α-Chymotrypsin-catalyzed enantioselective amidation of chiral amines using an N-protected amino acid carbamoylmethyl ester as acyl donor

-Chymotrypsin catalyzed the highly enantioselective amidation of chiral amines such as 1-(1-naphthyl)ethylamine using N-benzyloxycarbonyl-(S)-phenylalanine carbamoylmethyl ester as acyl donor (E = 25–660) in acetonitrile with low water content.     

氧化应激及天然抗氧化剂对阿尔茨海默病的缓解作用（英文）

衰老是阿尔茨海默病（Alzheimer’s disease,AD）等神经退行性疾病的主要危险因素。氧化应激和自由基具有重要的生物学功能,氧化还原失衡导致氧化应激,与包括AD在内的许多人类疾病的病理生理有关。本文综述了活性氧（ROS）参与神经退行性疾病发病的相关机制,特别是氧化应激与AD其他关键机制的相互作用,并总结了茶多酚、L-茶氨酸、虾青素、EGb761、大豆异黄酮和烟碱在细胞和动物模型中对AD的防护作用以及在临床上对相关疾病的缓解作用。希望该综述能为AD的预防和治疗策略提供一些见解。     

Ginkgolide B stimulates signaling events in neutrophils and primes defense activities

Ginkgolide B (GKB) is a bioactive component of the standardized extract from the leaves of the Ginkgo biloba tree (EGb 761), which is used in Chinese and in occidental medicine. GKB is known as a platelet-activating factor receptor antagonist. Here, we provide evidence that GKB per se (0.25-5 microM) stimulated tyrosine phosphorylation of proteins, phospholipase D activation, calcium transients, and activation of p38 but not p44/42 Map kinases in human polymorphonuclear leukocytes (PMN). These stimulatory effects remained relatively weak and primed PMN for subsequent stimulation of respiratory burst (RB) or directed locomotion by the chemoattractant fMet-Leu-Phe (fMLP) or complement-derived factor C5a. A similar RB priming was observed with rat exudate PMN after in vivo administration of EGb 761 (25 and 50 mg/kg) to rats before pleurisy induction. Thus, GKB primarily induces activation of intracellular signaling events and has the potential to prime cellular functions such as PMN defense activities.     

Ginkgo biloba prevents transient global ischemia-induced delayed hippocampal neuronal death through antioxidant and anti-inflammatory mechanism

We have previously reported neuroprotective properties of Ginkgo biloba/EGb 761® (EGb 761) in transient and permanent mouse models of brain ischemia. In a quest to extend our studies on EGb 761 and its constituents further, we used a model of transient global ischemia induced delayed hippocampal neuronal death and inflammation. Mice pretreated with different test drugs for 7 days were subjected to 8-min bilateral common carotid artery occlusion (tBCCAO) at day 8. After 7 days of reperfusion, mice brains were dissected out for TUNEL assay and immunohistochemistry. In situ detection of fragmented DNA (TUNEL staining) showed that out of all test drugs, only EGb 761 (13.6% ± 3.2) pretreatment protected neurons in the hippocampus against global ischemia (vs. vehicle, 85.1% ± 9.9; p < 0.05). Immunofluorescence-based studies demonstrated that pretreatment with EGb 761 upregulated the expression levels of heme oxygenase 1 (HO1), nuclear factor erythroid 2-related factor 2 (Nrf2), and vascular endothelial growth factor (VEGF) as compared to the vehicle group. In addition, increased number of activated astrocytes and microglia in the vehicle group was observed to be significantly lower in the EGb 761 pretreated group. Together, these results suggest that EGb 761 is a multifunctional neuroprotective agent, and the protection is in part associated with activation of the HO1/Nrf2 pathway, upregulation of VEGF and downregulation of inflammatory mediators such as astrocytes and microglia.     

银杏叶提取物对过氧化氢诱导的星形胶质细胞氧化损伤的保护作用

目的 研究银杏叶提取物（EGb761）对H2O2所致星形胶质细胞氧化损伤的保护作用。方法 用不同浓度的EGb761预处理细胞,再加入H2O2,通过噻唑蓝（MTT）实验、线粒体跨膜电位（△ψm）及细胞色素C释放实验、DNA损伤实验及半胱氨酰天冬氨酸特异性蛋白酶-3（Caspase-3）活性测定,观察EGb761对细胞存活率、线粒体膜通透性、DNA氧化损伤及Caspase-3活性的影响。结果 EGb761能明显降低Hz02对星形胶质细胞的氧化损伤,提高细胞的存活率;维持线粒体膜的完整性,抑制跨膜电位的耗散和细胞色素C的释放;抑制Caspase-3的活化和DNA的降解。结论 EGb761具有清除活性氧,减轻H2O2所致星形胶质细胞的氧化损伤,对星形胶质细胞有保护作用。     

Prevalence of known mutations and a novel missense mutation (M694K) in the MEFV gene in a population from the Eastern Anatolia Region of Turkey

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and serositis. Mutations in the Mediterranean fever gene (MEFV) localized on the short arm of chromosome 16 cause FMF. Over 90 MEFV missense/nonsense mutations have been identified so far in FMF patients, mostly in the 10th exon of the gene.     

Effects of Gingko Extract (EGb761) on oxidative damage under different conditions of serum supply

Standardized Ginkgo biloba extract EGb761 is known to have multivalent properties such as anti-oxidation and anti-apoptosis. In this study, we determined in rat pheochromocytoma (PC12) cells effects of EGb761 treatment on oxidative damage under three different conditions of serum supply: normal growth medium (NGM), serum deprivation (SE) and serum deprivation followed by re-supply (SERS). It was found that, under the condition of serum deprivation, oxidative damage induced less cell death than the condition of serum supply. This appears to be related to inhibition of mitochondrial metabolism. Moreover, after serum deprivation, serum re-supply exacerbated cell necrosis, possibly through enhancement of oxidative damage. EGb761 could attenuate oxidative damage under the condition of serum supply whereas no protective effect on serum-depleted cells was observed. These results suggest that, there is a synergistic effect between trophic factors and EGb761. EGb761 treatment may protect cells from possible oxidative damage induced by the trophic factors. On the other hand, trophic factors appear to strengthen the protective effect of EGb761. To fully understand the synergistic interaction between antioxidants and trophic factors will help to sort out rational use of drugs in clinic practice.     

银杏叶提取物(EGb761)导致人红细胞溶血作用的研究

本文用不同剂量的EGb761在37℃的环境下对健康人的红细胞(RBC)进行处理,发现EGb761对RBC有损伤作用,主要表现为导致溶血和诱导细胞形变,且其作用大小与浓度和时间呈正相关.这一实验结果对长期大剂量服用EGb761及其它银杏叶提取物的人群具有警示意义.EGb761对RBC损伤作用的机制仍不清楚,有待于进一步的研究.     

Dosage effects of EGb761 on hydrogen peroxide-induced cell death in SH-SY5Y cells

Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, is one of the most popular herbal supplements, taken for its multivalent properties. In this study, dosage effects of EGb761 on hydrogen peroxide (H₂O₂)-induced apoptosis of human neuroblastoma SH-SY5Y cells were investigated. It was found that H₂O₂-induced apoptotic cell death in SH-SY5Y cells, which was revealed in DNA fragmentation, mitochondrial membrane potential depolarization, and activation of Akt, c-Jun N-terminal kinases (JNK) and caspase 3. Low doses of EGb761 (50–100 μg/ml) inhibited H₂O₂-induced cell apoptosis via inactivation of Akt, JNK and caspase 3 while high doses of EGb761 (250–500 μg/ml) enhanced H₂O₂ toxicities via inactivation of Akt and enhancement of activation of JNK and caspase 3. Additional experiments revealed that H₂O₂ decreased intracellular GSH content, which was also inhibited by low concentrations of EGb761 but enhanced after high concentrations of EGb761 treatment. This further suggests to us that dosage effects of EGb761 on apoptotic signaling proteins may be correlated with regulation of cell redox state. Therefore, treatment dosage may be one of the vital factors that determine the specific action of EGb761 on oxidative stress-induced cell apoptosis. To understand the mechanisms of dosage effects of EGb761 may have important clinical implications.     

银杏叶提取物促进脑缺血半暗带神经元自噬提高神经保护作用

银杏叶提取物(ginkgo biloba extract-761,EGb-761)注射液在中国常作为辅助药物被用于治疗脑卒中,但是,其潜在的细胞和药理机制尚未完全了解。该研究旨在探讨EGb-761是否通过调节缺血性脑卒中半暗带神经元的自噬从而发挥保护作用。采用雄性SD大鼠大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)再灌注模型,将MCAO大鼠随机分为5组,分别为Sham组、MCAO+saline组、MCAO+EGb组、MCAO+EGb+3-MA组和MCAO+3-MA组。脑缺血大鼠用EGb-761药物腹腔注射7天后,并使用自噬抑制剂3-MA侧脑室注射进行干预,分别通过蛋白免疫印迹法(WB)、实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)和免疫荧光检测缺血半暗带的脑组织,以检测自噬的表达。另外,根据脑梗死体积、神经功能缺损和TUNEL检测神经元凋亡水平,以评估治疗效果。结果表明,与MCAO+saline相比,MCAO+EGb组的EGb-761显著提高了神经元自噬水平,同时,明显减轻了神经功能缺损、脑梗死面积和神经元凋亡。此外,相对于MCAO+EGb组,MCAO+EGb+3-MA组中的3-MA抵消了EGb增强神经元自噬的功效,并且仅使用3-MA继续加重了神经损伤。因此,EGB-761通过特异性促进脑缺血半暗带神经元自噬发挥神经保护作用。