Corticosteroid therapy is associated with the delay of SARS-CoV-2 clearance in COVID-19 patients.
This study aimed to explore the association between corticosteroid and viral clearance in COVID-19. The clinical data of COVID-19 patients from 10 hospitals of Jiangsu, China, were retrospectively collected. Cox regression and Kaplan-Meier analysis were used to analyze the adverse factors of virus clearance. Of the 309 COVID-19 patients, eighty-nine (28.8%) patients received corticosteroid treatment during hospitalization. Corticosteroid group showed higher C-reactive protein (median 11.1 vs. 7.0 mg/l, P = 0.018) and lower lymphocytes (median 0.9 vs. 1.4 × 109/l, P 
Source: European Journal of Pharmacology - September 14, 2020 Category: Drugs & Pharmacology Authors: Huang R, Zhu C, Jian Wang, Xue L, Li C, Yan X, Huang S, Zhang B, Zhu L, Xu T, Ming F, Zhao Y, Cheng J, Shao H, Zhao XA, Sang D, Zhao H, Guan X, Chen X, Chen Y, Wei J, Issa R, Liu L, Yan X, Wu C Tags: Eur J Pharmacol Source Type: research

Beneficial effects of sappanone A on lifespan and thermotolerance in Caenorhabditis elegans.
This study aimed to investigate the lifespan-extending and health-enhancing effects of SA, and the potential pharmacological mechanism in Caenorhabditis elegans (C. elegans). The worms were exposed to 0-50 μM SA. The effect on the lifespan was observed, and health status was evaluated by detecting motility, feeding, reproduction, thermotolerance, lipofuscin and ROS accumulation. To explore a possible mechanism, the transcription of the genes of the insulin/insulin-like growth factor-1 signalling pathway and heat stress response was detected by RT-qPCR. Moreover, subcellular distribution of green fluorescent protein-l...
Source: European Journal of Pharmacology - September 14, 2020 Category: Drugs & Pharmacology Authors: Zhao J, Zhu A, Sun Y, Zhang W, Zhang T, Gao Y, Shan D, Wang S, Li G, Zeng K, Wang Q Tags: Eur J Pharmacol Source Type: research

Alzheimer's disease: Recent treatment strategies.
Abstract Alzheimer Disease (AD) is a neurodegenerative disease characterized by two neuropathological hallmarks: extracellular deposition of amyloid plaques and intracellular neurofibrillary tangles. Current treatment for AD (donepezil, galantamine, rivastigmine and memantine) is only symptomatic and has modest benefits. Thus, the development of drugs with the potential to change the progression of the disease has been a priority. Therapies targeting amyloid β have been the focus for almost 30 years. However, highly promising drugs recently failed to show clinical benefits in phase III trials. Even the positi...
Source: European Journal of Pharmacology - September 14, 2020 Category: Drugs & Pharmacology Authors: Vaz M, Silvestre S Tags: Eur J Pharmacol Source Type: research

Longitudinal analysis of fecal microbiome and metabolome during renal fibrotic progression in a unilateral ureteral obstruction animal model.
Abstract Renal fibrosis is a major pathological process in the progression of various chronic kidney diseases to end-stage renal disease (ESRD). Growing evidence has suggested that gut microbiota dysbiosis is closely related to ESRD. However, the interplay between altered fecal microbiome and metabolome during the renal fibrotic process remains unclear. Herein, an integrated approach of 16S ribosomal DNA sequencing combined with an ultra-high performance liquid chromatography-mass spectrometry-based metabolomics platform was applied to investigate the dynamic changes of fecal microbiota and metabolites throughout ...
Source: European Journal of Pharmacology - September 13, 2020 Category: Drugs & Pharmacology Authors: Hu X, Xie Y, Xiao Y, Zeng W, Gong Z, Du J Tags: Eur J Pharmacol Source Type: research

Possibility of magnesium supplementation for supportive treatment in patients with COVID-19.
Abstract Magnesium as an enzymatic activator is essential for various physiological functions such as cell cycle, metabolic regulation, muscle contraction, and vasomotor tone. A growing body of evidence supports that magnesium supplementation (mainly magnesium sulfate and magnesium oxide) prevents or treats various types of disorders or diseases related to respiratory system, reproductive system, nervous system, digestive system, and cardiovascular system as well as kidney injury, diabetes and cancer. The ongoing pandemic coronavirus disease 19 (COVID-19) characterized by respiratory tract symptoms with different ...
Source: European Journal of Pharmacology - September 12, 2020 Category: Drugs & Pharmacology Authors: Tang CF, Ding H, Jiao RQ, Wu XX, Kong LD Tags: Eur J Pharmacol Source Type: research

Curcumin, a traditional spice component, can hold the promise against COVID-19?
Abstract The severity of the recent pandemic and the absence of any specific medication impelled the identification of existing drugs with potential in the treatment of Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Curcumin, known for its pharmacological abilities especially as an anti-inflammatory agent, can be hypothesized as a potential candidate in the therapeutic regimen. COVID-19 has an assorted range of pathophysiological consequences, including pulmonary damage, elevated inflammatory response, coagulopathy, and multi-organ damage. This review s...
Source: European Journal of Pharmacology - September 12, 2020 Category: Drugs & Pharmacology Authors: Soni VK, Mehta A, Ratre YK, Tiwari AK, Amit A, Singh RP, Sonkar SC, Chaturvedi N, Shukla D, Vishvakarma NK Tags: Eur J Pharmacol Source Type: research

Aloe-emodin induces autophagy and apoptotic cell death in non-small cell lung cancer cells via Akt/mTOR and MAPK signaling.
In this study, the bioassay results demonstrated that AE reduced the viability of the non-small cell lung cancer cell line A549 and NCI-H1299 in a dose- and time-dependent manner. Moreover, AE induced caspase-dependent apoptosis and autophagy. AE induced autophagy through activation of MAPK signaling and inhibition of the Akt/mTOR pathway. We also found that AE-induced autophagy was attenuated by the reactive oxygen species scavenger N-acetylcysteine, indicating that reactive oxygen species played a key role in AE-mediated autophagy in A549 and NCI-H1299 cells. Furthermore, AE induced reactive oxygen species-dependent au...
Source: European Journal of Pharmacology - September 11, 2020 Category: Drugs & Pharmacology Authors: Shen F, Ge C, Yuan P Tags: Eur J Pharmacol Source Type: research

Zinc as a plausible epigenetic modulator of glioblastoma multiforme.
Abstract Glioblastoma Multiforme (GBM) is an aggressive brain tumor (WHO grade 4 astrocytoma) with unknown causes and is associated with a reduced life expectancy. The available treatment options namely radiotherapy, surgery and chemotherapy have failed to improve life expectancy. Out of the various therapeutic approaches, epigenetic therapy is one of the most studied. Epigenetic therapy is involved in the effective treatment of GBM by inhibiting DNA methyltransferase, histone deacetylation and non-coding RNA. It also promotes the expression of the tumor suppressor gene and is involved in the suppression of the on...
Source: European Journal of Pharmacology - September 11, 2020 Category: Drugs & Pharmacology Authors: Balaji E V, Kumar N, Satarker S, Nampoothiri M Tags: Eur J Pharmacol Source Type: research

Should ACE2 be given a chance in COVID-19 therapeutics: A semi-systematic review of strategies enhancing ACE2.
Abstract The severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has resulted in almost 18 million cases of COVID-19 (Corona virus disease-2019) and more than 670000 deaths worldwide since December 2019. In the absence of effective antiviral therapy and vaccine, treatment of COVID-19 is largely symptomatic. By making use of its spike (S) protein, the virus binds to its primary human cell receptor, angiotensin converting enzyme 2 (ACE2) which is present in the pulmonary epithelial cells as well as other organs. SARS-CoV-2 may cause a downregulation of ACE2. ACE2 plays a protective role in the pulmonary sy...
Source: European Journal of Pharmacology - September 11, 2020 Category: Drugs & Pharmacology Authors: Kaur U, Acharya K, Mondal R, Singh A, Saso L, Chakrabarti S, Chakrabarti SS Tags: Eur J Pharmacol Source Type: research

COVID-19 associated complications and potential therapeutic targets.
Abstract The global pandemic COVID-19, caused by novel coronavirus SARS-CoV-2, has emerged as severe public health issue crippling world health care systems. Substantial knowledge has been generated about the pathophysiology of the disease and possible treatment modalities in a relatively short span of time. As of August 19, 2020, there is no approved drug for the treatment of COVID-19. More than 600 clinical trials for potential therapeutics are underway and the results are expected soon. Based on early experience, different treatment such as anti-viral drugs (remdesivir, favipiravir, lopinavir/ritonavir), cortic...
Source: European Journal of Pharmacology - September 11, 2020 Category: Drugs & Pharmacology Authors: Monpara JD, Sodha SJ, Gupta PK Tags: Eur J Pharmacol Source Type: research

Phthalide derivative CD21 alleviates cerebral ischemia-induced neuroinflammation: Involvement of microglial M2 polarization via AMPK activation.
Abstract Microglia can be activated to become the classic phenotype (M1) or alternative phenotype (M2), which play an important role in regulating neuroinflammatory response and tissue repair after ischemic stroke. CD21, a novel phthalide derivative, is a potential neuroprotectant against ischemic brain injury. The present study further investigated the effects of CD21 on post-ischemic microglial polarization and the underlying mechanisms. Transient middle cerebral artery occlusion (tMCAO) was used as a mouse model of ischemic stroke, while BV2 cells stimulated with conditioned medium collected from oxygen-glucose...
Source: European Journal of Pharmacology - September 11, 2020 Category: Drugs & Pharmacology Authors: Gan YM, Liu DL, Chen C, Duan W, Du JR Tags: Eur J Pharmacol Source Type: research

MiRNAs in tuberculosis: Their decisive role in the fate of TB.
We present here a comprehensive review on the role of miRNAs in TB immune escape mechanisms and the potential for miRNA-based TB therapeutics. Further validation studies are required to (i) elucidate the precise effect of TB on host miRNAs, (ii) determine the inhibition of mycobacterial burden using miRNA-based therapies and (iii) identify novel miRNA biomarkers that may prove useful in TB diagnosis and treatment monitoring. PMID: 32919937 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - September 10, 2020 Category: Drugs & Pharmacology Authors: Alipoor SD, Adcock IM, Tabarsi P, Folkerts G, Mortaz E Tags: Eur J Pharmacol Source Type: research

Macrophage responses associated with COVID-19: A pharmacological perspective.
Abstract COVID-19 has caused worldwide death and economic destruction. The pandemic is the result of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has demonstrated high rates of infectivity leading to great morbidity and mortality in vulnerable populations. At present, scientists are exploring various approaches to curb this pandemic and alleviate its health consequences, while racing to develop a vaccine. A particularly insidious aspect of COVID-19 is the delayed overactivation of the body's immune system that is manifested as the cytokine storm. This unbridled production of pro-inflamma...
Source: European Journal of Pharmacology - September 10, 2020 Category: Drugs & Pharmacology Authors: Booz GW, Altara R, Eid AH, Wehbe Z, Fares S, Zaraket H, Habeichi NJ, Zouein FA Tags: Eur J Pharmacol Source Type: research

CaMKII δ inhibition protects against myocardial ischemia/reperfusion injury: Role of Beclin-1-dependent autophagy.
This study was performed using isolated perfused rat hearts and H9c2 cardiac myoblasts. KN-93, but not KN-92, inhibited the phosphorylation of CaMKIIδ at Thr286 and its substrate phospholamban at Thr17 besides the CaMKIIδ activity in myocardial IR. KN-93, but not KN-92 significantly improved post-ischemic cardiac function and reduced cell death. In cultured H9c2 cardiac myoblasts, KN-93 or CaMKIIδ siRNA, but not KN-92, attenuated simulated IR (SIR)-induced cell death. Moreover, CaMKIIδ inhibition could alleviate IR-induced autophagic dysfunction as evidenced in reduced levels of Atg5, p62, and LC3BI...
Source: European Journal of Pharmacology - September 9, 2020 Category: Drugs & Pharmacology Authors: Kong L, Xiong F, Sun N, Xu C, Chen Y, Yang J, Su X Tags: Eur J Pharmacol Source Type: research

Naringenin and naringin in cardiovascular disease prevention: A preclinical review.
Abstract Cardiovascular disease is an important cause for morbidity and mortality worldwide. Flavonoids, such as naringin, and naringenin are important natural phytochemicals in the treatment or prevention of various disorders such as obesity, cardiac diseases, diabetes, and metabolic syndrome. Naringin and naringenin have significant therapeutic potential in several diseases through anti-oxidative, anti-inflammatory, and anti-apoptotic actions; these flavonoids play a protective role in human pathophysiology. In this review, based on the latest evidence, we present a summary of the impact of naringin, and naringe...
Source: European Journal of Pharmacology - September 7, 2020 Category: Drugs & Pharmacology Authors: Moghaddam RH, Samimi Z, Moradi SZ, Little PJ, Xu S, Farzaei MH Tags: Eur J Pharmacol Source Type: research

Cannabidiol inhibits multiple cardiac ion channels and shortens ventricular action potential duration in vitro.
me GA Abstract Cannabidiol (CBD) is a non-psychoactive component of Cannabis which has recently received regulatory consideration for the treatment of intractable forms of epilepsy such as the Dravet and the Lennox-Gastaut syndromes. The mechanisms of the antiepileptic effects of CBD are unclear, but several pre-clinical studies suggest the involvement of ion channels. Therefore, we have evaluated the effects of CBD on seven major cardiac currents shaping the human ventricular action potential and on Purkinje fibers isolated from rabbit hearts to assess the in vitro cardiac safety profile of CBD. We found that CBD...
Source: European Journal of Pharmacology - September 7, 2020 Category: Drugs & Pharmacology Authors: Le Marois M, Ballet V, Sanson C, Maizières MA, Carriot T, Chantoiseau C, Partiseti M, Bohme GA Tags: Eur J Pharmacol Source Type: research

Acute administration of diazepam or midazolam minimally alters long-term neuropathological effects in the rat brain following acute intoxication with diisopropylfluorophosphate.
in PJ Abstract Acute intoxication with organophosphorus cholinesterase inhibitors (OPs) can trigger seizures that rapidly progress to life-threatening status epilepticus. Diazepam, long considered the standard of care for treating OP-induced seizures, is being replaced by midazolam. Whether midazolam is more effective than diazepam in mitigating the persistent effects of acute OP intoxication has not been rigorously evaluated. We compared the efficacy of diazepam vs. midazolam in preventing persistent neuropathology in adult male Sprague-Dawley rats acutely intoxicated with the OP diisopropylfluorophosphate (DFP)....
Source: European Journal of Pharmacology - September 5, 2020 Category: Drugs & Pharmacology Authors: Supasai S, González EA, Rowland DJ, Hobson B, Bruun DA, Guignet MA, Soares S, Singh V, Wulff H, Saito N, Harvey DJ, Lein PJ Tags: Eur J Pharmacol Source Type: research

L-type calcium channel blockers decrease the iron overload-mediated oxidative stress in renal epithelial cells by reducing iron accumulation.
n Y Abstract Iron-mediated oxidative stress has been recognized as one of the leading causes of chronic kidney injury. The effect of L-type calcium channel (LTCC) blocker on iron overload has been shown in cardiomyocytes, liver cells, and nerve cells. So far, few studies have examined whether blockers improve kidney iron-mediated oxidative stress. Yet, the precise mechanism through which blockers regulate kidney iron transport still remains unclear. In the present work, treatment with nifedipine or verapamil decreased oxidative stress and reduced the cell apoptosis-induced by ferric ammonium citrate (P  0.05) ...
Source: European Journal of Pharmacology - September 5, 2020 Category: Drugs & Pharmacology Authors: Sun L, Pornprasert S, Lin X, Lü X, Ran B, Lin Y Tags: Eur J Pharmacol Source Type: research

The cannabinoid CB2 receptor agonist LY2828360 synergizes with morphine to suppress neuropathic nociception and attenuates morphine reward and physical dependence.
Abstract The opioid crisis has underscored the urgent need to identify safe and effective therapeutic strategies to overcome opioid-induced liabilities. We recently reported that LY2828360, a slowly signaling G protein-biased cannabinoid CB2 receptor agonist, suppresses neuropathic nociception and attenuates the development of tolerance to the opioid analgesic morphine in paclitaxel-treated mice. Whether beneficial effects of LY2828360 are dependent upon the presence of a pathological pain state are unknown and its impact on unwanted opioid-induced side-effects have never been investigated. Here, we asked whether ...
Source: European Journal of Pharmacology - September 4, 2020 Category: Drugs & Pharmacology Authors: Iyer V, Slivicki RA, Thomaz AC, Crystal JD, Mackie K, Hohmann AG Tags: Eur J Pharmacol Source Type: research

Histamine depolarizes rat intracardiac ganglion neurons through the activation of TRPC non-selective cation channels.
Abstract The cardiac plexus, which contains parasympathetic ganglia, plays an important role in regulating cardiac function. Histamine is known to excite intracardiac ganglion neurons, but the underlying mechanism is obscure. In the present study, therefore, the effect of histamine on rat intracardiac ganglion neurons was investigated using perforated patch-clamp recordings. Histamine depolarized acutely isolated neurons with a half-maximal effective concentration of 4.5 μM. This depolarization was markedly inhibited by the H1 receptor antagonist triprolidine and mimicked by the H1 receptor agonist 2-pyridyle...
Source: European Journal of Pharmacology - September 4, 2020 Category: Drugs & Pharmacology Authors: Sato A, Arichi S, Kojima F, Hayashi T, Ohba T, Cheung DL, Eto K, Narushima M, Murakoshi H, Maruo Y, Kadoya Y, Nabekura J, Ishibashi H Tags: Eur J Pharmacol Source Type: research

Central endothelin ETB receptor activation reduces blood pressure and catecholaminergic activity in the olfactory bulb of deoxycorticosterone acetate-salt hypertensive rats.
Abstract Endothelins regulate catecholaminergic activity in the olfactory bulb (OB) in normotensive and hypertensive animals. Administration of an endothelin ETA receptor antagonist decreases blood pressure in deoxycorticosterone acetate-salt (DOCA-salt) rats along with a reduction in tyrosine hydroxylase (TH) activity and expression. In the present work, we sought to establish the role of brain endothelin ETB receptor on blood pressure regulation and its relationship with the catecholaminergic system within the OB of DOCA-Salt rats. Sprague-Dawley male rats were divided into control and DOCA-Salt groups. Blood pr...
Source: European Journal of Pharmacology - September 4, 2020 Category: Drugs & Pharmacology Authors: Guil MJ, Soria C, Seijas M, Bianciotti LG, Vatta MS Tags: Eur J Pharmacol Source Type: research

KM-416, a novel phenoxyalkylaminoalkanol derivative with anticonvulsant properties exerts analgesic, local anesthetic, and antidepressant-like activities. Pharmacodynamic, pharmacokinetic, and forced degradation studies.
Abstract Anticonvulsant drugs are used to treat a wide range of non-epileptic conditions, including chronic, neuropathic pain. We obtained a phenoxyalkylaminoalkanol derivative, KM-416 which had previously demonstrated a significant anticonvulsant activity and had also been shown to bind to 5-HT1A, α2-receptors and SERT and not to exhibit mutagenic properties. As KM-416 is a promising compound in our search for drug candidates, in the present study we further assessed its pharmacological profile (analgesic, local anesthetic, and antidepressant-like activities) accompanied with patch-clamp studies. Considerin...
Source: European Journal of Pharmacology - September 4, 2020 Category: Drugs & Pharmacology Authors: Kubacka M, Rapacz A, Sałat K, Filipek B, Cios A, Pociecha K, Wyska E, Hubicka U, Żuromska-Witek B, Kwiecień A, Marona H, Waszkielewicz AM Tags: Eur J Pharmacol Source Type: research

A critical assessment of the potential of pharmacological modulation of aldehyde dehydrogenases to treat the diseases of bone loss.
Abstract Chronic alcoholism (CA) decreases bone mass and increases the risk of hip fracture. Alcohol and its main metabolite, acetaldehyde impairs osteoblastogenesis by increasing oxidative stress. Aldehyde dehydrogenase (ALDH) is the rate-limiting enzyme in clearing acetaldehyde from the body. The clinical relevance of ALDH in skeletal function has been established by the discovery of single nucleotide polymorphism, SNP (rs671) in the ALDH2 gene giving rise to an inactive form of the enzyme (ALDH2*2) that causes increased serum acetaldehyde and osteoporosis in the affected individuals. Subsequent mouse genetics s...
Source: European Journal of Pharmacology - September 4, 2020 Category: Drugs & Pharmacology Authors: Mittal M, Bhagwati S, Siddiqi MI, Chattopadhyay N Tags: Eur J Pharmacol Source Type: research

Confirming whether novel rhein derivative 4a induces paraptosis-like cell death by endoplasmic reticulum stress in ovarian cancer cells.
In this study, we aimed to explore the potential anticancer mechanisms of novel rhein derivative 4a, which was modified with rhein as a lead compound. The results showed that a wide range of vacuoles from the endoplasmic reticulum and mitochondria appeared in ovarian SKOV3, SKOV3-PM4, and A2780 cells treated with derivative 4a, and the cell death caused by derivative 4a is a type of non-apoptotic and non-autophagic death, which is caused by expansion and damage of the endoplasmic reticulum or mitochondria, showing the characteristics of para-apoptotic death. Furthermore, derivative 4a stimulated the unfolded protein reac...
Source: European Journal of Pharmacology - September 2, 2020 Category: Drugs & Pharmacology Authors: Pang HF, Li XX, Zhao YH, Kang JK, Li JY, Tian W, Wang CM, Hou HX, Li DR Tags: Eur J Pharmacol Source Type: research

Inhibition of intracellular Ca2+ mobilization and potassium channels activation are involved in the vasorelaxation induced by 7-hydroxycoumarin.
va DF Abstract Coumarins exhibit a wide variety of biological effects, including activities in the cardiovascular system and the aim of this study was to evaluate the vascular therapeutic potential of 7-Hydroxicoumarin (7-HC). The vascular effects induced by 7-HC (0.001 μM-300 μM), were investigated by in vitro approaches using isometric tension measurements in rat superior mesenteric arteries and by in silico assays using Ligand-based analysis. Our results suggest that the vasorelaxant effect of 7-HC seems to rely on potassium channels, notably through large conductance Ca2+-activated K+ (BKCa) channels...
Source: European Journal of Pharmacology - September 1, 2020 Category: Drugs & Pharmacology Authors: Alves QL, Moraes RDA, Froes TQ, Castilho MS, Aquino de Araújo RS, Barbosa-Filho JM, Meira CS, Pereira Soares MB, Silva DF Tags: Eur J Pharmacol Source Type: research

The effect of oleuropein on apoptotic pathway regulators in breast cancer cells.
Abstract In spite of advancements in breast cancer therapy, this disease is still one of the significant causes of women fatalities globally. Dysregulation of miRNA plays a pivotal role in the initiation and progression of cancer. Therefore, the administration of herbal compounds with anticancer effects through controlling microRNA expression can be considered as a promising therapy for cancer. Oleuropein is the most prevalent phenolic compound in olive. Given its domestic consumption, low cost, and nontoxicity for human beings, oleuropein can be used in combination with the standard chemotherapy drugs. To this en...
Source: European Journal of Pharmacology - September 1, 2020 Category: Drugs & Pharmacology Authors: Asgharzade S, Sheikhshabani SH, Ghasempour E, Heidari R, Rahmati S, Mohammadi M, Jazaeri A, Amini-Farsani Z Tags: Eur J Pharmacol Source Type: research

Norquetiapine blocks the human cardiac sodium channel Nav1.5 in a state-dependent manner.
Abstract Quetiapine, an atypical antipsychotic drug, is used for the treatment of schizophrenia and acute mania. Although a previous report showed that quetiapine blocked hERG potassium current, quetiapine has been considered relatively safe in terms of cardiovascular side effects. In the present study, we used the whole-cell patch-clamp technique to investigate the effect that quetiapine and its major metabolite norquetiapine can exert on human cardiac sodium channels (hNav1.5). The half-maximal inhibitory concentrations of quetiapine and norquetiapine at a holding potential of -90 mV near the resting potential o...
Source: European Journal of Pharmacology - August 31, 2020 Category: Drugs & Pharmacology Authors: Kim DH, Park KS, Park SH, Hahn SJ, Choi JS Tags: Eur J Pharmacol Source Type: research

The protective effect of piperine against isoproterenol-induced inflammation in experimental models of myocardial toxicity.
Abstract Myocardial infarction (MI) eventually exacerbates inflammatory response due to the release of inflammatory and pro-inflammatory factors. The aim of this study is to explore the protective efficacy of piperine supplementation against the inflammatory response in isoproterenol (ISO)-induced MI. Masson Trichome staining was executed to determine myocardial tissue architecture. Immunohistochemistry was performed for IL-6, TNF-α. RT-PCR studies were performed to ascertain the gene expression of IL-6, TNF-α, iNOS, eNOS, MMP-2, MMP-9, and collagen-III. Western blotting was performed to determine expr...
Source: European Journal of Pharmacology - August 31, 2020 Category: Drugs & Pharmacology Authors: Viswanadha VP, Dhivya V, Beeraka NM, Huang CY, Gavryushova LV, Minyaeva NN, Chubarev VN, Mikhaleva LM, Tarasov VV, Aliev G Tags: Eur J Pharmacol Source Type: research

The prophylaxis and treatment potential of supplements for COVID-19.
This article outlines the prophylaxis therapeutic potential of supplements vitamins and micronutrients in COVID-19. By ameliorating the inflammatory and oxidative stress associated with the disease and some direct antiviral effects, the application of these agents as adjuvants and other alternative approaches are discussed. Available clinical trials including those currently registered on these supplements are scrutinized. PMID: 32882216 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - August 31, 2020 Category: Drugs & Pharmacology Authors: Sahebnasagh A, Saghafi F, Avan R, Khoshi A, Khataminia M, Safdari M, Habtemariam S, Ghaleno HR, Nabavi SM Tags: Eur J Pharmacol Source Type: research

Has resveratrol a potential for mucopolysaccharidosis treatment?
Abstract Mucopolysaccharidoses (MPS) represent a devastating group of lysosomal storage diseases (LSD) affecting approximately 1 in 25,000 individuals, where degradation of glycosaminoglycans (GAG) by lysosomal enzymes is impaired due to mutations causing defects in one of GAG-degrading enzymes. The most commonly used therapy for MPS is enzyme replacement therapy, consisting of application of an active form of the missing enzyme. However, supply of the missing enzyme is not enough in case of MPS types whose symptoms are expressed in central nervous system (CNS), as enzyme does not cross the blood-brain barrier. Mo...
Source: European Journal of Pharmacology - August 30, 2020 Category: Drugs & Pharmacology Authors: Rintz E, Pierzynowska K, Podlacha M, Węgrzyn G Tags: Eur J Pharmacol Source Type: research

Melatonin and gastrointestinal cancers: Current evidence based on underlying signaling pathways.
Abstract Gastrointestinal (GI) cancers, leading causes of cancer-related deaths, have been serious challenging human diseases up to now. Because of high rates of mortality, late-stage diagnosis, metastasis to distant locations, and low effectiveness and adverse events of routine standard therapies, the quality of life and survival time are low in patients with GI cancers. Hence, many efforts need to be done to explore and find novel efficient treatments. Beneficial effects of melatonin have been reported in a wide variety of human diseases. Melatonin has antioxidant, anti-inflammatory, antimicrobial, and anticance...
Source: European Journal of Pharmacology - August 30, 2020 Category: Drugs & Pharmacology Authors: Pourhanifeh MH, Mehrzadi S, Kamali M, Hosseinzadeh A Tags: Eur J Pharmacol Source Type: research

The effects of taurine supplementation on obesity, blood pressure and lipid profile: A meta-analysis of randomized controlled trials.
Abstract Taurine plays a pivotal role in regulating glucose and lipid metabolism, blood pressure homeostasis, and obesity largely due to its cytoprotective, antioxidant, and anti-inflammatory actions. Despite promising data from animal studies in this scenario, the efficacy of taurine supplementation in human studies has been inconsistent. The main objective of this meta-analysis was to appraise the effects of taurine supplementation on liver markers and, secondarily, to explore anthropometric measures as well. Pubmed, SCOPUS, Web of Science, and Google Scholar were searched from inception to April 2020. There wer...
Source: European Journal of Pharmacology - August 29, 2020 Category: Drugs & Pharmacology Authors: Guan L, Miao P Tags: Eur J Pharmacol Source Type: research

GABAB receptor intracellular signaling: Novel pathways for depressive disorder treatment?
y M Abstract Affecting over 320 million people around the world, depression has become a formidable challenge for modern medicine. In addition, an increasing number of studies cast doubt on the monoamine theory of depressive disorder and, worryingly, antidepressant medications only significantly benefit patients with severe depression. Thus, it is not surprising that researchers have shown an increased interest in new theories attempting to explain the pathogenesis of this disease. One example is the excitatory/inhibitory transmission imbalance theory. These abnormalities involve glutamate and γ-aminobutyric...
Source: European Journal of Pharmacology - August 29, 2020 Category: Drugs & Pharmacology Authors: Korczak M, Kurowski P, Leśniak A, Grönbladh A, Filipowska A, Bujalska-Zadrożny M Tags: Eur J Pharmacol Source Type: research

The potential rewarding and reinforcing effects of the substituted benzofurans 2-EAPB and 5-EAPB in rodents.
Abstract Accounts regarding the use of novel psychoactive substances continue to escalate annually. These include reports on substituted benzofurans (SBs), such at 1-(1-benzofuran-2-yl)-N-ethylpropan-2-amine (2-EAPB) and 1-(1-benzofuran-5-yl)-N-ethylpropan-2-amine (5-EAPB). Reports on the deaths and adverse consequences from the use of SBs warrant the investigation of their mechanism, possibly predicting the effects of similar compounds. Accordingly, we investigated the possible rewarding and reinforcing effects of 2-EAPB and 5-EAPB through conditioned place preference (CPP), self-administration, and locomotor sen...
Source: European Journal of Pharmacology - August 29, 2020 Category: Drugs & Pharmacology Authors: Sayson LV, Perez Custodio RJ, Ortiz DM, Lee HJ, Kim M, Jeong Y, Lee YS, Kim HJ, Cheong JH Tags: Eur J Pharmacol Source Type: research

Tempol prevents isoprenaline-induced takotsubo syndrome via the reactive oxygen species/mitochondrial/anti-apoptosis /p38 MAPK pathway.
This study demonstrated, for the first time, a sudden increase in reactive oxygen species and effects of the downstream cascades play core roles in the development of TS. PMID: 32871175 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - August 29, 2020 Category: Drugs & Pharmacology Authors: Qi C, Liu X, Xiong T, Wang D Tags: Eur J Pharmacol Source Type: research

Icariin ameliorates the progression of experimental autoimmune encephalomyelitis by down-regulating the major inflammatory signal pathways in a mouse relapse-remission model of multiple sclerosis.
This study aimed at investigating whether treatment with icariin (ICA) could modulate the progression of experimental autoimmune encephalomyelitis (EAE) and its potential mechanisms in SJL/J mice. Female SJL/J mice were immunized with PLP139-151 peptide to induce relapse-remitting EAE and the immunized mice were treated with vehicle alone (EAE) or ICA (12.5 or 25 mg/body weights) by gavage daily for 42 days. Compared with the control, the EAE mice developed relapse-remitting EAE and reduced body weights (15.76 ± 0.61 vs. 17.60 ± 0.98 g on day 13; 17.35 ± 0.44 vs. 18.46 ± 0.66...
Source: European Journal of Pharmacology - August 29, 2020 Category: Drugs & Pharmacology Authors: Cong H, Zhang M, Chang H, Du L, Zhang X, Yin L Tags: Eur J Pharmacol Source Type: research

GLP-1 receptors are involved in the GLP-1 (7-36) amide-induced modulation of glucose homoeostasis, emesis and feeding in Suncus murinus (house musk shrew).
Abstract GLP-1 receptor agonists are used for the treatment of type 2 diabetes but they may reduce appetite and cause nausea and emesis. We investigated if GLP-1 (7-36) amide can modulate glucose homoeostasis, emesis and feeding via an exendin (9-39)-sensitive mechanism in Suncus murinus. The effect of GLP-1 (7-36) amide on glucose homeostasis was examined using an intraperitoneal glucose tolerance test. In conscious fasted animals, food and water consumption and behavior were measured for 1 h following drug administration. c-Fos expression in the brain was measured using immunohistochemistry. GLP-1 (7-36) amide...
Source: European Journal of Pharmacology - August 29, 2020 Category: Drugs & Pharmacology Authors: Lu Z, Chan SW, Tu L, Ngan MP, Rudd JA Tags: Eur J Pharmacol Source Type: research

Anticancer activity of functional polysuccinates with N-acetyl-cysteine in side chains.
zna M Abstract The synthesis and characteristics of functional polyesters with a potential anticancer activity have been described, followed by a post-modification process of biologically active polymers. First, biodegradable functional polysuccinates possessing pendant allyl groups, that are susceptible to thiol-ene reaction, were obtained by polyaddition of succinic anhydride and allyl glycidyl ether. The functionality of such polyesters was regulated by replacing a part of unsaturated glycidyl ether with saturated ones. Polymers containing 20-100% mers with allyl groups were reacted with N-acetyl-cysteine (NAC)...
Source: European Journal of Pharmacology - August 28, 2020 Category: Drugs & Pharmacology Authors: Mrówka M, Jaszcz K, Skonieczna M Tags: Eur J Pharmacol Source Type: research

Alogliptin reversed hippocampal insulin resistance in an amyloid-beta fibrils induced animal model of Alzheimer's disease.
In this study, we evaluated the efficacy of alogliptin (DPP-4 inhibitor) on hippocampal insulin resistance and associated AD complications. In the present study, amyloid-β (1-42) fibrils were produced and administered intrahippocampally for inducing AD in Wistar rats. After 7 days of surgery, rats were treated with 10 and 20 mg/kg of alogliptin for 28 days. Morris water maze (MWM) test was performed in the last week of our experimental study. Post 24 h of final treatment, rats were euthanized and hippocampi were separated for biochemical and histopathological investigations. In-silico analysis revealed that alogli...
Source: European Journal of Pharmacology - August 28, 2020 Category: Drugs & Pharmacology Authors: Rahman SO, Kaundal M, Salman M, Shrivastava A, Parvez S, Panda BP, Akhter M, Akhtar M, Najmi AK Tags: Eur J Pharmacol Source Type: research

GDF11 replenishment protects against hypoxia-mediated apoptosis in cardiomyocytes by regulating autophagy.
Abstract GDF11 has been reported to play a critical role in rejuvenating hypertrophy heart, skeletal muscle, and blood vessel regeneration in aged mice. Whether GDF11 can regulate autophagy in cardiomyocytes remains largely unknown. Thus, the purpose of the present study was to investigate the effects of GDF11 on cardiomyocyte autophagy induced by hypoxia, in addition to the underlying mechanisms. By using the MTT assay, Flow cytometry assay, LIVE/DEAD® Viability/Cytotoxicity Kit Stains and TUNEL assay, we found that exogenous GDF11 decreased apoptosis caused by prolonged hypoxia in cardiomyocytes. The express...
Source: European Journal of Pharmacology - August 27, 2020 Category: Drugs & Pharmacology Authors: Jiao L, Shao Y, Yu Q, Li M, Wang Y, Gong M, Yang X, Liu T, Li Z, Liu H, Zhang Y, Tan Z, Sun L, Xuan L, Yin H, Zhang Y, Cai B, Zhang Y, Yang B Tags: Eur J Pharmacol Source Type: research

Preclinical characterization of itacitinib (INCB039110), a novel selective inhibitor of JAK1, for the treatment of inflammatory diseases.
Abstract Pharmacological modulation of the Janus kinase (JAK) family has achieved clinically meaningful therapeutic outcomes for the treatment of inflammatory and hematopoietic diseases. Several JAK1 selective compounds are being investigated clinically to determine their anti-inflammatory potential. We used recombinant enzymes and primary human lymphocytes to assess the JAK1 specificity of itacitinib (INCB039110) and study inhibition of signal transducers and activators of transcription (STAT) signaling. Rodent models of arthritis and inflammatory bowel disease were subsequently explored to elucidate the efficacy...
Source: European Journal of Pharmacology - August 27, 2020 Category: Drugs & Pharmacology Authors: Covington M, He X, Scuron M, Li J, Collins R, Juvekar A, Shin N, Favata M, Gallagher K, Sarah S, Xue CB, Peel M, Burke K, Oliver J, Fay B, Yao W, Huang T, Scherle P, Diamond S, Newton R, Zhang Y, Smith P Tags: Eur J Pharmacol Source Type: research

Synergistic antitumor activity of DHA and JQ1 in colorectal carcinoma.
In this study, we evaluated the synergistic antitumor effects of the combination of BRD4 inhibitor JQ1 and docosahexaenoic acid (DHA) in colon cancer. We demonstrated that simultaneous exposure to JQ1 and DHA resulted in strong synergistic antiproliferative and proapoptotic effects related to inhibition of expression of c-Myc and activation of NF-κB in colon cancer cell lines. At the same time, the synergetic anticancer effect had been confirmed in vivo. For in vivo experiments, JQ1 and DHA resulted in more significant tumor growth inhibition (53.7%) in a human colon cancer HCT116 xenograft model, comparing with the ...
Source: European Journal of Pharmacology - August 27, 2020 Category: Drugs & Pharmacology Authors: Ding W, Zhang H, Mei G Tags: Eur J Pharmacol Source Type: research

The protective effect of 1,25(OH)2D3 against cardiac hypertrophy is mediated by the cyclin-dependent kinase inhibitor p21.
Abstract As a critical regulator of the cell cycle, cyclin-dependent kinase (CDK) inhibitor p21 or p21 is involved in the development of cardiac hypertrophy and heart failure. Calcitriol, or 1,25(OH)2D3, the bioactive form of vitamin D (VD), can activate p21 expression and attenuate cardiac hypertrophy. To simulate cardiac hypertrophy in vitro and ex vivo, respectively, mice and cardiomyocytes were treated with isoproterenol (ISO). Moreover, the p21 signaling pathway was examined in ISO + VD and ISO + VD p21 inhibitor-treated cardiomyocytes. We found that calcitriol treatment led to a significa...
Source: European Journal of Pharmacology - August 27, 2020 Category: Drugs & Pharmacology Authors: Liu N, Su H, Zhang Y, Kong J Tags: Eur J Pharmacol Source Type: research

Betulinic acid inhibits cell proliferation and migration in gastric cancer by targeting the NF- κB/VASP pathway.
In conclusion, these results suggest that BA could inhibit the expression of VASP by negatively regulating NF-κB, thereby inhibiting the proliferation and migration of the GC cells. Our study provides a theoretical basis for exploring the molecular mechanism underlying BA-induced inhibition of proliferation and migration in GC cells. PMID: 32860808 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - August 26, 2020 Category: Drugs & Pharmacology Authors: Chen X, Yuan XN, Zhang Z, Gong PJ, Yin WN, Jiang Q, Xu J, Xu XL, Gao Y, Chen WL, Chen FF, Tian YH, Wei L, Zhang JW Tags: Eur J Pharmacol Source Type: research

Puerarin attenuates the endothelial-mesenchymal transition induced by oxidative stress in human coronary artery endothelial cells through PI3K/AKT pathway.
Abstract Endothelial-mesenchymal transition (EndMT) is a process in which endothelial cells lose their specific morphology/markers and undergo a dramatic remodeling of the cytoskeleton. It has been implicated in the progression of cardiovascular diseases such as cardiac fibrosis and cardiac dysfunction. Recent study indicated that puerarin could inhibit EndMT against cardiac fibrosis. However, the precise role of puerarin in EndMT and the underlying molecular mechanisms remain unclear. EndMT was induced by H2O2 (150 μM) in human coronary artery endothelial cells (HCAECs). HCAECs were exposed to H2O2 for six d...
Source: European Journal of Pharmacology - August 26, 2020 Category: Drugs & Pharmacology Authors: Li X, Sun S, Chen D, Yuan T, Chen Y, Wang D, Fang L, Lu Y, Du G Tags: Eur J Pharmacol Source Type: research

Vagal apnea and hypotension evoked by systemic injection of an antinociceptive analogue of endomorphin-2.
Abstract PK20M (Dmt-D-Lys-Phe-Phe-OH) is a novel modified endomorphin-2 (EM-2) peptide producing strong dose- and time-dependent antinociceptive activity. Yet its prototype, endogenous EM-2, has been reported to trigger respiratory and vascular effects such as apnea and hypotension. The purpose of this study was to investigate the potency of the PK20M to evoke respiratory and cardiovascular responses in comparison to endogenous endomorphins. The engagement of the vagal pathway and μ opioid receptors in mediation of these responses was investigated. The effects of intravenous injections of PK20M, EM-1, and EM-2 ...
Source: European Journal of Pharmacology - August 26, 2020 Category: Drugs & Pharmacology Authors: Wojciechowski P, Kleczkowska P, Mollica A, Stefanucci A, Kaczyńska K Tags: Eur J Pharmacol Source Type: research

Fingolimod increases oligodendrocytes markers expression in epidermal neural crest stem cells.
Abstract Epidermal neural crest stem cells (EPI-NCSCs) are propitious candidates for cell replacement therapy and supplying neurotrophic factors in the neurological disorders. Considering the potential remyelinating and regenerative effects of fingolimod. in this study, we evaluated its effects on EPI-NCSCs viability and the expression of neurotrophic and oligodendrocyte differentiation factors. EPI-NCSCs, extracted from the bulge of rat hair follicles, were characterized and treated with fingolimod (0, 50, 100, 200, 400, 600, 1000, and 5000 nM). The cell viability was evaluated by MTT assay at 6, 24 and 72 h....
Source: European Journal of Pharmacology - August 26, 2020 Category: Drugs & Pharmacology Authors: Pournajaf S, Valian N, Shalmani LM, Khodabakhsh P, Jorjani M, Dargahi L Tags: Eur J Pharmacol Source Type: research

Targeting NLRP3 inflammasome as a promising approach for treatment of diabetic nephropathy: Preclinical evidences with therapeutic approaches.
Abstract Diabetes mellitus is an increasingly prevalent disease around the globe. The epidemic of diabetes mellitus and its complications pretenses the foremost health threat globally. Diabetic nephropathy is the notable complication in diabetes, leading to end-stage renal disease (ESRD) and premature death. Abundant experimental evidence indicates that oxidative stress and inflammation are the important mediators in diabetic kidney diseases and interlinked with various signal transduction molecular mechanisms. Inflammasomes are the critical components of innate immunity and are recognized as a critical mediator o...
Source: European Journal of Pharmacology - August 26, 2020 Category: Drugs & Pharmacology Authors: Ram C, Jha AK, Ghosh A, Gairola S, Syed AM, Murty US, Naidu VGM, Sahu BD Tags: Eur J Pharmacol Source Type: research

Intracellular adenosine released from THP-1 differentiated human macrophages is involved in an autocrine control of Leishmania parasitic burden, mediated by adenosine A2A and A2B receptors.
sco P Abstract Leishmania infected macrophages have conditions to produce adenosine. Despite its known immunosuppressive effects, no studies have yet established whether adenosine alter Leishmania parasitic burden upon macrophage infection. This work aimed at investigating whether endogenous adenosine exerts an autocrine modulation of macrophage response towards Leishmania infection, identifying its origin and potential pharmacological targets for visceral leishmaniasis (VL), using THP-1 differentiated macrophages. Adenosine deaminase treatment of infected THP-1 cells reduced the parasitic burden (29.1 ± 2.2%, P 
Source: European Journal of Pharmacology - August 25, 2020 Category: Drugs & Pharmacology Authors: Silva D, Moreira D, Cordeiro-da-Silva A, Quintas C, Gonçalves J, Fresco P Tags: Eur J Pharmacol Source Type: research

MicroRNA interplay between hepatic stellate cell quiescence and activation.
Abstract Hepatic stellate cells (HSCs) activation play a significant role in the progression of hepatic fibrosis. During chronic liver diseases, hepatocytes are damaged severely and secrete several pro-inflammatory markers and profibrogenic cytokines via modulation of a variety of signaling pathways that are responsible for the activation of HSCs. The microRNAs (miRNA or miR) have the potential to modulate fibrogenic signaling pathways in HSCs. A variety of miRNAs are identified as profibrogenic and are capable of activating HSCs by modulating fibrosis-associated signaling pathways such as transforming growth fact...
Source: European Journal of Pharmacology - August 25, 2020 Category: Drugs & Pharmacology Authors: Ezhilarasan D Tags: Eur J Pharmacol Source Type: research