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Drug development in targeting ion channels for brain edema.
Abstract Cerebral edema is a pathological hallmark of various central nervous system (CNS) insults, including traumatic brain injury (TBI) and excitotoxic injury such as stroke. Due to the rigidity of the skull, edema-induced increase of intracranial fluid significantly complicates severe CNS injuries by raising intracranial pressure and compromising perfusion. Mortality due to cerebral edema is high. With mortality rates up to 80% in severe cases of stroke, it is the leading cause of death within the first week. Similarly, cerebral edema is devastating for patients of TBI, accounting for up to 50% mortality. Curr...
Source: Acta Pharmacologica Sinica - August 26, 2020 Category: Drugs & Pharmacology Authors: Luo ZW, Ovcjak A, Wong R, Yang BX, Feng ZP, Sun HS Tags: Acta Pharmacol Sin Source Type: research

Total Glycosides of Cistanche deserticola Promote Neurological Function Recovery by Inducing Neurovascular Regeneration via Nrf-2/Keap-1 Pathway in MCAO/R Rats
ConclusionTGs are the main active components of C. deserticola against MCAO/R-induced cerebral injury, and protection is mainly via the Nrf-2/Keap-1 pathway.
Source: Frontiers in Pharmacology - March 16, 2020 Category: Drugs & Pharmacology Source Type: research

Endothelin-1 (ET-1) Promotes a Proinflammatory Microglia Phenotype in Diabetic Conditions.
Abstract Diabetes increases the risk and severity of cognitive impairment, especially after ischemic stroke. It is also known that the activation of ET system is associated with cognitive impairment and microglia around periinfarct area produce ET-1. However, little is known about the effect of ET-1 on microglial polarization, especially under diabetic conditions. We hypothesized that a) ET-1 activates microglia to proinflammatory M-1 like phenotype, and b) Hypoxia/LPS activates the microglial ET system and promotes microglial activation towards M-1 phenotype in diabetic conditions. Microglial cells (C8B4) culture...
Source: Canadian Journal of Physiology and Pharmacology - March 1, 2020 Category: Drugs & Pharmacology Authors: Abdul Y, Jamil S, He L, Li W, Ergul A Tags: Can J Physiol Pharmacol Source Type: research

Agomelatine protects against permanent cerebral ischaemia via the Nrf2-HO-1 pathway.
In this study, we focused on the effect of agomelatine on permanent cerebral ischaemia in a rat model. Male Wistar rats were randomly divided into the following four groups (n = 6/group): sham operating group, permanent ischaemic model group, permanent ischaemic model plus agomelatine (40 mg/kg, i.p) group and permanent ischaemic model plus melatonin (10 mg/kg, i.p) group. Twenty-four h after ischaemic onset, we investigated the neurological deficits and infarct volume using neurological deficit scores, 2,3,5-triphenyltetrazolium chloride (TTC) and transmission electron microscopy (Kochanski et al.). Moreover, we a...
Source: European Journal of Pharmacology - February 17, 2020 Category: Drugs & Pharmacology Authors: Chumboatong W, Khamchai S, Tocharus C, Govitrapong P, Tocharus J Tags: Eur J Pharmacol Source Type: research

Protective Effect of Stachydrine Against Cerebral Ischemia-Reperfusion Injury by Reducing Inflammation and Apoptosis Through P65 and JAK2/STAT3 Signaling Pathway
This study investigated the neuroprotective effect of stachydrine. Male Sprague-Dawley (SD) rats were randomly divided into sham, control, and stachydrine groups. The neurological deficit score was evaluated and the infarct size of the brain was measured using 2,3,5-triphenyltetra-zolium (TTC) chloride staining assay, and the pathological changes in the brain tissues were examined by HE staining. Nissl and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) staining were performed to assess the numbers of Nissl bodies and the levels of apoptosis in the neurons. The activities of supero...
Source: Frontiers in Pharmacology - February 17, 2020 Category: Drugs & Pharmacology Source Type: research

Renshen Shouwu extract enhances neurogenesis and angiogenesis via inhibition of TLR4/NF-κB/NLRP3 signaling pathway following ischemic stroke in rats
ConclusionsRSSW enhances neurogenesis and angiogenesis via inhibition of TLR4/NF-κB/NLRP3 inflammatory signaling pathway following ischemic stroke in rats. Hence, RSSW may be a promising Chinese Medicine for the treatment of ischemic stroke.Graphical abstract
Source: Journal of Ethnopharmacology - February 10, 2020 Category: Drugs & Pharmacology Source Type: research

Renshen Shouwu extract enhances neurogenesis and angiogenesis via inhibition of TLR4/NF¬κB/NLRP3 signaling pathway following ischemic stroke in rats
ConclusionsRSSW enhances neurogenesis and angiogenesis via inhibition of TLR4/NF¬κB/NLRP3 inflammatory signaling pathway following ischemic stroke in rats. Hence, RSSW may be a promising Chinese Medicine for the treatment of ischemic stroke.Graphical abstract
Source: Journal of Ethnopharmacology - January 31, 2020 Category: Drugs & Pharmacology Source Type: research

MiR-130a exerts neuroprotective effects against ischemic stroke through PTEN/PI3K/AKT pathway
ConclusionsOur data demonstrated that miR-130a prevented cerebral I/R damage by mediating the PTEN/PI3K/AKT axis. These preliminarily findings furthered our understanding of this mechanism and identified new potential therapeutic targets for ischemic stroke.
Source: Biomedicine and Pharmacotherapy - June 19, 2019 Category: Drugs & Pharmacology Source Type: research

MiR-130a exerts neuroprotective effects against ischemic stroke through PTEN/PI3K/AKT pathway.
CONCLUSIONS: Our data demonstrated that miR-130a prevented cerebral I/R damage by mediating the PTEN/PI3K/AKT axis. These preliminarily findings furthered our understanding of this mechanism and identified new potential therapeutic targets for ischemic stroke. PMID: 31226635 [PubMed - as supplied by publisher]
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - June 17, 2019 Category: Drugs & Pharmacology Authors: Zheng T, Shi Y, Zhang J, Peng J, Zhang X, Chen K, Chen Y, Liu L Tags: Biomed Pharmacother Source Type: research

Structural and molecular aspects of betaine-GABA transporter 1 (BGT1) and its relation to brain function.
Abstract ɣ-aminobutyric-acid (GABA) functions as the principal inhibitory neurotransmitter in the central nervous system. Imbalances in GABAergic neurotransmission are involved in the pathophysiology of various neurological diseases such as epilepsy, Alzheimer's disease and stroke. GABA transporters (GATs) facilitate the termination of GABAergic signaling by transporting GABA together with sodium and chloride from the synaptic cleft into presynaptic neurons and surrounding glial cells. Four different GATs have been identified that all belong to the solute carrier 6 (SLC6) transporter family: GAT1-3 (SLC6A1, SLC6A...
Source: Neuropharmacology - May 16, 2019 Category: Drugs & Pharmacology Authors: Kickinger S, Hellsberg E, BenteFrølund, Schousboe A, Ecker GF, Wellendorph P Tags: Neuropharmacology Source Type: research

Interleukin-11 treatment protected against cerebral ischemia/reperfusion injury
In this study, we investigated the effects of IL-11 on cerebral ischemia-reperfusion injury in a model of focal cerebral ischemia.MethodsMice were randomly divided into five groups the vehicle group, the middle cerebral artery occlusion (MCAO) group, the MCAO plus adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C group, the MCAO plus IL-11 treatment group, and the MCAO plus IL-11 treatment and compound C group. Focal cerebral ischemia was induced by occluding the left middle cerebral artery, and reperfusion was achieved by withdrawing the suture 2 h after ischemia. The protein expression levels...
Source: Biomedicine and Pharmacotherapy - May 15, 2019 Category: Drugs & Pharmacology Source Type: research

Interleukin-11 treatment protected against cerebral ischemia/reperfusion injury.
In this study, we investigated the effects of IL-11 on cerebral ischemia-reperfusion injury in a model of focal cerebral ischemia. METHODS: Mice were randomly divided into five groups the vehicle group, the middle cerebral artery occlusion (MCAO) group, the MCAO plus adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C group, the MCAO plus IL-11 treatment group, and the MCAO plus IL-11 treatment and compound C group. Focal cerebral ischemia was induced by occluding the left middle cerebral artery, and reperfusion was achieved by withdrawing the suture 2 h after ischemia. The protein expressio...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - May 12, 2019 Category: Drugs & Pharmacology Authors: Zhang B, Zhang HX, Shi ST, Bai YL, Zhe X, Zhang SJ, Li YJ Tags: Biomed Pharmacother Source Type: research

Orally Administered Crocin Protects Against Cerebral Ischemia/Reperfusion Injury Through the Metabolic Transformation of Crocetin by Gut Microbiota
Conclusion Collectively, pharmacokinetic and pharmacodynamic association studies provide evidence that the gut microbiota plays a vital role in the fate of crocin and crocetin in the gastrointestinal tract. In addition, the cross-interaction between gut microbiota and crocin might mediate the activation of the cerebral-protective effect of orally administered crocin. Ethics Statement This study was carried out in accordance with the recommendations of ‘Institutional Animal Research Committee guidelines, Animal Ethics Committee of China Pharmaceutical University.’ The protocol was approved by the ‘An...
Source: Frontiers in Pharmacology - April 29, 2019 Category: Drugs & Pharmacology Source Type: research

Ability to Suppress TGF- β-Activated Myofibroblast Differentiation Distinguishes the Anti-pulmonary Fibrosis Efficacy of Two Danshen-Containing Chinese Herbal Medicine Prescriptions
Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of “removing both phlegm and blood stasis” will better achieve co-protection of heart and lung in PHD. Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic ...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Geniposide Alleviates Glucocorticoid-Induced Inhibition of Osteogenic Differentiation in MC3T3-E1 Cells by ERK Pathway
Conclusion In summary, we demonstrated that geniposide alleviated GC-induced osteogenic suppression in MC3T3-E1 cells. The effects of geniposide were at least partially associated with activating ERK signaling pathway via GLP-1 receptor. Geniposide might be a potential therapeutic agent for protection against GC-induced osteoporosis. Author Contributions BX, DX, CZ, and LW participated in research design. BX, JW, YL, XW, and ZZ conducted the experiments. BX, DX, and LW contributed new reagents or analytic tools and wrote or contributed to the writing of the manuscript. BX, JW, CZ, and DX performed the data analysis. Fu...
Source: Frontiers in Pharmacology - April 17, 2019 Category: Drugs & Pharmacology Source Type: research

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