Network Pharmacology-Guided Development of a Novel Integrative Regimen to Prevent Acute Graft-vs.-Host Disease.


:Lapses in the graft-vs.-host disease (GVHD) prophylaxis and side effects of current standard care following allogeneic hematopoietic stem cell transplantation (allo-HSCT) call for novel regimens. Traditional approaches targeting T cells showed limited success in preventing acute GVHD (aGVHD). System medicine showed promising results treating complex diseases such as sepsis and multi-organ dysfunction syndrome (MODS). Adapting established network pharmacology analysis methods, we aimed to develop novel integrative regimens to prevent aGVHD. Our network pharmacology analysis predicted that Xuebijing injection (XBJ) targets a series of key node proteins in aGVHD network. It also unveiled that Salviae miltiorrhizae (Danshen), an herb in Xuebijing formula, which prevented aGVHD in rats, shares five out of six key GVHD node proteins targeted by XBJ. Interestingly, network pharmacology analysis indicated Xuebijing may share multiple aGVHD targets with Cyclosporin A (CsA), a first-line drug for preventing aGVHD in the clinic. Based on current information, we hypothesized that combination of XBJ and CsA may yield superior results in aGVHD prevention than either drug alone. We performed in vitro and in vivo assays to validate the predictions by the network pharmacology analysis. In vitro assays revealed XBJ prevented platelet aggregation and NF-κB nuclear translocation in macrophages. XBJ also promoted angiogenesis in tube-formation assay. Importantly, the combination of CsA and XBJ was effective in rescuing mice subjected to lethal GVHD. XBJ contributed to the rescue through preventing NF-κB nuclear translocation, attenuating inflammation and maintaining viability of macrophages. Overall, network pharmacology is a powerful tool to develop novel integrative regimens. Combination of XBJ and CsA may shed light on preventing aGVHD.


Front Pharmacol


Lyu M,Zhou Z,Wang X,Lv H,Wang M,Pan G,Wang Y,Fan G,Gao X,Feng Y,Zhu Y




Has Abstract


2018-12-13 00:00:00








  • The Reproductive Toxicity of Mequindox in a Two-Generation Study in Wistar Rats.

    abstract::Mequindox (MEQ), belonging to quinoxaline-di-N-oxides (QdNOs), has been extensively used as a synthetic antibacterial agent. To evaluate the reproductive toxicity of MEQ, different concentrations of MEQ were administered to Wistar rats by feeding diets containing 0, 25, 55, 110, and 275 mg/kg, respectively. Each group...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Liu Q,Lei Z,Wu Q,Awais I,Shabbir MAB,Ahmed S,Fatima Z,Wang X,Pan Y,Xie S,Yuan Z

    更新日期:2018-08-17 00:00:00

  • A Preliminary, Multicenter, Prospective and Real World Study on the Hemostasis, Coagulation, and Safety of Hemocoagulase Bothrops Atrox in Patients Undergoing Transurethral Bipolar Plasmakinetic Prostatectomy.

    abstract::Objective: To evaluate the hemostasis and coagulation effect of Hemocoagulase Bothrops Atrox in benign prostatic hyperplasia (BPH) patients undergoing transurethral bipolar plasmakinetic prostatectomy (TUPKP). Methods: This study adopted a multicenter, prospective, and real world design. BPH patients undergoing TUPKP ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Li BH,Yu ZJ,Wang CY,Zi H,Li XD,Wang XH,Ren XY,Liu TZ,Zheng H

    更新日期:2019-11-27 00:00:00

  • Antibacterial Properties of Medicinal Plants From Pakistan Against Multidrug-Resistant ESKAPE Pathogens.

    abstract::Local people in the Sudhnoti district of Pakistan share a rich practice of traditional medicine for the treatment of a variety of ailments. We selected nine plants from the Sudhnoti ethnopharmacological tradition used for the treatment of infectious and inflammatory disease. Our aim was to evaluate the in vitro anti-i...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Khan MF,Tang H,Lyles JT,Pineau R,Mashwani ZU,Quave CL

    更新日期:2018-08-02 00:00:00

  • Targeted Delivery of Curcumin to Polyethylene-Induced Osteolysis by Magnetically Guided Zoledronate-Anchored Poly Lactic-Co-Glycolic Acid Nanoparticles via Repressing NF-κB Signaling.

    abstract::Aseptic loosening induced by periprosthetic osteolysis (PPO) is the leading complication of total joint arthroplasty (TJA) and results in patients having to receive revision surgery. However, there is still no efficient drug to prevent or even slow the pathological process. Herein, we report novel dual-targeted, curcu...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Li J,Niu C,Jiang Z,Zhang Z,Pan Y,Xing Q,Guo Q,An S,Hu Y,Wang L

    更新日期:2020-12-04 00:00:00

  • Emerging microRNA Therapeutic Approaches for Cystic Fibrosis.

    abstract::Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and remains the most common life-shortening diseases affecting the exocrine organs. The absence of this channel results in an imbalance of ion concentrations across the cell membrane and results in more a...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Bardin P,Sonneville F,Corvol H,Tabary O

    更新日期:2018-10-08 00:00:00

  • Chidamide Inhibits Acute Myeloid Leukemia Cell Proliferation by lncRNA VPS9D1-AS1 Downregulation via MEK/ERK Signaling Pathway.

    abstract::Irregular histone modification and aberrant lncRNAs expression are closely related to the occurrence of tumors including acute myeloid leukemia (AML). However, the effects and specific underlying molecular mechanism of histone deacetylase inhibitors on lncRNA expression in AML cells are unclear. Here, we reported the ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Lin L,Que Y,Lu P,Li H,Xiao M,Zhu X,Li D

    更新日期:2020-10-19 00:00:00

  • A Pharmacological Overview of Alpinumisoflavone, a Natural Prenylated Isoflavonoid.

    abstract::Over the last decade, several studies demonstrated that prenylation of flavonoids enhances various biological activities as compared to the respective nonprenylated compounds. In line with this, the natural prenylated isoflavonoid alpinumisoflavone (AIF) has been explored for a number of biological and pharmacological...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Ateba SB,Mvondo MA,Djiogue S,Zingué S,Krenn L,Njamen D

    更新日期:2019-09-10 00:00:00

  • Thioredoxin Delays Photoreceptor Degeneration, Oxidative and Inflammation Alterations in Retinitis Pigmentosa.

    abstract::Retinitis pigmentosa (RP) is an inherited ocular disorder with no effective treatment. RP onset and progression trigger a cascade of retinal disorders that lead to the death of photoreceptors. After photoreceptors death, neuronal, glial and vascular remodeling can be observed in the retina. The purpose of this study w...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Gimeno-Hernández R,Cantó A,Fernández-Carbonell A,Olivar T,Hernández-Rabaza V,Almansa I,Miranda M

    更新日期:2020-12-23 00:00:00

  • Sodium New Houttuyfonate Affects Transcriptome and Virulence Factors of Pseudomonas aeruginosa Controlled by Quorum Sensing.

    abstract::As a major opportunistic pathogen, Pseudomonas aeruginosa can produce various virulence factors and form biofilms. These processes are controlled by the quorum sensing (QS) system. Sodium new houttuyfonate (SNH) is an adduct of houttuyfonate, the main component of the common Chinese medicine plant Houttuynia cordata, ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Zhao Y,Mei L,Si Y,Wu J,Shao J,Wang T,Yan G,Wang C,Wu D

    更新日期:2020-10-02 00:00:00

  • Oroxyloside A Overcomes Bone Marrow Microenvironment-Mediated Chronic Myelogenous Leukemia Resistance to Imatinib via Suppressing Hedgehog Pathway.

    abstract::Imatinib (IM), as first inhibitor of the oncogenic tyrosine kinase BCR-ABL, has been widely used to treat chronic myeloid leukemia (CML) for decades in clinic. However, resistance to IM usually occurs in CML patients. The bone marrow (BM), as the predominant microenvironment of CML, secretes an abundant amount of cyto...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Zhang X,Liu Y,Lu L,Huang S,Ding Y,Zhang Y,Guo Q,Li Z,Zhao L

    更新日期:2017-08-11 00:00:00

  • Risk of Upper Gastrointestinal Bleeding in a Cohort of New Users of Low-Dose ASA for Secondary Prevention of Cardiovascular Outcomes.

    abstract::The Health Improvement Network UK primary care database was used to identify a cohort of 38 077 individuals aged 50-84 years with a first prescription of low-dose acetylsalicylic acid (ASA; 75-300 mg/day) for secondary prevention of cardiovascular or cerebrovascular events during 2000-2007. From this cohort, 169 incid...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Cea Soriano L,Rodríguez LA

    更新日期:2010-10-14 00:00:00

  • Pharmacokinetics and Metabolite Profiling of Trepibutone in Rats Using Ultra-High Performance Liquid Chromatography Combined With Hybrid Quadrupole-Orbitrap and Triple Quadrupole Mass Spectrometers.

    abstract::Trepibutone was widely used for cholelithiasis, cholecystitis, biliary tract dyskinesia, cholecystectomy syndrome, and chronic pancreatitis in clinic. However, few investigations on trepibutone have been conducted. In this study, an accurate, sensitive, and selective analytical method was developed and successfully ap...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Sun Z,Yang J,Liu L,Xu Y,Zhou L,Jia Q,Shi Y,Du X,Kang J,Zuo L

    更新日期:2019-11-04 00:00:00

  • Drugs for Autoimmune Inflammatory Diseases: From Small Molecule Compounds to Anti-TNF Biologics.

    abstract::Although initially described as an anti-tumor mediator, tumor necrosis factor-alpha (TNF) is generally considered as the master pro-inflammatory cytokine. It plays a crucial role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, ankylosing spondylitis (AS), an...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Li P,Zheng Y,Chen X

    更新日期:2017-07-12 00:00:00

  • A Significant Association Between Rhein and Diabetic Nephropathy in Animals: A Systematic Review and Meta-Analysis.

    abstract::Background: Rhein is considered to have beneficial influence on diabetic nephropathy. Animal experiments suggested that the mechanisms of rhein against diabetic nephropathy may involve many processes, but the credibility of the evidence is unclear. Therefore, we conducted systematic review and meta-analysis of pre-cli...

    journal_title:Frontiers in pharmacology



    authors: Hu HC,Zheng LT,Yin HY,Tao Y,Luo XQ,Wei KS,Yin LP

    更新日期:2019-12-13 00:00:00

  • Alleviation of Synovial Inflammation of Juanbi-Tang on Collagen-Induced Arthritis and TNF-Tg Mice Model.

    abstract::Rheumatoid arthritis (RA) is a chronic autoimmune disease that is primarily characterized by synovial inflammation. In this study, we found that a traditional Chinese decoction, Juanbi-Tang (JBT), JBT attenuated the symptoms of collagen-induced arthritis (CIA) mice and in tumor necrosis factor transgenic (TNF-Tg) mice...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Wang T,Jia Q,Chen T,Yin H,Tian X,Lin X,Liu Y,Zhao Y,Wang Y,Shi Q,Huang C,Xu H,Liang Q

    更新日期:2020-02-14 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


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

    更新日期:2020-08-13 00:00:00

  • The Effect of Glycemic Control on Endothelial and Cardiac Dysfunction Induced by Red Blood Cells in Type 2 Diabetes.

    abstract::Red blood cells (RBCs) from patients with type 2 diabetes mellitus (T2DM) induce endothelial dysfunction and impair cardiac function following ischemia via increase in RBC arginase and oxidative stress. Here, we aimed to elucidate whether the effect of RBC-mediated cardiac impairment following ischemia and endothelial...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Mahdi A,Jiao T,Yang J,Kövamees O,Alvarsson M,von Heijne M,Zhou Z,Pernow J

    更新日期:2019-08-02 00:00:00

  • Human α-Defensin-5 Efficiently Neutralizes Clostridioides difficile Toxins TcdA, TcdB, and CDT.

    abstract::Infections with the pathogenic bacterium Clostridioides (C.) difficile are coming more into focus, in particular in hospitalized patients after antibiotic treatment. C. difficile produces the exotoxins TcdA and TcdB. Since some years, hypervirulent strains are described, which produce in addition the binary actin ADP-...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Korbmacher M,Fischer S,Landenberger M,Papatheodorou P,Aktories K,Barth H

    更新日期:2020-08-12 00:00:00

  • Antithrombotic Regimens in Patients With Percutaneous Coronary Intervention Whom an Anticoagulant Is Indicated: A Systematic Review and Network Meta-Analysis.

    abstract::Background: Patients undergoing percutaneous coronary intervention (PCI) who require anticoagulant therapy are at increased risk of bleeding. The optimal regimen for these patients is uncertain. This study aimed to compare safety and efficacy of antithrombotic regimens used in patients undergoing PCI with concomitant ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Bunmark W,Jinatongthai P,Vathesatogkit P,Thakkinstian A,Reid CM,Wongcharoen W,Chaiyakunapruk N,Nathisuwan S

    更新日期:2018-11-19 00:00:00

  • Salvianolic Acid B Inhibits Activation of Human Primary Hepatic Stellate Cells Through Downregulation of the Myocyte Enhancer Factor 2 Signaling Pathway.

    abstract::Various isoforms of myocyte enhancer factor 2 (MEF2) have been shown to play a role in the activation of rat hepatic stellate cells (HSCs) in culture. The signals that regulate MEF2 in HSCs are unknown. In addition, whether MEF2s regulate the activation of human HSCs (H-HSCs) is unclear. Here, we studied the expressio...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Zhang W,Ping J,Zhou Y,Chen G,Xu L

    更新日期:2019-04-11 00:00:00

  • Atorvastatin Inhibits Inflammatory Response, Attenuates Lipid Deposition, and Improves the Stability of Vulnerable Atherosclerotic Plaques by Modulating Autophagy.

    abstract::Atherosclerosis is a chronic disease comprising intima malfunction and arterial inflammation. Recent studies have demonstrated that autophagy could inhibit inflammatory response in atherosclerosis and exert subsequent atheroprotective effects. Our previous study also demonstrated the role of autophagy in the inhibitio...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Peng S,Xu LW,Che XY,Xiao QQ,Pu J,Shao Q,He B

    更新日期:2018-05-03 00:00:00

  • From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery.

    abstract::Animal poisons and venoms are comprised of different classes of molecules displaying wide-ranging pharmacological activities. This review aims to provide an in-depth view of toxin-based compounds from terrestrial and marine organisms used as diagnostic tools, experimental molecules to validate postulated therapeutic t...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Bordon KCF,Cologna CT,Fornari-Baldo EC,Pinheiro-Júnior EL,Cerni FA,Amorim FG,Anjolette FAP,Cordeiro FA,Wiezel GA,Cardoso IA,Ferreira IG,de Oliveira IS,Boldrini-França J,Pucca MB,Baldo MA,Arantes EC

    更新日期:2020-07-24 00:00:00

  • Antimutagenic and Chemopreventive Properties of 6-(Methylsulfinyl) Hexyl Isothiocyanate on TK6 Human Cells by Flow Cytometry.

    abstract::6-(methylsulfinyl) hexyl isothiocyanate (6-MITC), is the main bioactive compound present in Wasabia japonica rhizome. Several scientific studies have shown that 6-MITC possesses interesting antimicrobial, anti-inflammatory, antiplatelet and antioxidant properties which therefore suggested us it could have an interesti...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Cocchi V,Hrelia P,Lenzi M

    更新日期:2020-08-18 00:00:00

  • Corrigendum: Ginsenoside Rb1 Enhances Atherosclerotic Plaque Stability by Improving Autophagy and Lipid Metabolism in Macrophage Foam Cells.

    abstract::[This corrects the article on p. 727 in vol. 8, PMID: 29114222.]. ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,已发布勘误


    authors: Qiao L,Zhang X,Liu M,Liu X,Dong M,Cheng J,Zhang X,Zhai C,Song Y,Lu H,Chen W

    更新日期:2018-01-09 00:00:00

  • Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols.

    abstract::Postoperative ileus (POI) and postoperative gastrointestinal tract dysfunction (POGD) are well-known complications affecting patients undergoing intestinal surgery. GI symptoms include nausea, vomiting, pain, abdominal distention, bloating, and constipation. These iatrogenic disorders are associated with extended hosp...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审


    authors: Mazzotta E,Villalobos-Hernandez EC,Fiorda-Diaz J,Harzman A,Christofi FL

    更新日期:2020-11-24 00:00:00

  • Acteoside From Ligustrum robustum (Roxb.) Blume Ameliorates Lipid Metabolism and Synthesis in a HepG2 Cell Model of Lipid Accumulation.

    abstract::We aimed to ascertain the mechanism underlying the effects of acteoside (ACT) from Ligustrum robustum (Roxb.) Blume (Oleaceae) on lipid metabolism and synthesis. ACT, a water-soluble phenylpropanoid glycoside, is the most abundant and major active component of L. robustum; the leaves of L. robustum, known as kudingcha...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Sun L,Yu F,Yi F,Xu L,Jiang B,Le L,Xiao P

    更新日期:2019-05-24 00:00:00

  • Correlation of Proton Pump Inhibitors with Pulmonary Tuberculosis: A Case-Control Study in Taiwan.

    abstract::Background and Objectives: Although the relationship between the use of proton pump inhibitors (PPIs) and pulmonary tuberculosis (TB) in Taiwan published in 2014. Due to just only one article and not enough comprehensively, we explore this issue. Methods: We conducted a population-based case-control study to identify ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Cheng KC,Liao KF,Lin CL,Lai SW

    更新日期:2017-07-19 00:00:00

  • Validation and Psychometric Properties of the Arabic Version of the Duke Anticoagulation Satisfaction Scale (DASS).

    abstract::Background: To assess the health-related quality of life (HRQoL) of oral anticoagulant therapy users, different types of instruments are available, either general or specific tools like Duke Anticoagulation Satisfaction Scale (DASS). These tools allow the clinician to adjust the treatment regimen to focus on increasin...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: AlAmmari M,Sultana K,AlHarbi SN,Marenga AS,AlTuraiki A,Althemery AU,Alfaifi AA,AlShehri A,Aqeel BF

    更新日期:2020-12-17 00:00:00

  • Small Molecules, Inhibitors of DNA-PK, Targeting DNA Repair, and Beyond.

    abstract::Many current chemotherapies function by damaging genomic DNA in rapidly dividing cells ultimately leading to cell death. This therapeutic approach differentially targets cancer cells that generally display rapid cell division compared to normal tissue cells. However, although these treatments are initially effective i...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Davidson D,Amrein L,Panasci L,Aloyz R

    更新日期:2013-01-31 00:00:00

  • Activation of CXCL6/CXCR1/2 Axis Promotes the Growth and Metastasis of Osteosarcoma Cells in vitro and in vivo.

    abstract::Osteosarcoma (OS) is a malignant primary bone tumor with high metastatic rate. C-X-C motif chemokine ligand 6 (CXCL6) and its receptor C-X-C motif chemokine receptor 1/2 (CXCR1/2) have been found to participate in the process of carcinogenesis. In this study, we evaluated the role of CXCL6/CXCR1/2 axis in proliferatio...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章


    authors: Liu G,An L,Zhang H,Du P,Sheng Y

    更新日期:2019-03-28 00:00:00