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121.
Shuai Shi Xinyu Ji Jingjing Shi Shuqing Shi Fei She Qiuyan Zhang Yu Dong Hanming Cui Yuanhui Hu 《Bioscience reports》2022,42(7)
Objective: Andrographis paniculata (Burm.f.) Nees is a medicinal plant that has been traditionally used as an anti-inflammatory and antibacterial remedy for several conditions. Andrographolide (AG), the active constituent of A. paniculata (Burm.f.) Nees, has anti-lipidic and anti-inflammatory properties as well as cardiovascular protective effects. The present study aimed to explore the effects of AG on the progression of atherosclerosis and to investigate related mechanisms via network pharmacology.Materials and methods: Compound-related information was obtained from the PubChem database. Potential target genes were identified using STITCH, SwissTargetPrediction, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Comparative Toxicogenomics Database. Genes involved in atherosclerosis were obtained from DisGeNet and compared with AG target genes to obtain an overlapping set. Protein–protein interactions were determined by STRING. Gene ontology (GO) analysis was performed at WebGestalt, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was analyzed using Metascape. The final network showing the relationship between compounds, targets, and pathways was constructed using Cytoscape. After that, oxLDL-induced RAW264.7 cells were used to further validate a part of the network pharmacology results.Result: Eighty-one potential AG target genes were identified. PPI, GO, and KEGG enrichment revealed genes closely related to tumor progression, lipid transport, inflammation, and related pathways. AG improves the reverse cholesterol transport (RCT) through NF-κB/CEBPB/PPARG signaling in oxLDL-induced RAW264.7 cells.Conclusion: We successfully predict AG’s potential targets and pathways in atherosclerosis and illustrate the mechanism of action. AG may regulate NF-κB/CEBPB/PPARG signaling to alleviate atherosclerosis. 相似文献
122.
网络药理学与药物发现研究进展 总被引:2,自引:0,他引:2
将生物学网络与药物作用网络整合,分析药物在网络中与节点或网络模块的关系,由寻找单一靶点转向综合网络分析,就形成了网络药理学.通过系统生物学的研究方法进行网络药理学分析,能够在分子水平上更好的理解细胞以及器官的行为,加速药物靶点的确认以及发现新的生物标志物.这使得我们有可能系统地预测和解释药物的作用,优化药物设计,发现影响药物作用有效性和安全性的因素,从而设计多靶点药物或药物组合.本文综述了网络药理学的新近研究进展,介绍在生物学网络的各个层面上网络药理学的研究和应用,展望网络药理未来的发展方向,对药物发现具有重要意义. 相似文献
123.
本文旨在通过网络药理学和分子对接方法探讨丹参-丹皮活性成分治疗脑卒中的潜在分子机制.首先基于中药系统药理学分析平台筛选丹参、丹皮的活性成分及其作用靶点,利用CTD、TTD和GeneCards数据库收集脑卒中相关靶点.然后将药物和疾病靶点取交集,借助STRING数据库获取靶点间相互作用关系,利用R语言的Cluster-P... 相似文献
124.
Jingyi Wang Alexander Kuryatov Aarati Sriram Zhuang Jin Theodore M. Kamenecka Paul J. Kenny Jon Lindstrom 《The Journal of biological chemistry》2015,290(22):13907-13918
Neuronal nicotinic acetylcholine receptors containing α4, β2, and sometimes other subunits (α4β2* nAChRs) regulate addictive and other behavioral effects of nicotine. These nAChRs exist in several stoichiometries, typically with two high affinity acetylcholine (ACh) binding sites at the interface of α4 and β2 subunits and a fifth accessory subunit. A third low affinity ACh binding site is formed when this accessory subunit is α4 but not if it is β2. Agonists selective for the accessory ACh site, such as 3-[3-(3-pyridyl)-1,2,4-oxadiazol-5-yl]benzonitrile (NS9283), cannot alone activate a nAChR but can facilitate more efficient activation in combination with agonists at the canonical α4β2 sites. We therefore suggest categorizing agonists according to their site selectivity. NS9283 binds to the accessory ACh binding site; thus it is termed an accessory site-selective agonist. We expressed (α4β2)2 concatamers in Xenopus oocytes with free accessory subunits to obtain defined nAChR stoichiometries and α4/accessory subunit interfaces. We show that α2, α3, α4, and α6 accessory subunits can form binding sites for ACh and NS9283 at interfaces with α4 subunits, but β2 and β4 accessory subunits cannot. To permit selective blockage of the accessory site, α4 threonine 126 located on the minus side of α4 that contributes to the accessory site, but not the α4β2 sites, was mutated to cysteine. Alkylation of this cysteine with a thioreactive reagent blocked activity of ACh and NS9283 at the accessory site. Accessory agonist binding sites are promising drug targets. 相似文献
125.
Wei Ling Xiang Li Xiaoyu Liu Qian Wu Weilong Wang Jin Meng Baochang Sun Binbin Lv 《化学与生物多样性》2023,20(5):e202201228
Guizhi granules mainly treat colds and improve overall health. They are widely used in clinical practice, but their protective effect and anti-inflammatory mechanism against influenza are unclear. In this study, the therapeutic effect of Guizhi granules on influenza was verified in vitro. The active compounds, targets, and cellular pathways of Guizhi granules against influenza were predicted using network pharmacology. The protein-protein interaction and component-target networks identified 5 core targets (JUN, TNF-α, RELA, AKT1, and MAPK1) and components (dihydrocapsaicin, kumatakenin, calycosin, licochalcone A, and berberine). GO and KEGG enrichment analyses revealed the anti-influenza pathways of Guizhi granules as antiviral and anti-inflammatory pathways. Molecular docking further verified that the core targets and components have good or strong binding activity. Therefore, the active ingredients, targets, and molecular mechanisms of Guizhi granules involved in influenza treatment were elucidated. 相似文献
126.
Francisco Sahli Costabal Jiang Yao 《Computer methods in biomechanics and biomedical engineering》2018,21(3):232-246
A common but serious side effect of many drugs is torsades de pointes, a rhythm disorder that can have fatal consequences. Torsadogenic risk has traditionally been associated with blockage of a specific potassium channel and an increased recovery period in the electrocardiogram. However, the mechanisms that trigger torsades de pointes remain incompletely understood. Here we establish a computational model to explore how drug-induced effects propagate from the single channel, via the single cell, to the whole heart level. Our mechanistic exposure–response simulator translates block-concentration characteristics for arbitrary drugs into three-dimensional excitation profiles and electrocardiogram recordings to rapidly assess torsadogenic risk. For the drug of dofetilide, we show that this risk is highly dose-dependent: at a concentration of 1x, QT prolongation is 55% but the heart maintains its regular sinus rhythm; at 5.7x, QT prolongation is 102% and the heart spontaneously transitions into torsades de points; at 30x, QT prolongation is 132% and the heart adapts a quasi-depolarized state with numerous rapidly flickering local excitations. Our simulations suggest that neither potassium channel blockage nor QT interval prolongation alone trigger torsades de pointes. The underlying mechanism predicted by our model is early afterdepolarization, which translates into pronounced U waves in the electrocardiogram, a signature that is correctly predicted by our model. Beyond the risk assessment of existing drugs, our exposure–response simulator can become a powerful tool to optimize the co-administration of drugs and, ultimately, guide the design of new drugs toward reducing life threatening drug-induced rhythm disorders in the heart. 相似文献
127.
综述了红景天属(RhodiolaL.)植物的植物化学和药理方面的研究进展及其开发应用前景。 相似文献
128.
129.
1. One binding component with aK
d value of 200×10–9 M and half-life of the ligand binding component of 30 min was found. 2. Chloride ions produced a significant increase ofl-[3H]aspartate andl-[3H]glutamate binding. 3.l-Glutamate,l-ibotenate,l-quisqualate, anddl-homocysteic acid were potent inhibitors ofl-[3H]aspartate binding. 4. In all brain regions major increases of binding were observed during the third week of the in ovo period of life. 相似文献
130.
Julia E. Chrubasik Basil D. Roufogalis Hildebert Wagner Sigrun A. Chrubasik 《Phytomedicine》2007,14(6):423-435
Nettle herb is recommended for complaints associated with rheumatoid arthritis, osteoarthritis and urinary tract infections. We therefore conducted a comprehensive review of the literature to summarize the pharmacological and clinical effects of this plant material. Although clinical and experimental studies suggest that nettle herb has some anti-inflammatory properties, clinical evidence beyond doubt is lacking. Nettle preparations exert a number of promising in vitro and in vivo effects, however, further studies are needed to support these results and to find out if these effects are surrogates for clinical relevant effects in humans. 相似文献