scholarly journals Computational Systems Pharmacology, Molecular Docking and Experiments Reveal the Protective Mechanism of Li-Da-Qian Mixture in the Treatment of Glomerulonephritis

2021 ◽  
Vol Volume 14 ◽  
pp. 6939-6958
Author(s):  
Wei Zhou ◽  
Yugen Sha ◽  
Jingxia Zeng ◽  
Xiaoyue Zhang ◽  
Aihua Zhang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Protective Mechanism ◽  
Systems Pharmacology ◽  
Computational Systems

scholarly journals Elucidating the Mechanisms of Action of Lianhua Qingwen decoction for the Treatment of COVID-19 via Systems Pharmacology Approaches

2021 ◽  
Author(s):  
Xiting Wang ◽  
Tao Lu
Keyword(s):  
Molecular Docking ◽  
Blood Circulation ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Detection Algorithm ◽  
Network Pharmacology ◽  
Systems Pharmacology ◽  
Protein Protein Interaction ◽  
Further Development ◽  
Protein Protein Interaction Network

Abstract Due to the severity of the COVID-19 epidemic, to identify a proper treatment for COVID-19 is of great significance. Traditional Chinese Medicine (TCM) has shown its great potential in the prevention and treatment of COVID-19. One of TCM decoction, Lianhua Qingwen decoction displayed promising treating efficacy. Nevertheless, the underlying molecular mechanism has not been explored for further development and treatment. Through systems pharmacology and network pharmacology approaches, we explored the potential mechanisms of Lianhua Qingwen treating COVID-19 and acting ingredients of Lianhua Qingwen decoction for COVID-19 treatment. Through this way, we generated an ingredients-targets database. We also used molecular docking to screen possible active ingredients. Also, we applied the protein-protein interaction network and detection algorithm to identify relevant protein groupings of Lianhua Qingwen. Totally, 605 ingredients and 1,089 targets were obtained. Molecular Docking analyses revealed that 35 components may be the promising acting ingredients, 7 of which were underlined according to the comprehensive analysis. Our enrichment analysis of the 7 highlighted ingredients showed relevant significant pathways that could be highly related to their potential mechanisms, e.g. oxidative stress response, inflammation, and blood circulation. In summary, this study suggests the promising mechanism of the Lianhua Qingwen decoction for COVID-19 treatment. Further experimental and clinical verifications are still needed.

scholarly journals Uncovering the Molecular Mechanism of the Qiang-Xin 1 Formula on Sepsis-Induced Cardiac Dysfunction Based on Systems Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-26
Author(s):  
Shasha He ◽  
Jingxia Zhao ◽  
Xiaolong Xu ◽  
Xuran Cui ◽  
Ning Wang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cardiac Dysfunction ◽  
Cardiac Tissue ◽  
Multiorgan Failure ◽  
Cecal Ligation ◽  
Tanshinone Iia ◽  
Protective Mechanism ◽  
Systems Pharmacology ◽  
Active Components ◽  
Immune Balance

Cardiac dysfunction is a critical manifestation of sepsis-induced multiorgan failure and results in the high mortality of sepsis. Our previous study demonstrated that a traditional Chinese medicine formula, Qiang-Xin 1 (QX1), ameliorates cardiac tissue damage in septic mice; however, the underlying pharmacology mechanism remains to be elucidated. The present study was aimed at clarifying the protective mechanism of the QX1 formula on sepsis-induced cardiac dysfunction. The moderate sepsis model of mice was established by cecal ligation and puncture surgery. Treatment with the QX1 formula improved the 7-day survival outcome, attenuated cardiac dysfunction, and ameliorated the disruption of myocardial structure in septic mice. Subsequent systems pharmacology analysis found that 63 bioactive compounds and the related 79 candidate target proteins were screened from the QX1 formula. The network analysis showed that the QX1 active components quercetin, formononetin, kaempferol, taxifolin, cryptotanshinone, and tanshinone IIA had a good binding activity with screened targets. The integrating pathway analysis indicated the calcium, PI3K/AKT, MAPK, and Toll-like receptor signaling pathways may be involved in the protective effect of the QX1 formula on sepsis-induced cardiac dysfunction. Further, experimental validation showed that the QX1 formula inhibited the activity of calcium/calmodulin-dependent protein kinase II (CaMKII), MAPK (P38, ERK1/2, and JNK), and TLR4/NF-κB signaling pathways but promoted the activation of the PI3K/AKT pathway. A cytokine array found that the QX1 formula attenuated sepsis-induced upregulated levels of serum IFN-γ, IL-1β, IL-3, IL-6, IL-17, IL-4, IL-10, and TNF-α. Our data suggested that QX1 may represent a novel therapeutic strategy for sepsis by suppressing the activity of calcium, MAPK, and TLR4/NF-κB pathways, but promoting the activation of AKT, thus controlling cytokine storm and regulating immune balance. The present study demonstrated the multicomponent, multitarget, and multipathway characteristics of the QX1 formula and provided a novel understanding of the QX1 formula in the clinical application on cardiac dysfunction-related diseases.

scholarly journals Computational Systems Pharmacology-Target Mapping for Fentanyl-Laced Cocaine Overdose

2019 ◽  
Vol 10 (8) ◽  
pp. 3486-3499 ◽  
Author(s):  
Jin Cheng ◽  
Siyi Wang ◽  
Weiwei Lin ◽  
Nan Wu ◽  
Yuanqiang Wang ◽  
...  
Keyword(s):  
Systems Pharmacology ◽  
Computational Systems

scholarly journals A quantitative systems pharmacology analysis of KRAS G12C covalent inhibitors

2017 ◽  
Author(s):  
Edward C. Stites ◽  
Andrey S. Shaw
Keyword(s):  
Human Cancer ◽  
Conventional Wisdom ◽  
Ras Signaling ◽  
Systems Pharmacology ◽  
Ras Pathway ◽  
Ras Protein ◽  
Oncogenic Mutation ◽  
Ras Activation ◽  
Covalent Inhibitors ◽  
Computational Systems

AbstractThe KRAS oncogene is the most common, activating, oncogenic mutation in human cancer. KRAS has proven difficult to target effectively. Two different strategies have recently been described for covalently targeting the most common activating KRAS mutant in lung cancer, KRAS G12C. Previously, we have developed a computational model of the processes that regulate Ras activation and this model has proven useful for understanding the complex behaviors of Ras signaling. Here, we use this model to perform a computational systems pharmacology analysis of KRAS G12C targeted covalent inhibitors. After updating our model to include Ras protein turnover, we verified the validity of our model for problems in this domain by comparing model behaviors with experimental behaviors. The model naturally reproduces previous experimental data, including several experimental observations that were interpreted as being contrary to conventional wisdom. Overall, this suggests that our model describes the Ras system well, including those areas where conventional wisdom struggles. We then used the model to investigate possible strategies to improve the ability of KRAS G12C inhibitors to inhibit Ras pathway signaling. We identify one, as of yet unexplored mechanism, that, if optimized, could improve the effectiveness of one class of KRAS inhibitor. We also simulated resistance to targeted therapies and found that resistance promoting mutations may reverse which class of KRAS G12C inhibitor inhibits the system better, suggesting that there may be value to pursuing both types of KRAS G12C inhibitors. Overall, this work demonstrates that systems biology approaches can provide insights that inform the drug development process.

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