Abstract:
:Depression is a widespread chronic medical illness affecting thoughts, mood, and physical health. However, the limited and delayed therapeutic efficacy of monoaminergic drugs has led to intensive research efforts to develop novel antidepressants. ARN-3236 is the first potent and selective inhibitor of salt-inducible kinase 2 (SIK2). In this study, a multidisciplinary approach was used to explore the antidepressant-like actions of ARN-3236 in mice. Chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioral tests, high performance liquid chromatography-tandem mass spectrometry, stereotactic infusion, viral-mediated gene transfer, western blotting, co-immunoprecipitation and immunofluorescence were used together. It was found that ARN-3236 could penetrate the blood-brain barrier. Repeated ARN-3236 administration induced significant antidepressant-like effects in both the CSDS and CUMS models of depression, accompanied with fully preventing the stress-enhanced SIK2 expression and cytoplasmic translocation of cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) in the hippocampus. ARN-3236 treatment also completely reversed the down-regulating effects of CSDS and CUMS on the hippocampal brain-derived neurotrophic factor (BDNF) system and neurogenesis. Moreover, we demonstrated that the hippocampal CRTC1-CREB-BDNF pathway mediated the antidepressant-like efficacy of ARN-3236. Collectively, ARN-3236 possesses strong protecting effects against chronic stress, and could be a novel antidepressant beyond monoaminergic drugs.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Liu Y,Tang W,Ji C,Gu J,Chen Y,Huang J,Zhao X,Sun Y,Wang C,Guan W,Liu J,Jiang Bdoi
10.3389/fphar.2020.624429subject
Has Abstractpub_date
2021-01-14 00:00:00pages
624429issn
1663-9812pii
624429journal_volume
11pub_type
杂志文章abstract::Epigenetics refers to heritable changes in gene expression and chromatin structure without change in a DNA sequence. Several epigenetic modifications and respective regulators have been reported. These include DNA methylation, chromatin remodeling, histone post-translational modifications, and non-coding RNAs. Emergin...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00992
更新日期:2020-08-13 00:00:00
abstract::Excessive bone resorption conducted by osteoclasts is considered as the main cause of osteoclast-related bone diseases such as osteoporosis. Therefore, the suppression of excessive osteoclast formation and function is one of the strategies to treat osteoclast-related bone diseases. Fumitremorgin C (Fum) is a mycotoxin...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00238
更新日期:2020-03-10 00:00:00
abstract::The present paper continues a more complex research related to the increased synergism in terms of both anti-inflammatory and analgesic effect obtained by the addition of chlorpheniramine (CLF) to the common acetylsalicylic acid (ASA), acetaminophen (PAR), and caffeine (CAF) combination. This synergistic effect was pr...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00607
更新日期:2019-06-20 00:00:00
abstract::The recent publication of the σ1R crystal structure is an important cornerstone for the derivation of more accurate activity prediction models. We report here a comparative study involving a set of more than 25,000 structures from our internal database that had been screened for σ1R affinity. Using the recently publis...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00519
更新日期:2019-05-31 00:00:00
abstract::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 tu...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00379
更新日期:2020-03-27 00:00:00
abstract::The increasing use of antibiotics is being driven by factors such as the aging of the population, increased occurrence of infections, and greater prevalence of chronic diseases that require antimicrobial treatment. The excessive and unnecessary use of antibiotics in humans has led to the emergence of bacteria resistan...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00692
更新日期:2019-06-21 00:00:00
abstract::Cardiac remodeling, which is characterized by mechanical and electrical remodeling, is a significant pathophysiological process involved in almost all forms of heart diseases. MicroRNAs (miRNAs) are a group of non-coding RNAs of 20-25 nucleotides in length that primarily regulate gene expression by promoting mRNA degr...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.00903
更新日期:2018-08-17 00:00:00
abstract::Recently, the use of plant-derived medicines is increasing interest in the prevention and treatment of a variety of disorders including metabolic syndromes. Metabolic syndrome is one of the major risk factors for cardiovascular diseases (CVDs) and incidence of mortality worldwide. Scientific evidence suggests that And...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2017.00571
更新日期:2017-08-23 00:00:00
abstract::Fingolimod is used for the treatment of multiple sclerosis (MS) and targets receptors for the bioactive sphingolipid sphingosine-1-phosphate (S1P). Whether fingolimod or other MS therapies conversely affect plasma concentrations of sphingolipids has, however, not yet been analyzed. Herein, we quantified 15 representat...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00412
更新日期:2016-11-03 00:00:00
abstract::Autophagy is an evolutionary conserved physiological process with a fundamental role during development, differentiation, and survival of eukaryotic cells. On the other hand, autophagy dysregulation is observed in many pathological conditions, including cancer. In particular, tumor growth and progression are accompani...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.01141
更新日期:2020-07-24 00:00:00
abstract::Purpose: This study aimed to identify the active components of Fuzheng Huayu (FZHY) formula and the mechanism by which they inhibit the viability of hepatic stellate cells (HSCs) by a combination of network pharmacology and transcriptomics. Methods: The active components of FZHY formula were screened out by text minin...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00525
更新日期:2018-05-24 00:00:00
abstract::The orexin system regulates feeding, nutrient metabolism and energy homeostasis. Acute pharmacological blockade of orexin receptor 1 (OXR-1) in rodents induces satiety and reduces normal and palatable food intake. Genetic OXR-1 deletion in mice improves hyperglycemia under high-fat (HF) diet conditions. Here we invest...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2013.00165
更新日期:2013-12-30 00:00:00
abstract::G protein-coupled receptor kinase 2 (GRK2) is a ubiquitous member of the GRK family that restrains cellular activation by G protein-coupled receptor (GPCR) phosphorylation leading to receptor desensitization and internalization, but has been identified to regulate a variety of signaling molecules, among which may be a...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00059
更新日期:2019-02-04 00:00:00
abstract::The entactogen MDMA (3,4-methylenedioxy-methamphetamine, "Ecstasy") exerts its psychotropic effects acting primarily as a substrate of the serotonin transporter (SERT) to induce a non-exocytotic release of serotonin. Nevertheless, the roles of specific positions of the aromatic ring of MDMA associated with the modulat...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00157
更新日期:2019-02-28 00:00:00
abstract::Aging is associated with age-related diseases and an increase susceptibility of cancer. Dissecting the molecular mechanisms that underlie aging and longevity would contribute to implications for preventing and treating the age-dependent diseases or cancers. Multiple signaling pathways such as the insulin/IGF-1 signali...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2017.00548
更新日期:2017-08-23 00:00:00
abstract:Ethnopharmacological Relevance:Diarrhea is a major medical problem in clinical practice. According to the theory of traditional Chinese medicine (TCM), different types of diarrhea should be treated with different TCM formulations based on the targeted medical condition. Dampness-heat diarrhea (DHD) is a serious diarrhe...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00197
更新日期:2020-03-03 00:00:00
abstract::Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and remains the most common life-shortening diseases affecting the exocrine organs. The absence of this channel results in an imbalance of ion concentrations across the cell membrane and results in more a...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.01113
更新日期:2018-10-08 00:00:00
abstract::Particulate matter poses health risk to developing organisms. To investigate particulate matters with a diameter smaller than 2.5 um (PM2.5)-induced developmental cardiotoxicity, fertile chicken eggs were exposed to PM2.5 via air cell injection at doses of 0.05, 0.2, 0.5, 2, and 5 mg/egg kg. Morphological changes in t...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00841
更新日期:2020-06-05 00:00:00
abstract::The abscisic acid (ABA) is a phytohormone involved in plant growth, development and environmental stress response. Recent study showed ABA can also be detected in other organisms, including mammals. And it has been reported that ABA can improve learning and memory in rats. In this study, we attempted to investigate th...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01141
更新日期:2018-10-09 00:00:00
abstract::Purpose: The present study compared the risk of ischemic stroke in atrial fibrillation (AF) patients receiving digoxin and amiodarone. Methods: A retrospective cohort study was conducted using the longitudinal population-based database of Taiwan's National Health Insurance program. Patients with AF who received amioda...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00448
更新日期:2018-05-07 00:00:00
abstract::At present there is no effective treatment of pathologies associated with the death of neurons and glial cells which take place as a result of physical trauma or ischemic lesions of the nervous system. Thus, researchers have high hopes for a treatment based on the use of stem cells (SC), which are potentially able to ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2017.00628
更新日期:2017-09-08 00:00:00
abstract::The interaction between programmed cell death protein 1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) induces exhaustions of cytotoxic lymphocytes in the tumor microenvironment, which facilitates tumor immune evasion. PD-1/PD-L1 blockade therapy, which prevents the receptors and ligands from binding to each ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00726
更新日期:2019-07-02 00:00:00
abstract::We aimed to ascertain the mechanism underlying the effects of acteoside (ACT) from Ligustrum robustum (Roxb.) Blume (Oleaceae) on lipid metabolism and synthesis. ACT, a water-soluble phenylpropanoid glycoside, is the most abundant and major active component of L. robustum; the leaves of L. robustum, known as kudingcha...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00602
更新日期:2019-05-24 00:00:00
abstract::In-depth research on processing can promote the globalization of processed herbs. The purpose of this study is to propose an improved strategy for processing effect investigation. Frankincense and processed frankincense were used as research subjects. First, high-speed countercurrent chromatography (HSCCC) and prepara...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01482
更新日期:2018-12-18 00:00:00
abstract::Objective: Children with autism spectrum disorder (ASD) commonly exhibit comorbid symptoms such as aggression, hyperactivity and anxiety. Several studies are being conducted worldwide on cannabidiol use in ASD; however, these studies are still ongoing, and data on the effects of its use is very limited. In this study ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01521
更新日期:2019-01-09 00:00:00
abstract::Background: Cefoperazone/sulbactam is a broad-spectrum antibacterial agent. Drug-induced immune hemolytic anemia is a rare but serious condition, and reactive thrombocytosis is caused by processes extrinsic to the megakaryocyte. Limited data are available for cefoperazone/sulbactam-associated hemolytic anemia and reac...
journal_title:Frontiers in pharmacology
pub_type:
doi:10.3389/fphar.2019.01342
更新日期:2019-11-08 00:00:00
abstract::l-3,4-Dihydroxyphenylalanine (l-DOPA) is the most effective therapeutic agent for Parkinson's disease (PD). l-DOPA is traditionally believed to be an inert amino acid that exerts actions and effectiveness in PD through its conversion to dopamine. In contrast to this generally accepted idea, l-DOPA is proposed to be a ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.01119
更新日期:2019-10-03 00:00:00
abstract::Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase recently implicated in biochemical, physiological, and behavioral responses to ethanol. Thus, manipulation of ALK signaling may represent a novel approach to treating alcohol use disorder (AUD). Ethanol induces adaptations in glutamatergic synapses onto nu...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00533
更新日期:2017-08-15 00:00:00
abstract::Oxidative insult, inflammation, apoptosis and autophagy play a pivotal role in the etiology of diabetic nephropathy, a global health concern. Ferulic acid, a phytochemical, is reported to protect against varied diseased conditions. However, the ameliorative role and mechanisms of ferulic acid in averting STZ-mediated ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00027
更新日期:2019-02-05 00:00:00
abstract::Drug-induced liver injury (DILI) is a major clinical problem where natural compounds hold promise for its abrogation. Khaya grandifoliola (Meliaceae) is used in Cameroonian traditional medicine for the treatment of liver related diseases and has been studied for its hepatoprotective properties. Till date, reports show...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00653
更新日期:2017-09-19 00:00:00