Esculetin Inhibits Cancer Cell Glycolysis by Binding Tumor PGK2, GPD2, and GPI
Glycolysis can improve the tolerance of tissue cells to hypoxia, and its intermediates provide raw materials for the synthesis and metabolism of the tumor cells. If it can inhibit the activity of glycolysis-related enzymes and control the energy metabolism of tumor, it can be targeted for the treatment of malignant tumor. The target proteins phosphoglycerate kinase 2 (PGK2), glycerol-3-phosphate dehydrogenase (GPD2), and glucose-6-phosphate isomerase (GPI) were screened by combining transcriptome, proteomics, and reverse docking. We detected the binding constant of the active compound using microscale thermophoresis (MST)....
Source: Frontiers in Pharmacology - March 27, 2020 Category: Drugs & Pharmacology Source Type: research

Berberine Promotes OATP1B1 Expression and Rosuvastatin Uptake by Inducing Nuclear Translocation of FXR and LXR α
In conclusion, berberine-induced nuclear translocation of FXR and LXRα could activate OATP1B1 promoter, resulting in enhanced expression of OATP1B1 and increased uptake of rosuvastatin. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 27, 2020 Category: Drugs & Pharmacology Source Type: research

Aldehyde Dehydrogenase 2 Protects Against Post-Cardiac Arrest Myocardial Dysfunction Through a Novel Mechanism of Suppressing Mitochondrial Reactive Oxygen Species Production
In this study, we evaluated the effect of enhanced activity or expression of ALDH2 on post-cardiac arrest myocardial dysfunction and survival in a rat cardiac arrest model. Furthermore, we elucidated the underlying mechanisms with a focus on mitochondrial reactive oxygen species (ROS) production in a cell hypoxia/reoxygenation model. A total of 126 rats were used for the ALDH2 activation or cardiac overexpression of ALDH2 studies. Randomization was done 10 min before the respective agonist injection or in vivo gene delivery. We showed that enhanced activity or expression of ALDH2 significantly improved contractile function...
Source: Frontiers in Pharmacology - March 27, 2020 Category: Drugs & Pharmacology Source Type: research

Treatment With Lipopolysaccharide Induces Distinct Changes in Metabolite Profile and Body Weight in 129Sv and Bl6 Mouse Strains
This study seeks to characterize behavioral and metabolomic profiles of two widely used mouse lines, 129S6/SvEvTac (129Sv) and C57BL/6NTac (Bl6), to acute administration of lipopolysaccharide (LPS). LPS caused a significant suppression of locomotor activity and a decline in body weight (BW) in both strains within 24 h. However, the BW loss was more pronounced in Bl6 than in 129Sv. Comparison of strains revealed clear differences between their metabolomic profiles. According to the general linear model analysis (GLM), the 1.5 h LPS challenge in Bl6 caused a decrease of propionylcarnitine (C3), glucogenic amino acids, and ac...
Source: Frontiers in Pharmacology - March 27, 2020 Category: Drugs & Pharmacology Source Type: research

Protective Effects Oncorneal Endothelium During Intracameral Irrigation Using N-(2)-l-alanyl-l-Glutamine
Corneal endothelial disease is a global sight-threatening disease, and corneal transplantation using donor corneas remains the sole therapeutic option. A previous work demonstrated that N (2)-alanyl-glutamine (Ala-Gln) protected against apoptosis and cellular stress, and maintained intestinal tissue integrity. In this pursuit, the present study aimed to examine the effect of Ala-Gln in the protection of the corneal endothelium and expand its range of potential clinical applications. Mice in the control group were intracamerally irrigated with Ringers lactate injection, whereas those in the experimental group were irrigated...
Source: Frontiers in Pharmacology - March 27, 2020 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and Metabolism of Naringin and Active Metabolite Naringenin in Rats, Dogs, Humans, and the Differences Between Species
ConclusionThe results can be used to design a dosage regimen, deepen understanding of mechanisms, and accelerate new drug development.Clinical Trial Registrationhttp://www.chinadrugtrials.org.cn/eap/main, identifiers CTR20130704 and CTR20190127. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 27, 2020 Category: Drugs & Pharmacology Source Type: research

4 β-Hydroxycholesterol Signals From the Liver to Regulate Peripheral Cholesterol Transporters
In conclusion, PXR activation-elevated 4βHC is a signaling molecule that represses cholesterol influx and induces efflux. The PXR-4βHC-LXR pathway could link the hepatic xenobiotic exposure and the regulation of cholesterol transport in peripheral tissues. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 27, 2020 Category: Drugs & Pharmacology Source Type: research

Pregnenolone Inhibits Osteoclast Differentiation and Protects Against Lipopolysaccharide-Induced Inflammatory Bone Destruction and Ovariectomy-Induced Bone Loss
Osteolytic bone disease is characterized by excessive osteoclast bone resorption leading to increased skeletal fragility and fracture risk. Multinucleated osteoclasts formed through the fusion of mononuclear precursors are the principle cell capable of bone resorption. Pregnenolone (Preg) is the grand precursor of most if not all steroid hormones and have been suggested to be a novel anti-osteoporotic agent. However, the effects of Preg on osteoclast biology and function has yet to be shown. Here we examined the effect of Preg on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation and b...
Source: Frontiers in Pharmacology - March 27, 2020 Category: Drugs & Pharmacology Source Type: research

Molecular Targets for Combined Therapeutic Strategies to Limit Glioblastoma Cell Migration and Invasion
The highly invasive nature of glioblastoma imposes poor prospects for patient survival. Molecular evidence indicates glioblastoma cells undergo an intriguing expansion of phenotypic properties to include neuron-like signaling using excitable membrane ion channels and synaptic proteins, augmenting survival and motility. Neurotransmitter receptors, membrane signaling, excitatory receptors, and Ca2+ responses are important candidates for the design of customized treatments for cancers within the heterogeneous central nervous system. Relatively few published studies of glioblastoma multiforme (GBM) have evaluated pharmacologic...
Source: Frontiers in Pharmacology - March 27, 2020 Category: Drugs & Pharmacology Source Type: research

Prospective Risk Assessment of Medicine Shortages in Europe and Israel: Findings and Implications
ConclusionThe study indicates a lack of systematically organized tools used to prospectively analyze clinical as well as operationalized risk stemming from medicine shortages in healthcare. There is also a lack of legal instruments and sufficient data confirming the necessity and usefulness of risk assessment in mitigating medicine shortages in Europe. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 26, 2020 Category: Drugs & Pharmacology Source Type: research

Atractylenolide I Induces Apoptosis and Suppresses Glycolysis by Blocking the JAK2/STAT3 Signaling Pathway in Colorectal Cancer Cells
In this study, we aimed to examine the anti-cancer properties of AT-I and the associated functional mechanisms in vitro and in vivo. We found that AT-I treatment significantly suppressed the viability of CRC cell lines and inhibited colony formation, but to a lesser extent in NCM460 cells. Annexin V/PI staining showed that AT-I induced apoptosis in CRC cells, accompanied by increased caspase-3 and PARP-1 cleavage, enhanced expression of Bax, and reduced expression of Bcl-2. Furthermore, AT-I blocked cell glycolysis by inhibiting both glucose uptake and lactate production in CRC cells, and specifically downregulated the exp...
Source: Frontiers in Pharmacology - March 26, 2020 Category: Drugs & Pharmacology Source Type: research

A GLP-1 Analog Liraglutide Reduces Intimal Hyperplasia After Coronary Stent Implantation via Regulation of Glycemic Variability and NLRP3 Inflammasome/IL-10 Signaling in Diabetic Swine
This study aimed to explore whether treatment with the glucagon-like peptide-1 (GLP-1) analog liraglutide reduces intimal hyperplasia after coronary stent implantation via regulation of glycemic variability, the NLRP3 inflammasome, and IL-10 in diabetic swine.MethodsFifteen pigs were divided into a diabetes mellitus (DM) group (n = 6), a DM + liraglutide treatment group (L group) (n = 6) and a sham group (n = 3). A total of 24 everolimus-eluting stents were implanted in the left anterior descending and right coronary arteries at 3 weeks. A novel continuous glucose monitoring system (GMS) was used for 2 weeks. The means and...
Source: Frontiers in Pharmacology - March 26, 2020 Category: Drugs & Pharmacology Source Type: research

Effects of D-Chiro-Inositol on Glucose Metabolism in db/db Mice and the Associated Underlying Mechanisms
In this study, we observed the effect of D-chiro-inositol (DCI) on glucose consumption in type 2 diabetic db/db mice, and investigated the relevant mechanism. We discovered that the stability of 24-h blood glucose under the nonfasting condition and decreased glucose tolerance were both alleviated after treatment with DCI. Moreover, the content of glycosylated protein and advanced glycation end products in the serum was reduced, the damage in the liver tissue was alleviated, and the synthesis of liver glycogen was significantly promoted. In addition, DCI increased the expression of insulin receptor substrate 2 (IRS2), phosp...
Source: Frontiers in Pharmacology - March 26, 2020 Category: Drugs & Pharmacology Source Type: research

Human Amniotic Fluid Mesenchymal Stem Cells Improve Ovarian Function During Physiological Aging by Resisting DNA Damage
Many studies have shown that mesenchymal stem cells have the ability to restore function in models of premature ovarian insufficiency disease, but few studies have used stem cells in the treatment of ovarian physiologic aging (OPA). This experimental study was designed to determine whether human amniotic fluid mesenchymal stem cells (hAFMSCs) have the ability to recover ovarian vitality and to determine how they function in this process. Mice (12–14 months old) were used in this study, and young fertile female mice (3–5 months old) were the control group. Ovarian markers for four stages of folliculogenesis and ...
Source: Frontiers in Pharmacology - March 26, 2020 Category: Drugs & Pharmacology Source Type: research

Danhong Injection Protects Hemorrhagic Brain by Increasing Peroxiredoxin 1 in Aged Rats
Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with a high incidence, mortality and disability rate. Danhong injection (DHI) is beneficial for ischemic stroke, but is prohibited for ICH due to risk of bleeding. The present study aims to explore the potential therapeutic time window and molecular mechanism of DHI in a collagenase-induced ICH model in aged rats. DHI administration after ICH could significantly improve body weight and neurological deficits, and reduce the hematoma volume and brain water content when compared to the vehicle control. Furthermore, the protective effect of DHI administration o...
Source: Frontiers in Pharmacology - March 25, 2020 Category: Drugs & Pharmacology Source Type: research

Traditional Chinese Medicine Formula Kang Shuai Lao Pian Improves Obesity, Gut Dysbiosis, and Fecal Metabolic Disorders in High-Fat Diet-Fed Mice
High-fat diet (HFD)-induced obesity is a risk factor for many metabolic disorders including cardiovascular diseases, diabetes, and fatty liver disease. Although there are accumulating evidences supporting the assumption that regulating gut microbiota as well as its metabolic status is able to mitigate obesity, the inner relationship between the obesity-related gut microbiota and the relevant metabolites are not well defined. In current study, we applied a traditional herbal formula Kang Shuai Lao Pian (KSLP) to HFD-fed mice and evaluated its effect against obesity. Emphases were addressed on identifying profiles of gut mic...
Source: Frontiers in Pharmacology - March 25, 2020 Category: Drugs & Pharmacology Source Type: research

Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors
This study adds to the evidence that the putative entourage effect cannot be explained by direct effects at CB1 or CB2. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 25, 2020 Category: Drugs & Pharmacology Source Type: research

Noninvasive 40-Hz Light Flicker Rescues Circadian Behavior and Abnormal Lipid Metabolism Induced by Acute Ethanol Exposure via Improving SIRT1 and the Circadian Clock in the Liver-Brain Axis
This study investigated the effects of 40-Hz light flicker in a mouse model of ALD. RNA sequencing (RNA-seq) analysis was performed to explore the potential pathways affected by 40-Hz light flicker. We found that 40-Hz light flicker significantly decreased the acute ethanol-induced increases in serum alanine aminotransferase (ALT) and serum triglyceride (TG) levels and reduced fat-droplet accumulation in mouse livers. Additionally, 40-Hz light flicker significantly suppressed ethanol-induced increases in sterol regulatory element binding protein 1 (SREBP-1) and fatty acid synthase (Fasn) levels. Furthermore, the ethanol in...
Source: Frontiers in Pharmacology - March 25, 2020 Category: Drugs & Pharmacology Source Type: research

Mitochondrial MPTP: A Novel Target of Ethnomedicine for Stroke Treatment by Apoptosis Inhibition
Mammalian mitochondrial permeability transition pore (MPTP), across the inner and outer membranes of mitochondria, is a nonspecific channel for signal transduction or material transfer between mitochondrial matrix and cytoplasm such as maintenance of Ca2+ homeostasis, regulation of oxidative stress signals, and protein translocation evoked by some of stimuli. Continuous MPTP opening has been proved to stimulate neuronal apoptosis in ischemic stroke. Meanwhile, inhibition of MPTP overopening-induced apoptosis has shown excellent efficacy in the treatment of ischemic stroke. Among of which, the potential molecular mechanisms...
Source: Frontiers in Pharmacology - March 25, 2020 Category: Drugs & Pharmacology Source Type: research

α1-Blockers and 5α-Reductase Inhibitors Are the Most Recommended Drugs in Treating Benign Prostatic Hyperplasia: An Evidence-Based Evaluation of Clinical Practice Guidelines
ConclusionThe recommendations from different guidelines were basically similar, only showing conflicts in some areas. The quality of included guidelines remains to be unified, and their context can provide valuable implications for development or improvement. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 25, 2020 Category: Drugs & Pharmacology Source Type: research

Polyherbal Medicine Divya Sarva-Kalp-Kwath Ameliorates Persistent Carbon Tetrachloride Induced Biochemical and Pathological Liver Impairments in Wistar Rats and in HepG2 Cells
In conclusion, SKK showed pharmacological effects in improving the CCl4 stimulated liver injuries in HepG2 cells and in Wistar rats. Furthermore, no adverse effects were observed up to 10× higher human equivalent dose of SKK during 28-days repeated dose exposure in Wistar rats. Based on the literature search on the identified plant metabolites, SKK was found to act in multiple ways to ameliorate CCl4 induced hepatotoxicity. Therefore, polyherbal SKK medicine has shown remarkable potentials as a possible alternative therapeutics for reducing liver toxicity induced by drugs, and other toxins. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 25, 2020 Category: Drugs & Pharmacology Source Type: research

Heat Shock Protein 22 Attenuates Doxorubicin-Induced Cardiotoxicity via Regulating Inflammation and Apoptosis
ConclusionIn summary, Hsp22 overexpression in the heart could suppress cardiac injury in response to DOX treatment through blocking TLR4/NLRP3 activation. Hsp22 may become a new therapeutic method for treating cardiac injury induced by DOX in cancer patients. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 25, 2020 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic Studies of Antisense Oligonucleotides Using MALDI-TOF Mass Spectrometry
In this study, MALDI-TOF mass spectrometry (MS) was utilized to establish a robust and fast method to sensitively detect and accurately quantify anti-microRNA (antimiR) oligonucleotides in blood plasma. An antimiR oligonucleotide isolation protocol containing an ethanol precipitation step with glycogen as oligonucleotide carrier as well as a robust and reproducible MS-analysis procedure has been established. Proteinase K treatment was crucial for releasing antimiR oligonucleotides from plasma- as well as cellular proteins and reducing background derived from biological matrices. AntimiR oligonucleotide detection was achiev...
Source: Frontiers in Pharmacology - March 25, 2020 Category: Drugs & Pharmacology Source Type: research

Electrospun Nanofiber Meshes With Endometrial MSCs Modulate Foreign Body Response by Increased Angiogenesis, Matrix Synthesis, and Anti-Inflammatory Gene Expression in Mice: Implication in Pelvic Floor
ConclusionThis study reveals that eMSC modulate the foreign body response to degradable P nanomeshes in vivo by altering the expression profile of mouse genes. eMSC reduce acute inflammatory and increase ECM synthesis, angiogenesis and anti-inflammatory gene expression at 6 weeks while forming newly synthesized collagen within the nanomeshes and neo-vasculature in close proximity. From a tissue engineering perspective, this is a hallmark of a highly successful implant, suggesting significant potential as alternative surgical constructs for the treatment of POP. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 24, 2020 Category: Drugs & Pharmacology Source Type: research

The Impacts of Herbal Medicines and Natural Products on Regulating the Hepatic Lipid Metabolism
The dysregulation of hepatic lipid metabolism is one of the hallmarks in many liver diseases including alcoholic liver diseases (ALD) and non-alcoholic fatty liver diseases (NAFLD). Hepatic inflammation, lipoperoxidative stress as well as the imbalance between lipid availability and lipid disposal, are direct causes of liver steatosis. The application of herbal medicines with anti-oxidative stress and lipid-balancing properties has been extensively attempted as pharmaceutical intervention for liver disorders in experimental and clinical studies. Although the molecular mechanisms underlying their hepatoprotective effects wa...
Source: Frontiers in Pharmacology - March 24, 2020 Category: Drugs & Pharmacology Source Type: research

A Review of the Pharmacological Action of Astragalus Polysaccharide
Astragalus membranaceus (A. membranaceus) is a type of traditional Chinese medicine with a long history of clinical application. It is used in the improvement and treatment of various diseases as medicine and food to invigorate the spleen and replenish qi. The main components of A. membranaceus are Astragalus polysaccharide (APS), flavonoids compounds, saponins compounds, alkaloids, etc. APS is the most important natural active component in A. membranaceus, and possesses multiple pharmacological properties. At present, APS possess the huge potential to develop a drug improving or treating different diseases. In this review...
Source: Frontiers in Pharmacology - March 24, 2020 Category: Drugs & Pharmacology Source Type: research

Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Radix Puerariae for Treatment of Hypertension
This study shows that RP probably acts by influencing the proliferation module, apoptosis module, inflammation module, and others when treating hypertension. This study provides novel insights for researchers to systematically explore the mechanism of action of TCM. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 24, 2020 Category: Drugs & Pharmacology Source Type: research

Ribosomal Protein S6 Hypofunction in Postmortem Human Brain Links mTORC1-Dependent Signaling and Schizophrenia
The mechanistic target of rapamycin (also known as mammalian target of rapamycin) (mTOR)-dependent signaling pathway plays an important role in protein synthesis, cell growth, and proliferation, and has been linked to the development of the central nervous system. Recent studies suggest that mTOR signaling pathway dysfunction could be involved in the etiopathogenesis of schizophrenia. The main goal of this study was to evaluate the status of mTOR signaling pathway in postmortem prefrontal cortex (PFC) samples of subjects with schizophrenia. For this purpose, we quantified the protein expression and phosphorylation status o...
Source: Frontiers in Pharmacology - March 24, 2020 Category: Drugs & Pharmacology Source Type: research

Antitumor Drug Combretastatin-A4 Phosphate Aggravates the Symptoms of Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice
In this study, we examined the pharmacological effects of CA4P administration on dextran sulfate sodium (DSS)-induced inflammation in a mouse model of UC. C57BL/6 mice were administered 2.5% DSS in the drinking water to induce acute UC. CA4P (11 mg/kg/d) was injected intraperitoneally daily. The Disease Activity Index (DAI) score and histological score were evaluated to determine the severity of UC. Colon tissues and blood samples were collected for histological analyses. The results show that CA4P plus DSS significantly decreased colon length (P
Source: Frontiers in Pharmacology - March 24, 2020 Category: Drugs & Pharmacology Source Type: research

A Ganoderma-Derived Compound Exerts Inhibitory Effect Through Formyl Peptide Receptor 2
Formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCRs) widely expressed in neutrophils and other phagocytes. FPRs play important roles in host defense, inflammation, and the pathogenesis of infectious and inflammatory diseases. Because of these functions, FPRs are potential targets for anti-inflammatory therapies. In order to search for potentially novel anti-inflammatory agents, we examined Ganoderma (Lingzhi), a Chinese medicinal herbs known for its anti-inflammatory effects, and found that compound 18 (C18) derived from Ganoderma cochlear could limit the inflammatory response through FPR-related signali...
Source: Frontiers in Pharmacology - March 24, 2020 Category: Drugs & Pharmacology Source Type: research

Both Pharmacokinetic Variability and Granuloma Heterogeneity Impact the Ability of the First-Line Antibiotics to Sterilize Tuberculosis Granulomas
Tuberculosis (TB) remains as one of the world's deadliest infectious diseases despite the use of standardized antibiotic therapies. Recommended therapy for drug-susceptible TB is up to 6 months of antibiotics. Factors that contribute to lengthy regimens include antibiotic underexposure in lesions due to poor pharmacokinetics (PK) and complex granuloma compositions, but it is difficult to quantify how individual antibiotics are affected by these factors and to what extent these impact treatments. We use our next-generation multi-scale computational model to simulate granuloma formation and function together with antibiotic ...
Source: Frontiers in Pharmacology - March 24, 2020 Category: Drugs & Pharmacology Source Type: research

Pharmacotherapy of Alzheimer ’s Disease: Seeking Clarity in a Time of Uncertainty
Alzheimer’s disease (AD) is recognized as a major health hazard that mostly affects people older than 60 years. AD is one of the biggest medical, economic, and social concerns to patients and their caregivers. AD was ranked as the 5th leading cause of global deaths in 2016 by the World Health Organization (WHO). Many drugs targeting the production, aggregation, and clearance of Aβ plaques failed to give any conclusive clinical outcomes. This mainly stems from the fact that AD is not a disease attributed to a single-gene mutation. Two hallmarks of AD, Aβ plaques and neurofibrillary tangles (NFTs), can simult...
Source: Frontiers in Pharmacology - March 24, 2020 Category: Drugs & Pharmacology Source Type: research

LncRNA LINC00588 Suppresses the Progression of Osteosarcoma by Acting as a ceRNA for miRNA-1972
Long non-coding RNAs (lncRNAs) are being found to play an increasingly important role in the development of tumors. However, their biological functions and the underlying mechanisms remain unclear. Using information from GEO Datasets, we found that the lncRNA LINC00588 was downregulated in osteosarcoma (OS) in bone but was upregulated in the metastatic tumor present in the lung. We assessed the function of LINC00588 using both overexpression and knock-out studies. We performed colony formation assay, CCK-8 assay, flow cytometry, wound healing assay, transwell assay, and RT-qPCR assay and used a xenograft model to investiga...
Source: Frontiers in Pharmacology - March 24, 2020 Category: Drugs & Pharmacology Source Type: research

Chaiyu-Dixian Formula Exerts Protective Effects on Ovarian Follicular Abnormal Development in Chronic Unpredictable Mild Stress (CUMS) Rat Model
ConclusionsCYDXF (at dose of both 2.73 and 5.46 g/kg) attenuated chronic stress-induced abnormal ovarian follicular development by relieving depression-like behaviors and improving ovarian function through partly the regulation of the BDNF-mediated PI3K/Akt pathway. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 24, 2020 Category: Drugs & Pharmacology Source Type: research

Assessing the Identity of Commercial Herbs From a Cambodian Market Using DNA Barcoding
In this study, we collected 50 types of traditional Cambodian medicinal plants that could not be identified by their appearance from a domestic market. We utilized the DNA barcoding technique, combined with the literature survey, to trace their identities. In the end, 33 species were identified at the species level and 7 species were identified at the genus level. The ethnopharmacological information of 33 medicinal plants was documented. The DNA barcoding technique is useful in the identification of medicinal plants with no previous information. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 24, 2020 Category: Drugs & Pharmacology Source Type: research

Muscone Ameliorates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor- κb Ligand-Induced Osteoclastogenesis by Suppressing TNF Receptor–Associated Factor 6-Mediated Signaling Pathways
Postmenopausal osteoporosis is caused by the deficiency of estrogen, which breaks bone homeostasis and induces levels of pro-inflammatory cytokines. Muscone is a potent anti-inflammatory agent and is used to treat bone fracture in traditional Chinese medicine. However, its anti-osteoclastogenic effects remain unclear. For in vitro study, morphology tests of osteoclastogenesis were firstly performed. And then, factors in RANK-induced NF-κB and MAPK pathways were examined by RT-PCR and Western blot, and the binding of TNF receptor–associated factor (TRAF)6 to RANK was inspected by coimmunoprecipitation and immuno...
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

Network Pharmacology-Based Dissection of the Anti-diabetic Mechanism of Lobelia chinensis
Diabetes mellitus (DM) is a chronic inflammatory disease, and the rapidly increasing DM is becoming a major problem of global public health. Traditional Chinese medicine (TCM) has a long history of treating diabetes. It has been developed and utilized because of its good efficacy and no toxic side effects. Lobelia chinensis is a traditional whole grass herbal. With the continuous deepening of pharmacological research on TCM, the active ingredients of L. chinensis are continuously revealed, which contained the alkaloids, flavonoids, flavonoid glycosides and amino acids that have the good effects of anti-inflammatory, anti-v...
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents
Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficien...
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

Effect of Protein Binding on Exposure of Unbound and Total Mycophenolic Acid: A Population Pharmacokinetic Analysis in Chinese Adult Kidney Transplant Recipients
ConclusionsThe established model adequately described the popPK characteristics of the uMPA, tMPA, and MPAG. The estimated CLuMPA/F and unbound fraction of MPA (FUMPA) in Chinese kidney transplant recipients cotreated with CsA were comparable to those published previously in Caucasians. We recommend monitoring uMPA instead of tMPA to optimize mycophenolate mofetil (MMF) dosing for patients with lower ALB levels. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

Serum Metabolic Profiling Reveals the Antidepressive Effects of the Total Iridoids of Valeriana jatamansi Jones on Chronic Unpredictable Mild Stress Mice
ConclusionThe results confirmed that IRFV exerted an antidepressive effect by regulating multiple metabolic pathways, including the tricarboxylic acid cycle, the synthesis of neurotransmitters, and amino acid metabolism. These findings provide insights into the antidepressive mechanisms of IRFV. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

Antitumor Effects and the Compatibility Mechanisms of Herb Pair Scleromitrion diffusum (Willd.) R. J. Wang –Sculellaria barbata D. Don
This study aimed to explore the in vitro and in vivo antitumor effects of HD-SB extract and to elucidate the underlying compatibility mechanisms. HD, SB, and HD-SB extracts were prepared, and the components were detected by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method. The in vitro antitumor effects of various concentrations of these extract were detected on several tumor cell lines using MTS assay. The in vivo antitumor effects were evaluated in Panc28 cells–bearing nude mice model. The compatibility mechanisms of herb pair HD-SB were evaluated based on the s...
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

Different Processed Products of Curcumae Radix Regulate Pain-Related Substances in a Rat Model of Qi Stagnation and Blood Stasis
This study was aimed at evaluating the effect of different processed products of HSYJ on chemical constituents and pain-related substances to explore underlying mechanisms of HSYJ in treating pain caused by Qi stagnation and blood stasis.MethodsThe effects of different processing methods on the paste yield of water decoction were analyzed, and the content of the main constituents were detected by HPLC. A rat model of Qi stagnation and blood stasis was established by tail clamp stimulation combined with subcutaneous adrenaline injection. After treatment and intervention with HSYJ and its processed products, β-endorphin...
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

Progressive 3D Printing Technology and Its Application in Medical Materials
Three-dimensional (3D) printing enables patient-specific anatomical level productions with high adjustability and resolution in microstructures. With cost-effective manufacturing for high productivity, 3D printing has become a leading healthcare and pharmaceutical manufacturing technology, which is suitable for variety of applications including tissue engineering models, anatomical models, pharmacological design and validation model, medical apparatus and instruments. Today, 3D printing is offering clinical available medical products and platforms suitable for emerging research fields, including tissue and organ printing. ...
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

Effect of Different Doses of Intrathecal Dexmedetomidine as an Adjuvant Combined With Hyperbaric Ropivacaine in Patients Undergoing Cesarean Section
In this study, we aim to investigate the effect of different doses of dexmedetomidine as an adjuvant to hyperbaric ropivacaine in spinal anesthesia for cesarean section.MethodsSeventy-five parturients with American Society of Anesthesiologists (ASA) I or II were anesthetized with intrathecal ropivacaine (12.5 mg) alone (R group) or in combination with dexmedetomidine 3 μg (RD3 group) and 5 μg (RD5 group) to undergo a cesarean section. The anesthetic parameters, postoperative analgesia, stress responses and neonates outcomes were monitored.ResultsThe onset time of sensory block to T10, T4, and peak level in the RD3 gr...
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

Tracing the Edible and Medicinal Plant Pueraria montana and Its Products in the Marketplace Yields Subspecies Level Distinction Using DNA Barcoding and DNA Metabarcoding
This study demonstrated that DNA barcoding is a powerful tool for the identification of P. montana var. lobata and P. montana var. thomsonii at the subspecies level, and we conclude that DNA barcodes can be broadly applied to trace the raw materials of food and herbal products. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

Non-dopaminergic Alterations in Depression-Like FSL Rats in Experimental Parkinsonism and L-DOPA Responses
This study demonstrates that behavioral and transcriptional responses of non-dopaminergic systems to experimental parkinsonism and L-DOPA are modified in a genetic rat model of depression. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

A Pro-resolving Role for Galectin-1 in Acute Inflammation
Galectin-1 (Gal-1) exerts immune-regulatory and anti-inflammatory actions in animal models of acute and chronic inflammation. Its release into the extracellular milieu often correlates with the peak of inflammation suggesting that it may serve a pro-resolving function. Gal-1 is reported to inhibit neutrophil recruitment and induce surface exposure of phosphatidylserine (PS), an “eat me” signal on the surface of neutrophils, yet its role in resolution remains to be fully elucidated. We hypothesized that the anti-inflammatory and pro-resolving properties of Gal-1 are mediated through its ability to inhibit neutro...
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

Screening of Novel Pharmacogenetic Candidates for Mercaptopurine-Induced Toxicity in Patients With Acute Lymphoblastic Leukemia
In conclusion, variants in CYP2A7 and COMT may be considered as novel potential pharmacogenetic markers for 6MP-induced toxicities, but additional independent validations with large sample size and investigations on related mechanisms are further needed. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

Review of Ongoing Activities and Challenges to Improve the Care of Patients With Type 2 Diabetes Across Africa and the Implications for the Future
ConclusionThere are a number of ongoing activities across Africa to improve the management of patients with diabetes including co-morbidities. However, more needs to be done considering the high and growing burden of T2DM in Africa. Ongoing research will help further benefit resource allocation and subsequent care. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 20, 2020 Category: Drugs & Pharmacology Source Type: research

Bulleyaconitine A Exerts Antianxiety and Antivisceral Hypersensitivity Effects
In conclusion, our study demonstrated, for the first time, that BAA exerted marked antivisceral pain and antianxiety effects, which expands the analgesic spectrum and clinical application of BAA. Furthermore, it also it provides a better guidance for the clinical use of BAA. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 19, 2020 Category: Drugs & Pharmacology Source Type: research