决明子的化学成分及药理作用研究

总结近几年的决明子文献,从其化学成分和药理作用对决明子做阐述,为决明子的药用开发发展提供科学依据。本文还阐述了决明子的良好开发前景,为合理用药提供依据,临床用药安全提供保证。     

基于PCA及PLS-DA算法分析决明子炒制前后化学成分的变化

目的：分析决明子炒制前后化学成分的变化规律,筛选影响决明子炒制前后主要差异的物质基础。方法：采用HPLC-PDAD技术建立决明子及炒决明子的化学指纹图谱,利用《中药色谱指纹图谱相似度评价系统》进行Mark峰匹配,以SIMCA-P 11.0统计软件进行主成分分析（principal component analysis,PCA）及偏最小二乘判别分析（partial least-squares discriminant analysis,PLS-DA）,建立决明子及炒决明子PCA模型和PLC-DA模型,获取得分图和载荷图及Variable Importance （VIP）值,筛选并分析影响决明子炒制前后主要差异的物质基础。结果：构建了决明子及炒决明子的PCA （R₂X=0.844,Q₂=0.667）和PLC-DA （R₂Y=0.944,Q₂=0.861）模型,筛选出VIP值大于1的7个色谱峰。与决明子相比,炒决明子的色谱峰的峰面积均增大,且有显著性差异（P<0.01）,其中保留时间为54.189 min,VIP值为1.395 6的色谱峰为大黄素。结论：决明子炒制前后化学成分的含量发生改变。保留时间为58.252,62.825 min的成分（待分离鉴定）和大黄素为影响决明子炒制前后差异的主要物质基础。     

决明子润肠通便的化学成分及临床应用研究

目的了解决明子的化学成分及临床应用的国内外研究状况,为决明子的研究和应用提供参考。方法通过参考国内外相关研究文献,总结分析决明子泻下的化学成分、炮制及其临床应用。结果决明子在临床上用于润肠通便疗效好。结论决明子具有很好的药用价值和保健作用。     

高效液相色谱法分析市售决明子药材的蒽醌化合物

目的：建立并优化高效液相色谱（HPLC）法对决明子药材中6种蒽醌化合物的分析方法,对市售决明子（包括伪品）进行含量分析,为决明子的质量控制提供方法。方法：采用HPLC法对决明子中的橙黄决明素、芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚进行分析。比较了不同产地、不同品种、不同贮藏时间决明子中蒽醌含量的差异。结果：钝叶决明、小决明、茳芒决明蒽醌的含量差异明显,不同产地决明子（钝叶决明）在橙黄决明素、大黄素、大黄酚、大黄素甲醚的含量上存在差异,其中大黄酚的含量差异较大。其中符合《中国药典》2015年版一部决明子项对于大黄酚的含量要求的只有50%;不同贮藏时间是大黄酚含量差异较大的原因。结论：该方法准确、简便、重现性好,可作为决明子质量控制的方法;决明子采收和产地加工对于决明子大黄酚的含量至关重要。     

决明子富钒培育研究

目的:探讨决明子生芽、决明子耐钒和富钒能力.方法:用不同浓度的偏钒酸钠水溶液培育决明子芽,用石墨炉原子吸收分光光度计测定富钒决明子芽的钒含量.结果:决明子对偏钒酸钠有较强的耐受力,能够耐受的最大偏钒酸钠浓度是1200 mg·L-1.结论:当培养液中偏钒酸钠浓度为800 mg·L-1时,决明子芽中钒含量最高.     

决明子抗衰老系列实验I：决明子体外抗氧化与抑制胰脂肪酶活性研究

目的在氧化应激假说的指导下,本文对决明子进行体外抗氧化活性和抑制胰脂肪酶活性的测定,为探究决明子的抗衰老作用机制提供理论和实验依据。方法以不同溶媒,采用加热回流法制备决明子提取液。用DPPH法测定各提取液的抗氧化活性,采用滴定法测定各提取液的抑制胰脂肪酶能力,并比较。结果决明子不同溶媒提取液具有不同程度的体外抗氧化活性。在一定生药浓度范围内,决明子无水乙醇提取液的抗氧化能力比75％乙醇溶液提取液、85％乙醇溶液提取液、水提取液强;但抑制胰脂肪酶能力以水提取物最强,相当于阳性对照药奥利司他的水平。结论不同溶媒决明子提取物的体外抗氧化活性与胰脂肪酶的抑制作用效果显著,为探究决明子的药理作用机制提供了理论和实验依据。     

决明子降血脂作用机制研究

目的 :探讨决明子降血脂作用机理。方法 :采用体外大鼠肝细胞培养 ,以Folin -酚试剂法测定肝细胞蛋白质含量 ,并以液体闪烁计数法测定肝细胞中合成 14C -胆固醇的量。结果 :决明子浸膏剂对 14C -胆固醇的合成有一定的阻抑作用 ,而决明子苷B未出现明显的抑制合成 14C -胆固醇的作用。结论 :决明子浸膏剂降血脂作用是在一定程度上抑制了胆固醇的合成 ,而决明子苷B降血脂的主要途径不是抑制胆固醇的合成。     

不同浸种处理对决明子发芽率的影响

目的:研究不同浸种处理对决明子种子发芽率的影响.方法:测定决明子种子的千粒重,并将种子分别置于40℃、60℃、80℃的条件下,进行10 min、30 min、2h的浸种处理,观察和记录决明子的发芽率.结果:不同温度、不同时间的浸种处理对决明子种子的发芽率有显著的差异,其中以60℃温水条件下浸种2h处理的效果最佳,发芽率达到97.5％.结论:优选决明子的浸种条件对中药决明子的种植具有现实的指导意义.     

决明子蒽醌提取方法的研究

目的　研究决明子蒽醌的提取方法。方法　以决明子总蒽醌含量为主要考察指标,对决明子的蒽醌类成分采用乙醇提取的方法,用正交设计法对影响提取工艺的因素进行了研究。结果　用 8倍量 5 0 %乙醇回流提取 1 5h,再加 6倍量5 0 %乙醇回流提取 1 5h,效果最好。结论　本试验为决明子蒽醌类成分的提取、富集和开发产提供了有义参考     

Fisher成分分析法用于决明子化学指纹特征相似性研究

目的:探求Fisher成分分析法用于大、小决明子化学指纹特征相似的研究,为大、小决明子的分类提供依据。方法:对获得的指纹图谱进行数字化处理并得到大、小决明子的标准指纹图谱,然后用Fisher成分分析法提取大、小决明子化学指纹图谱中的隐含化学特征,对大、小决明子进行质量模式分类,并与主成分分析法及标准图谱法进行分类效果对比研究。结果:Fisher成分分析法能更好地表征大、小决明子的化学模式特征,分类准确性高。结论:根据Fisher成分分析法可识别大、小决明子的化学指纹特征的内在差异,可用于鉴别中药材真伪。     

急性创伤性血胸凝血功能异常的临床研究

目的探讨急性创伤性血胸患者的凝血功能变化特点及与出血量严重程度、预后的关系。方法1将126例急性创伤性血胸患者分为小量、中量、大量3组，测定患者入院当时、24 h、及72 h的血浆凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、纤维蛋白原（FIB）、血小板（BPC）值，并与43例健康对照组比较。2入院、24 h、72 h将各组血胸的凝血指标异常发生情况进行比较。结果1各型血胸中入院时PT、APTT、FIB、BPC均有异常，随着胸腔出血量增大，PT、APTT均升高，FIB、BPC降低。2入院24 h各组血胸的凝血指标异常发生率无明显差异。3入院72 h大量血胸组患者的凝血指标异常发生率和中、小量血胸组相比有明显差异。结论小量血胸患者的凝血功能无异常改变，中、大量血胸患者的凝血功能异常，且与血胸量程度相关，大量血胸组患者的入院72 h凝血指标异常发生率显著提高，可为急性创伤性血胸的治疗和判断预后提供依据。     

Depletion of securin increases arsenite-induced chromosome instability and apoptosis via a p53-independent pathway.

Arsenic is a pathologic factor of cardiovascular diseases and cancers; nevertheless, it also acts as an anticancer agent effective on acute promyelocytic leukemia and multiple myeloma. Securin, a proposed proto-oncogene, regulates cell proliferation and tumorigenesis. However, roles of securin on the arsenic-induced cell cycle arrest and apoptosis remain unknown. In this study, the effects of sodium arsenite on the expression of securin in two tissue types of cell lines, the vascular endothelial and colorectal epithelial cells, were investigated. Arsenite (8-16 microM, 24 h) increased the cytotoxicity, apoptosis, and growth inhibition in both endothelial and epithelial cells. The levels of phospho-CDC2 (threonine-161), CDC2, and cyclin B1 proteins were decreased, and the G2/M fractions were increased by arsenite. Concomitantly, arsenite markedly diminished the securin protein expression and induced the abnormal sister chromatid separation. The depletion of securin proteins increased the induction of mitotic arrest, aberrant chromosome segregation, and apoptosis after arsenite treatment. p53, a tumor suppressor protein, balances the cell survival and apoptosis. Arsenite raised the levels of phospho-p53 (serine-15) and p53 (DO-1) proteins in both the securin-wild-type and -null cells. The p53-functional cells were more susceptible than the p53-mutational cells to arsenite on the cytotoxicity and apoptosis. Besides, arsenite decreased the levels of securin proteins to a similar degree in both the p53-functional and -mutational cells. Together, it is the first time to demonstrate that the inhibition of securin expression induced by arsenite increases the chromosomal instability and apoptosis via a p53-independent pathway.     

新癀片抗炎镇痛作用机制的蛋白组学研究

目的分析新癀片抗炎镇痛作用机制,通过蛋白组学方法寻找其作用的蛋白靶点。方法大鼠随机分成对照组、模型组、吲哚美辛(2 mg/kg)组以及新癀片23.8、47.5、95.0 mg/kg组。给药组均ig给药10 m L/kg,对照组及模型组ig给予同体积去离子水。1次/d,连续3 d。于末次给药后30 min,除对照组外,在大鼠右后足垫部sc 1%角叉菜胶0.05 m L/只致炎。在致炎前和致炎后1、2 h,记录大鼠抬足潜伏期。剖杀大鼠取肝脏,肝组织蛋白经提取、双向电泳、染色和图谱分析,确定差异表达蛋白,进行蛋白质质谱分析。结果与模型组比较,新癀片23.8、47.5、95 mg/kg组差异表达蛋白个数依次为67、71、94,其中上调个数为10、11、33,下调个数为57、60、61;新癀片95 mg/kg组与吲哚美辛(2 mg/kg)组比较,差异表达蛋白89个,其中上调27个,下调62个。共鉴定出11个差异蛋白质。与模型组比较,新癀片组均可以抑制Shank3、ANXA5、TPI、PSMA2表达,增强PAH、LZTS1表达。结论新癀片可调节的蛋白明显增多,能够抑制多种相关炎症因子和肿瘤因子,增强抗炎因子及抑癌因子的表达,为新癀片"增效"作用机制提供重要理论依据。     

Integrating bioinformatics to identify and analyze feature genes of acute myocardial infarction and potential Chinese medicine prediction

In the present study, the Gene Expression Omnibus (GEO) dataset combined with machine learning was used to study differential genes in acute myocardial infarction (AMI) and to predict potential components and herbal medicines with regulatory effects. The human genome datasets of AMI (GSE66360 and GSE61145) were downloaded from the GEO database, and GSE66360 was used as the test set. After correction by normalization Between Arrays package of R, the limma package was used to obtain differentially expressed genes (DEGs). Then, we carried out Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) enrichment analysis of DEGs. The feature genes were screened by SVM and random forest tree method, and the obtained feature genes were verified by the GSE61145 dataset. The components of traditional Chinese medicine (TCM) corresponding to AMI feature genes were found by the CTD database, and the corresponding TCM components were mapped by the Coremine database. According to the Dictionary of Traditional Chinese Medicine, Chinese Materia Medica, and Chinese Pharmacopoeia, the frequency, the four qi, five flavors, and meridian tropism of the obtained TCM were summarized. Through the analysis of the GSE66360 dataset, 317 DEGs were obtained, of which 306 were up-regulated, and 11 were down-regulated. GO and KEGG enrichment analyses showed that the DEGs of AMI were mainly involved in neutrophil-mediated inflammation and immune response, abnormal lipid metabolism, lipid, and atherosclerosis-related pathways. DO enrichment analysis showed that the DEGs were closely related to atherosclerotic cardiovascular diseases and lung diseases. Six feature genes were obtained by SVM and random forest tree method, including ZFP36, GADD45A, PELI1, METRNL, MMP9, and CXCL16. Moreover, we found that the treatment of AMI Chinese medicine to sweet, bitter, and warm mostly attributed to the spleen, stomach, and liver. Besides, the components corresponding to the feature genes regulating AMI (ZFP36, GADD45A, PELI1, METRNL, MMP9, CXCL16) mainly included benzo(a)pyrene, tetrachlorodibenzodioxin, acetaminophen, and so on, and the corresponding TCMs included Camellia sinensis, Curcumaaromatica Salisb, Panax ginseng, and so on. In addition, a sweet taste, bitter taste, warm taste, and channel entry mainly belonged to the spleen, stomach, and liver meridians.     

京万红软膏对糖尿病足大鼠的作用及其机制研究

目的 探究京万红软膏对糖尿病足大鼠的作用及其机制。方法 选取40只健康大鼠,分为对照、模型、京万红软膏、重组人表皮生长因子（rhEGF）4组,每组10只。除对照组外,其余大鼠均建立糖尿病足模型,建模成功后第2天给药,将大鼠足部创面周围用生理盐水清洁后上药,模型组大鼠每日涂抹生理盐水,并与对照组大鼠进行常规喂养;京万红软膏组每天外敷涂抹3 g/kg京万红软膏覆盖创面,rhEGF组每天给予1次rhEGF外用溶液4 000 U。各组均连续给药15 d。通过大鼠足部图像观察创面愈合情况;采用酶联免疫吸附法（ELISA）检测糖基化终末产物（AGEs）、糖基化终末产物受体（RAGE）及血糖水平;苏木精–伊红（HE）染色观察病理学变化情况;免疫印迹检测结缔组织生长因子（CTGF）、细胞外信号调节蛋白激酶（ERK）、p-ERK蛋白表达情况;PCR法检测HMGBA、HMGB1、ERK1、ERK2 mRNA表达情况。结果 与模型组比较,京万红软膏组和rhEGF组大鼠的创面均减小,并以京万红软膏组的效果最为显著（P＜0.05）。与模型组比较,京万红软膏组和rhEGF组大鼠血清中AGEs、RAGE、血糖水平均显著降低（P＜0.05）,以京万红软膏组的降低最为显著（P＜0.05）。对照组大鼠皮肤组织结构完整且胶原含量丰富,模型组大鼠表皮结构损伤,有大量炎性及坏死组织;京万红软膏组大鼠表皮生长速度较快,创面组织生长活跃,毛细血管和成纤维细胞数量增多;rhEGF组大鼠组织结构稍显完整,炎性浸出物降低。与模型组比较,京万红软膏组和rhEGF组大鼠创伤组织中CTGF、ERK、p-ERK蛋白表达均明显降低,且以京万红软膏组的降低最为显著（P＜0.05）。与模型组比较,京万红软膏组和rhEGF组大鼠创伤组织中HMGBA、HMGB1、ERK1、ERK2 mRNA表达显著降低,以京万红软膏组的降低最为显著（P＜0.05）。结论 京万红软膏可促进糖尿病足大鼠的创面愈合、减小创伤面积,降低AGEs、RAGE水平,作用机制可能与抑制HMGB及ERK相关通路有关。     

The acute effects of cannabinoids on memory in humans: a review

Rationale Cannabis is one of the most frequently used substances. Cannabis and its constituent cannabinoids are known to impair several aspects of cognitive function, with the most robust effects on short-term episodic and working memory in humans. A large body of the work in this area occurred in the 1970s before the discovery of cannabinoid receptors. Recent advances in the knowledge of cannabinoid receptors’ function have rekindled interest in examining effects of exogenous cannabinoids on memory and in understanding the mechanism of these effects.Objective The literature about the acute effects of cannabinoids on memory tasks in humans is reviewed. The limitations of the human literature including issues of dose, route of administration, small sample sizes, sample selection, effects of other drug use, tolerance and dependence to cannabinoids, and the timing and sensitivity of psychological tests are discussed. Finally, the human literature is discussed against the backdrop of preclinical findings.Results Acute administration of Δ-9-THC transiently impairs immediate and delayed free recall of information presented after, but not before, drug administration in a dose- and delay-dependent manner. In particular, cannabinoids increase intrusion errors. These effects are more robust with the inhaled and intravenous route and correspond to peak drug levels.Conclusions This profile of effects suggests that cannabinoids impair all stages of memory including encoding, consolidation, and retrieval. Several mechanisms, including effects on long-term potentiation and long-term depression and the inhibition of neurotransmitter (GABA, glutamate, acetyl choline, dopamine) release, have been implicated in the amnestic effects of cannabinoids. Future research in humans is necessary to characterize the neuroanatomical and neurochemical basis of the memory impairing effects of cannabinoids, to dissect out their effects on the various stages of memory and to bridge the expanding gap between the humans and preclinical literature.     

基于斑马鱼模型的抗结核药物肝脏毒性比较研究#br#

目的 以肝脏绿色荧光转基因斑马鱼Tg(L-FABP:EGFP)为模型,研究一线抗结核药物异烟肼、吡嗪酰胺和乙胺丁醇对斑马鱼肝脏的影响以及比较其肝毒性大小。方法 用不同浓度的异烟肼、吡嗪酰胺和乙胺丁醇分别处理发育至72h的斑马鱼,于加药后24、48和72hpe(hour post-exposure)观察斑马鱼的死亡率、畸形率和肝脏形态变化情况,荧光显微镜下观察药物对斑马鱼肝脏荧光面积和荧光强度的影响。结果 随着给药浓度的增加和给药时间的延长,异烟肼、吡嗪酰胺和乙胺丁醇导致斑马鱼死亡率、畸形率升高。在72hpe,与空白对照组相比,1、2.5和5mmol/L吡嗪酰胺组斑马鱼肝脏荧光面积显著下降,5mmol/L异烟肼组斑马鱼肝脏荧光面积显著下降,10、20和30mmol/L乙胺丁醇组斑马鱼肝脏荧光面积显著下降。5mmol/L浓度下,异烟肼导致斑马鱼肝脏荧光面积降低程度高于吡嗪酰胺。结论 异烟肼、吡嗪酰胺和乙胺丁醇均有肝脏毒性,乙胺丁醇肝毒性最小。1和2.5mmol/L浓度下吡嗪酰胺导致斑马鱼发生肝损伤程度强于异烟肼,但5mmol/L下异烟肼肝脏损伤程度强于吡嗪酰胺,其有关机制需进一步研究。     

Effects on the central and peripheral nervous activity in rats elicited by acute administration of lead, mercury and manganese, and their combinations

Adult male Wistar rats were treated with inorganic lead, mercury and manganese, and their double combinations, in acute application. The aim was to study the effects on spontaneous and stimulus-evoked cortical, and evoked peripheral, nervous activity, to detect any interaction of the metals and any correlation between the changes caused in the spontaneous and stimulus-evoked electrical activity of the primary somatosensory cortical area, and the compound action potential of the tail nerve. In the frequency distribution of the spontaneous cortical activity, a shift to lower frequencies was seen. The cortical responses evoked by whisker or tail stimulation showed an increase of the peak-to-peak amplitude and peak latency on administration of the metals and metal combinations. With the metal combinations, synergism was observed. Correlations found between alterations of the spontaneous and evoked, or between cortical and peripheral, activity were evaluated in terms of mechanism. According to the results, combined exposure to the three heavy metals studied might lead to synergistic action, indicating an increased health risk in settings with exposure to several heavy metals.     

New generation azole antifungals in clinical investigation

Considerable progress in treating systemic mycoses has been achieved in the past years through development of new drugs in association with more advanced diagnostic procedures. Here, we review the pharmacological, microbiological and clinical development progress with the so-called ‘second generation’ triazoles: voriconazole, posaconazole, ravuconazole, isavuconazole and albaconazole. All these drugs exhibit a favourable pharmacokinetic and toxicity profile and possess high activity against resistant and emerging pathogens. However, only voriconazole and posaconazole have been adequately investigated in Phase III studies and have been approved by the regulatory agencies in the treatment and prophylaxis of invasive fungal infections, respectively. On the contrary, ravuconazole, isavuconazole and albaconazole have not been investigated in adequate clinical trials and, in the absence of proper data, the real possibilities of these agents as competitors for the treatment and prevention of invasive mycoses in the clinical setting are still unknown. The drug interactions and the variability in the absorption and/or metabolism of the triazoles, in particular voriconazole and posaconazole, may determine an unpredictable exposure of the pathogens to the antifungal treatments. Literature evidences strongly support the use of therapeutic drug monitoring for these triazoles which may be crucial for the proper management of severe invasive fungal infections.     

Differential modulation of catecholamines by chlorotriazine herbicides in pheochromocytoma (PC12) cells in vitro.

Epidemiological, wildlife, and laboratory studies have pointed to the possible adverse health effects of chlorotriazine herbicide (i.e. , atrazine, simazine, and cyanazine) exposure. However, the cellular mechanism(s) of action of these compounds remains unknown. Recently, it was reported by Cooper et al. (2000, Toxicol. Sci. 53, 297-307) that atrazine disrupts ovarian function by altering hypothalamic catecholamine concentrations and subsequently the regulation of luteinizing hormone (LH) and prolactin (PRL) secretion by the pituitary. In this study, we examined the effect of three chlorotriazines on catecholamine metabolism in vitro using PC12 cells. Intracellular norepinephrine (NE) and dopamine (DA) concentrations and spontaneous NE release were measured following treatment with different concentrations of atrazine, simazine (0, 12. 5, 25, 50, 100, and 200 microM) and cyanazine (0, 25, 50, 100, and 400 microM) for 6, 12, 18, 24, and 48 h. Atrazine and simazine significantly decreased intracellular DA concentration in a concentration-dependent manner. Intracellular NE concentration was also significantly decreased by 100 and 200 microM atrazine and 200 microM simazine. Similarly, there was a dose-dependent inhibition of NE release with 100 and 200 microM concentrations of both compounds. Although 100 and 400 microM cyanazine increased intracellular NE concentration, 50, 100, and 400 microM cyanazine significantly increased NE release at 24 and 36 h. In contrast, intracellular DA concentration was decreased by cyanazine, but only at 400 microM. The GABA(A)-receptor agonist, muscimol (0, 0.01, 0.1, and 1.0 microM) had no effect on either the release or on intracellular catecholamine concentrations from 6 through 24 h of treatment. Cell viability was somewhat lower in the groups exposed to 100 and 200 microM atrazine and simazine. However, the reduction in viability was significant only in the highest dose of atrazine used (200 microM) at 24 h. Cyanazine did not have an effect on the viability at any of the doses tested, and the cells were functional, even up to 48 h of exposure. These data indicate that both atrazine and simazine inhibit the cellular synthesis of DA mediated by the tyrosine hydroxylase (TH), and NE mediated by dopamine beta-hydroxylase (DbetaH), and, as a result, there is a partial or significant inhibition of NE release. Cyanazine, on the other hand, stimulated the synthesis of intracellular NE, and not DA. Thus, chlorotriazine compounds presumably act at the enzymatic steps or sites of CA biosynthesis to modulate monoaminergic activity in PC12 cells.