Inhaled Phosphodiesterase 4 (PDE4) Inhibitors for Inflammatory Respiratory Diseases
PDE4 inhibitors can suppress a variety of inflammatory cell functions that contribute to their anti-inflammatory actions in respiratory diseases like chronic obstructive pulmonary disease (COPD) and asthma. The systemically delivered PDE4 inhibitor roflumilast has been approved for use in a subset of patients with severe COPD with chronic bronchitis and a history of exacerbations. Use of systemically delivered PDE4 inhibitors has been limited by systemic side effects. Inhaled PDE4 inhibitors have been considered as a viable alternative to increase tolerability and determine the maximum therapeutic potential of PDE4 inhibit...
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Asking More of Our EHR Systems to Improve Outcomes for Pediatric Patients
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Dendrobium officinale Polysaccharide Protected CCl4-Induced Liver Fibrosis Through Intestinal Homeostasis and the LPS-TLR4-NF- κB Signaling Pathway
We explored the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on CCl4-induced liver fibrosis with respect to the intestinal hepatic axis using a rat model. Histopathological staining results showed that DOP alleviated extensive fibrous tissue proliferation in interstitium and lessened intestinal mucosal damage. Western blot and PCR results showed that DOP maintained intestinal balance by upregulating the expression of tight junction proteins such as occludin, claudin-1, ZO-1, and Bcl-2 proteins while downregulating the expression of Bax and caspase-3 proteins in the intestine. The transepithelial electr...
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

A Novel Sulfonyl-Based Small Molecule Exhibiting Anti-cancer Properties
Phenotypic screening is an ideal strategy for the discovery of novel bioactive molecules. Using a customized high-throughput screening (HTS) assay employing primary T lymphocytes, we screened a small library of 4,398 compounds with unknown biological function/target to identify compounds eliciting immunomodulatory properties and discovered a sulfonyl-containing hit, we named InhiTinib. This compound inhibited interferon (IFN)-gamma production and proliferation of primary CD3+ T cells without inducing cell death. In contrast, InhiTinib triggered apoptosis in several murine and human cancer cell lines. Besides, the compound ...
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation
In this study, we evaluated the potential of very early intervention with the active form of vitamin D (1,25-dihydroxyvitamin D3) to control neuroinflammation during EAE development. EAE was induced in C57BL/6J mice and 1,25-dihydroxyvitamin D3 administration began 1 day after disease induction. This procedure decreased prevalence, clinical score, inflammation, and demyelination. It also reduced MHCII expression in macrophages and microglia as well as the level of oxidative stress and messenger RNA (mRNA) expression for NLRP3, caspase-1, interleukin (IL)-1β, CX3CR1, CCL17, RORc and Tbx21 at the CNS. Otherwise, mRNA ex...
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Medicinal Plants and Phytochemicals for the Treatment of Pulmonary Hypertension
ConclusionStudies have shown that herbs and phytochemicals used to treat PH do their effects from six mechanisms. These mechanisms include antiproliferative, antioxidant, antivascular remodeling, anti-inflammatory, vasodilatory and apoptosis inducing actions. According to the present study, many of these medicinal plants and phytochemicals can have effects that are more therapeutic than chemical drugs if used appropriately. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

Hypertension Is Associated With Intestinal Microbiota Dysbiosis and Inflammation in a Brazilian Population
Hypertension is a major global health challenge, as it represents the main risk factor for stroke and cardiovascular disease. It is a multifactorial clinical condition characterized by high and sustained levels of blood pressure, likely resulting from a complex interplay of endogenous and environmental factors. The gut microbiota has been strongly supposed to be involved but its role in hypertension is still poorly understood. In an attempt to fill this gap, here we characterized the microbial composition of fecal samples from 48 hypertensive and 32 normotensive Brazilian individuals by next-generation sequencing of the 16...
Source: Frontiers in Pharmacology - March 12, 2020 Category: Drugs & Pharmacology Source Type: research

The Tripartite Nexus: Autophagy, Cancer, and Tripartite Motif-Containing Protein Family Members
Autophagy is a cellular degradative process that has multiple important actions in cancer. Autophagy modulation is under consideration as a promising new approach to cancer therapy. However, complete autophagy dysregulation is likely to have substantial undesirable side effects. Thus, more targeted approaches to autophagy modulation may prove clinically beneficial. One potential avenue to achieving this goal is to focus on the actions of tripartite motif-containing protein family members (TRIMs). TRIMs have key roles in an array of cellular processes, and their dysregulation has been extensively linked to cancer risk and p...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Synergistic Effects of Erzhi Pill Combined With Methotrexate on Osteoblasts Mediated via the Wnt1/LRP5/ β-Catenin Signaling Pathway in Collagen-Induced Arthritis Rats
This study demonstrated that EZP in combination with MTX played a synergistic role in regulating OBs in RA, which was connected to the modulatory effect of EZP and MTX on the Wnt1/LRP5/β-catenin signaling pathway. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Herbal Therapy for the Treatment of Acetaminophen-Associated Liver Injury: Recent Advances and Future Perspectives
Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury worldwide, and mitochondrial oxidative stress is considered the major event responsible for APAP-associated liver injury (ALI). Despite the identification of N-acetyl cysteine, a reactive oxygen species scavenger that is regarded as an effective clinical treatment, therapeutic effectiveness remains limited due to rapid disease progression and diagnosis at a late phase, which leads to the need to explore various therapeutic approaches. Since the early 1990s, a number of natural products and herbs have been found to have hepatoprotective effects ...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Editorial: The Canonical and Non-Canonical Endocannabinoid System as a Target in Cancer and Acute and Chronic Pain
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Astaxanthin Ameliorated Parvalbumin-Positive Neuron Deficits and Alzheimer ’s Disease-Related Pathological Progression in the Hippocampus of AppNL-G-F/NL-G-F Mice
Growing evidence suggests that oxidative stress due to amyloid β (Aβ) accumulation is involved in Alzheimer’s disease (AD) through the formation of amyloid plaque, which leads to hyperphosphorylation of tau, microglial activation, and cognitive deficits. The dysfunction or phenotypic loss of parvalbumin (PV)-positive neurons has been implicated in cognitive deficits. Astaxanthin is one of carotenoids and known as a highly potent antioxidant. We hypothesized that astaxanthin’s antioxidant effects may prevent the onset of cognitive deficits in AD by preventing AD pathological processes associated with o...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Neuroprotective Effect of Danhong Injection on Cerebral Ischemia-Reperfusion Injury in Rats by Activation of the PI3K-Akt Pathway
In this study, we investigated the neuroprotective effect of DHI against cerebral ischemia-reperfusion injury mediated via the PI3K-Akt signaling pathway. After establishing the model of middle cerebral artery occlusion (MCAO), 60 male Sprague–Dawley rats were allocated to six groups as follows: sham, MCAO, DHI (MCAO + DHI), LY294002 (MCAO + LY294002 [PI3K-Akt pathway specific inhibitor]), DHI + LY294002 (MCAO + DHI + LY294002), and NMDP + LY294002 (MCAO + NMDP [nimodipine] + LY294002). Hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used to evaluate t...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Chronic Fluoxetine Impairs the Effects of 5-HT1A and 5-HT2C Receptors Activation in the PAG and Amygdala on Antinociception Induced by Aversive Situation in Mice
Growing evidence suggests an important role of fluoxetine with serotonin 5-HT1A and 5-HT2C receptors in the modulation of emotion and nociception in brain areas such as the amygdala and periaqueductal gray (PAG). Acute fluoxetine impairs 5-HT2C (but not 5-HT1A) receptor activation in the amygdaloid complex. Given that fluoxetine produces its clinical therapeutic effects only when given chronically, this study investigated the effects of chronic treatment with fluoxetine on the effects produced by 5-HT1A or 5-HT2C receptors activation in the amygdala or PAG on fear-induced antinociception. We recorded the effects of chronic...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Repurposing Clinical Drugs as AdoMetDC Inhibitors Using the SCAR Strategy
With the escalating costs in drug development, discovering new uses of approved drugs, i.e., drug repurposing, has attracted increasing interest. Spermidine and spermine are important polyamines for most cells and their biosynthesis are strictly regulated by the polyamine metabolic network. In cancerous cells and tumor environments, the concentrations of polyamines are much higher than in normal cells. During the synthesis of spermidine and spermine, an amino-propyl group is provided by decarboxylated S-adenosylmethionine, and the latter is generated from S-adenosylmethionine by AdoMetDC (AdoMet decarboxylase). Therefore, ...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

The Reliability of Histamine Pharmacodynamic Response Phenotype Classification in Children With Allergic Disease
We have identified distinct histamine pharmacodynamic response phenotypes in children with allergic disease utilizing histamine iontophoresis with laser Doppler (HILD). These response phenotypes may be relevant in guiding therapeutic decision making for agents targeting the allergic response pathways. However, the reliability of these response phenotypes has not been assessed. Therefore, we performed HILD in children with allergic rhinitis and/or asthma on two to three separate occasions. HILD response-time data were analyzed in NONMEM using a linked effect PKPD model. Examination of observed vs. classified response phenot...
Source: Frontiers in Pharmacology - March 11, 2020 Category: Drugs & Pharmacology Source Type: research

Erratum: Effect of Triptolide on Dextran Sodium Sulfate-Induced Ulcerative Colitis and Gut Microbiota in Mice
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A
In conclusion, miR-18a-5p may be a useful drug target for pathologic ocular neovascularization. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Ancient Chinese Medicine Herbal Formula Huanglian Jiedu Decoction as a Neoadjuvant Treatment of Chemotherapy by Improving Diarrhea and Tumor Response
Conclusion: Our study suggests the potential of HLJDD as a neoadjuvant treatment of chemotherapy by reducing diarrhea and improving tumor response. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

The Role of Fibroblast Growth Factor 10 Signaling in Duodenal Atresia
ConclusionDetermining the etiology of DA in humans is a clinical and scientific imperative. Fgf10/Fgfr2b murine models represent current science’s best key to unlocking this mystery. However, further research is required to understand the complex role of FGF10/FGFR2b signaling in DA development. Such complexity is expected, given the lethality of their associated defects makes ubiquitous interruption of either Fgf10 or Fgfr2b genes an unlikely cause of DA in humans. Rather, local or tissue-specific mutation in Fgf10, Fgfr2b, or their downstream targets, is the hypothesized basis of DA etiology. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

In silico Docking Studies of Fingolimod and S1P1 Agonists
We examined the binding properties of the endogenous substrate as well as a selection of synthetic sphingosine-derived S1P1 modulators of S1P1 with in silico docking simulations using the software package Molecular Operating Environment® (MOE®). The modeling studies reveal the relevance of phosphorylation, i.e., the presence of a phosphate or phosphonate moiety within the substrate for successful binding to occur, and indicate which residues are responsible for S1P1 binding of the most prominent sphingosine-1-phosphate receptor (S1PR) modulators, including fingolimod and its structural relatives. Furthermore, trend...
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

SIRT1 Mediates Effects of FGF21 to Ameliorate Cisplatin-Induced Acute Kidney Injury
In this study, we show that the expression of FGF21 is significantly upregulated in both in vitro and in vivo cisplatin-induced AKI models. Administration of recombinant FGF21 to cisplatin-induced AKI mice resulted in significantly decreased blood urea nitrogen (BUN) and serum creatinine levels, as well as significantly reduced protein levels of kidney injury molecule-1 (TIM-1), C-caspase 3, and Bax. H&E-stained kidney sections from cisplatin-induced AKI mice treated with recombinant FGF21 showed a relatively normal renal tissue structure, a reduced number of necrotic sites and vacuolar changes, and decreased casts, su...
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Fumitremorgin C Attenuates Osteoclast Formation and Function via Suppressing RANKL-Induced Signaling Pathways
In this study, we aim to find out whether Fum can inhibit the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and function. The results showed that Fum could significantly attenuate osteoclast formation and function at concentrations from 2.5 to 10 µM. The protein expression of bone resorption factors such as NFATc1, cathepsin K, V-ATPase-d2, and c-Fos was suppressed with the treatment of Fum at a concentration of 10 µM. In addition, Fum was also shown to suppress the activity of NF-κB, intracellular reactive oxygen species level, and MAPK pathway. Taken together,...
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Targeting Neuroinflammation in Neovascular Retinal Diseases
Retinal blood vessels provide the necessary energy, nutrients and oxygen in order to support visual function and remove harmful particles from blood, thus acting to protect neuronal cells. The homeostasis of the retinal vessels is important for the maintenance of retinal visual function. Neovascularization is the most common cause of blindness in patients with retinopathy. Previous studies have shown that inflammatory mediators are known key regulators in retinopathy, but their causal link has been elusive. Although inflammation is often thought to arise from inflammatory cells like macrophages, neutrophils, and resident m...
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Circulating Retinol-Binding Protein 4 as a Possible Biomarker of Treatment Response for Ankylosing Spondylitis: An Array-Based Comparative Study
ConclusionA dysregulated serum protein profile existed in AS. ADA exerted a considerable but not entire alteration toward the dysregulation. RBP4 could be a biomarker for predicting and monitoring ADA treatment response. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Dihydroartemisinin-Loaded Magnetic Nanoparticles for Enhanced Chemodynamic Therapy
Recently, chemodynamic therapy (CDT) has represented a new approach for cancer treatment with low toxicity and side effects. Nonetheless, it has been a challenge to improve the therapeutic effect through increasing the amount of reactive oxygen species (ROS). Herein, we increased the amount of ROS agents in the Fenton-like reaction by loading dihydroartemisinin (DHA) which was an artemisinin (ART) derivative containing peroxide groups, into magnetic nanoparticles (MNP), thereby improving the therapeutic effect of CDT. Blank MNP were almost non-cytotoxic, whereas three MNP loading ART-based drugs, MNP-ART, MNP-DHA, and MNP-...
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Hepatic Proteomic Changes and Sirt1/AMPK Signaling Activation by Oxymatrine Treatment in Rats With Non-alcoholic Steatosis
ConclusionThe present study has confirmed the significant efficacy of OMT for improving steatosis and revealed hepatic proteomic changes and Sirt1/AMPK signaling activation by OMT treatment in rats with steatosis. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Dazhu Hongjingtian Preparation as Adjuvant Therapy for Unstable Angina Pectoris: A Meta-Analysis of Randomized Controlled Trials
Conclusion: Adjuvant treatment with DZHJT has an add-on effect in reducing angina pectoris attacks in patients with UAP. The beneficial effect may be correlated with regulating whole-blood viscosity, plasma viscosity, fibrinogen, thromboxanes B2, and CRP level. However, future well-designed prospective, randomized, double-blind placebo-controlled trials with large sample sizes are required to evaluate the evidence. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

The Value of Herbarium Collections to the Discovery of Novel Treatments for Alzheimer ’s Disease, a Case Made With the Genus Eriodictyon
Plants, in particular those with a history in traditional medicine, hold enormous potential as sources of new therapies for dementias such as Alzheimer’s disease (AD). The largest collections of plants can be found in herbaria all over the world, but the value of these collections to AD drug discovery has been significantly neglected. As a proof of principle, we investigated the neuroprotective activity of herbarium specimens of Eriodictyon (yerba santa), a genus with a long history of usage by the indigenous tribes in California to treat respiratory and age-related complications. Dichloromethane extracts were prepar...
Source: Frontiers in Pharmacology - March 10, 2020 Category: Drugs & Pharmacology Source Type: research

Corrigendum: Sensing Technology to Monitor Behavioral and Psychological Symptoms and to Assess Treatment Response in People With Dementia. A Systematic Review
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Editorial: Redox Biology of Skin Aging and Carcinogenesis: the Role of Natural Antioxidants as Potential Protective Agents
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Resolvin D1 Modulates the Intracellular VEGF-Related miRNAs of Retinal Photoreceptors Challenged With High Glucose
Stimulation of retinal photoreceptors with elevated glucose concentration (30 mM) for 96 h, served as diabetic retinopathy in vitro model to study Resolvin D1 (50 nM) effects on neovascularization. VEGF and anti-angiogenic miR-20a-3p, miR-20a-5p, miR-106a-5p, and miR-20b expression was assessed either in photoreceptors exposed to HG or in exosomes released by those cells. High glucose increased VEGF levels and concurrently decreased anti-angiogenic miRNAs content in photoreceptors and exosomes. RvD1 reverted the effects of glucose damage in photoreceptors and exosomal pro-angiogenic potential, tested with the HUVEC angioge...
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Marketing and Pricing Strategies of Blockbuster Drugs in the South Korean Market: A 15-Year Retrospective Cohort Study for Choline Alfoscerate
ConclusionThe Korean market appears to be an example of perfect competition when we focus on the number of manufacturers. However, the market is near-monopolistic when examining the price of generic drugs. While product competition between different forms of drugs is effective in lowering price, product competition within the same form of a drug does not exist in the market. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Identification and Quantification of Bioactive Molecules Inhibiting Pro-inflammatory Cytokine Production in Spent Coffee Grounds Using Metabolomics Analyses
In this study, we assessed the anti-inflammatory properties of spent coffee grounds. Methanolic extracts of spent coffee grounds obtained from 3 Arabica cultivars possess compounds that exerted inhibitory effects on the secretion of inflammatory mediators (TNF-α, IL-6, and IL-10) induced by a human pro-monocytic cell line differentiated with PMA and stimulated with lipopolysaccharide (LPS). Our results indicated that the cytokine suppressive activities of the spent coffee ground (SCG) extracts were different among coffee cultivars tested. Hawaiian Kona extracts exhibited inhibitory effects on the expression of 3 exam...
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Effect of Diosgenin on the Circulating MicroRNA Profile of Ovariectomized Rats
The present study aimed to assess the changes in circulating microRNA (miRNA) expression profiles associated with the potential osteoprotective effect of diosgenin (DIO) in ovariectomized (OVX) rats. Wistar rats (female) were subjected to a sham operation (SHAM group) or ovariectomy. OVX rats were treated with DIO (DIO group) or vehicle (OVX group) for 12 weeks. Following treatment, the serum estradiol, bone turnover biomarker levels, and the microarchitecture of tibias were assayed. Based on miRNA microarray and qRT-PCR analyses, differentially expressed (DE) circulating miRNAs were identified between the OVX and SHAM gro...
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Dose- and Time-Dependent Cytotoxicity of Carteolol in Corneal Endothelial Cells and the Underlying Mechanisms
Carteolol is a non-selective β-adrenoceptor antagonist used for the treatment of glaucoma, and its abuse might be cytotoxic to the cornea. However, its cytotoxicity and underlying mechanisms need to be elucidated. Herein, we used an in vivo model of feline corneas and an in vitro model of human corneal endothelial cells (HCECs), respectively. In vivo results displayed that 2% carteolol (clinical dosage) could induce monolayer density decline and breaking away of feline corneal endothelial (FCE) cells. An in vitro model of HCECs that were treated dose-dependently (0.015625–2%) with carteolol for 2–28 h, res...
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Cancer Stem Cells: A Potential Breakthrough in HCC-Targeted Therapy
Cancer stem cells (CSCs) are subpopulations of cells with stem cell characteristics that produce both cancerous and non-tumorigenic cells in tumor tissues. The literature reports that CSCs are closely related to the development of hepatocellular carcinoma (HCC) and promote the malignant features of HCC such as high invasion, drug resistance, easy recurrence, easy metastasis, and poor prognosis. This review discusses the origin, molecular, and biological features, functions, and applications of CSCs in HCC in recent years; the goal is to clarify the importance of CSCs in treatment and explore their potential value in HCC-ta...
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Activation of BK Channels Prevents Hepatic Stellate Cell Activation and Liver Fibrosis Through the Suppression of TGF β1/SMAD3 and JAK/STAT3 Profibrotic Signaling Pathways
Large-conductance and Ca2+-activated K+ (BK) channels are expressed in human hepatic stellate cells (HSCs), where they have roles in normal hepatic microcirculation, as well as in portal hypertension in liver cirrhosis through the regulation of contractility in activated HSCs. Nevertheless, whether BK channel activity exerts protective effects against aberrant HSC activation and hepatic fibrosis is unknown. Here, we report that BK channels are expressed in activated primary rat HSCs as well as in a human HSC line. Moreover, whole-cell K+ currents recorded from activated HSCs were markedly increased by exposure to rottlerin...
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Modular Characteristics and Mechanism of Action of Herbs for Endometriosis Treatment in Chinese Medicine: A Data Mining and Network Pharmacology –Based Identification
In conclusion, we identified some important targets, target pairs, and regulatory networks, using bioinformatics and data mining. The combination of data mining and network pharmacology may offer an efficient method for drug discovery and development from herbal medicines. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Shenlian Extract Against Myocardial Injury Induced by Ischemia Through the Regulation of NF- κB/IκB Signaling Axis
Ischemic heart disease (IHD), caused predominantly by atherosclerosis, is a leading cause of global mortality. Our previous studies showed that Shenlian extract (SL) could prevent the formation of atherosclerosis and enhance the stability of atherosclerotic plaques. To further investigate the protective effects of SL on myocardial ischemic injury and its possible mechanisms, anesthetized dogs, ex vivo rat hearts, and H9c2 cardiomyocytes were used as models. The results showed that SL had a significant protective effect on the anesthetized dog ligating coronary artery model, reduced the degree of myocardial ischemia (&Sigma...
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases
Cannabis sativa, commonly known as marijuana, contains a pool of secondary plant metabolites with therapeutic effects. Besides Δ9-tetrahydrocannabinol that is the principal psychoactive constituent of Cannabis, cannabidiol (CBD) is the most abundant nonpsychoactive phytocannabinoid and may represent a prototype for anti-inflammatory drug development for human pathologies where both the inflammation and oxidative stress (OS) play an important role to their etiology and progression. To this regard, Alzheimer's disease (AD), Parkinson's disease (PD), the most common neurodegenerative disorders, are characterized by exte...
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Inhibition of Tyrosinase by Mercury Chloride: Spectroscopic and Docking Studies
Inorganic mercury compounds have been used in skin-lightening products since ancient times. Although a previous study demonstrated that mercury impeded the transfer of Cu2+ to the apotyrosinase, the effect of mercury on tyrosinase is still unclear. In the present study, the mechanism of mercury chloride (HgCl2) induced inactivation of tyrosinase was investigated for the first time. The IC50 values were 29.97 and 77.93 μmol/L for monophenolase and diphenolase, respectively. A kinetic analysis revealed that HgCl2 inhibited tyrosinase activity in an irreversible non-competitive manner. The strong intrinsic fluorescence que...
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Jiang Tang Xiao Ke Granule Protects Hepatic Tissue of Diabetic Mice Through Modulation of Insulin and Ras Signaling – A Bioinformatics Analysis of MicroRNAs and mRNAs Network
ObjectiveTo investigate the impact of JTXK granule on the miRNA expression profiles in hepatic tissue of diabetic mice, and to explore the molecular targets and associated signaling pathways of JTXK granule in its anti-diabetic effect.MethodsEight mice were randomly selected as normal group fed with chow diet. Then high fat diet was used to induce diabetic model, and the mice were subsequently divided into JTXK-treated group (J group, n = 6) and model group (M group, n = 6). After 8 weeks’ intervention we examined the fasting blood glucose and observed the histopathologic changes in hepatic tissue between these two g...
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

Processing and Polyherbal Formulation of Tetradium ruticarpum (A. Juss.) Hartley: Phytochemistry, Pharmacokinetics, and Toxicity
Herbal medicine is a major part of traditional Chinese medicine (TCM), which is evolved as a system of medical practice from ancient China. The use of herbal medicine is mainly based on practice and theories and concepts rooted in ancient philosophy. In the era of evidence-based medicine, it is essential to accurately evaluate herbal remedy with standard/modern medical practice approaches. Tetradium ruticarpum (A. Juss.) Hartley (TR), a medicinal plant with diversify bioactive components, has been broadly used to treat pain and gastrointestinal disorders in TCM. However, TR has also been reported to have potential toxicity...
Source: Frontiers in Pharmacology - March 6, 2020 Category: Drugs & Pharmacology Source Type: research

A Metabolic Insight Into the Neuroprotective Effect of Jin-Mai-Tong (JMT) Decoction on Diabetic Rats With Peripheral Neuropathy Using Untargeted Metabolomics Strategy
Jin-Mai-Tong (JMT) decoction is a traditional Chinese compound prescription for treating diabetic peripheral neuropathy (DPN). The aim of this study is to investigate the neuroprotective effect of JMT decoction on diabetic rats with peripheral neuropathy and to elucidate the potential mechanism based on a metabolomics approach. Sprague-Dawley (SD) rats were randomly divided into four groups: control group, Streptozotocin (STZ) induced model group, JMT low dose (JMT-L) treated group and JMT high dose (JMT-H) treated group. After 12 weeks of treatment, behavioral changes, small fiber loss, and histopathological damages of sc...
Source: Frontiers in Pharmacology - March 5, 2020 Category: Drugs & Pharmacology Source Type: research

1H-NMR Metabolomics and LC-MS Analysis to Determine Seasonal Variation in a Cosmeceutical Plant Leucosidea sericea
Leucosidea sericea is an evergreen shrub belonging to the Rosaceae family with previous studies that indicated that L. sericea extracts exhibited strong anti-bacterial properties against Propionibacterium acnes, showing potential as a cosmeceutical. The plant is traditionally used as a vermifuge, as an astringent and to treat conjunctivitis. Commercial production is, however, not possible as no information is available on cultivation and the effect of external environmental factors such as seasonal variation on the medicinal properties of the plant. Seasonal variation was investigated and it was found that significant diff...
Source: Frontiers in Pharmacology - March 5, 2020 Category: Drugs & Pharmacology Source Type: research

Structure-Function of the High Affinity Substrate Binding Site (S1) of Human Norepinephrine Transporter
The human norepinephrine transporter (hNET) is a member of the neurotransmitter/sodium symporter family, which also includes the neuronal monoamine transporters for serotonin (SERT) and dopamine (DAT). Its involvement in chronic pain and many neurological disorders underlies its pharmaceutical importance. Using the X-ray crystal structures of the human serotonin transporter (hSERT) (PDB 5I6X) and Drosophila melanogaster dopamine transporter (dDAT) (PDB 4M48 and PDB 4XPA) as templates, we developed molecular models for norepinephrine (NE) bound to its high affinity binding site (S1) in the hNET. Our model suggests that the ...
Source: Frontiers in Pharmacology - March 5, 2020 Category: Drugs & Pharmacology Source Type: research

Connexin43 Hemichannel Targeting With TAT-Gap19 Alleviates Radiation-Induced Endothelial Cell Damage
ConclusionOur findings suggest that endothelial Cx43 hemichannels contribute to various IR-induced processes, such as ROS, cell death, inflammation, and senescence, resulting in an increase in endothelial cell damage, which could be protected by blocking these hemichannels. Thus, targeting Cx43 hemichannels may potentially exert radioprotective effects. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 5, 2020 Category: Drugs & Pharmacology Source Type: research

Development of a Novel Hematological Malignancy Specific Patient-Reported Outcome Measure (HM-PRO): Content Validity
ConclusionThe findings of this study confirm that the HM-PRO possesses a strong content validity, includes all the issues important to patients and is easy to read, understand and respond to spontaneously. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 5, 2020 Category: Drugs & Pharmacology Source Type: research

Functional Selectivity and Antinociceptive Effects of a Novel KOPr Agonist
Kappa opioid receptor (KOPr) agonists represent alternative analgesics for their low abuse potential, although relevant adverse effects have limited their clinical use. Functionally selective KOPr agonists may activate, in a pathway-specific manner, G protein-mediated signaling, that produces antinociception, over β-arrestin 2-dependent induction of p38MAPK, which preferentially contributes to adverse effects. Thus, functionally selective KOPr agonists biased toward G protein-coupled intracellular signaling over β-arrestin-2-mediated pathways may be considered candidate therapeutics possibly devoid of many of the...
Source: Frontiers in Pharmacology - March 5, 2020 Category: Drugs & Pharmacology Source Type: research