A network pharmacology integrated pharmacokinetics strategy for uncovering pharmacological mechanism of compounds absorbed into the blood of Dan-Lou tablet on coronary heart disease

Ding, Mingya; Ma, Wenfang; Wang, Xiaoyan; Chen, Shujing; Zou, Shuhan; Wei, Jinna; Yang, Yuqiao; Li, Jin; Yang, Xuejing; Wang, Hui; Li, Yuhong; Wang, Qilong; Mao, Haoping; Gao, Xiumei; Chang, Yan‐xu

doi:10.1016/j.jep.2019.112055

Cited by 45 publications

(33 citation statements)

References 22 publications

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“…Meanwhile, the multipeak phenomenon was observed for PF. The result is similar to the PK study of PF in the previously published articles [ 13 , 21 ]. Possible reasons for this phenomenon could be attributed to hepatoenteral circulation, drug-drug interaction, multiple sites absorption, etc.…”

Section: Resultssupporting

confidence: 91%

Simultaneous Determination of Multiple Active Components from Bushen Pills and Application in a Pharmacokinetic Study in Rats

Wang

Yuan

et al. 2020

Journal of Analytical Methods in Chemistry

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Bushen Pills (BSPs), as a traditional Chinese medicine (TCM), is widely used in clinic to enrich Yang, nourish Yin, stem essence, and strengthen kidneys. Two chromatographic methods, liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), were applied to analyze the multiple active components of BSPs in dosage form for quality evaluation and in rat plasma for pharmacokinetics study, respectively. Three active constituents of BSPs, including paeoniflorin (PF), berberine hydrochloride (BBR), and schizandrin (SCH), were simultaneously determined by the established LC-MS method with electrospray ionization (ESI) in positive selected ion monitoring (SIM) mode at m/z 503.1, 336.0, and 455.2. The contents of PF, BBR, and SCH were (6.112 ± 0.166) mg/g, (335.1 ± 14.95) μg/g, and (5.867 ± 0.136) μg/g in BSPs. On this basis, PF and BBR were selected as targeted analytes for the pharmacokinetic study of BSPs in rats. Memantine hydrochloride was used as an internal standard (IS), and the plasma samples were processed by liquid-liquid extraction with ethyl acetate. All the analytes were separated on a C18 reversed phase column, eluted with a mobile phase consisting of acetonitrile-formic acid (0.01%) (25 : 75, v/v), and detected by ESI in the selected ion mode with multiple reaction monitoring (MRM). The target fragment ions were m/z 525.3 ⟶ 449.5 for PF, 336.2 ⟶ 320.2 for BBR, and 180.1 ⟶ 163.1 for IS. The linear ranges of PF and BBR were 5–500 ng/mL and 0.1–20 ng/mL with good linearity (r2 > 0.99). No obvious matrix effect was observed, and acceptable accuracy, precision, recovery, and stability were obtained. The proposed method has been successfully applied to the pharmacokinetic study of BSPs in rats after a single dose.

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Section: Resultssupporting

confidence: 91%

Simultaneous Determination of Multiple Active Components from Bushen Pills and Application in a Pharmacokinetic Study in Rats

Wang

Yuan

et al. 2020

Journal of Analytical Methods in Chemistry

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“…However, due to the limitation of this method, many previous researches usually collected TCM components from related TCM databases to establish the compound–target map. The candidate compounds might not be in line with the components actually delivered into the blood circulatory system, which unavoidably produced unreal results ( Ding et al, 2019 ; Zhang et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Integrated network pharmacology and molecular docking approaches to reveal the synergistic mechanism of multiple components in Venenum Bufonis for ameliorating heart failure

Ren

Luo

Pan

et al. 2020

PeerJ

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Venenum Bufonis (VB), also called Chan Su in China, has been extensively used as a traditional Chinese medicine (TCM) for treating heart failure (HF) since ancient time. However, the active components and the potential anti-HF mechanism of VB remain unclear. In the current study, the major absorbed components and metabolites of VB after oral administration in rats were first collected from literatures. A total of 17 prototypes and 25 metabolites were gathered. Next, a feasible network-based pharmacological approach was developed and employed to explore the therapeutic mechanism of VB on HF based on the collected constituents. In total, 158 main targets were screened out and considered as effective players in ameliorating HF. Then, the VB components–main HF putative targets–main pathways network was established, clarifying the underlying biological process of VB on HF. More importantly, the main hubs were found to be highly enriched in adrenergic signalling in cardio-myocytes. After verified by molecular docking studies, four key targets (ATP1A1, GNAS, MAPK1 and PRKCA) and three potential active leading compounds (bufotalin, cinobufaginol and 19-oxo-bufalin) were identified, which may play critical roles in cardiac muscle contraction. This study demonstrated that the integrated strategy based on network pharmacology and molecular docking was helpful to uncover the synergistic mechanism of multiple constituents in TCM.

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“…However, its pharmacological mechanisms are still unclear. Network pharmacology refers to the integrated analysis of a system biology network and pharmacology, which is in accordance with the core concept of the holistic philosophy of TCM, and provides insight into the detailed compound-target and target-pathway relationships of herbs used to treat complicated diseases [ 13 – 15 ]. Therefore, the pharmacological network of the QSBD TCM granule on CHD was investigated in this study to further uncover its potential targets and pathways.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Network Reveals the Active Mechanism of Qi‐Replenishing, Spleen‐Strengthening, Phlegm‐Dispelling, and Blood‐Nourishing Fufang on Coronary Heart Disease

Zhang

Liu

Zheng

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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This study aimed to investigate the potential targets and pathways of qi-replenishing, spleen-strengthening, phlegm-dispelling, and blood-nourishing Fufang in the treatment of coronary heart disease (CHD). The composition of Fufang was identified, followed by screening of the active components using ADME. The targets of active components were predicted and screened based on the TCMSP and BATMAN databases and were cross-validated using the CTD database and DisGeNET. A functional enrichment analysis was performed using the ClueGO + CluePedia plugins and clusterProfiler in the R package. The protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape. Finally, a pharmacological network was constructed. A total of 27 overlapping targets were obtained after cross-validation. ALB, IL-6, and TNF were the hub genes in the PPI network. The pharmacological network included 59 nodes and 189 relation pairs. Among the 59 nodes, there were 2 herbal medicine nodes (Salvia miltiorrhiza and Astragalus mongholicus), 8 chemical component nodes (magnesium lithospermate B, neocryptotanshinone II, heteratisine, daphneolone, tanshinone IIA, tanshinone IIB, soyasapogenol B, and astragaloside II), 27 target protein nodes (such as ALB, TNF, IL-6, NFKB1, APOA1, APOA2, CYP1A1, and CYP1A2), and 22 pathway nodes (such as the toll-like receptor signaling pathway, IL-17 signaling pathway, and TNF signaling pathway). Therefore, we found that the genes TNF, IL-6, NFKB1, ALB, CYP1A1, CYP1A2, APOA1, and APOA2 might be important targets of the key active compounds neocryptotanshinone II and astragaloside II. These genes targeted by the key active compounds might regulate inflammation-related pathways and the level of albumin and cholesterol in CHD.

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A network pharmacology integrated pharmacokinetics strategy for uncovering pharmacological mechanism of compounds absorbed into the blood of Dan-Lou tablet on coronary heart disease

Cited by 45 publications

References 22 publications

Simultaneous Determination of Multiple Active Components from Bushen Pills and Application in a Pharmacokinetic Study in Rats

Simultaneous Determination of Multiple Active Components from Bushen Pills and Application in a Pharmacokinetic Study in Rats

Integrated network pharmacology and molecular docking approaches to reveal the synergistic mechanism of multiple components in Venenum Bufonis for ameliorating heart failure

Pharmacological Network Reveals the Active Mechanism of Qi‐Replenishing, Spleen‐Strengthening, Phlegm‐Dispelling, and Blood‐Nourishing Fufang on Coronary Heart Disease

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