Research on Q-markers of Qiliqiangxin capsule for chronic heart failure treatment based on pharmacokinetics and pharmacodynamics association

Zhang, Fugeng; Yu, Zhang; Li, Xiaofeng; Zhang, Shaoqiang; Zhu, Min; Du, Wei; Xiao, Xuefeng

doi:10.1016/j.phymed.2018.03.003

Cited by 33 publications

(25 citation statements)

References 20 publications

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“…Moreover, quercetin and isorhamnetin can inhibit the PI3K/AKT signaling pathway activation to protect heart from cardiac hypertrophy and HF [27,28]. Study shows that calycosin and formononetin inhibit the activation of the renin-angiotensin-aldosterone system to improve the symptoms of HF [29]. Kaempferol plays a cardioprotective role by inhibiting Nrf2, NF-κB, and Akt/GSK-3β signaling pathways to reduce apoptosis [30].…”

Section: Discussionmentioning

confidence: 99%

Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology

Tao

Huang

Wang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Heart failure (HF), a clinical syndrome with a high incidence due to various reasons, is the advanced stage of most cardiovascular diseases. Huangqi is an effective treatment for cardiovascular disease, which has multitarget, multipathway functions. Therefore, we used network pharmacology to explore the molecular mechanism of Huangqi in treating HF. In this study, 21 compounds of Huangqi, which involved 407 targets, were obtained and reconfirmed using TCMSP and PubChem databases. Moreover, we used Cytoscape 3.7.1 to construct compound-target network and screened the top 10 compounds. 378 targets related to HF were obtained from CTD and GeneCards databases and HF-target network was constructed by Cytoscape 3.7.1. The 46 overlapping targets of HF and Huangqi were gotten by Draw Venn Diagram. STRING database was used to set up a protein-protein interaction network, and MCODE module and the top 5 targets with the highest degree for overlapping targets were obtained. GO analysis performed by Metascape indicated that the overlapping targets were mainly enriched in blood vessel development, reactive oxygen species metabolic process, response to wounding, blood circulation, and so on. KEGG analysis analyzed by ClueGO revealed that overlapping targets were mainly enriched in AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, c-type lectin receptor signaling pathway, relaxin signaling pathway, and so on. Finally, molecular docking showed that top 10 compounds of Huangqi also had good binding activities to important targets compared with digoxin, which was carried out in CB-Dock molecular docking server. In conclusion, Huangqi has potential effect on regulating overlapping targets and GE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, and so on to be a latent multitarget, multipathway treatment for HF.

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Section: Discussionmentioning

confidence: 99%

Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology

Tao

Huang

Wang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…QLQX is a Chinese patent medicine developed according to the theory of collateral disease. It has exhibited remarkable curative effect in clinical applications and holds the traditional functions of strengthening heart, diuresis and vasodilation [17,19,20,24]. Basic research shows that QLQX could restrain hypoxia-induced injury in primary rat cardiac microvascular endothelial cells via promoting glycolysis in a HIF-1a-dependent manner [27].…”

Section: Discussionmentioning

confidence: 99%

“…But there is a lack of scientific explanation on the mechanism of its effect. It has been reported QLQX could improves cardiac function and attenuates cardiac remodeling in rats with experimental myocardial infarction [18] .Recent studies have demonstrated the beneficial effects of QLQX on chronic heart failure [19], Shen S′ study also indicated that QLQX attenuates adverse cardiac remodeling after MI in ovariectomized mice via activation of PPARγ [20]. QLQX can also inhibit cardiomyocyte apoptosis on H9c2 cardiomyocytes [21].. Tao L also think QLQX warrants further investigation as a therapeutic intervention to mitigate remodeling and heart failure after AMI in mice [17].…”

Section: Introductionmentioning

confidence: 99%

Qiliqiangxin reduced cardiomyocytes apotosis and improved heart function in infarcted heart through Pink1/Parkin -mediated mitochondrial autophagy

Zhou

Wang

Luo

et al. 2020

BMC Complement Med Ther

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Background: Qiliqiangxin (QLQX) is a preparation refined from a traditional Chinese medicine compound. It plays an important role in protecting cardiac function after myocardial infarction (MI). However, the underline mechanism of QLQX action is not clear. The purpose of this study was to detect the effects of QLQX on mitophagy after MI. Methods: Male FVB/NJ mice aged 8-10 weeks were underwent left coronary artery ligation and were orally administered either QLQX (0.25 g/kg/d) or saline. Twenty-eight days after surgical operation, the cardiac function of mice was detected by echocardiography. Electron Microscopy was used to observe the microstructure of cardiomyocytes. Myocardial apoptosis was examined by TdT-mediated dUTP Nick-End Labeling (TUNEL) and western blot. H9c2 cells were cultured in a hypoxic incubator chamber (5% CO 2 , 1% O 2 , 94% N 2) for 12 h and pretreated with or without QLQX (0.5 mg/mL). The cell apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential and mitophagy were detected. Results: When compared to sham group, the cardiac function of MI mice decreased significantly, and their cardiomyocyte apoptosis and mitochondrial damage were more serious. These MI-induced cardiac changes could be reversed by QLQX treatment. In vitro experiments also confirmed that QLQX could protect cardiomyocytes from hypoxia-induced apoptosis and mitochondrial damage. Further study indicated that QLQX could increase the expression of Pink1 and Parkin in cardiomyocytes. Conclusion: Qiliqiangxin could reduce cardiomyocytes apotosis and improved heart function in infarcted heart through Pink1-mediated mitochondrial autophagy.

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“…High-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) analysis (Shimadzu Co., Japan) was performed to assess the pharmacokinetic properties of 29 components in QLQX according to the method described in our previous study (Zhang et al, 2018). Briefly, chromatographic separation was achieved on an Agilent ZOBRAX XDB-C 18 column (4.6 mm × 50 mm, 3.5 µm) maintained at 40°C.…”

Section: Methodsmentioning

confidence: 99%

“…Then, the whole blood was centrifuged at 12,000 rpm for 10 min, the supernatant was obtained, and stored at −80°C until analysis. The preparation of blood samples was conducted according to our previous research (Zhang et al, 2018). This study was carried out in accordance with the principles of the Basel Declaration and recommendations of guidelines of the National Institutes of Health.…”

Section: Methodsmentioning

confidence: 99%

Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure

Zhu

Zhang

et al. 2019

Front. Pharmacol.

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Objectives: The purpose of this study was to propose an integrated strategy for investigating the mechanism of Qiliqiangxin capsule (QLQX) to treat chronic heart failure (CHF). Methods: Pharmacokinetics analysis was performed to screen the active components of QLQX using high-performance liquid chromatography–tandem mass spectrometry techniques. We then constructed the component–target network between the targets of active components in QLQX and CHF using Cytoscape. A network analysis, including topological parameters, clustering, and pathway enrichment, was established to identify the hub targets and pathways. Finally, some of the predicted hub targets were validated experimentally in human cardiac microvascular endothelial cell (HCMEC). Results: We identified 29 active components in QLQX, and 120 consensus potential targets were determined by the pharmacokinetics analysis and network pharmacology approach. Further network analysis indicated that 6 target genes, namely, VEGFA, CYP1A1, CYP2B6, ATP1A1, STAT3, and STAT4, and 10 predicted functional genes, namely, KDR, FLT1, NRP2, JAK2, EGFR, IL-6, AHR, ATP1B1, JAK1, and HIF1A, may be the primary targets regulated by QLQX for the treatment of CHF. Among these targets, VEGFA, IL-6, p-STAT3, and p-JAK2 were selected for validation in the HCMEC. The results indicated that QLQX may inhibit inflammatory processes and promote angiogenesis in CHF via the JAK/STAT signaling pathway. Conclusions: This study provides a strategy for understanding the mechanism of QLQX against CHF by combining pharmacokinetics study, network pharmacology, and experimental validation.

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Research on Q-markers of Qiliqiangxin capsule for chronic heart failure treatment based on pharmacokinetics and pharmacodynamics association

Cited by 33 publications

References 20 publications

Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology

Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology

Qiliqiangxin reduced cardiomyocytes apotosis and improved heart function in infarcted heart through Pink1/Parkin -mediated mitochondrial autophagy

Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure

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