Identification of Pharmacokinetic Markers for Guanxin Danshen Drop Pills in Rats by Combination of Pharmacokinetics, Systems Pharmacology, and Pharmacodynamic Assays.

Abstract:

:This paper reported a feasibility study strategy of identifying pharmacokinetic (PK) markers for a cardiovascular herbal medicine, Guanxin Danshen drop pill (GDDP). First, quantification analysis revealed the constituent composition in the preparation by high-performance liquid chromatography (HPLC). Subsequently, physiochemical property calculation predicted the solubility and intestinal permeability of the constituents in the preparation. Furthermore, HPLC-MS analysis ascertained the absorbable ingredients and their PK properties in rat plasma. The main effective substances from the ingredients absorbed into blood and their cardiovascular effects were also predicted by systems pharmacology study, and were further confirmed by in vivo protective effects on isoprenaline-induced myocardial injury in mice. Finally, the ingredients with high content, representative structure feature, favorable PK properties, high relevant degree to myocardial ischemia (MI) issues, and validated therapeutic effects were considered as the PK markers for the preparation. Ginsenosides Rg1, Rb1, and tanshinone (TS) IIA were identified originally as PK markers for representing PK properties of GDDP. In addition, integrated PK studies were carried out according to previous reports, viz. drug concentration sum method and the AUC weighting method, to understand the in vivo process of GDDP comprehensively. The present study maybe provide a reference approach to identify PK markers for cardiovascular herbal medicines.

journal_name

Front Pharmacol

authors

Yao H,Huang X,Xie Y,Huang X,Ruan Y,Lin X,Huang L,Shi P

doi

10.3389/fphar.2018.01493

subject

Has Abstract

pub_date

2018-12-21 00:00:00

pages

1493

issn

1663-9812

journal_volume

9

pub_type

杂志文章
  • Akt Regulated Phosphorylation of GSK-3β/Cyclin D1, p21 and p27 Contributes to Cell Proliferation Through Cell Cycle Progression From G1 to S/G2M Phase in Low-Dose Arsenite Exposed HaCat Cells.

    abstract::Arsenic is a toxic environmental contaminant. Long-term exposure to arsenic through drinking water induces human cancers. However, it is as yet uncertain about the mechanisms of arsenic induced carcinogenesis. Although the effects of low-dose arsenicals on proliferation and cell cycle have been revealed by short time ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.01176

    authors: Chen Y,Liu X,Wang H,Liu S,Hu N,Li X

    更新日期:2019-10-11 00:00:00

  • Convenience versus Biological Significance: Are PMA-Differentiated THP-1 Cells a Reliable Substitute for Blood-Derived Macrophages When Studying in Vitro Polarization?

    abstract::Human peripheral-blood monocytes are used as an established in vitro system for generating macrophages. For several reasons, monocytic cell lines such as THP-1 have been considered as a possible alternative. In view of their distinct developmental origins and phenotypic attributes, we set out to assess the extent to w...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00071

    authors: Tedesco S,De Majo F,Kim J,Trenti A,Trevisi L,Fadini GP,Bolego C,Zandstra PW,Cignarella A,Vitiello L

    更新日期:2018-02-22 00:00:00

  • Inhibition of Soluble Epoxide Hydrolase Limits Mitochondrial Damage and Preserves Function Following Ischemic Injury.

    abstract:AIMS:Myocardial ischemia can result in marked mitochondrial damage leading to cardiac dysfunction, as such identifying novel mechanisms to limit mitochondrial injury is important. This study investigated the hypothesis that inhibiting soluble epoxide hydrolase (sEH), responsible for converting epoxyeicosatrienoic acids...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2016.00133

    authors: Akhnokh MK,Yang FH,Samokhvalov V,Jamieson KL,Cho WJ,Wagg C,Takawale A,Wang X,Lopaschuk GD,Hammock BD,Kassiri Z,Seubert JM

    更新日期:2016-06-07 00:00:00

  • Rationale for COVID-19 Treatment by Nebulized Interferon-β-1b-Literature Review and Personal Preliminary Experience.

    abstract::The inflammatory response to COVID-19 is specifically associated with an impaired type I interferon (IFN) response and complete blockade of IFN-β secretion. Clinically, nebulization of IFN-α-2b has been historically used in China to treat viral pneumonia associated with SARS-CoV. Very recent data show that the use of ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.592543

    authors: Mary A,Hénaut L,Macq PY,Badoux L,Cappe A,Porée T,Eckes M,Dupont H,Brazier M

    更新日期:2020-11-30 00:00:00

  • Anti-Proliferative and Apoptosis-Inducing Effect of Theabrownin against Non-small Cell Lung Adenocarcinoma A549 Cells.

    abstract::With the highest cancer incidence rate, lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer death in the world. Tea (leaves of Camellia sinensis) has been widely used as a traditional beverage beneficial to human health, including anti-NSCLC activity. Theabrownin (TB) is one majo...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2016.00465

    authors: Wu F,Zhou L,Jin W,Yang W,Wang Y,Yan B,Du W,Zhang Q,Zhang L,Guo Y,Zhang J,Shan L,Efferth T

    更新日期:2016-12-02 00:00:00

  • N-n-butyl Haloperidol Iodide Protects against Hypoxia/Reoxygenation Injury in Cardiac Microvascular Endothelial Cells by Regulating the ROS/MAPK/Egr-1 Pathway.

    abstract::Endothelium dysfunction induced by reactive oxygen species (ROS) is an important initial event at the onset of myocardial ischemia/reperfusion in which the Egr-1 transcription factor often serves as a master switch for various damage pathways following reperfusion injury. We hypothesized that an intracellular ROS/MAPK...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2016.00520

    authors: Lu S,Zhang Y,Zhong S,Gao F,Chen Y,Li W,Zheng F,Shi G

    更新日期:2017-01-05 00:00:00

  • CTRP5-Overexpression Attenuated Ischemia-Reperfusion Associated Heart Injuries and Improved Infarction Induced Heart Failure.

    abstract::Aims: C1q/tumor necrosis factor (TNF)-related protein 5 (CTRP5) belongs to the C1q/TNF-α related protein family and regulates glucose, lipid metabolism, and inflammation production. However, the roles of CTRP5 in ischemia/reperfusion (I/R) associated with cardiac injuries and heart failure (HF) needs to be elaborated....

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.603322

    authors: Peng M,Liu Y,Zhang XQ,Xu YW,Zhao YT,Yang HB

    更新日期:2020-12-22 00:00:00

  • Parecoxib Shortens the Duration of Acute Postoperative Pain After Laparoscopic-Assisted Vaginal Hysterectomy.

    abstract::The effect of parecoxib sodium on the duration and severity of acute postoperative pain after laparoscopic-assisted vaginal hysterectomy has been inadequately studied. This randomized, controlled trial compared the effects of parecoxib, methylprednisolone, and placebo on the duration of acute postoperative pain after ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.00689

    authors: Yang S,Xiao W,Wang S,Meng L,Zhou L,Wan A,Liu Y,Feng S,Wang T

    更新日期:2019-06-18 00:00:00

  • History of innate immunity in neurodegenerative disorders.

    abstract::The foundations of innate immunity in neurodegenerative disorders were first laid by Del Rio Hortega (1919). He identified and named microglia, recognizing them as cells of mesodermal origin. Van Furth in 1969 elaborated the monocyte phagocytic system with microglia as the brain representatives. Validation of these co...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2011.00077

    authors: McGeer PL,McGeer EG

    更新日期:2011-12-02 00:00:00

  • Orally Administered Koumine Persists Longer in the Plasma of Aged Rats Than That of Adult Rats as Assessed by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.

    abstract::Aging leads to changes in nearly all pharmacokinetic phases. Koumine (KM), an alkaloid derived from Gelsemium elegans Benth., is effective against age-associated chronic diseases, but its dose proportionality following oral administration in aged individuals remains unknown. Herein, we established and validated a simp...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.01113

    authors: Ye LX,Xu Y,Zhang SH,Cao DX,Chen LF,Su YP,Huang HH,Yu CX

    更新日期:2020-07-21 00:00:00

  • MiR-3188 Inhibits Non-small Cell Lung Cancer Cell Proliferation Through FOXO1-Mediated mTOR-p-PI3K/AKT-c-JUN Signaling Pathway.

    abstract::This study investigated the role of miR-3188 on the proliferation of non-small cell lung cancer cells and its relationship to FOXO1-modulated feedback loop. Two non-small cell lung cancer (NSCLC) cell lines A549 and H1299 were used. RNA silencing was achieved by lentiviral transfection. Cell proliferation was assessed...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.01362

    authors: Wang C,Liu E,Li W,Cui J,Li T

    更新日期:2018-12-11 00:00:00

  • Altered Expression of Endoplasmic Reticulum Stress Associated Genes in Hippocampus of Learned Helpless Rats: Relevance to Depression Pathophysiology.

    abstract::The unfolded protein response (UPR) is an evolutionarily conserved defensive mechanism that is used by cells to correct misfolded proteins that accumulate in the endoplasmic reticulum. These proteins are misfolded as a result of physical stress on a cell and initiate a host of downstream effects that govern processes ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2015.00319

    authors: Timberlake MA 2nd,Dwivedi Y

    更新日期:2016-01-12 00:00:00

  • Microalgae as Potential Anti-Inflammatory Natural Product Against Human Inflammatory Skin Diseases.

    abstract::The skin is the first line of defense against pathogen and other environmental pollutant. The body is constantly exposed to reactive oxygen species (ROS) that stimulates inflammatory process in the skin. Many studies have linked ROS to various inflammatory skin diseases. Patients with skin diseases face various challe...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2020.01086

    authors: Choo WT,Teoh ML,Phang SM,Convey P,Yap WH,Goh BH,Beardall J

    更新日期:2020-07-31 00:00:00

  • Trends and Development in Enteral Nutrition Application for Ventilator Associated Pneumonia: A Scientometric Research Study (1996-2018).

    abstract::Background: This study aimed to explore the intellectual landscape of the studies investigating the clinical application of enteral nutrition (EN) in patients with ventilator associated pneumonia (VAP), and to identify thematic development trends and research frontiers in this area. Methods: Scientometric research was...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.00246

    authors: Chen S,Bie R,Lai Y,Shi H,Ung COL,Hu H

    更新日期:2019-03-20 00:00:00

  • Acinetobacter baumannii Ventilator-Associated Pneumonia: Clinical Efficacy of Combined Antimicrobial Therapy and in vitro Drug Sensitivity Test Results.

    abstract::Objective: To evaluate therapeutic efficacy of different combined antimicrobial treatments against Acinetobacter baumannii ventilator-associated pneumonia (VAP). Methods: Clinical outcomes were retrospectively analyzed to elucidate the efficacy of four combined antimicrobial regimens. The chessboard and micro broth di...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.00092

    authors: Huang Y,Zhou Q,Wang W,Huang Q,Liao J,Li J,Long L,Ju T,Zhang Q,Wang H,Xu H,Tu M

    更新日期:2019-02-13 00:00:00

  • Krukovine Suppresses KRAS-Mutated Lung Cancer Cell Growth and Proliferation by Inhibiting the RAF-ERK Pathway and Inactivating AKT Pathway.

    abstract::Oncogenic activation of the KRAS gene via point mutations occurs in 20-30% of patients with non-small cell lung cancer (NSCLC). The RAS-RAF-ERK and RAS-PI3K-AKT pathways are the major hyper-activated downstream pathways in RAS mutation, which promotes the unlimited lifecycle of cancer cells and their metastasis in hum...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00958

    authors: Lai H,Wang Y,Duan F,Li Y,Jiang Z,Luo L,Liu L,Leung ELH,Yao X

    更新日期:2018-08-22 00:00:00

  • MiR-409-3p Inhibits Cell Proliferation and Invasion of Osteosarcoma by Targeting Zinc-Finger E-Box-Binding Homeobox-1.

    abstract::Osteosarcoma (OS) is the most common bone cancer worldwide. There is evidence that microRNA-409 (miR-409-3p) is involved in tumorigenesis and cancer progression, however, its possible role in OS requires clarification. In the present study, we evaluated the expression level, clinical significance, and mode of action o...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.00137

    authors: Wu L,Zhang Y,Huang Z,Gu H,Zhou K,Yin X,Xu J

    更新日期:2019-02-21 00:00:00

  • Simvastatin Enhances Activity and Trafficking of α7 Nicotinic Acetylcholine Receptor in Hippocampal Neurons Through PKC and CaMKII Signaling Pathways.

    abstract::Simvastatin (SV) enhances glutamate release and synaptic plasticity in hippocampal CA1 region upon activation of α7 nicotinic acetylcholine receptor (α7nAChR). In this study, we examined the effects of SV on the functional activity of α7nAChR on CA1 pyramidal cells using patch-clamp recording and explored the underlyi...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00362

    authors: Chen T,Wang Y,Zhang T,Zhang B,Chen L,Zhao L,Chen L

    更新日期:2018-04-12 00:00:00

  • Therapeutic Potential of Exosomes in Pulmonary Fibrosis.

    abstract::Pulmonary fibrosis is closely associated with the recruitment of fibroblasts from capillary vessels with damaged endothelial cells, the epithelial mesenchymal transition (EMT) of type II alveolar epithelial cells, and the transformation of fibroblasts to myofibroblasts. Recent studies suggest that EMT is a key factor ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2020.590972

    authors: Xie L,Zeng Y

    更新日期:2020-12-04 00:00:00

  • Salidroside Promotes the Pathological α-Synuclein Clearance Through Ubiquitin-Proteasome System in SH-SY5Y Cells.

    abstract::Parkinson's disease (PD) is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the presence of Lewy bodies (LBs) in the surviving SNc neurons. LBs formation is caused by the accumulation of α-synuclein (α-syn) or phosphorylated α-syn at serine-129 (pSer129-α-syn), wh...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00377

    authors: Li T,Feng Y,Yang R,Wu L,Li R,Huang L,Yang Q,Chen J

    更新日期:2018-04-19 00:00:00

  • Inhibition of Neutrophil Functions and Antibacterial Effects of Tarragon (Artemisia dracunculus L.) Infusion-Phytochemical Characterization.

    abstract::The aim of the study was to characterize phytochemicals in an infusion of the aerial parts of tarragon (Artemisia dracunculus L.) using ultra-high-performance liquid chromatography diode array detector electrospray ionisation tandem mass spectrometry UHPLC-DAD-ESI-MS/MS method, as well as an evaluation of its effects ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.00947

    authors: Majdan M,Kiss AK,Hałasa R,Granica S,Osińska E,Czerwińska ME

    更新日期:2020-08-13 00:00:00

  • Semen cassiae Extract Inhibits Contraction of Airway Smooth Muscle.

    abstract::β2-adrenoceptor agonists are commonly used as bronchodilators to treat obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), however, they induce severe side effects. Therefore, developing new bronchodilators is essential. Herbal plants were extracted and the extracts' effect on ai...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.01389

    authors: She YS,Ma LQ,Liu BB,Zhang WJ,Qiu JY,Chen YY,Li MY,Xue L,Luo X,Wang Q,Xu H,Zang DA,Zhao XX,Cao L,Shen J,Peng YB,Zhao P,Yu MF,Chen W,Nie X,Shen C,Chen S,Chen S,Qin G,Dai J,Chen J,Liu QH

    更新日期:2018-12-04 00:00:00

  • Increased Levels of miRNA-146a in Serum and Histologic Samples of Patients with Uveal Melanoma.

    abstract::Purpose: To analyze MiRs expression in serum of UM patients, respect to healthy donors, and to compare this data with MiRs expressed in formalin-fixed, paraffin-embedded UM samples. Methods: Expression profile of 754 miRNAs was performed in serum of patients with uveal melanoma who underwent primary enucleation. The l...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2016.00424

    authors: Russo A,Caltabiano R,Longo A,Avitabile T,Franco LM,Bonfiglio V,Puzzo L,Reibaldi M

    更新日期:2016-11-15 00:00:00

  • Inhibition of P-Glycoprotein and Multidrug Resistance-Associated Protein 2 Regulates the Hepatobiliary Excretion and Plasma Exposure of Thienorphine and Its Glucuronide Conjugate.

    abstract::Thienorphine (TNP) is a novel partial opioid agonist that has completed phase II clinical evaluation as a promising drug candidate for the treatment of opioid dependence. Previous studies have shown that TNP and its glucuronide conjugate (TNP-G) undergo significant bile excretion. The purpose of this study was to inve...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2016.00242

    authors: Kong LL,Shen GL,Wang ZY,Zhuang XM,Xiao WB,Yuan M,Gong ZH,Li H

    更新日期:2016-08-09 00:00:00

  • Ubc9 Attenuates Myocardial Ischemic Injury Through Accelerating Autophagic Flux.

    abstract:Aims:SUMOylation is a post-translational modification that plays a crucial role in the cellular stress response. We aimed to demonstrate whether and how the SUMO E2 conjugation enzyme Ubc9 affects acute myocardial ischemic (MI) injury. Methods and Results:Adenovirus expressing Ubc9 was administrated by multipoint inje...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.561306

    authors: Xiao Q,Chen XH,Jiang RC,Chen SY,Chen KF,Zhu X,Zhang XL,Huang JJ,Qin Y,Zhang GP,Yi Q,Luo JD

    更新日期:2020-09-15 00:00:00

  • OSU-2S/Sorafenib Synergistic Antitumor Combination against Hepatocellular Carcinoma: The Role of PKCδ/p53.

    abstract::Background: Sorafenib (Nexavar®) is an FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC). However, the low efficacy and adverse effects at high doses limit the clinical application of sorafenib and strongly recommend its combination with other agents aiming at ameliorating its drawbacks. OSU-2S...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2016.00463

    authors: Omar HA,Tolba MF,Hung JH,Al-Tel TH

    更新日期:2016-11-30 00:00:00

  • Transcriptome Profiling and Cytological Assessments for Identifying Regulatory Pathways Associated With Diorcinol N-Induced Autophagy in A3 Cells.

    abstract::Fungal secondary metabolites serve as a rich resource for exploring lead compounds with medicinal importance. Diorcinol N (DN), a fungal secondary metabolite isolated from an endophytic fungus, Arthrinium arundinis, exhibits robust anticancer activity. However, the anticancer mechanism of DN remains unclear. In this s...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.570450

    authors: Yuan XL,Li XQ,Xu K,Hou XD,Zhang ZF,Xue L,Liu XM,Zhang P

    更新日期:2020-10-15 00:00:00

  • Eriodictyol Attenuates Myocardial Ischemia-Reperfusion Injury through the Activation of JAK2.

    abstract::Myocardial ischemia-reperfusion (I/R) injury remains the leading risk factor of disability and mortality worldwide. In this study, the myocardial protective effect of eriodictyol (EDT) and the underlying mechanism in an ex vivo model of global myocardial I/R was investigated. After treatment with different concentrati...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00033

    authors: Li D,Lu N,Han J,Chen X,Hao W,Xu W,Liu X,Ye L,Zheng Q

    更新日期:2018-01-30 00:00:00

  • Chymase Inhibitor as a Novel Therapeutic Agent for Non-alcoholic Steatohepatitis.

    abstract::Non-alcoholic steatohepatitis (NASH) is characterized by inflammation and fibrosis, in addition to steatosis, of the liver, but no therapeutic agents have yet been established. The mast cell protease chymase can generate angiotensin II, matrix metalloproteinase-9 and transforming growth factor-β, all of which are asso...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2018.00144

    authors: Takai S,Jin D

    更新日期:2018-02-21 00:00:00

  • Aflatoxin B1 Degradation and Detoxification by Escherichia coli CG1061 Isolated From Chicken Cecum.

    abstract::Aflatoxin B1 (AFB1) is one of the most hazardous mycotoxins contamination in food and feed products, which leads to hepatocellular carcinoma in humans and animals. In the present study, we isolated and characterized an AFB1 degrading bacteria CG1061 from chicken cecum, exhibited an 93.7% AFB1 degradation rate by HPLC....

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.01548

    authors: Wang L,Wu J,Liu Z,Shi Y,Liu J,Xu X,Hao S,Mu P,Deng F,Deng Y

    更新日期:2019-01-17 00:00:00