C13 Megastigmane Derivatives From Epipremnum pinnatum: β-Damascenone Inhibits the Expression of Pro-Inflammatory Cytokines and Leukocyte Adhesion Molecules as Well as NF-κB Signaling
In order to identify active constituents and to gain some information regarding their mode of action, extracts from leaves of Epipremnum pinnatum were tested for their ability to inhibit inflammatory gene expression in endothelial- and monocyte-like cells (HUVECtert and THP-1, respectively). Bioactivity-guided fractionation using expression of PTGS2 (COX-2) mRNA as a readout resulted in the isolation of two C13 megastigmane glycosides, gusanlungionoside C (1) and citroside A (3), and the phenylalcohol glycoside phenylmethyl-2-O-(6-O-rhamnosyl)-ß-D-galactopyranoside (2). Further analysis identified six additional mega...
Source: Frontiers in Pharmacology - November 28, 2019 Category: Drugs & Pharmacology Source Type: research

Sleep Disorders in Rodent Models of Parkinson ’s Disease
Sleep disorders are frequently diagnosed in Parkinson’s disease and manifested in the prodromal and advanced stages of the disease. These conditions, which in some cases affect more than 50% of Parkinson’s disease (PD) patients, include hypersomnia, often manifested as excessive daytime sleepiness, insomnia, characterized by delayed initiation and fragmentation of sleep at night, and disruption of rapid eye movement (REM) sleep, resulting in loss of atonia and dream enactment. Standard dopamine replacement therapies for the treatment of motor symptoms are generally inadequate to combat sleep abnormalities, whic...
Source: Frontiers in Pharmacology - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

Effect of Bronchodilator and Steroid Use on Heart Disease and Stroke Risks in a Bronchiectasis –Chronic Obstructive Pulmonary Disease Overlap Cohort: A Propensity Score Matching Study
Conclusions: Compared with patients without bronchiectasis and COPD, BCOS patients with recent SABAs, past ICSs, and past anti-arrhythmia drugs use; a low or medium SABAs ICSs, and OSs dose; and a low SAMAs dose had a higher risk of HDS. LAMAs were not associated with HDS. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

Crataegus Extract WS ®1442 Stimulates Cardiomyogenesis and Angiogenesis From Stem Cells: A Possible New Pharmacology for Hawthorn?
Extracts from the leaves and flowers of Crataegus spp. (i.e., hawthorn species) have been traditionally used with documented preclinical and clinical activities in cardiovascular medicine. Based on reported positive effects on heart muscle after ischemic injury and the overall cardioprotective profile, the present study addressed potential contributions of Crataegus extracts to cardiopoietic differentiation from stem cells. The quantified Crataegus extract WS®1442 stimulated cardiomyogenesis from murine and human embryonic stem cells (ESCs). Mechanistically, this effect was found to be induced by promoting differenti...
Source: Frontiers in Pharmacology - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

Network Pharmacology-Based Prediction of Active Ingredients and Mechanisms of Lamiophlomis rotata (Benth.) Kudo Against Rheumatoid Arthritis
Conclusion: The active ingredients and mechanisms of LR against RA were firstly investigated using network pharmacology. This work provides scientific evidence to support the clinical effect of LR on RA, and a research basis for further expounding the active ingredients and mechanisms of LR against RA. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

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
This study adopted a multicenter, prospective, and real world design. BPH patients undergoing TUPKP were divided into two groups according to whether they adopted Hemocoagulase Bothrops Atrox (group B) or not (group A) during perioperative period. The electronic clinical data on every included subject, including the international prostate symptom score (IPSS) and the quality of life scale (QoL), maximum urinary flow rate (Qmax), complete blood count, coagulation screening test and adverse events, were measured and compared between the two groups.Results: Finally, 695 patients, 443 in group A and 252 in group B were include...
Source: Frontiers in Pharmacology - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

The Antimalarial Chloroquine Reduces the Burden of Persistent Atrial Fibrillation
In clinical practice, reducing the burden of persistent atrial fibrillation by pharmacological means is challenging. We explored if blocking the background and the acetylcholine-activated inward rectifier potassium currents (IK1 and IKACh) could be antiarrhythmic in persistent atrial fibrillation. We thus tested the hypothesis that blocking IK1 and IKACh with chloroquine decreases the burden of persistent atrial fibrillation. We used patch clamp to determine the IC50 of IK1 and IKACh block by chloroquine and molecular modeling to simulate the interaction between chloroquine and Kir2.1 and Kir3.1, the molecular correlates o...
Source: Frontiers in Pharmacology - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

Bazhu Decoction, a Traditional Chinese Medical Formula, Ameliorates Cognitive Deficits in the 5xFAD Mouse Model of Alzheimer ’s Disease
Alzheimer’s disease (AD) is the most common neurodegenerative disorder associated with aging. There are currently no effective treatments for AD. Bazhu decoction (BZD), a traditional Chinese medicine (TCM) formula, has been employed clinically to alleviate AD. However, the underlying molecular mechanisms are still unclear. Here we found that middle- and high-doses of BZD ameliorated the behavioral aspects of 5xFAD transgenic mice in elevated plus maze, Y maze and Morris water maze tests. Moreover, BZD reduced the protein levels of BACE1 and PS1, resulting in a reduction of Aβ plaques. We also identified a benefi...
Source: Frontiers in Pharmacology - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

Chemical Composition, Toxicity, Antinociceptive, and Anti-Inflammatory Activity of Dry Aqueous Extract of Varronia multispicata (Cham.) Borhidi (Cordiaceae) Leaves
Varronia multispicata (Cham.) Borhidi (Cordiaceae), an herbaceous plant distributed in tropical and subtropical regions is native of Brazil and widely used in folk medicine to treat respiratory and digestive diseases, inflammation, and some types of infections. Thus, this study aimed to investigate acute oral toxicity, antinociceptive, and anti-inflammatory activities of dry aqueous extract of V. multispicata (AEVm) and to identify its compounds. Extract was obtained by lyophilized leaf infusion and its composition was analyzed by ultra-performance liquid chromatography-high resolution mass spectrometry (LC-MS). Acute oral...
Source: Frontiers in Pharmacology - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

Reimbursement Status and Recommendations Related to Orphan Drugs in European Countries
Conclusions: On average, more than 60% of identified orphan drugs were reimbursed from public funds in the included countries, and the majority of reimbursement recommendations were found to be positive. The agreement between reimbursement recommendations and reimbursement status differed between the countries, but overall, it did not show any patterns, as it ranged from -0.03 to 1 (κ coefficient). (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

Pharmacodynamic Evaluation of Shenfu Injection in Rats With Ischemic Heart Failure and Its Effect on Small Molecules Using Matrix-Assisted Laser Desorption/Ionization –Mass Spectrometry Imaging
Conclusion: Shenfu injection induced obvious myocardial protective effects in rats with ischemic heart failure by stimulating antioxidation and changing the phospholipid levels and distribution. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Usefulness of Bnet, a Simple Linear Metric in Discerning Torsades De Pointes Risks in 28 CiPA Drugs
The Comprehensive in vitro Proarrhythmia Assay (CiPA) project suggested the torsade metric score (TMS) which requires substantial computing resources as a useful biomarker to predict proarrhythmic risk from human ether-à-go-go–related gene (hERG) and a few other ion channel block data. The TMS was useful to predict low TdP risks of drugs blocking Na+ (ranolazine) and Ca2+ (verapamil) channels as well as the hERG channel. However, Mistry asserted that the simple linear metric, Bnet reflecting net blockade of a few influential ion channels has similar predictive power. Here we compared the predictability of Bnet...
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial: Natural Products-Based Drugs: Potential Therapeutics Against Alzheimer ’s Disease and Other Neurological Disorders
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Pharmacological Antagonism of T-Type Calcium Channels Constrains Rebound Burst Firing in Two Distinct Subpopulations of GABA Neurons in the Rat Ventral Tegmental Area: Implications for α-Lipoic Acid
The ventral tegmental area (VTA) is a midbrain region highly involved in motivation and reward. A large body of work has investigated synaptic plasticity and ion channel excitability in this area, which has strong implication in drug abuse. We recently provided electrophysiological and pharmacological evidence that the CaV3.1 isoform of T-type voltage-gated calcium channels contributes to the excitability of VTA dopamine (DA) neurons. However, the role of T-channels in excitability of VTA gamma-amino-butyric acid (GABA) neurons remained unaddressed. Here, with a population study of rat VTA GABA neurons, we provide evidence...
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Improvement of Sepsis Prognosis by Ulinastatin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Background: Ulinastatin has been prescribed to treat sepsis. However, there is doubt regarding the extent of any improvement in outcomes to guide future decision making.Objectives: To evaluate the effects of ulinastatin on mortality and related outcomes in sepsis patients.Methods: Thirteen randomized controlled trials and two prospective studies published before September 1, 2018, that included 1358 patients with sepsis, severe sepsis, or septic shock were evaluated. The electronic databases searched in this study were PubMed, Medline, Embase, and China National Knowledge Infrastructure (CNKI) for Chinese Technical Periodi...
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Robotic Therapy: Cost, Accuracy, and Times. New Challenges in the Neonatal Intensive Care Unit
Conclusions: The I.V. Station® improved the therapeutic process in our NICU. The benefits included increased precision in drug preparation, improved safety, lowered cost, and saved time. These advantages are particularly important in areas such as the NICU, where the I.V. Station® could improve the delivery of the high complexity of care and a large amount of intravenous therapy typically required. In addition, these benefits may lead to the reduction in medication errors and improve patient and family care; however, additional studies will be required to confirm this hypothesis. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Dermaseptins, Multifunctional Antimicrobial Peptides: A Review of Their Pharmacology, Effectivity, Mechanism of Action, and Possible Future Directions
Dermaseptins are a group of α-helical shaped polycationic peptides isolated from the Hylid frogs, with antimicrobial effects against bacteria, parasites, protozoa, viruses in vitro. Besides, anti-tumor effects have been demonstrated. However, few animal experiments and no clinical trials have been conducted thus far. This review summarizes the current knowledge on the pharmacology, ethno pharmacology, effectivity against infectious pathogens and tumors cells and the mechanism of action of the Dermaseptins. Future research should focus on further clarification of the mechanisms of action, the effectivity of Dermasepti...
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Anti-Osteoporotic Activity of an Edible Traditional Chinese Medicine Cistanche deserticola on Bone Metabolism of Ovariectomized Rats Through RANKL/RANK/TRAF6-Mediated Signaling Pathways
Given the limitations of existing therapeutic agents for treatment of postmenopausal osteoporosis, there still remains a need for more options with both efficacy and less adverse effects. Cistanche deserticola Y. C. Ma is known as a popular tonic herb traditionally used to treatment deficiency of kidney energy including muscle weakness in minority area of Asian counties. Based on the theory of “kidney dominate bone,” an ovariectomized (OVX) rat model of postmenopausal osteoporosis was used to evaluate the therapeutic effect of C. deserticola extract (CDE) on bone loss. Forty eight female Sprague-Dawley rats, ag...
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Anti-Cancer Effects of Panax ginseng Berry Polysaccharides via Activation of Immune-Related Cells
In this study, ginseng berry polysaccharides were evaluated for their immunostimulant and anti-cancer effects. Ginseng berry polysaccharide portion (GBPP) was used to investigate its effects on anti-complementary activity, peritoneal macrophage activation, and natural killer (NK) cell cytotoxicity. Moreover, both intravenous (i.v.) and oral administration of GBPP prior to B16-BL6 melanoma implantation in mice was evaluated. GBPP significantly increased the anti-complementary activity and cytokine production including interleukin (IL)-6, IL-12, and tumor necrosis factor (TNF)-α, dose-dependently. Splenocytes obtained ...
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Additive Dose Response Models: Defining Synergy
In synergy studies, one focuses on compound combinations that promise a synergistic or antagonistic effect. With the help of high-throughput techniques, a huge amount of compound combinations can be screened and filtered for suitable candidates for a more detailed analysis. Those promising candidates are chosen based on the deviance between a measured response and an expected non-interactive response. A non-interactive response is based on a principle of no interaction, such as Loewe Additivity or Bliss Independence. In a previous study, we introduced, an explicit formulation of the hitherto implicitly defined Loewe Additi...
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Antiarrhythmic Properties of Ranolazine: Inhibition of Atrial Fibrillation Associated TASK-1 Potassium Channels
Conclusions: In this study, we show that ranolazine inhibits TASK-1 channels. We suggest that inhibition of TASK-1 may contribute to the observed antiarrhythmic effects of Ranolazine. This puts forward ranolazine as a prototype drug for the treatment of atrial arrhythmia because of its combined efficacy on atrial electrophysiology and lower risk for ventricular side effects. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Association Study of the Complement Component C4 Gene in Tardive Dyskinesia
Tardive dyskinesia (TD) is a movement disorder that may develop in schizophrenia patients being treated long-term with antipsychotic medication. TD interferes with voluntary movements and leads to stigma, and can be associated with treatment non-adherence. The etiology of TD is unclear, but it appears to have a genetic component. There is emerging evidence of immune dysregulation in TD. In the current study, we set out to investigate the complex schizophrenia-associated complement component 4 (C4) gene for possible association with TD occurrence and TD severity as assessed by the Abnormal Involuntary Movement Scale (AIMS) ...
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Wnt/ β-Catenin Pathway-Regulated Fibromodulin Expression Is Crucial for Breast Cancer Metastasis and Inhibited by Aspirin
Emerging evidence suggests that fibromodulin (FMOD), an extracellular matrix protein, is associated with cancer, and yet little is known about the regulation of FMOD expression and its role in cancer metastasis. Aspirin, a classic anti-inflammatory drug, has been indicated to offer anticancer benefits, but its action targets and mechanisms remain obscure. In the present study using cell lines, animal model and database analysis, we show that FMOD is crucial for breast cancer cell migration and invasion (BCCMI) via activation of ERK; expression of FMOD is regulated positively by the Wnt/β-catenin pathway, wherein the &...
Source: Frontiers in Pharmacology - November 26, 2019 Category: Drugs & Pharmacology Source Type: research

Qishen Granule Improved Cardiac Remodeling via Balancing M1 and M2 Macrophages
In this study, we aimed to explore the effect of QSG on the release of splenic monocytes, the recruitment of monocytes into heart tissues and the differentiation of macrophages under ischemic conditions. Our results showed that QSG could suppress the release of monocytes from the spleen and recruitment of monocytes to heart tissues via inhibiting splenic angiotensin (Ang) II/AT1-cardiac monocyte chemotactic protein (MCP)-1/CC chemokine receptor 2 (CCR2) pathway. The anti-fibrotic effect of QSG was exerted by inhibiting M1 macrophage-activated transforming growth factor (TGF)-β1/Smad3 pathway. Meanwhile, QSG could prom...
Source: Frontiers in Pharmacology - November 25, 2019 Category: Drugs & Pharmacology Source Type: research

Therapeutic Anabolic and Anticatabolic Benefits of Natural Chinese Medicines for the Treatment of Osteoporosis
Osteoporosis is a bone disease characterized by increasing osseous fragility and fracture due to the reduced bone mass and microstructural degradation. Primary pharmacological strategies for the treatment of osteoporosis, hormone replacement treatment (HRT), and alendronate therapies may produce adverse side-effects and may not be recommended for long-term usage. Some classic and bone-specific natural Chinese medicine are very popularly used to treat osteoporosis and bone fracture effectively in clinical with their potential value in bone growth and development, but with few adverse side-effects. Current evidence suggests ...
Source: Frontiers in Pharmacology - November 25, 2019 Category: Drugs & Pharmacology Source Type: research

Immediate Effects of Dasatinib on the Migration and Redistribution of Na ïve and Memory Lymphocytes Associated With Lymphocytosis in Chronic Myeloid Leukemia Patients
We report here for the first time that dasatinib intake is associated with inhibition of peripheral blood T-cell migration toward the homeostatic chemokines CCL19 and CCL21, which control the trafficking toward secondary lymphoid organs, mainly the lymph nodes. Accordingly, the proportion of lymphocytes in blood expressing CCR7, the chemokine receptor for both CCL19 and CCL21, decreased after the intake including both naïve CD45RA+ and central memory CD45RO+ T-cells. Similarly, naïve B-cells diminished with dasatinib. Finally, such changes in the migratory patterns did not occur in those patients whose lymphocyte...
Source: Frontiers in Pharmacology - November 25, 2019 Category: Drugs & Pharmacology Source Type: research

The Role of Intercellular Adhesion Molecule-1 in the Pathogenesis of Psychiatric Disorders
Intercellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein that is overexpressed in many pathological states. Although, like many other immune molecules, ICAM-1 plays only a limited role in the abundant concert of the immune response, it may be more important than we realize. In the central nervous system (CNS), ICAM-1 is expressed in microglial cells and astrocytes and in endothelial cells in the white and gray matter of the human forebrain. It is of particular interest in psychiatric disorders for two reasons: It has a key function for the blood–brain barrier, which plays an important role in the bi...
Source: Frontiers in Pharmacology - November 23, 2019 Category: Drugs & Pharmacology Source Type: research

The Fruits of Siraitia grosvenorii: A Review of a Chinese Food-Medicine
Siraitia grosvenorii (Swingle) C. Jeffrey, a member of the family Cucurbitaceae, is a unique economic and medicinal plant grown in China. For more than 300 years, S. grosvenorii has been used as a natural sweetener and as a traditional medicine for the treatment of pharyngitis, pharyngeal pain, as well as an anti-tussive remedy in China. It is one of the first approved medicine food homology species in China. It has been widely studied as a natural product with high development potential. Therefore, the present paper provides a review of the botanical characterization, traditional uses and ethnopharmacology, food and nutri...
Source: Frontiers in Pharmacology - November 22, 2019 Category: Drugs & Pharmacology Source Type: research

The Effects of Melatonin on the Descending Pain Inhibitory System and Neural Plasticity Markers in Breast Cancer Patients Receiving Chemotherapy: Randomized, Double-Blinded, Placebo-Controlled Trial
Conclusions: These results suggest that oral melatonin, together with the first ACBC counteracts the dysfunction in the inhibitory DPMS and improves pain perception measures. Also, it shows that changes in the neuroplasticity state mediate the impact of melatonin on pain.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT03205033. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - November 22, 2019 Category: Drugs & Pharmacology Source Type: research

Comparative Network Pharmacology Analysis of Classical TCM Prescriptions for Chronic Liver Disease
Chronic liver disease (CLD) has become a major global health problem while herb prescriptions are clinically observed with significant efficacy. Three classical Traditional Chinese Medicine (TCM) formulae, Yinchenhao Decoction (YCHT), Huangqi Decoction (HQT), and Yiguanjian (YGJ) have been widely applied in China to treat CLD, but no systematic study has yet been published to investigate their common and different mechanism of action (MOA). Partial limitation may own to deficiency of effective bioinformatics methods. Here, a computational framework of comparative network pharmacology is firstly proposed and then applied to...
Source: Frontiers in Pharmacology - November 22, 2019 Category: Drugs & Pharmacology Source Type: research

Treatment of Arachnoid Cyst With Spontaneous Hemorrhage With Atorvastatin
As one of the common neurological diseases, pediatric middle fossa arachnoid cysts(MFACs) can develop intracystic hemorrhage and subdural hematoma. Risk factors for pediatric arachnoid cyst rupture/hemorrhage is very complicated in mechanism. Although surgery is the first choice for children with MFACs and subdural hematoma, the rate of recurrence of the subdural hematoma is very high after 1 or more surgeries. Atorvastatin has proven to be a bold and safe choice in the management of subdural hematoma with mild symptoms. The present study has described a 7-year-old child with a recurrent rupture of arachnoid cyst develops ...
Source: Frontiers in Pharmacology - November 22, 2019 Category: Drugs & Pharmacology Source Type: research

Brain Metabolic Dysfunction in Early Neuropsychiatric Symptoms of Dementia
Neuropsychiatric symptoms (NPS) including behavioral and psychiatric symptoms are common in the dementia stages of Alzheimer's disease (AD) and are associated with poorer outcomes in cognition, functional states, quality of life, and accelerated progression to severe dementia or death. NPS are also increasingly observed in the mild cognitive impairment stage of AD and may predict incipient dementia. As such, there is an emerging conceptual framework, which support NPS as early non-cognitive symptoms of dementia. [18F]fluorodeoxyglucosepositron emission tomography is a technique that is sensitive in detecting resting metabo...
Source: Frontiers in Pharmacology - November 22, 2019 Category: Drugs & Pharmacology Source Type: research

Immune and Smooth Muscle Cells Interactions in Atherosclerosis: How to Target a Breaking Bad Dialogue?
Inflammation is a well-known pathophysiological factor of atherosclerosis but its therapeutic targeting has long been ignored. However, recent advances in the understanding of the immune mechanisms implicated in atherosclerosis have unveiled several therapeutic targets currently undergoing clinical trials. These studies have also shed light on a dialogue between the immune compartment and vascular smooth muscle cells (VSMCs) that plays a critical role in atherosclerotic disease initiation, progression, and stabilization. Our review focuses on the link between cellular and soluble immune effectors and VSMC behavior at diffe...
Source: Frontiers in Pharmacology - November 22, 2019 Category: Drugs & Pharmacology Source Type: research

Serum Testosterone and Cortisol Concentrations After Single-Dose Administration of 100-Mg Transdermal Testosterone in Healthy Men
The growing interest in testosterone's effects on men's social behaviors, in particular aggressive, risk-taking, or status maintenance behaviors, is accompanied by a paucity of dose-dependent pharmacokinetic data. Examining the neurophysiological effects of transdermal testosterone typically includes a 4h delay before further brain-behavior measurements. Nevertheless, high heterogeneity regarding the timing of follow-up measurements and dosage remains. In a double-blind placebo-controlled design, we examined the short-term pharmacokinetic profile of 100-mg transdermal testosterone (Testotop®) to determine the optimal t...
Source: Frontiers in Pharmacology - November 21, 2019 Category: Drugs & Pharmacology Source Type: research

Choline Attenuates Cardiac Fibrosis by Inhibiting p38MAPK Signaling Possibly by Acting on M3 Muscarinic Acetylcholine Receptor
Choline has been reported to produce a variety of cellular functions including cardioprotection via activating M3 muscarinic acetylcholine receptor (M3R) under various insults. However, whether choline offers similar beneficial effects via the same mechanism in cardiac fibrosis remained unexplored. The present study aimed to investigate the effects of choline on cardiac fibrosis and the underlying signaling mechanisms, particularly the possible involvement of M3R. Transverse aortic constriction (TAC) mouse model was established to simulate the cardiac fibrosis. Transforming growth factor (TGF)-β1 treatment was employe...
Source: Frontiers in Pharmacology - November 21, 2019 Category: Drugs & Pharmacology Source Type: research

Huang-Lian-Jie-Du Decoction Ameliorates Acute Ulcerative Colitis in Mice via Regulating NF- κB and Nrf2 Signaling Pathways and Enhancing Intestinal Barrier Function
In this study, the UC model of BABL/c mice were established by DSS [3.5% (w/v)], and HLJDD was given orally for treatment at the same time. During the experiment, the clinical symptoms of mice were scored by disease activity index (DAI). Besides, the effects of HLJDD on immune function, oxidative stress, colon NF-κB and Nrf2 signaling pathway, and intestinal mucosal barrier function in UC mice were also investigated. The results showed that HLJDD could alleviate body weight loss and DAI score of UC mice, inhibit colonic shortening and relieve colonic pathological damage, and reduce plasma and colon MPO levels. In add...
Source: Frontiers in Pharmacology - November 21, 2019 Category: Drugs & Pharmacology Source Type: research

Thiazide Diuretics and the Incidence of Osteoporotic Fracture: A Systematic Review and Meta-Analysis of Cohort Studies
Background: Thiazide diuretics may improve bone mineral density. However, results are inconsistent for studies evaluating the association between thiazides and risk of osteoporotic fracture. We performed an updated meta-analysis of cohort studies to determine the association between thiazides use and fracture risk.Methods: Relevant studies were identified via systematic search of PubMed and Embase. A random-effect model was used for meta-analysis. Subgroup analyses were performed to explore the potential influences of study characteristics on the outcome.Results: Seventeen cohort studies with 3,537,504 participants were in...
Source: Frontiers in Pharmacology - November 21, 2019 Category: Drugs & Pharmacology Source Type: research

Astrocyte-Derived Paracrine Signals: Relevance for Neurogenic Niche Regulation and Blood –Brain Barrier Integrity
Astrocytes are essential for proper regulation of the central nervous system (CNS). Importantly, these cells are highly secretory in nature. Indeed they can release hundreds of molecules which play pivotal physiological roles in nervous tissues and whose abnormal regulation has been associated with several CNS disorders. In agreement with these findings, recent studies have provided exciting insights into the key contribution of astrocyte-derived signals in the pleiotropic functions of these cells in brain health and diseases. In the future, deeper analysis of the astrocyte secretome is likely to further increase our curre...
Source: Frontiers in Pharmacology - November 21, 2019 Category: Drugs & Pharmacology Source Type: research

2 ′-Hydroxychalcone Induced Cytotoxicity via Oxidative Stress in the Lipid-Loaded Hepg2 Cells
Licorice is a common herb used in traditional Chinese medicine, and has been widely used clinically. Physiologically, although it is relatively safe, licorice-induced hepatotoxicity in the presence of other diseases needs to be evaluated. The present study was conducted to investigate the toxicological effects of the bioactive components of licorice in HepG2 cells cultured with or without free fatty acid (FFA). The compounds, isoliquiritigenin, licorice chalcone A, bavachalcone, and 2′-hydroxy chalcone (2′-HC) inhibited cell proliferation at certain concentrations in lipid loaded cells with limited effects on t...
Source: Frontiers in Pharmacology - November 20, 2019 Category: Drugs & Pharmacology Source Type: research

Impact of Vaptans on Clinical Outcomes in Cirrhosis Patients: A Meta-Analysis of Randomized Controlled Trials
Background: Vaptans have been confirmed to mobilize ascites and improve hyponatremia in cirrhosis patients. However, the effects of vaptans on all-cause mortality, ascites-related complications, and adverse events in cirrhosis patients have not been fully determined.Objectives: To systematically evaluate the impact of vaptans on the clinical outcomes in patients with cirrhosis.Materials and Methods: A systematic review and meta-analysis was performed. The PubMed, Embase, and Cochrane’s Library electronic databases were systematically searched for randomized controlled trials (RCTs) investigating the clinical efficacy...
Source: Frontiers in Pharmacology - November 20, 2019 Category: Drugs & Pharmacology Source Type: research

RU486 Metabolite Inhibits CCN1/Cyr61 Secretion by MDA-MB-231-Endothelial Adhesion
Successful adhesion of circulating tumor cells (CTCs) to microvascular endothelium of distant metastatic tissue is the key starting step of metastatic cascade that could be effectively chemoprevented as we demonstrated previously. Here, we hypothesize that the hetero-adhesion may produce secretory biomarkers that may be important for both premetastatic diagnosis and chemoprevention. We show that co-incubation of triple-negative breast cancer (TNBC) cell line MDA-MB-231 with human pulmonary microvascular endothelial monolayers (HPMEC) secretes Cyr61 (CCN1), primarily from MDA-MB-231. However, addition of metapristone (RU486...
Source: Frontiers in Pharmacology - November 20, 2019 Category: Drugs & Pharmacology Source Type: research

Structure –Effect Relationships of Novel Semi-Synthetic Cannabinoid Derivatives
Conclusion: The CBD- and CBDV-derivatives studied are suitable for targeting CB-receptors. Some may be used as selective CB2 agonists. The length of the aliphatic rest at R2 of CBD (pentyl) and CBDV (propyl) did not correlate with the binding affinity. Higher polarity at R1 appeared to favor the agonistic activity at CB2-receptors. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - November 20, 2019 Category: Drugs & Pharmacology Source Type: research

The Impact of Ayahuasca on Suicidality: Results From a Randomized Controlled Trial
Suicide is a major public health problem. Given increasing suicide rates and limitations surrounding current interventions, there is an urgent need for innovative interventions for suicidality. Although ayahuasca has been shown to target mental health concerns associated with suicidality (i.e., depression and hopelessness), research has not yet explored the impact of ayahuasca on suicidality. Therefore, we conducted secondary analyses of a randomized placebo-controlled trial in which individuals with treatment-resistant depression were administered one dose of ayahuasca (n = 14) or placebo (n = 15). Suicidality was assesse...
Source: Frontiers in Pharmacology - November 19, 2019 Category: Drugs & Pharmacology Source Type: research

The Availability, Pricing, and Affordability of Essential Diabetes Medicines in 17 Low-, Middle-, and High-Income Countries
Conclusion: Availability of generic form of insulin is poor; IB of insulin was more affordable in high-income countries than low-income countries. Most of the LPGs was reasonably priced and affordable to the lowest-paid unskilled worker. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - November 19, 2019 Category: Drugs & Pharmacology Source Type: research

Gut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic Target
Cardiovascular disease (CVD) is the leading cause of death worldwide, especially in developed countries, and atherosclerosis (AS) is the common pathological basis of many cardiovascular diseases (CVDs) such as coronary heart disease (CHD). The role of the gut microbiota in AS has begun to be appreciated in recent years. Trimethylamine N-oxide (TMAO), an important gut microbe-dependent metabolite, is generated from dietary choline, betaine, and L-carnitine. Multiple studies have suggested a correlation between plasma TMAO levels and the risk of AS. However, the mechanism underlying this relationship is still unclear. In thi...
Source: Frontiers in Pharmacology - November 19, 2019 Category: Drugs & Pharmacology Source Type: research

Emerging Roles for NLRC5 in Immune Diseases
Innate immunity activates the corresponding immune response relying on multiple pattern recognition receptors (PRRs) that includes pattern recognition receptors (PRRs), like NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and C-type lectin receptors (CLRs), which could accurately recognize invasive pathogens. In particular, NLRs belong to a large protein family of pattern recognition receptors in the cytoplasm, where they are highly correlated with activation of inflammatory response system followed by rapid clearance of invasive pathogens. Among the NLRs family, NLRC5, also known as NOD4 or NOD27, accounts for a l...
Source: Frontiers in Pharmacology - November 19, 2019 Category: Drugs & Pharmacology Source Type: research

Therapeutic Dose Response of Acoustic Cluster Therapy in Combination With Irinotecan for the Treatment of Human Colon Cancer in Mice
Introduction: Acoustic Cluster Therapy (ACT) comprises coadministration of a formulation containing microbubble-microdroplet clusters (PS101) together with a regular medicinal drug and local ultrasound (US) insonation of the targeted pathological tissue. PS101 is confined to the vascular compartment and when the clusters are exposed to regular diagnostic imaging US fields, the microdroplets undergo a phase shift to produce bubbles with a median diameter of 22 µm. Low frequency, low mechanical index US is then applied to drive oscillations of the deposited ACT bubbles to induce biomechanical effects that locally enhan...
Source: Frontiers in Pharmacology - November 19, 2019 Category: Drugs & Pharmacology Source Type: research

XIAOPI Formula Inhibits Breast Cancer Stem Cells via Suppressing Tumor-Associated Macrophages/C-X-C Motif Chemokine Ligand 1 Pathway
Macrophages are the most abundant stromal cells associated with the host immune system in multiple malignancies including breast cancer. With proven clinical efficacy and no noticeable adverse effects, XIAOPI formula (XPS) has been approved for breast hyperplasia treatment by the State Food and Drug Administration of China (SFDA) in 2018. The existing knowledge about the anti-breast cancer activities and mechanisms of XPS has been very limited. The present study aimed to investigate whether XPS could exert an anti-breast cancer effect by regulating tumor-associated macrophages (TAMs) in tumor microenvironment. Herein, brea...
Source: Frontiers in Pharmacology - November 15, 2019 Category: Drugs & Pharmacology Source Type: research

Corrigendum: SCD1 Confers Temozolomide Resistance to Human Glioma Cells Via the Akt/GSK3 β/β-Catenin Signaling Axis
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - November 15, 2019 Category: Drugs & Pharmacology Source Type: research

Synthesis of Chalcone Derivatives: Inducing Apoptosis of HepG2 Cells via Regulating Reactive Oxygen Species and Mitochondrial Pathway
In this study, apoptosis, cycle arrest, assessment of reactive oxygen species (ROS) level, and measurement of mitochondrial membrane potential were adopted to explore the inhibitory mechanism of a14 towards HepG2. Compound a14 could effectively block the division of HepG2 cell lines in the G2/M phase and robustly induced generation of ROS, demonstrating that the generation of ROS induced by a14 was the main reason for resulting in the apoptosis of HepG2 cells. Moreover, the mitochondrial membrane potential (MMP) of HepG2 cells treated with a14 was significantly decreased, which was closely related to the enhanced ROS level...
Source: Frontiers in Pharmacology - November 15, 2019 Category: Drugs & Pharmacology Source Type: research