Iridoid Glycosides from Buddleja lindeyana

Aim To study the chemical constituents of Buddleja lindeyana. Methods The constituents were separated and purified by different methods of chromatography, and their structures were elucidated by IR, MS and NMR. Results Three iridoid glycosides and two other compounds were isolated from Buddleja lindeyana. Their structures were elucidated to be 6-O-feruloylajugol ( 1 ), erythro-6-oxo-4′-( 3-methoxyl-4-hydroxyphenylglycol-8')-feruloylaj-ugol ( 2 ), threo-6-oxo-4′-(3-methoxyl-4-hydroxyphenylglycol-8')-feruloylajugol ( 3 ), tetra-cosanoic acid 2,3-dihydroxypropyl ester (4), and galactitol (5). Conclusion All the compounds have been isolated from this plant for the first time. Compounds 1, 2 and 3 have protective effect agains MPP+ -induced apoptosis.

TWO NEW IRIDOID GLYCOSIDES FROM PEDICULARIS PLICATA

Two new iridoid glycosides,plicatoside A and plicatoside B,were isolated from whole plants of Pedicularis plicata.Their structures were identified as 2'-O-β-D-glucosyl ixoroside and 4'-O-β-D-xylosyl mussaenoside by means of chemical evidence and spectral data.

A new iridoid glycoside from Gardenia jasminoides

A new iridoid glycoside, 6＇-O-sinapoylgeniposide, was isolated from Gardeniajasminoides Ellis and its structure was elucidated on the basis of 1D and 2D NMR, HR-ESI-MS techniques.

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.

A New Iridoid Glycoside and a New Iridoid from Pedicularis kansuensis f. albiflora

A new iridoid glycoside 1 and a new iridoid 2 were isolated from the whole plant of Pedicularis kansuensis f. albiflora. Their structures were elucidated by spectroscopie methods.

A new iridoid glycoside from Veronica sibirica

A new iridoid glycoside,versibirioside（1）,and a known iridoid glycoside,verbaspinoside（2）,were isolated from the whole plant of Veronica sibirica L.Their structures were elucidated by spectroscopic methods,including 2D-NMR spectra.

Cornel Iridoid Glycoside Suppresses Hyperactivity Phenotype in rTg4510 Mice through Reducing Tau Pathology and Improving Synaptic Dysfunction

rTg4510 mice are transgenic mice expressing P301L mutant tau and have been developed as an animal model of tauopathies including Alzheimer’s disease(AD).Besides cognitive impairments,rTg4510 mice also show abnormal hyperactivity behavior.Cornel iridoid glycoside(CIG)is an active ingredient extracted from Cornus officinalis,a traditional Chinese herb.The purpose of the present study was to investigate the effects of CIG on the emotional disorders such as hyperactivity,and related mechanisms.The emotional hyperactivity was detected by locomotor activity test and Y maze test.Immunofluorescent and immunohistochemical analyses were conducted to measure neuron loss and phosphorylated tau.Western blotting was used to detect the expression of related proteins.The results showed that intragastric administration of CIG for 3 months decreased the hyperactivity phenotype,prevented neuronal loss,reduced tau hyperphosphorylation and aggregation in the amygdala of rTg4510 mice.Meanwhile,CIG alleviated the synaptic dysfunction by increasing the expression of N-methyl-D-aspartate receptors(NMDARs)subunits GluN1 and GluN2A andαamino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor(AMPAR)subunits GluA1 and GluA2,and increased the level of phosphorylated Ca2+/calmodulin dependent protein kinase IIα(p-CaMK IIα)in the brain of rTg4510 mice.In conclusion,CIG may have potential to treat the emotional disorders in tauopathies such as AD through reducing tau pathology and improving synaptic dysfunction.

Cornel Iridoid Glycoside Regulates Modification of Tau and Alleviates Synaptic Abnormalities in Aged P301S Mice

Alzheimer’s disease(AD),also defined as a tauopathology,is a common neurodegenerative disease.Hyper-phosphorylation,cleavage or truncation,and aggregation of tau contribute to AD.Thus,targeting the post-translational modifications on tau may be a therapeutic strategy to treat AD.This study understood how cornel iridoid glycoside(CIG)affects tau post-translational modifications and synaptic abnormalities.The 10-month old P301S tau transgenic mice were given CIG at 100 and 200 mg/kg every day orally for 1 month.Hyperphosphorylated and truncated tau,synapse-associated proteins and glutamatergic receptors were all detected using Western blotting.The interactions between Morroniside(MOR)or Loganin(LOG)and tau were detected using Autodock and Surface Plasmon Resonance(SPR).The effects of CIG on the aggregation of tau were investigated using a cell-free system.CIG attenuated tau hyperphosphorylation at Thr205,Ser212,Ser262,Thr231 and Ser235(AT180),but had no effect on tau truncation in the brains of 10-month old P301S mice.Binding free energies and interactions revealed that MOR and LOG bound with tau.We also found that CIG upregulated synapse-associated proteins such as PSD-95,syntaxin1A and synaptotagmin.In addition,CIG restored N-methyl-D-aspartic acid receptor and glutamate receptor levels.CIG improves post-translational modification of tau as well as synaptic abnormalities.The data presented here reveal that CIG may be used in the treatment of AD.

Cornel iridoid glycoside inhibits tau hyper-phosphorylation by enhancing PP2A activity

OBJECTIVE The aim of the present study was to investigate the effect of cornel iridoid glycoside(CIG)on tau hyperphosphorylation induced by wortmannin(WT)and GF-109203X(GFX)and the underlying mechanisms.METHODS Human neuroblastoma SK-N-SH cells were pre-incubated with CIG(50,100,and 200μg·mL-1,respectively)for 24 h,and then exposed to WT 10μmol·L-1 and GFX 10μmol·L-1for 3hafter washing out CIG.Immuno-fluorescence was used to observe the microtubular cytoskeleton of the cultured cells.Western blotting was used to measure the phosphorylation level of tau protein,glycogen synthase kinase 3β(GSK-3β)and protein phosphatase 2A(PP2A).The activity of PP2 Awas detected by a biochemical assay.RESULTS Pre-incubation of CIG significantly attenuated the WT/GFX-induced tau hyperphosphorylation at the sites of Thr205,Thr212,Ser214,Thr217Ser396 and PHF-1,and improved the damage of morphology and microtubular cytoskeleton of the cells.CIG did not prevent the decrease in p-AKT-ser473 and pGSK3β-ser9 induced by WT/GFX.However,CIG significantly elevated the activity of PP2 Aby reducing the demethylation of PP2AC at Leu309 and the ratio of PME-1/LCMT in the WT/GFX-treated cells.CONCLUSION CIG obviously attenuated WT/GFX-induced tau hyper-phosphorylation at multiple AD-related sites by increasing the activity of PP2A.The mechanism may be involved in the reduced demethylation of PP2 Avia down regulating the ratio of PME/LCMT.

Cornel iridoid glycoside protects against white matter lesions induced by cerebral ischemia via activation of neuregulin-1 pathway in rats

Ischemic stroke often elicits profound white matter lesions, which results in poor neurological outcomes and impairing the recovery in post-stroke. However, few studies have focused on white matter lesions caused by cerebral ischemia. The present study was aimed to investigate the effects of cornel iridoid glycoside(CIG), a main active component extracted from Cornus officinalis, on the white matter injury induced by ischemic stroke. CIG(60 and 120 mg·kg-1) were administered intragastrically 6 h after middle cerebral artery occlusion reperfusion(MCAO) surgery once a day for 7 d. A series of behavioral tests were carried out to evaluate the neurological function of MCAO rats. White matter structure was detected by luxol fast blue staining and transmission electron microscopy. Immunohistochemical staining was used to assess myelin loss, oligodendrocytes maturation and glial activation. Results showed that CIG remarkably decreased neurological deficit score, accelerated the recovery of somatosensory and motor functions, and ameliorated the memory deficit in MCAO rats. CIG alleviated white matter lesions and demyelination, increased myelin basic protein expression and the number of mature oligodendrocytes in the corpus callosum of MCAO rats. Besides, CIG inhibited the activation of microglia and astrocytes. Further data obtained by western blot analysis indicated that CIG increased the expression of brain-derived neurotrophic factor(BDNF)/p-Trk B, neuregulin-1/Erb B, and PI3 K p110α/p-Akt/p-m TOR in the corpus callosum of MCAO rats. Our findings demonstrated that CIG protected against white matter lesions induced by cerebral ischemia and the mechanisms were partially contributed to increasing BDNF and activating neuregulin-1/Erb B signaling and its downstream PI3 K/Akt/m TOR pathway in white matter.

Cornel iridoid glycoside inhibits PP2Ac demethylation by regulationg PME-1

OBJECTIVE PP2Ac demethyl⁃ation is regulated by LCMT(a specific leucine carboxyl methyltransferase catalyzing methyla⁃tion of PP2A)and PME(a specific methylester⁃ase catalyzing demethylation of PP2A.This study was to investigate the mechanism of Cor⁃nel iridoid glycoside(CIG)on PP2A catalytic sub⁃unit C(PP2Ac).METHODS Recombined lentivi⁃rus vector was used to deliver PME-1 genetic materials into N2a cells or transfected LCMT-1 siRNA into N2a cells to block the expression of LCMT-1.Twenty-four hours later,cells were rinsed twice with cold PBS(pH 7.4)and CIG at different concentrations(50,100 and 200 g·L^(-1),respectively)were added for 24 h.Western blotting was used to PP2Ac,demethylaion/methylation PP2Ac,LCMT-1 and PME-1.The ac⁃tivity of PP2A was detected by a biochemical as⁃say.RESULTS①Lentivirus transferred PME-1 was expressed at high level in the N2a cells after transduction.Correspondingly,the demethylation of PP2Ac was increasing and PP2A activity was decreasing after transduction.Treatment with CIG for 24 h reversed the increase of PME-1 and demethylation of PP2Ac without influencing LCMT-1 expression.PP2A activity was also sig⁃nificantly enhanced in CIG treatment group,compared with the cells after PME-1 transduc⁃tion.②LCMT-1 siRNA significantly decreased LCMT-1 expression.CIG did not affect LCMT-1expression.however,demethylation of PP2Ac is increased in siRNA-transfected cells and CIG could reversed the high demethylation of PP2Ac and PP2A activity.CONLUSION CIG increases methylation of PP2A subunit C by inhibiting PME-1.

山银花茎叶化学成分及其抗炎活性研究

目的对山银花茎叶化学成分进行分离和结构鉴定,并进行体外抗炎活性评价。方法山银花茎叶80%甲醇提取物采用Diaion HP20SS、Sephadex LH-20、高速逆流色谱、反相半制备液相色谱等进行分离纯化,根据理化性质及波谱数据鉴定所得化合物的结构。通过测定单体化合物抑制LPS诱导小鼠巨噬细胞RAW264.7释放NO水平评价其抗炎活性。结果从山银花茎叶中分离得到13个化合物,分别鉴定为苄醇-O-β-D-吡喃葡萄糖-(1→6)-β-D-吡喃葡萄糖苷(1)、獐牙菜苷(2)、表断马钱子苷半缩醛内酯(3)、马钱子苷半缩醛内酯(4)、裂环马钱苷(5)、断氧化马钱苷(6)、裂马钱素二甲基乙缩醛(7)、绿原酸甲酯(8)、芹菜素-7-O-β-D-葡萄糖苷(9)、木犀草素-7-O-β-D-葡萄糖苷(10)、野漆树苷(11)、木犀草素-7-O-α-L-吡喃阿拉伯糖(1→6)-β-D-吡喃葡萄糖苷(12)、忍冬苷(13);化合物2~8、11~13可抑制LPS诱导RAW264.7细胞释放NO。结论化合物1首次从忍冬属植物中分离得到,化合物3、5、7、9、11~12首次从山银花茎叶中发现。化合物2~8、11~13具有一定的抗炎活性。

正交试验优化鸡矢藤总环烯醚萜苷的提取工艺

为研究鸡矢藤叶中总环烯醚萜苷的最佳提取工艺,以总环烯醚萜苷提取率为指标,通过单因素试验和正交试验,考察乙醇浓度、提取时间、料液比、提取温度、提取次数等因素的影响。结果显示总环烯醚萜苷的最佳提取条件为:80%乙醇作为提取溶剂、提取时间2 min、料液比1∶90 g/mL、提取温度45℃、提取次数6次,在此条件下总环烯醚萜苷的提取率达到46.59 mg/g。本文研究的提取方法高效、稳定、合理,可为鸡矢藤叶中总环烯醚萜苷的研究奠定一定基础。

高效液相色谱法测定藏药翼首草药材中10种成分的含量

目的:建立一种高效液相色谱法同时测定藏药翼首草药材中10个成分的含量方法。方法:采用SWELL Chomplus^(R) C_(18)色谱柱(4.6 mm×250 mm,5μm),流动相为0.2%磷酸水溶液-乙腈梯度洗脱,流速为1.0 mL/min,柱温30℃;采用237、325 nm双波长检测;进样量10μL。结果:目标成分在各自检测范围内表现出良好的线性关系(r>0.9990),平均加样回收率和相对标准差分别为96.79%-103.69%、RSD 1.08%-4.14%。结论:该方法具有精密稳定,简便快速、重复性良好的特点,可作为翼首草质量检测和控制的有效手段。

山茱萸环烯醚萜苷的化学成分及生物活性研究进展

山茱萸是我国药食两用的大宗药材之一,广泛应用于内外妇儿各类患者及保健品的开发等。山茱萸环烯醚萜苷(cornel iridoid glycosides, CIG)为山茱萸的特征活性成分群,综述近10年的文献报道,已有103种CIG被分离鉴定。研究将对CIG的化学成分、裂解规律、体内代谢产物研究进行归纳总结,并从药理药效、作用通路及分子机制等方面综述CIG在降血糖、神经保护、心脏保护、肝脏保护、肾脏保护、睾丸保护等多种生物活性的研究进展,以期为CIG进一步的研究、开发及应用提供新的思路。

HPLC法测定杜仲叶提取物中京尼平苷酸、绿原酸、京尼平苷、芦丁含量

研究旨在建立高效液相色谱法同时测定杜仲叶提取物中尼平苷酸、绿原酸、京尼平苷、芦丁含量的方法。试验选择Agilent ZORBAX SB-C18色谱柱,以乙腈-0.4%磷酸溶液为流动相,流速1.0 mL/min,柱温30℃,进样量10μL,波长235 nm。结果显示:4种成分在检测范围中所呈现出的线性关系良好,平均加样回收率为100.8%~103.0%,相对标准偏差(RSD)为0.90%~2.37%。不同生产厂家的杜仲叶提取物中4种成分含量存在一定差异。研究表明,试验建立的方法操作简单、稳定可靠、重复性好,可以用于杜仲叶提取物的质量控制。

正交-满意度函数优化秦艽黄酮和环烯醚萜苷超声共提取条件

目的:优化秦艽黄酮和环烯醚萜苷超声提取工艺条件。方法:以秦艽黄酮和环烯醚萜苷提取率为考察指标,以乙醇体积分数、料液比、提取温度及提取时间为影响因素,进行单因素试验;采用正交-满意度优化秦艽黄酮和环烯醚萜苷提取工艺。结果:优选出秦艽中黄酮及环烯醚萜苷提取的最佳工艺条件为乙醇体积分数60%,料液比1∶30 g/mL,提取温度60℃,提取时间40 min,在此条件下的提取率黄酮为2.20%,环烯醚萜苷为9.32%,平均满意度为0.997,RSD=0.28%。结论:优选的条件方法简便、高效、易于实现,适合秦艽中黄酮与环烯醚萜苷的提取。

血管性痴呆大鼠脑内时钟基因在不同发病时程中的改变及山茱萸环烯醚萜苷的调节作用

目的观察血管性痴呆大鼠脑内时钟基因在不同发病时程中的改变及山茱萸环烯醚萜苷(CIG)的调节作用。方法选取45只SPF级雄性SD大鼠,6~8周,体重150~180 g,选取15只作为假手术组,其余采用双侧颈总动脉结扎(2VO)术制作慢性脑缺血模型。造模成功后采用随机数字表法将假手术动物分为3组,造模动物分为6组,每组5只。具体为造模1个月组(Sham组、2VO组、2VO+CIG60组、2VO+CIG120组、2VO+丁苯酞组);造模1.5个月组(Sham组、2VO组);造模3个月组(Sham组、2VO组)。造模6 h后2VO+CIG60组灌胃CIG 60 mg/(kg·d)、2VO+CIG120组灌胃CIG 120 mg/(kg·d)、2VO+丁苯酞组灌胃丁苯酞100 mg/(kg·d),Sham组与2VO组灌胃等量的生理盐水。造模后1、1.5、3个月时,取大鼠的下丘脑和中脑检测时钟基因CRY1、PER1、PER2、NPAS2 mRNA的水平,观察时钟基因的改变情况。结果在下丘脑中,与Sham组比较,造模1个月2VO组PER2 mRNA降低(P<0.01);造模1.5个月2VO组时钟基因PER2 mRNA、NPAS2 mRNA升高(P<0.05或P<0.01)。在中脑中,与Sham组比较,造模1个月2VO组CRY1 mRNA、PER1 mRNA升高(P<0.05或P<0.01);造模3个月2VO组PER2 mRNA升高(P<0.05)。在下丘脑中,与Sham组比较,2VO组PER2 mRNA降低(P<0.01);与2VO组比较,2VO+CIG60组NPAS2 mRNA升高,2VO+CIG120组PER1 mRNA降低(P<0.05)。在中脑中,与Sham组比较,2VO组CRY1 mRNA、PER1 mRNA升高(P<0.05或P<0.01);与2VO组比较,2VO+CIG120组CRY1 mRNA降低(P<0.01)。结论血管性痴呆模型大鼠的下丘脑和中脑中时钟基因表达紊乱,引起调节昼夜节律的反馈环破坏,而CIG能纠正下丘脑和中脑时钟基因紊乱表达现象。

山茱萸环烯醚萜苷对延缓大鼠脑动脉瘤进展的影响

目的 探讨山茱萸环烯醚萜苷(CLG)通过Ras同源基因家族蛋白(Rho)/Rho关联含卷曲螺旋结合蛋白激酶(Rock)信号通路对大鼠动脉瘤进展的影响。方法 选取50只雄性大鼠建立脑动脉瘤(CA)模型,48只造模成功大鼠随机分为模型组、CLG低剂量、中剂量和高剂量组(各12只),未造模大鼠取12只为对照组。CLG低剂量、中剂量和高剂量组灌胃100、150、200 mg·kg^(-1)的CLG溶液(蒸馏水配制),连续30 d,对照组及模型组给予等量蒸馏水。检测各组大鼠血压变化;ELISA法检测各组大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1)、白细胞介素-6(IL-6)水平;HE染色观察脑组织病理学变化;RT-PCR和Western blot检测大鼠脑组织Rho、Rock2 mRNA和蛋白表达情况。结果 与模型组比较,3组大鼠收缩压、舒张压、平均动脉压、TNF-α、IL-1、IL-6、Rho、Rock2 mRNA和蛋白表达水平降低(P<0.05),与CLG低剂量组比较,CLG中剂量、高剂量组诸项指标水平降低(P<0.05),与CLG中剂量组比较,CLG高剂量组诸项指标水平降低(P<0.05)。结论 CLG可调节CA大鼠血压水平、降低炎性因子水平,在一定程度上抑制动脉瘤样扩张,可能与抑制Rho/Rock信号通路有关。

环烯醚萜苷类化合物治疗2型糖尿病及并发症机制研究概述

环烯醚萜苷类化合物是中药有效活性成分之一,目前国内外研究发现其在2型糖尿病及并发症的治疗中发挥积极作用。本文总结近二十年环烯醚萜苷治疗2型糖尿病作用的国内外文献,阐述其相关作用机制。环烯醚萜主要结构类型有环烯醚萜苷、裂环环烯醚萜和环烯醚萜酯,其中环烯醚萜苷是发挥治疗2型糖尿病作用的主要有效成分。本文将从以下四个方面分别论述:环烯醚萜苷可通过调节胰岛素代谢通路蛋白表达以及影响细胞线粒体生物信号改善细胞代谢等方式对2型糖尿病胰岛素抵抗有改善作用;环烯醚萜苷可抑制β细胞中质子载体表达以及促进胰高糖素样肽-1分泌发挥促进β细胞胰岛素分泌作用;环烯醚萜苷可通过降低葡萄糖转运蛋白5抗体的表达以及抑制α-糖苷酶活性起到延缓碳水化合物吸收作用;环烯醚萜苷可通过抑制核因子-κB等转录因子的活性以及清除晚期糖基化终产物,抑制晚期糖基化终末产物通路等途径发挥改善糖尿病炎症水平的作用。本文通过对相关文献进行综述,旨在对环烯醚萜苷治疗2型糖尿病及并发症的临床工作提供理论依据。