Cornel iridoid glycoside induces autophagy to protect against tau oligomer neurotoxicity induced by activation of glycogen synthase kinase-3β

Tau oligomers are the etiologic molecules of Alzheimer disease(AD), and correlate strongly with neuronal loss and exhibit neurotoxicity. Recent evidence indicates that small tau oligomers are the most relevant toxic aggregate species. The aim of the present study was to investigate the mechanisms of cornel iridoid glycoside(CIG) on tau oligomers and cognitive functions. We injected wortmannin and GF-109203 X(WM/GFX, 200 μmol·L-1 each) into the lateral ventricles to induce tau oligomer and memory impairment in rats. When oral y administered with CIG at 60 and 120 mg·kg-1 per day for 14 d, CIG decreased the escape latency in Morris water maze test. We also found that CIG restored the expression of presynaptic p-synapsin, synaptophysin, and postsynaptic density-95(PSD-95) decreased by WM/GFX in rat cortex. CIG reduced the accumulation of tau oligomers in the brain of WM/GFX rats and in cells transfected with wild type glycogen synthase kinase-3β(wt GSK-3β). In addition, CIG up-regulated the levels of ATG7, ATG12, Beclin-1, and LC3 II in vivo and in vitro, suggesting the restoration of autophagy function. These results suggest that CIG could ameliorate memory deficits and regulate memory-associated synaptic proteins through the clearance of tau oligomers accumulation. Moreover, CIG clears tau oligomers by restoring autophagy function.

Isolation and Confirmation of Quercetin-3-O-Glycosides from Rubber Cassava Leaves

The core of the natural product chemistry laboratory is isolation secondary metabolites. One of the potential secondary metabolites for isolation in the natural product chemistry laboratory is routine (quercetin-3-O-glycosides). Routine (Quercetin-3-O-glycoside) has been isolated from ethanol extract of rubber cassava leaves (Manihot glaziovii MA). Isolation was done by maceration and recrystallization. The isolation method used in this study is complemented by the isolation method published. The isolated (Quercetin-3-O-glycoside) routine using this method obtained a yield of 0.118% of the total dried leaf extract. The routine (Quercetin-3-O-glycoside) was identified using a standard routine. Routine can be further utilized in the world of medicine as an amplifier of capillary structure, reducing the permeability and fragility of blood vessels.

Two New Flavonoid Glycosides from Chrysanthemum morifolium

Two new flavonoid glycosides were isolated from the flowering heads of Chrysanthemum morifolium. Their structures were determined to be luteolin 4＇-methoxy-7- O-（6＂-O-acetyl）-β-D-glucopyranoside （1） and acacetin 7-O-（3＂-O-acetyl）-β-D-glucopyranoside （2） by means of 1H and 13C NMR spectroscopic analysis, including 2D NMR technique.

A New Flavone Glycoside from Epimedium koreanum

A novel flavone glycoside named 3＇＇＇-carbonyl-2＇＇-β-L-quinovosyl icariside Ⅱ was isolated from the aerial parts of Epimedium koreanum. Its chemical structure was elucidated on the basis of spectral analysis.

Two New Flavonol Glycosides from Bridelia tomentosa

Two new flavonol glycosides, tamarixetin 3-O-β-D-xylopyranosyl-（1-2）-α-L-ribopyranoside （1） and tamarixetin 3-O-α-L-ribopyranoside （2） were isolated from the leaves of Bridelia tomentosa. Their structures were elucidated by 1D and 2D NMR analysis, as well as MS and IR spectra.

Synthesis of α,β-Unsaturated Ketones using Potassium fluoridealumina Catalyst by Microwave Irradiation

Microwave irradiation can accelerate the rate of the synthetic reaction of α,β-unsaturated ketones by using KF-Al2O3 as catalyst. The rate enhancement of the reaction is 360-860 fold.

New Triterpene Glycoside from Thalictrum smithii

A new triterpene glycoside, 24S-cycloartane-3 beta, 16 beta, 24, 25, 30-pentaol 3-O-(2-O-beta-D-xylosyl)-beta-D-xyloside was isolated from Thalictrum smithii. Its structure was determined by spectroscopic and chemical methods.

The Mechanism of Cornus officinalis Total Glycosides and Cornus Polysaccharide on Myocardial Protection in Rats with Acute Myocardial Infarction

Objective: To investigate effects of Cornus officinalis Total Glycosides (COTG) and Cornus Polysaccharide (CP) on myocardial protection and on expression of mitochondria biogenesis related gene of acute myocardial infarction (AMI) rats, Materials and Methods: Ninety-six SD rats of SPF level were randomly divided into 5 groups: sham operation group, model group, preventive treatment group, COTG treatment group, CP treatment group, and there were 12 cases in each one. By legating the left anterior descending branch of coronary artery method, acute myocardial infarction model was established. The rat of sham operation group and model group was intragastric administered with physiological saline;other groups were given with corresponding drugs. The cardiac function, the myocardial infarct area, the expression of mitochondrial biogenesis genes such as PGC-1α, PGC-1β, NRF-1mRNA and GSK-3β mRNA, GSK-3β Protein Expression were analyzed. Results: The results revealed that compared with model group, myocardial infarction size, LVDs, LVDd, LVESV, LVEDP, and -dp/dt decreased;LVSP increased in preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05);LVEDV increased in preventive treatment group (p < 0.05), PGC 1 alpha, and PGC 1 beta;the NRF-1 mRNA expression increased in preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05). Compared with CP and COTG treatment group, PGClpha, beta PGC 1, the NRF-1 mRNA expression increased in preventive treatment group (p < 0.05). Compared with the sham operation group, GSK-3 beta mRNA and protein expression increased in model group, preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05). Compared with model group, GSK-3 beta mRNA expression reduced in preventive treatment group, COTG treatment group, and CP treatment group (p Cornus officinalis total glycosides and Cornus polysaccharides can effectively protect myocardial mitochondria of acute myocardial infarction rats by activating GSK-3β signaling pathways, and reduce the myocardial infarct size, which has great significance for improving cardiac function.

Two New Flavonol Glycosides from Knoxia corymbosa

Two new flavonol glycosides (1 and 2) together with two known flavonoides (3 and 4), were isolated from the whole plant of Knoxia corymbosa willd. The structures of 1 and 2 were elucidated as kaempferol-7-O-α-L-arabinosyl-3-O-β-D-6'-acetylglucopyranoside and kaempferol -7-O-α-L-arabinosyl-3-O-β-D-3',6'-diacetylglucopyranoside respectively.

New Flavonoid Glycoside from Thalictrum przewalskii

A new flavonoid glycoside, 5, 7-dihydroxy-4'-methoxyflavonoid 7-Q-[6-O-(4-O-acetyl-alpha-L-rhamnosyl)-3-O-beta-D-glucosyl]-6-O-acetyl-beta-D-glucoside was isolated from Thalictrum przewalskii. Its structure was determined on basis of spectroscopic evidences.

Stereoselective cycloaddition of N-acyliminium cations withα,β-unsaturated ketones and esters

The cycloaddition of N-acyliminium cations with some deactivated alkenes such as α,β-unsaturate ketones and esters has been investigated. In most cases, the N-acyliminium cations produced from 3-hydroxy-2-arylisoindol-1-ones in the presence of BFa.OEt2 could be reacted with α,β-unsaturated ketones and esters to afford stereoselectively the cycloaddition products 6-acylisoindolo[2,1- a]quinolin-11-ones in moderate to high yields. C 2009 Wei Zhang. Published by Elsevier B.V, on behalf of Chinese Chemical Society. All rights reserved.

顺-3-己烯基-β-D-吡喃葡萄糖苷的合成、纯化与表征

为开发热稳定型香原料,采用改进的Koenigs-knorr法立体选择性地合成了顺-3-己烯基-β-D-吡喃葡萄糖苷即叶醇糖苷(LGLY)——一种糖苷类香料前体;以反相液相色谱法(RP-HPLC)检测并确定最优反应条件.优化后的反应条件为:在新制备加担持剂的银盐催化剂作用下,在二氯甲烷溶剂中避光回流反应4 h.硅胶柱层析色谱梯度洗脱分离制备样品,收率56%,产物纯度99.6%.然后综合IR,LC-MS-MS,1H-NMR,13C-NMR进行了结构鉴定,确证产物为目标糖苷.对香料前体叶醇糖苷的合成、纯化及结构表征进行了系统的研究.

RP-HPLC法同时测定蒙药复方协日嘎-4中栀子苷、京尼平-1-O-β-D-龙胆二糖苷、西红花苷-1、西红花苷-3的含量

建立同时测定蒙药复方协日嘎-4药材中栀子苷、京尼平-1-O-β-D-龙胆二糖苷、西红花苷-1、西红花苷-3的高效液相色谱含量测定方法:采用反相高效液相色谱法,色谱柱为Elite C18(4.6mm×250mm,5μm),以乙腈(A)-0.1%磷酸水溶液(B)为流动相,流速1.0mL·min^(-1),检测波长分别为238nm、238nm、380nm、380nm,柱温20℃,进样量20μL.本方法可使京尼平-1-O-β-D-龙胆二糖苷、栀子苷、西红花苷-1、西红花苷-3有效分离,在检测范围内线性良好,精密度、稳定性和重复性良好,平均加样回收率分别为100.16%(RSD=0.69%),99.19%(RSD=1.29%),100.59%(RSD=0.80%),99.06%(RSD=1.02%),(n=6).经方法学验证,该方法可同时准确、简便、快速的测定蒙药复方协日嘎-4中栀子苷、京尼平-1-O-β-D-龙胆二糖苷、西红花苷-1、西红花苷-3的含量,可以作为蒙药复方协日嘎-4的质量控制方法.

四种天然槲皮素-3-糖苷的合成

以芦丁为原料,经苄基化、酸水解得到关键中间体3',4',7-O-三苄基槲皮素(3),3与相应的1-溴代乙酰糖在四丁基溴化铵催化下在氯仿-0.25mol?L-1K2CO3溶液中缩合成相应的糖苷,脱去保护基得天然槲皮素3-糖苷类化合物1a～1d.其结构经IR,1HNMR,MS及元素分析确证.

雷公藤多苷通过JAK2/STAT3信号通路减轻溃疡性结肠炎大鼠肠黏膜细胞凋亡及炎症的实验研究

目的 研究雷公藤多苷(TG)通过Janus激酶2(JAK2)/信号转导与转录激活子3(STAT3)信号通路对溃疡性结肠炎(UC)大鼠肠黏膜细胞凋亡及炎症的调节作用。方法将SD大鼠分为对照组、UC组、TG组、AG490组,UC组、TG组、AG490组采用三硝基苯磺酸/乙醇灌肠的方式建立UC模型,TG组给予TG灌胃干预,AG490组给予JAK2/STAT3抑制剂AG490干预。检测肠黏膜细胞凋亡率、凋亡基因及JAK2/STAT3表达、炎症细胞因子含量。结果UC大鼠肠黏膜细胞凋亡率、Caspase-9、Caspase-3、p-JAK2、p-STAT3的表达水平及TNF-α、IL-1β、IL-6的含量均明显高于对照组,Bcl-2、Bcl-xL的表达水平明显低于对照组(P<0.05);TG组大鼠肠黏膜细胞凋亡率、Caspase-9、Caspase-3、p-JAK2、p-STAT3的表达水平及TNF-α、IL-1β、IL-6的含量均明显低于UC组,Bcl-2、Bcl-xL的表达水平明显高于UC组(P<0.05)。AG490组大鼠肠黏膜细胞凋亡率、Caspase-9及Caspase-3的表达水平、TNF-α、IL-1β、IL-6的含量均明显低于UC组,Bcl-2、Bcl-xL的表达水平明显高于UC组(P<0.05)。结论TG能够通过JAK2/STAT3信号通路减轻UC大鼠肠黏膜细胞的凋亡及炎症。

脱水淫羊藿素─3─O─甙类化合物的核磁共振谱研究

用远程１Ｈ－１３ＣＣＯＳＹ（ＨＭＢＣ）技术研究了从朝鲜淫羊藿中分离出的二个脱水淫羊藿素─３－Ｏ－甙类化合物，朝藿甙Ａ和箭藿甙Ｂ，确定了其骨架碳的化学位移．并重新评估了前期文献对该类化合物Ｃ－５、Ｃ－７和Ｃ－４′信号的归属．

双特异性磷酸酶3和TNF-α对雷公藤多苷片治疗类风湿关节炎的预后作用及其受调节机制

目的探讨双特异性磷酸酶3(dual specificity protein phosphatase 3,DUSP3)和TNF-α作为雷公藤多苷(tripterygium glycosides,TG)片治疗类风湿关节炎(rheumatoid arthritis,RA)预后生物标记物的可行性和调节机制。方法选取本院于2016年3月至2018年1月收治的67例RA患者及67例健康志愿者,RT-PCR检测治疗前后外周血单个核细胞(peripheral blood mononuclear cells,PBMC)中DUSP3和TNF-α表达,并进行ROC分析。以TG处理脂多糖刺激的U937细胞,模拟TG片治疗RA,通过RT-PCR、Western blot和免疫共沉淀实验检测DUSP3和TNF-α之间的关系,及其上下游通路。结果与健康志愿者相比,RA患者(用药前)PBMC中DUSP3表达降低而TNF-α表达升高(P <0. 05)。TNF-α和DUSP3进行ROC分析的AUC分别为0. 948和0. 908。治疗后RA患者DAS28,ESR和CRP值下降,DUSP3和TNF-α表达分别升高和降低(P <0. 05)。TG片用药响应和不响应(骨侵蚀指标)的RA患者的DUSP3和TNF-α表达水平差异显著(P <0. 05)。以用药后DAS28表达变化区分RA患者是否响应TG片治疗,ROC分析显示DUSP3和TNF-α的AUC分别为0. 821和0. 747。在LPS刺激的U937细胞中,改变DUSP3或TNF-α表达不相互影响表达。Western blot结果显示NF-κB介导TG对TNF-α调节。ChIP结果证实TG抑制了HDAC1与DUSP3启动子区相互作用。Western blot结果表明TG给药抑制了LPS诱导的HDAC1上调和DUSP3下调。结论 TG片对RA有较好的治疗效果。其中,DUSP3和TNF-α可以作为TG片治疗RA的预后因子。TG给药降低了TNF-α的表达,并解除了对DUSP3的抑制。

刺蒺藜总皂苷对雷公藤多苷诱导的急性肝损伤小鼠肝组织Caspase-3表达的影响

目的:探讨刺蒺藜总皂苷对急性药物性肝损伤的防治作用及其机理。方法:60只小鼠随机分为模型组,刺蒺藜总皂苷低、中、高剂量组,甘利欣对照组和空白组,分别以相应剂量药物灌胃7 d,然后以雷公藤多苷灌胃1次造模,观察小鼠血清ALT、AST水平变化及肝组织Caspase-3表达情况。结果:刺蒺藜总皂苷可有效降低小鼠血清ALT、AST水平,与模型组比较,有显著统计学意义(P<0.05),并使肝组织Caspase-3表达降低,尤以高、中剂量组效果最佳。结论:刺蒺藜总皂苷对雷公藤多苷诱导的急性肝损伤具有较好保护作用,其机理与降低Caspase-3表达、抑制肝细胞凋亡有关。

槲皮素-3-葡萄糖苷对肾缺血-再灌注损伤大鼠的保护作用

目的:观察槲皮素-3-葡萄糖苷对急性肾缺血-再灌注损伤大鼠的保护作用。方法:采用夹闭大鼠双侧肾动脉45min后再灌注60min的方法,建立大鼠急性肾缺血-再灌注损伤的动物模型。通过测定血清丙二醛(MDA)、超氧化物歧化酶(SOD)、血清肌酐(Cr)、尿素氮(BUN),和TUNEL法分析肾小管上皮细胞的凋亡情况,探讨槲皮素-3-葡萄糖苷对急性肾缺血-再灌注损伤大鼠的保护作用及可能机制。结果:槲皮素-3-葡萄糖苷组MDA值显著降低(P<0.05);血清SOD含量升高明显;血清NO含量较模型组明显下降,两组比较有显著性差异(P<0.05)。槲皮素-3-葡萄糖苷组的TUNEL阳性细胞数与模型组相比明显减少(P<0.05)。结论:槲皮素-3-葡萄糖苷可以减轻肾小管细胞的损伤,对肾缺血-再灌注损伤大鼠具有保护作用,其作用机制可能是通过清除氧自由基,抑制脂质过氧化,进而改善肾功能。

白首乌中抗肿瘤活性成分告达庭-3-O-β-D-磁麻糖苷在大鼠体内的代谢产物分析

目的研究白首乌中甾苷成分告达庭-3-O-β-D-磁麻糖苷在大鼠体内的代谢情况。方法大鼠单剂量灌胃给予20 mg/kg的告达庭-3-O-β-D-磁麻糖苷,分别收集24 h内的血浆、尿液、粪便和胆汁,样品经处理后,采用UPLC-Q-TOF分析,结合MetabolynxTM软件初步鉴定告达庭-3-O-β-D-磁麻糖苷在大鼠血浆、尿液、粪便和胆汁中的代谢产物。结果在血浆、尿液、粪便和胆汁样品中发现了告达庭-3-O-β-D-磁麻糖苷的原型、水解及去甲基化代谢物,其中尿液中有原型,血浆和胆汁中有水解产物,粪便中有去2个甲基化产物,胆汁中有去1个和去3个甲基化产物。结论告达庭-3-O-β-D-磁麻糖苷在大鼠体内可发生较为广泛的代谢,其中主要代谢类型有水解和去甲基化。