Validation of flavonoids as potential dipeptidyl peptidase III inhibitors: Experimental and computational approach

Fifteen flavonoids were studied for their inhibitory activity against human dipeptidyl peptidase III (hDPP III) combining an in vitro assay with an in silico molecular modeling study. All analyzed flavonoids showed inhibitory effects against hDPP III with the IC₅₀ values ranging from 22.0 to 437.2 μm . Our 3D QSAR studies indicate that the presence of hydrophilic regions at a flavonoid molecule increases its inhibitory activity, while the higher percentage of hydrophobic surfaces has negative impact on enzyme inhibition. Furthermore, molecular dynamics (MD) simulations of the complex of hDPP III with one of the most potent inhibitors, luteolin, were performed, and binding mode analysis revealed that the 3′ and 4′ hydroxyl group on B‐ring as well as 5 and 7 hydroxyl group on A‐ring helps luteolin to interact with the Asn391, Asn406, Tyr417, His450, Glu451, Val447, Glu512, Asn545, Gln566, and Arg572 residues. The MD results clearly provide valuable information explaining the importance of flavonoid hydroxyl groups in the mechanism for the binding pattern at the active site of hDPP III.     

不同产地滇黄精丛枝菌根真菌、深色有隔内生真菌定殖调查及与主要功效成分含量相关性分析

目的调查不同产地滇黄精根系中丛枝菌根真菌(AMF)和深色有隔内生真菌(DSE)定殖情况,并探讨其与主要功效成分之间的相关性。方法以产自于云南省5个样地的滇黄精为研究对象,采用碱解离-酸性品红染色法,调查AMF和DSE在滇黄精须根部位的定殖情况,并对典型形态结构进行拍照分析;采用硫酸苯酚法、香草醛-冰醋酸-高氯酸比色法、分光光度法和醇溶热浸法测定滇黄精根状茎中多糖、薯蓣皂苷元、总黄酮和浸出物含量,并通过皮尔森相关系数法分析AMF及其典型结构定殖率、DSE及其典型结构定殖率与4种功效成分含量之间的相关性。结果在5个样地中,AMF和DSE在滇黄精须根中的平均定殖率范围分别为26.25%～57.54%、31.67%～45.19%,其中样地红河州蒙自县(HHMZ)AMF和DSE定殖率均高于其他样地。4种功效成分与AMF、DSE定殖率及典型结构定殖率之间均呈正相关,其中多糖、薯蓣皂苷元和总黄酮含量与AMF、DSE定殖率相关性相对较高,AMF/DSE相关系数分别为0.838/0.887、0.819/0.703、0.785/0.855,且多糖含量与AMF菌丝定殖率、DSE定殖率呈显著相关。此外,AMF及典型结构定殖率与DSE及典型结构定殖率之间、4种功效成分含量两两之间均存有较高的相关性。结论 AMF和DSE在滇黄精须根中有着较高的定殖率,且与主要功效成分含量之间呈正相关。本研究为实施滇黄精生态种植、采用生物手段增产增收提供了数据支持和实验依据。     

青龙衣黄酮类化学成分研究

目的研究青龙衣(核桃楸Juglans mandshurica未成熟果实的外果皮)的化学成分。方法采用反复硅胶柱色谱、SephadexLH-20柱色谱和ODS柱色谱法等进行分离纯化,并运用NMR波谱技术鉴定化合物的结构。结果从青龙衣95%乙醇提取物中分离得到14个化合物,分别鉴定为芹菜素(1)、苜蓿素(2)、异泽兰黄素(3)、3,7,8,3′-四羟基-4′-甲氧基黄酮(4)、3,5-二羟基-7-甲氧基-3′,4′-亚甲二氧基黄酮(5)、花旗松素(6)、槲皮素-3-O-(6″-没食子酰基)-β-D-半乳糖苷(7)、槲皮素-3-O-(4″-O-乙酰基)-α-L-鼠李糖苷(8)、黄杞苷(9)、异黄杞苷(10)、山柰酚-3-O-β-D-吡喃葡萄糖苷(11)、槲皮素-3-O-β-D-葡萄糖醛酸苷(12)、槲皮素-3-O-β-D-吡喃葡萄糖苷(13)、杨梅素-3-O-β-D-葡萄糖醛酸苷(14)。结论化合物1～10、12、14为首次从青龙衣中分离得到。     

青蒿化学成分及药理作用研究进展

青蒿为常用中药,主要含有倍半萜、二萜、黄酮、苯丙酸、香豆素、黄酮和挥发油等多种类型化学成分,具有抗疟疾、抗肿瘤、抑菌杀虫、解热抗炎、免疫调节等药理活性。显著的抗疟活性使青蒿较早就用于疟疾的治疗。对近年来有关青蒿的化学成分及药理活性进行综述,以期为其进一步的开发与合理利用提供参考。     

山银花、金银花中绿原酸和总黄酮含量及抗氧化活性测定

目的对3个不同产地山银花和金银花中绿原酸、总黄酮含量及抗氧化活性进行分析,并比较之间的差异。方法对绿原酸提取条件进行优化,最佳提取条件为65℃下60%乙醇溶液按料液比1∶20超声提取30 min;总黄酮最佳提取条件为65℃下用60%甲醇溶液按料液比1∶10超声提取30 min。分别采用高效液相色谱法和紫外分光光度法对样品的绿原酸和总黄酮进行含量测定,并用DPPH自由基清除率来检测山银花、金银花的抗氧化活性。结果建立了良好的绿原酸和总黄酮含量分析方法,绿原酸在0.119～1.190 mg/m L内线性关系良好,r2为0.999 2(n=6);总黄酮在8.48～50.88μg/m L内线性关系良好,r2为0.999 5(n=6)。湖南产地山银花绿原酸量、总黄酮量及自由基清除率分别为3.99%、13.43%、62.41%。重庆产地山银花绿原酸量、总黄酮量及自由基清除率分别为3.29%、10.08%、51.48%。广西产地金银花绿原酸量、总黄酮量、自由基清除率分别为2.55%、7.10%、39.51%。结论提出了结合化学成分分析和抗氧化性活性来比较不同产地山银花和金银花之间区别的分析方法,从"谱-效"结合思路,为山银花和金银花质量控制及鉴别提供一种新的模式。     

菊花化学成分、药理作用的研究进展及质量标志物预测分析

菊花作为我国传统的一味中药材,种类繁多,分布广泛,具有很高的药用价值。菊花在药用和保健中都有很好的效果,是我国卫生部发布的第一批药食两用药材。近年来,菊花在药品及保健食品中的应用越来越广泛,其主要的药效成分为黄酮、挥发油和苯丙素类化合物。在对其化学成分及药理作用综述的基础上,结合质量标志物概念,基于化学成分、临床药效、药动学、传统药性、传统药效、不同储藏条件以及不同加工方法的影响等几个方面对菊花质量标志物进行预测分析,为菊花质量评价研究提供科学依据。     

基于UPLC结合比色法的葛桑降糖胶囊质量控制研究

目的构建葛桑降糖胶囊的质量控制方法。方法采用比色法测定葛桑降糖胶囊粗多糖、总皂苷和总黄酮含量;采用UPLC建立葛桑降糖胶囊的指纹图谱,测定了10个批次产品;并利用中药色谱指纹图谱相似度评价系统(2012版本)进行相似度评价,确定共有峰。结果 3批次葛桑降糖胶囊中粗多糖平均质量分数为4.56%,总皂苷平均质量分数为2.97%,总黄酮平均质量分数为2.61%;建立了10批次葛桑降糖胶囊的UPLC指纹图谱,确立15个共有峰,经对照品指认出7个共有峰,分别是葛根素、芦丁、三七皂苷R1、人参皂苷Rg1、商陆苷、人参皂苷Rb1、商陆黄素,对应1、5、8、10、12、14、15号峰。结论此方法可用于葛桑降糖胶囊的质量控制。     

核桃多类型化学物质研究进展及产业开发现状与发展途径

核桃Juglans regia主要含有多糖、黄酮、酚酸、皂苷、酯和醌类等多种化合物,具有抑菌、抗氧化、抗肿瘤、降血糖等作用,不仅可用于药物或功能性食品的开发,在食品行业等领域也具有良好应用基础和市场前景,这些活性物质是核桃中极具开发潜能的资源性物质。本文针对核桃的化学成分及其药理作用进行系统梳理,并在此基础上对其产业应用与发展途径进行了分析,以期为我国核桃资源的开发利用提供依据。     

布渣叶总黄酮离子液体协同超声辅助提取工艺考察及其调血脂活性研究

目的 探讨布渣叶总黄酮（total flavones from Microcos paniculata,MPTF）的高效绿色环保提取方法,并考察其调血脂活性。方法 采用离子液体协同超声辅助提取MPTF,对提取工艺进行单因素实验及正交试验考察;采用高脂饲料造模,将Wistar大鼠随机分为正常对照组、阳性对照组（瑞舒伐他丁钙片5.2 mg/kg）、高脂模型组和MPTF低、中、高剂量组（ig给药MPTF 300、600、900 mg/kg）,每组各10只,测定总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）水平。结果 离子液体超声辅助提取MPTF的最佳工艺条件：离子液体为[BMIM]Cl,浓度为0.30 mol/L,料液比为1：40,提取溶剂为60%乙醇水溶液,提取时间为30 min,提取温度为50℃;验证实验结果表明,该提取工艺所得总黄酮提取率高,工艺稳定。调血脂实验结果表明,MPTF各剂量组均能够降低TC、TG、LDL-C水平,升高HDL-C水平（P<0.05）,且随着MPTF剂量增加各指标变化趋势明显,具有一定的剂量依赖性。结论 离子液体协同超声辅助提取MPTF工艺稳定可行,为离子液体协同超声辅助提取中药中难溶性有效成分提供参考;MPTF提取物具有较好的调血脂作用。     

Very Long-term Outcomes and Predictors of Percutaneous Coronary Intervention with Drug-eluting Stents Versus Coronary Artery Bypass Grafting for Patients with Unprotected Left Main Coronary Artery Disease

Background:

There are limited data on longer-term outcomes (>5 years) for patients with unprotected left main coronary artery (ULMCA) disease who underwent percutaneous coronary intervention (PCI) in the drug-eluting stents (DES) era. This study aimed at comparing the long-term (>5 years) outcomes of patients with ULMCA disease underwent PCI with DES and coronary artery bypass grafting (CABG) and the predictors of adverse events.

Methods:

All consecutive patients with ULMCA disease treated with DES implantation versus CABG in our center, between January 2003 and July 2009, were screened for analyzing. A propensity score analysis was carried out to adjust for potential confounding between the two groups.

Results:

Nine hundred and twenty-two patients with ULMCA disease were enrolled for the analyses (DES = 465 vs. CABG = 457). During the median follow-up of 7.1 years (interquartile range 5.3–8.2 years), no difference was found between PCI and CABG in the occurrence of death (P = 0.282) and the composite endpoint of cardiac death, myocardial infarction (MI) and stroke (P = 0.294). Rates of major adverse cardiac and cerebrovascular events were significantly higher in the PCI group (P = 0.014) in large part because of the significantly higher rate of repeat revascularization (P < 0.001). PCI was correlated with the lower occurrence of stroke (P = 0.004). Multivariate analysis showed ejection fraction (EF) (P = 0.012), creatinine (P = 0.016), and prior stroke (P = 0.031) were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age (P = 0.026) and EF (P = 0.002) were independent predictors in the CABG group.

Conclusions:

During a median follow-up of 7.1 years, there was no difference in the rate of death between PCI with DES implantation and CABG in ULMCA lesions in the patient cohort. CABG group was observed to have significantly lower rates of repeat revascularization but higher stroke rates compared with PCI. EF, creatinine, and prior stroke were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age and EF were independent predictors in the CABG group.