黄精多糖的研究概况

黄精（Rhizoma Polyonafi），别名仙人余粮、老虎姜、鸡头参等，是百合科黄精属多年生草本植物。气味平和，质地滋润，有补养肺之阴、润燥生津之功效。黄精主要成分有三大类：（1）为脂溶性的甾体皂苷类化物。如：呋哺甾烷类皂苷（黄精皂苷A，sibiricosides A）、螺旋甾烷类皂苷（黄精皂苷B，sibi-ricosides B）等。（2）为黄酮、葱醌类化合物。如：牡荆素术糖苷（vitexinxylo-side）、5、4＇-、二羟基黄酮的糖苷，吖啶-2-羟酸（azetidine-2car-borylic acid）以及多种葱酯类化合物。（3）为水溶性成分——黄精多糖（Pohygonatum Sibiricmu Polyxaccharides，PSP）。     

黄精总皂苷和多糖的药理作用及其提取方法的研究进展

黄精是常用滋补中药。系百合科黄精属（Polygonatum-Mill．）多年生草本植物,药用其根茎。世界上有40多种,我国就有30余种,药用品种10余种。《中国药典》规定,药用黄精有3种原生药：黄精（P．sibiricum Redoute）、多花黄精（P．cyrtonemaHua）和滇黄精（P．kingianum Coll．et Hemsl）。黄精性平、味甘;归脾、肺、肾经;具有补气养阴、健脾、润肺、益。肾等功能;用于脾胃虚弱、体倦乏力、     

气候背景下鸡头黄精适宜区预测

目的：通过分析影响鸡头黄精（Polygonatum sibiricum Red.）生长的气候因子,对鸡头黄精在中国的适宜分布区进行预测,为鸡头黄精的种质资源调查、人工栽培以及开发利用等提供一定的科学依据。方法：通过专业数据库查询、文献检索等方法筛选得到168条鸡头黄精的分布点信息,利用最大熵模型分析出影响鸡头黄精分布的主导气候因子,并结合ArcGIS软件对鸡头黄精的适宜分布区进行预测。结果：ROC曲线下面积AUC值大于0.9(AUC=0.981),表明模型预测精度高,运行结果可靠;预测结果显示,影响鸡头黄精分布的主导气候因子是7月降水量(prec＿7)、10月太阳辐射（srad＿10）、年平均温度（bio＿1）;我国鸡头黄精的高适生区包括贵州省,湖北省,江苏省,安徽省,陕西省,河南省,山东省,河北省,吉林省等地区。结论：本研究结果与鸡头黄精的实际资源分布区域及其生长习性所需气候条件大致吻合,可为扩大鸡头黄精的栽培区域提供一定的参考价值。     

黄精多糖调控SIRT1/AMPK/PGC-1α信号通路改善H2O2诱导的HT22细胞氧化损伤

目的 研究黄精多糖对H₂O₂诱导的HT22细胞氧化应激损伤及其对SIRT1/AMPK/PGC-1α信号通路关键信号分子的影响。方法 建立H₂O₂诱导HT22细胞氧化损伤模型，黄精多糖干预后，观察黄精多糖对HT22细胞活性乳酸脱氢酶（lactate dehydrogenase，LDH）释放的影响，检测超氧化物歧化酶（superoxide dismutase，SOD）活性、丙二醛（malondialdehyde，MDA）含量、还原型谷胱甘肽（glutathione，GSH）含量、线粒体呼吸链酶复合体Ⅰ活性、腺嘌呤核苷三磷酸（adenosine triphosphate，ATP）含量，Western blotting检测细胞中SIRT1、AMPK、p-AMPK及PGC-1α蛋白的表达。结果 与模型组相比，黄精多糖（100，200，400 μmicro；g·mL^-1）明显提高细胞活性（P<0.05或P<0.01），降低LDH释放（P<0.05或P<0.01），减少MDA的产生（P<0.05或P<0.01），增加SOD活力和GSH含量（P<0.05或P<0.01），可提高ATP含量及线粒体呼吸链酶复合体Ⅰ活性。此外，黄精多糖还能够上调细胞中SIRT1、p-AMPK及PGC-1α蛋白的表达。结论 黄精多糖能通过增强细胞内抗氧化活性，提高HT22细胞的存活率，改善线粒体功能，从而保护细胞抗氧化损伤，其作用机制与激活SIRT1/AMPK/PGC-1α信号通路有关。     

黄精对衰老大鼠海马组织SOD活性及MDA含量影响的研究

目的探讨黄精对D-半乳糖致衰老大鼠（即AD大鼠）海马组织中SOD活力和MDA含量的影响。方法将SD大鼠分为4组,其中模型组、黄精高剂量组、低剂量组均颈部皮下注射D-半乳糖致亚急性衰老大鼠模型,同时给予黄精进行干预,正常组颈部皮下注射等量生理盐水。6周后测量海马组织内超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量,探讨黄精的抗衰老作用。结果模型组海马组织中SOD活性明显降低,MDA含量显著增加,与生理盐水组相比均有显著性差异（P〈0.01）,说明造模成功。黄精高剂量组较模型组相比有显著性差异（0P〈0.01）,但与正常组相比无显著性差异（0P〈0.01）。黄精低剂量组较模型组相比无显著性差异（0P〈0.01）。结论高剂量黄精能显著消除衰老大鼠体内自由基的增加.提高超氧化物歧化酶的活性,达到的抗衰延年作用。     

基于网络药理学联合加权基因共表达网络分析黄精治疗代谢性相关脂肪性肝病的作用机制

目的 运用网络药理学结合加权基因共表达网络分析（WGCNA）探究黄精治疗代谢性相关脂肪性肝病的作用机制。方法 利用中药系统药理数据分析平台（TCMSP）检索黄精主要活性成分，并采用Pharm Mapper平台挖掘黄精活性成分相关靶点。在GeneCards数据库中下载并整理了代谢性相关脂肪性肝病相关基因。通过GEO平台下载代谢性相关脂肪性肝病相关基因芯片GSE89632，使用R软件limma包进行差异分析，并运用WGCNA筛选出的模块基因作为疾病靶点基因。R软件Venn Diagram包进行交集分析并可视化。采用R软件clusterProfiler包对交集靶点基因进行基因本体论（GO）功能富集和京都基因与基因组百科全书（KEGG）信号通路富集分析。采用Cytoscape软件进行“药物–活性成分–共同靶点”网络的构建与分析。将交集靶点基因上传至String数据库，把结果数据导入至Cytoscape软件构建蛋白相互作用（PPI）网络并筛选核心靶点基因。采用MOE软件进行分子对接。结果 共筛选出黄精活性成分12个，成分相关靶点327个；GeneCards数据库整理获得代谢性相关脂肪性肝病相关基因1 227个；WGCNA关联模块基因2 639个；最终获得黄精治疗代谢性相关脂肪性肝病靶点基因18个。富集分析发现18个靶点基因通过调控胰岛素抵抗、脂质和动脉粥样硬化、代谢性相关脂肪性肝病等信号通络，参与细胞间信号传导、脂质代谢、氧化应激、炎症反应等生物过程。分子对接研究显示核心靶点与相关黄精活性成分结合稳定。结论 黄精具有治疗代谢性相关脂肪性肝病的作用，且在治疗代谢性相关脂肪性肝病中具有多靶点、多成分、协同作用的特点。     

基于聚类和主成分分析的不同产地黄精主要成分比较

目的 对35份不同产地黄精原植物（多花黄精、鸡头黄精和滇黄精）的主要成分进行测定,为黄精种质资源保护及综合开发利用提供理论基础。方法 测定还原糖、总蛋白质、总氨基酸和淀粉4种营养成分,浸出物、黄精多糖、总黄酮、总皂苷、总酚5种药用成分,并采用相关性分析、聚类分析和主成分分析进行综合评价。结果 35份黄精还原糖、总蛋白质、总氨基酸和淀粉含量分别为10.127～48.697mg/g、32.334～49.667mg/g、8.675～21.229mg/g、18.978～57.842mg/g,其中鸡头黄精的营养成分总含量相对较高,辽宁鞍山的蛋白质和氨基酸含量最高、河北承德的淀粉和还原糖含量最高。药用成分浸出物、黄精多糖、总皂苷、总黄酮和总酚含量分别为47.291%～76.335%、6.883%～20.326%、0.857%～2.265%、0.293%～0.735%和0.127%～0.559%。湖南洪江的多花黄精浸出物含量最高,为（76.335±0.948）%;湖南新晃的多花黄精多糖含量最高,为（20.326±0.346）%;湖南安化的多花黄精总皂苷含量最高,为（2.265±0.049）%;河北遵...     

黄精对D-半乳糖致衰老模型大鼠学习能力的改善作用

目的用黄精作为干预因素,观察其对D一半乳糖致衰老大鼠（即AD大鼠）学习记忆能力的影响。方法以D一半乳糖致亚急性衰老大鼠为模型,同时给予黄精进行干预,6周后用Morris水迷宫试验来评价Wistar大鼠学习记忆能力,以全面观察黄精对学习记忆的影响。结果Morris水迷宫试验,逃避潜伏期（EL）：模型组较生理盐水组明显延长（P〈0．01）;黄精高剂量组较模型组明显缩短（P〈0．01）,与正常对照组相比无明显差异（P〉0．05）。黄精低剂量组较模型组比较无明显差异（P〉0．05）;撤离平台后120s内穿过原平台象限内游泳的距离占整个游泳距离的百分比：模型组较正常组有明显差异（P〈0．01）,黄精高剂量组较模型组有显著性差异（P〈0．01）,但与正常组相比无显著性差异,黄精低剂量组较模型组相比无明显差异;每分钟穿越平台所在象限的次数：模型组最少,用药组明显增多,但仍然低于生理盐水组。结论黄精对衰老大鼠学习记忆功能有明显的改善作用。     

黄精药材中黄精多糖的含量测定

目的建立黄精中黄精多糖的含量测定方法。方法采用分光光度法，测定波长为582nm。结果无水葡萄糖线性范围为33．27～199．62μg（r=0．9997），平均回收率为100．38％，RSD=1．80％。结论该方法灵敏、准确、重现性好，可用于黄精药材的质量控制。     

调脂小验方

黄精30克，桑寄生15克，乌龟1只（约200克，去肠杂），红枣5枚，共放入沙锅煮汤，调味食用。     

Synthesis and biological activity of dynorphin-(1 - 13) and analogs substituted in positions 8 and 10

Dynorphin-(1–13) (Dyn-(1–13)) and various analogs substituted in positions 8 and 10 were synthesized by the solid-phase technique and analyzed for their ability to inhibit the electrically evoked contraction of the guinea pig ileum (GPI) and to compete with the binding of [³H]-ethylketocyclazocine (EKC, k ligand), [³H]-[D-Ala², MePhe⁴-Gly-ol⁵]-enkephalin (DAGO, μ ligand) and [³H]-[D-Ser², Thr⁶]-Leu-enkephalin (DSLET, δ ligand) to membrane preparations of the guinea pig cerebellum or rat brain. Introduction of Ala in position 8 decreased the activity of the peptide on the GPI by 50% but induced a 2.22-fold increase in its affinity for the k receptor ([³H]-EKC binding displacement from guinea pig cerebellum; Ki of 0.05 nM as compared with 0.11 nM for Dyn-(1–13)). On the other hand, the ability of [Ala⁸]-Dyn-(1–13) to displace the binding of [³H]-DSLET from rat brain membranes was decreased by a factor of 1.7 while its affinity for the μ receptor was not greatly affected ([³H]-DAGO displacement; Ki of 0.44nM as compared with 0.50nM for Dyn-(1–13)). Replacement of position 8 by D-Ala caused similar changes in the activity of the peptide but the increase in its affinity for the k site was somewhat smaller (Ki of 0.08 nM as compared with 0.11 nM). [D-Pro¹⁰]-Dyn-(1–13) was equipotent to [Ala⁸]-Dyn-(1–13) in the GPI but its affinity for the μ binding site was decreased by a factor of 2.7 as compared with Dyn-(1–13). The affinity of [D-Pro¹⁰]-Dyn-(1–13) for the other binding sites (k and δ) was not greatly affected. Replacement of positions 8 or 10 by Trp or D-Trp decreased the activity on the GPI by more than 50% as well as the affinity for most receptor types. These data indicate that the selectivity of Dyn(1–13) for the k opioid receptor can be increased either by increasing its affinity for the K binding site ([Ala⁸]-Dyn-(1–13)) or lowering its potency for other binding sites, [Ala⁸]-Dyn-(1–13) being less potent on δ sites and [D-Pro¹⁰]-Dyn-(1–13) less potent on μ sites.     

Cytochrome P450 2A13 mediates aflatoxin B1-induced cytotoxicity and apoptosis in human bronchial epithelial cells

Cytochrome P450 (CYP) 2A13 is mainly expressed in the respiratory system and has the ability to metabolize aflatoxin B(1) (AFB(1)). However, the role of CYP2A13-mediated AFB(1) metabolism and its consequences in human lung epithelial cell is not clear. Therefore, the objectives of this study were to investigate the significance of CYP2A13 in AFB(1)-induced cytotoxicity, DNA adducts, and apoptosis. To achieve these objectives, CYP2A13 was stably over-expressed in immortalized human bronchial epithelial BEAS-2B cells (B-2A13) and its significance in AFB(1)-induced cytotoxicity, DNA adducts, and apoptosis was compared to cells with stably expression of CYP1A2 (B-1A2), the predominant AFB(1) metabolizing enzyme in liver, as well as CYP2A6 (B-2A6) as controls. AFB(1) induced B-2A13 cytotoxicity and apoptosis in a dose- and time-dependent manner. The cytotoxic and apoptotic effects of AFB(1) were significantly remarkable in B-2A13 cells than those of B-1A2 and B-2A6 cells. The increased expression of pro-apoptotic proteins, such as C-PARP, C-caspase-3, and Bax, and decreased expression of anti-apoptotic proteins, such as caspase-3, Bcl-2, and p-Bad further confirmed the data of AFB(1)-induced cytotoxicity and apoptosis. Furthermore, increased DNA adduct was observed in B-2A13 after AFB(1) treatment as compared to B-1A2 cells and B-2A6 cells. Finally, treatment with nicotine, a competitor of AFB(1), and 8-methoxypsoralen (8-MOP), an inhibitor of CYP enzyme, further confirm the critical role of CYP2A13 in AFB(1)-induced cytotoxicity and apoptosis. Collectively, these findings suggest adverse effects of AFB(1) in respiratory diseases mediated by CYP2A13.     

Ergolines as selective 5-HT1 agonists

The synthesis and serotonin receptor subtype affinity of a series of ergolines are described. High selectivity for the 5-HT1 subtype was found with a number of 8-substituted (3 beta, 5 beta)-9,10-didehydro-6-methylergolines. The more potent and selective of these compounds increased the concentration of serotonin and decreased the concentration of 5-HIAA in rat brain and increased corticosterone concentration in rat serum. Oral administration of 13, (3 beta)-2,3-dihydrolysergine, produced long-lasting decreases in serotonin turnover. Compound 13 lacked substantial dopaminergic activity as measured by its effects on dopamine turnover in whole brain or striatum and its affinity for alpha-adrenergic binding sites was significantly less than for 5-HT1 binding sites. The increases in serum corticosterone concentrations produced by 13 were not blocked by the serotonin uptake inhibitor fluoxetine or by the serotonin synthesis inhibitor p-chlorophenylalanine, suggesting that 13 exerts its effects through direct stimulation of serotonin receptors.     

RP-HPLC法测定YF-13-1含量及有关物质

目的:采用反相高效液相色谱法建立YF-13-1原料药质量控制的方法。方法:色谱柱为KROMASIL-C18(4.6 mm×200 mm,5μm),流动相为0.02 mol.L-1磷酸二氢钾溶液(磷酸调节pH 4.5)-甲醇(40∶60),流速为1.0 mL.min-1,室温,检测波长235 nm。结果:YF-13-1与中间体及各降解产物分离良好,YF-13-1浓度在1.05～520.34 mg.L-1范围时与峰面积呈良好线性关系(r=0.9995,n=7),日内、日间精密度RSD均在5%以下,检测限0.5μg.L-1。结论:该方法可用于YF-13-1原料药的含量测定和有关物质检查。     

Fmc，镰刀菌来源的多巴胺1受体抑制剂

应用以中枢神经系统为主的八个体外受体筛选系统,从15株真菌和12株放线菌中筛选出能产生具有与多巴胺1受体竞争性结合活性的镰刀菌Fusarium moniliflore;从其菌体中分离出活性成分Fmc。通过元素分析和质谱,确定其分子式为C10H13O2N。综合紫外光谱、红外光谱、^1H-NMR和^13C-NMR等图谱数据的解析,确定Fmc的结构与镰刀属真菌（Fusarium moniliflore)发酵液分离出来的夫西地酸（fusaric acid)一致,化学命名为：5－正丁基吡啶酸。但关于其作用于中枢神经系统多巴胺1受体的活性未见报道。     

海绵状血管瘤铜针埋置术后的病理分析

目的分析铜针治疗血管瘤后的组织病理学改变,评价其疗效以及相关影响,探索其方法的改进。方法收集铜针埋置治疗后1～13年的血管瘤标本13例,采用HE染色方法分析其病理学改变。结果铜针埋置后局部组织存在着针眼瘢痕形成及色素沉着,显微镜下可以见到血管的轮廓,血管腔内血栓形成,血管腔闭塞,管壁增厚,纤维化,部分管壁玻璃样变,血管周围有较多纤维组织增生。结论铜针治疗血管瘤疗效肯定,但局部仍存在着瘢痕形成及色素沉着等缺点,若将铜针进行改进,使其直径变小,术后进行弹性压迫,则可能可减少其副反应。     

Structural modification of an angiogenesis inhibitor discovered from traditional Chinese medicine and a structure-activity relationship study

Pseudolaric acid B (PAB), discovered as a promising angiogensis inhibitor, was served as the anticancer drug lead, and a series of its derivatives were synthesized. Among them, some derivatives, such as 13c- 13k, exhibited potent inhibition on the HMEC-1 cell proliferation and strong cytotoxic activities against the tested six tumor cell lines. The PAB derivatives 13c- 13k also showed significant and specific inhibition on HMEC-1 cell migration in vitro, and only 13d expressed moderate activity against HMEC-1 cell tube formation. The in vitro anticancer tests of the selected natural PAB analogs and the structurally modified PAB derivatives have led to the establishment of a clear structure-activity relationship.     

Synthesis and characterization of monohydroxylated derivatives of 7H-dibenzo[c,g]carbazole.

The synthesis of several monohydroxylated derivatives of the potent carcinogen 7H-dibenzo[c,g]carbazole (DBC), including 1-hydroxy-7H-dibenzo[c,g]carbazole (1-OH-DBC), 13-c-hydroxydibenzo[c,g]carbazole (13-c-OH-DBC), and 5-hydroxy-7H-dibenzo[c,g]carbazole (5-OH-DBC), is described. 1-OH-DBC was prepared from 8-methoxy-2-tetralone and 2-naphthyl-hydrazine via Fischer indole synthesis followed by boron tribromide demethylation. The rearrangement and hydrolysis reactions to give 13-c-OH-DBC from DBC and benzoyl peroxide are discussed. The preparation and isolation of 5-OH-DBC, by hydrolysis of 5-acetoxy-N-acetyl-DBC, and the formation of its intermediate 5-acetoxy-DBC and its byproduct 6,6'-bis-(5-OH-DBC) are described in detail.     

Identification of Stabilized Dynorphin Derivatives for Suppressing Tolerance in Morphine-Dependent Rats

PURPOSE: Modulatory actions on morphine-induced effects, such as tolerance and withdrawal, have been noted for dynorphin A(1-13) [Dyn A(1-13)] and similar peptides. These are currently of limited therapeutic potential due to extensive metabolism by human metabolic enzymes resulting in a half-life of less than 1 min in human plasma. The purpose of this study was to identify stabilized dynorphin A (Dyn A) derivatives, to determine their metabolic routes in human plasma, and to assess whether the pharmacodynamic activity is retained. METHODS: The stability of peptides in human plasma was tested using in vitro metabolism studies with and without enzyme inhibitors. Identification of the generated metabolites was performed by mass spectrometry after high performance liquid chromatography (HPLC) separation. The in vivo activity of a stabilized dynorphin was tested by tail-flick assay in morphine-tolerant rats. RESULTS: Though amidation of the Dyn A(1-13) was able to stop the majority of C-terminal degradation, metabolism of Dyn A(1-10) amide continued by captopril sensitive enzymes, suggesting that Dyn A(1-13) amide is a better candidate for additional stabilization. Two Dyn A(1-13) amide derivatives further stabilized at the N-terminal end, [D-Tyr1]-Dyn A(1-13) amide and [N-Met-Tyr1]-Dyn A(1-13) amide, showed half-lives in plasma of 70 and 130 min, respectively. The most stable derivative [N-Met-Tyr1]-Dyn A(1-13) amide was tested successfully for retention of the pharmacological activity in modulating antinociceptive activity. CONCLUSIONS: [N-Met-Tyr1]-Dyn A(1-13) amide showed significant stability and antinociceptive activity in the tail-flick test, thus pointing to the clinical potential of this derivative in the management of pain as well as its potential activity in suppressing opiate tolerance and withdrawal.