Dataset Information

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

ABSTRACT: Monitoring of the inhibition of TNF-?, 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-?, 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-? 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-? 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-? rather than LPS directly. The pharmacodynamic model allowed a well understanding of the cellular pharmacodynamic mechanism of baicalein in the treatment of inflammatory diseases.

SUBMITTER: Xiang L

PROVIDER: S-EPMC6058255 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

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

Xiang Li L Hu Ying-Fan YF Wu Jia-Si JS Wang Li L Huang Wen-Ge WG Xu Chen-Si CS Meng Xian-Li XL Wang Ping P

Frontiers in pharmacology 20180718

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 cellul ...[more]

PMID: 30072902

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Project description:Recent studies confirm that chronic low-grade inflammation is closely associated with metabolic syndromes, and anti-inflammatory therapy is a potential approach for treating cardiovascular diseases and type 2 diabetes. Accumulating evidence suggests that GPR120 activation is a feasible solution to ameliorating chronic inflammation and improving glucose metabolism. In this study we investigated whether ginsenoside Rb2 (Rb2), which exhibited regulatory activities in glucose and lipid metabolism, affected GPR120 expression in lipopolysaccharide (LPS)-activated mouse macrophage RAW264.7 cells, and examined the contribution of GPR120 activation to reducing the LPS-induced inflammatory response. LPS (100 ng/mL) activated the macrophages, resulting in dramatic increases in TNF-α, IL-6, IL-1β and NO production. Treatment with a ω-3 fatty acid α-linolenic acid (ALA, 50 μmol/L) produced moderate reduction in LPS-stimulated inflammatory cytokines and NO production (TNF-α and IL-6 were decreased by 46% and 42%, respectively). Pre-incubation with Rb2 (1 or 10 μmol/L) for 12 h before ALA treatment dramatically amplified the inhibitory effects of ALA (TNF-α and IL-6 were decreased by 74% and 86%, respectively). Compared to the treatment with ALA alone, pre-incubation with Rb2 resulted in a more prominent reduction in LPS-stimulated expression of iNOS and COX-2 and LPS-stimulated IKK/NF-κB phosphorylation and MAPK pathway activation. Rb2 (0.1-100 μmol/L) dose- and time-dependently increased both mRNA and protein expression of GPR120 in RAW264.7 cells, but treatment with Rb2 alone did not exert anti-inflammatory effect in LPS-activated RAW264.7 cells. In RAW264.7 cells transfected with GPR120 shRNA, the ameliorating effects of Rb2 on LPS-induced inflammation were abolished. In conclusion, Rb2 exerts anti-inflammatory effect in LPS-stimulated mouse macrophage RAW264.7 cells in vitro by increasing GPR120 expression and subsequently enhancing ω-3 fatty acid-induced GPR120 activation.

Dataset Information

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

Publications

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

Similar Datasets

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