Presentation_1_Semi-Mechanism-Based Pharmacodynamic Model for the Anti-Inflammatory Effect of Baicalein in LPS-Stimulated RAW264.7 Macrophages.PDF (1.27 MB)

Presentation_1_Semi-Mechanism-Based Pharmacodynamic Model for the Anti-Inflammatory Effect of Baicalein in LPS-Stimulated RAW264.7 Macrophages.PDF

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posted on 18.07.2018, 09:34 by Li Xiang, Ying-Fan Hu, Jia-Si Wu, Li Wang, Wen-Ge Huang, Chen-Si Xu, Xian-Li Meng, Ping Wang

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® 2016R1.1The 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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