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Semi-Mechanism-Based Pharmacodynamic Model for the Anti-Inflammatory Effect of Baicalein in LPS-Stimulated RAW264.7 Macrophages
by
Huang, Wen-Ge
, Wu, Jia-Si
, Wang, Li
, Meng, Xian-Li
, Hu, Ying-Fan
, Xu, Chen-Si
, Xiang, Li
, Wang, Ping
in
Anti-inflammatory agents
/ Cell culture
/ Cytokines
/ Drug development
/ Drugs
/ Inflammation
/ Inflammatory diseases
/ Interleukin 6
/ Lipopolysaccharides
/ Macrophages
/ Mathematical models
/ Monoclonal antibodies
/ Nitric-oxide synthase
/ Pharmacodynamics
/ Pharmacology
/ Physiology
/ Proteins
/ Tumor necrosis factor-TNF
/ Tumor necrosis factor-α
2018
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Semi-Mechanism-Based Pharmacodynamic Model for the Anti-Inflammatory Effect of Baicalein in LPS-Stimulated RAW264.7 Macrophages
by
Huang, Wen-Ge
, Wu, Jia-Si
, Wang, Li
, Meng, Xian-Li
, Hu, Ying-Fan
, Xu, Chen-Si
, Xiang, Li
, Wang, Ping
in
Anti-inflammatory agents
/ Cell culture
/ Cytokines
/ Drug development
/ Drugs
/ Inflammation
/ Inflammatory diseases
/ Interleukin 6
/ Lipopolysaccharides
/ Macrophages
/ Mathematical models
/ Monoclonal antibodies
/ Nitric-oxide synthase
/ Pharmacodynamics
/ Pharmacology
/ Physiology
/ Proteins
/ Tumor necrosis factor-TNF
/ Tumor necrosis factor-α
2018
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Semi-Mechanism-Based Pharmacodynamic Model for the Anti-Inflammatory Effect of Baicalein in LPS-Stimulated RAW264.7 Macrophages
by
Huang, Wen-Ge
, Wu, Jia-Si
, Wang, Li
, Meng, Xian-Li
, Hu, Ying-Fan
, Xu, Chen-Si
, Xiang, Li
, Wang, Ping
in
Anti-inflammatory agents
/ Cell culture
/ Cytokines
/ Drug development
/ Drugs
/ Inflammation
/ Inflammatory diseases
/ Interleukin 6
/ Lipopolysaccharides
/ Macrophages
/ Mathematical models
/ Monoclonal antibodies
/ Nitric-oxide synthase
/ Pharmacodynamics
/ Pharmacology
/ Physiology
/ Proteins
/ Tumor necrosis factor-TNF
/ Tumor necrosis factor-α
2018
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Semi-Mechanism-Based Pharmacodynamic Model for the Anti-Inflammatory Effect of Baicalein in LPS-Stimulated RAW264.7 Macrophages
Journal Article
Semi-Mechanism-Based Pharmacodynamic Model for the Anti-Inflammatory Effect of Baicalein in LPS-Stimulated RAW264.7 Macrophages
2018
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Overview
Monitoring of the inhibition of TNF-α, IL-6, iNOS, and NO is used to effectively evaluate anti-inflammatory drugs. Baicalein was found to have good anti-inflammatory activities, but its detailed cellular pharmacodynamic events have not been expatiated by any other study. The inflammatory mediators, including TNF-α, IL-6, iNOS, and NO production in RAW264.7 macrophage induced by LPS, were measured. It was found that these data showed a sequential pattern on time and based on these points a cellular pharmacodynamic model was developed and tested. TNF-α and IL-6 were quantified by ELISA, NO was detected by Griess and iNOS expression was measured by Western blot. The pharmacodynamic model was developed using a NLME modeling program Monolix® 2016R1.The results showed that baicalein quickly suppressed release of TNF-α in a concentration-dependent manner, and consequently causing the diminution of IL-6 and iNOS/NO. The pharmacodynamic model simulation successfully described the experimental data, supporting the hypothesis that IL-6 and iNOS /NO release after LPS stimulation is mediated by TNF-α rather than LPS directly. The pharmacodynamic model allowed a well understanding of the cellular pharmacodynamic mechanism of baicalein in the treatment of inflammatory diseases.
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