基于网络药理学的大黄治疗阿尔茨海默病作用机制研究

基于网络药理学探讨大黄治疗阿尔茨海默病(AD)的作用机制。借助TCMSP数据库及Uniprot数据库筛选出大黄有效成分及靶点基因。通过Drugbank、Dis Ge NET和TTD数据库筛选出阿尔茨海默病的靶点基因;成分靶点与疾病靶点映射后使用Cytoscape 3.7.1软件构建药物有效成分-靶点蛋白相互作用网络,使用String数据库绘制靶点蛋白-靶点蛋白相互作用网络;对靶点蛋白利用Metascape数据库进行GO分析和KEGG分析,最后采用MTT实验、ELISA法、比色法和荧光实时定量PCR对网络药理学主要分析结果进行验证。研究共筛选出大黄的有效成分17个,对应靶点276个,与阿尔茨海默病相关靶点共107个,KEGG相关信号通路前10条,GO分析前20个生物学过程。细胞实验证实了大黄能有效提高PC12细胞的细胞存活率及抑制PC12细胞的炎症反应、细胞凋亡、氧化应激反应,并促进PI3K/Akt/Nrf2/HO-1信号通路的激活,下调NF-κB信号通路。大黄主要是通过抗炎、抗凋亡、抗氧化应激等对阿尔茨海默病产生重要的治疗作用,为后续临床治疗阿尔茨海默病提供新的思路。     

姜黄在理血方剂中的配伍规律及系统药理机制分析

姜黄可以有效治疗各种疾病,本研究使用广义规则归纳(GRI)算法分析了《中药方剂大词典》中含姜黄的理血方剂配伍规律。通过利用生物信息学数据挖掘技术和MTT、Elisa和Western blotting实验验证了姜黄关键配方的系统药理机制。发现“姜黄-川芎-当归”配方可以代表姜黄在理血方剂中的关键组方。PPI网络和KEGG途径富集分析表明“姜黄-川芎-当归”能通过调节PI3K/Akt、MAPK、Toll样受体,T细胞受体,EGFR,VEGFR,细胞凋亡,HIF-1等通路(P<0.05),发挥抗炎、改善微循环和抗肿瘤作用。MTT,Elisa法和Western blotting实验表明,“姜黄-川芎-当归”组方能下调p-EGFR、p-PI3K、p-Akt、VEGF和HIF-的表达,抑制人肺癌A549细胞增殖。“姜黄-川芎-当归”组方可能具有多靶点、多途径的药理作用,治疗炎症,微循环障碍,心血管疾病和癌症。总之,本研究找到了一种新的中药配方,为后续研究姜黄的药理机制提供了理论依据和参考。     

当归芍药散对新型冠状病毒肺炎的临床疗效及其作用机制的网络药理学研究

为探讨当归芍药散对新型冠状病毒肺炎(COVID-19)的临床疗效及其作用机制,随机选取2020年1月20日~3月20日武汉协和医院收治的100例COVID-19患者作为研究对象,观察当归芍药散联合常规治疗前后患者的基本体征、主要症状、实验室指标、核酸转阴、CT影像学的变化情况,发现以上症状及指标均较前明显好转。同时运用网络药理学分析当归芍药散治疗COVID-19的潜在作用靶点,得到作用靶点18个,GO功能富集180条目,KEGG通路富集109条。结果提示当归芍药散可能通过多靶点、多通路发挥抗病毒、抗炎、抗氧化等作用,进而达到治疗COVID-19的效果。     

基于网络药理学和分子对接技术探讨冬虫夏草治疗肾纤维化的潜在作用机制

为了探究冬虫夏草治疗肾纤维化的分子机制,本研究运用网络药理学方法筛选出冬虫夏草抗肾纤维化的活性成分、潜在作用靶点及相关信号通路,并对关键的化合物和靶点进行分子对接。结果表明,冬虫夏草共有22个化合物和364个潜在靶点参与治疗肾纤维化,蛋白互作（PPI）分析出IL-6、TNF-α、MAPK3、EGFR、SRC、CASP3和MAPK1等关键潜在靶点,KEGG通路富集筛选得到163条信号通路。分子对接结果显示,冬虫夏草治疗肾纤维化过程中,其核心化合物金色酰胺醇酯、啤酒甾醇、酒渣碱、花生四烯酸、11,14-二十碳二烯酸分别与PIK3CA、PIK3CB、PIK3CD、MAPK1、MAPK3、RELA等具有良好的结合性能。分析结果显示,冬虫夏草具有通过多成分、多靶点、多通路减缓肾纤维化的潜力,为其抗肾纤维化临床使用提供了一定的依据。     

COVID-19: Antiviral Agents,Antibody Development and Traditional Chinese Medicine

Virologica Sinica - The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) is the first pandemic caused by coronavirus named severe acute respiratory syndrome...     

Übersicht über die celastraceen-inhaltsstoffe: Chemie,chemotaxonomie, biosynthese,pharmakologie

In this review all important chemical constituents of the Celastraceae family isolated up to 1 March 1978 are surveyed and discussed from a chemical, pharmacological, biosynthetic and chemotaxonomic point of view.     

Modeling the influence of chronopharmacological administration of synthetic glucocorticoids on the hypothalamic-pituitary-adrenal axis

ABSTRACT

Natural glucocorticoids, a class of cholesterol-derived hormones, modulate an array of metabolic, anti-inflammatory, immunosuppressive and cognitive signaling. The synthesis of natural glucocorticoids, largely cortisol in humans, is regulated by the hypothalamic-pituitary-adrenal (HPA) axis and exhibits pronounced circadian variation. Considering the central regulatory function of endogenous glucocorticoids, maintenance of the circadian activity of the HPA axis is essential to host survival and chronic disruption of such activity leads to systemic complications. There is a great deal of interest in synthetic glucocorticoids due to the immunosuppressive and anti-inflammatory properties and the development of novel dosing regimens that can minimize the disruption of endogenous activity, while still maintaining the pharmacological benefits of long-term synthetic glucocorticoid therapy. Synthetic glucocorticoids are associated with an increased risk of developing the pathological disorders related to chronic suppression of cortisol rhythmicity as a result of the potent negative feedback by synthetic glucocorticoids on the HPA axis precursors. In this study, a mathematical model was developed to explore the influence of chronopharmacological dosing of exogenous glucocorticoids on the endogenous cortisol rhythm considering intra-venous and oral dosing. Chronic daily dosing resulted in modification of the circadian rhythmicity of endogenous cortisol with the amplitude and acrophase of the altered rhythm dependent on the administration time. Simulations revealed that the circadian features of the endogenous cortisol rhythm can be preserved by proper timing of administration. The response following a single dose was not indicative of the response following long-term, repeated chronopharmacological dosing of synthetic glucocorticoids. Furthermore, simulations revealed the inductive influence of long-term treatment was only associated with low to moderate doses, while high doses generally led to suppression of endogenous activity regardless of the chronopharmacological dose. Finally, chronic daily dosing was found to alter the responsiveness of the HPA axis, such that a decrease in the amplitude of the cortisol rhythm resulted in a partial loss in the time-of-day dependent response to CRH stimulation, while an increase in the amplitude was associated with a more pronounced time-of-day dependence of the response.     

Label-free optical biosensor: A tool for G protein-coupled receptors pharmacology profiling and inverse agonists identification

Current GPCR cell-based assays often rely on the measurement of a loaded fluorescent dye, fluorescently tagged targets, or the expression of a reporter. These manipulations may alter the cellular physiology of the target GPCR, and the measurements may be subject to off-target interference of compounds. Label-free optical biosensor-based technologies that provide a noninvasive methodology to study GPCR activation and signaling have been developed. These technologies enable the evaluation of drug effects on various GPCRs that couple to different signal transduction pathways using only one assay platform. This technology is highly sensitive and detects inverse agonism, therefore providing a convenient tool to study the pharmacology of drugs. Furthermore, its real-time kinetic measurements give researchers additional information about the biological responses induced by the drug. This assay platform when applied in early drug discovery efforts can provide valuable information on the mechanism of action and pharmacology profiles of drug candidates.     

菌物生药学——一个充满生机的边缘学科

菌物生药学是一门新兴的边缘学科,它涉及菌物学、生药学、中药学等许多学科,以菌物药为研究对象,运用现代自然科学的理论知识和技术方法,研究和探讨菌物药的来源、性状、显微特征、理化鉴别、质量指标以及引种驯化、发酵等生物工程和寻找新药源的理论和实践问题。随着现代科学尤其是现代生命科学的飞速发展,菌物药的研究在当今世界也有重要的理论和实践意义。本文从菌物生药学的发展历史,研究内容以及与其他学科关系等几个方面进行阐述,旨在将这一具有理论和实践价值的学科得以发展。     

基于网络药理学的柿果药理功能定位及作用机制

基于网络药理学,通过国内外文献检索获取柿果中的化合物,采用Swiss target prediction数据库对化合物进行潜在靶点垂钓以探讨柿果的药理功能定位及作用机制。以Cytoscape软件构建化合物-靶点网络,靶点-疾病名称-疾病分类网络,同时对靶点进行蛋白相互作用(PPI)网络构建,采用DAVID数据库对靶点进行通路富集分析。本研究共收集到柿果中16个化合物,可作用于68个靶点,这些靶点主要作用于心血管疾病、神经精神性疾病等。PPI网络图包含84个节点,226条边,其中degree值排前10的关键蛋白分别为ERS1、PGS2、MMP2、TIMP1、MMP9、MMP1、AR、SLC6A3、PRKCB、CYP19A1。上述靶点可调节氮素代谢、血清素能突触以及TRP通道炎症介质的调节等信号通路。本研究为阐明柿果的药理功能定位及其作用机制研究提供了可靠的依据。