 production, which is at least partly involved in inhibiting IL-6/STAT3 signaling pathway and IL-23/IL-17 axis. Moreover, Ginaton itself does not cause inflammatory change in normal mice. These results support that Ginaton can be as a potential clinical treatment for ulcerative colitis (UC).
    Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis. Li Xiaoqiang,Zhang Deli,Bai Yinliang,Xiao Jiyuan,Jiao Haisheng,He Rongxia Neuropsychiatric disease and treatment Purpose:The present study was carried out to confirm the protective effect of extract of (Ginaton) against ischemic neuronal damage post-treatment at 24 h after reperfusion in rats with middle cerebral artery occlusion (MCAO) and further reveal its possible mechanisms. Methods:Adult male Sprague-Dawley rats were modeled by MCAO for 2 h. The rats were divided into three groups: sham, model, and Ginaton (50 mg/kg). All animals received treatment once a day for 14 days from 24 h after reperfusion. Modified neurological severity score test was performed in 1, 7 and 14 days after MCAO, and beam walking test was performed only 14 days after MCAO. Hematoxylin-eosin straining was implemented to measure infarct volume and immunohistochemical analysis was performed to calculate the number of neurons in ischemic cortex penumbra. Western blot was used to evaluate the expression of autophagy (Beclin1, LC3, AMPK, mTOR, ULK), mitochondrial dynamic protein (Parkin, DRP1, OPA1) and apoptosis (Bcl-2, Bax). Results:Post-treatment with Ginaton for 14 days decreased neurological deficit score, promoted the recovery of motor function, and noticeably reduced infarct size. Besides, Ginaton also alleviated the loss of NeuN-positive cells in ischemic cortex penumbra. In ischemic cortex, Ginaton increased the expression of Beclin1 and LC3-Ⅱ, elevated the AMPK, mTOR and ULK1, and induced autophagy. Moreover, Ginaton treatment upregulated Parkin, DRP1, and OPA1, and elevated the ratio of Bcl-2/Bax in 14 days after MCAO reperfusion injury. Conclusion:Ginaton exhibited obvious neuroprotective effects in MCAO rats with initial administered 24 h after MCAO. The mechanism of Ginaton included induction of autophagy via activation of the AMPK pathway, maintenance of mitochondrial homeostasis and inhibition of apoptosis. 10.2147/NDT.S205612