A miniature pig model of pharmacological tolerance to long-term sedation with the intravenous benzodiazepines; midazolam and remimazolam.
Abstract As a new and ultra fast-acting IV benzodiazepine, pharmacological tolerance may be anticipated during long-term treatment with remimazolam e.g. in intensive care. In this context, tolerance is particularly relevant for withdrawal syndrome. However, apart from primates, existing models of sedative tolerance are unsuitable for remimazolam due to its excessive metabolic clearance (i.e. in rodents) or paradoxical responses (in dogs). Pigs are a well-established model species, especially for in-vivo drug safety studies, and appear well suited as model for evaluation of remimazolam. In a series of experiments f...
Source: European Journal of Pharmacology - January 22, 2021 Category: Drugs & Pharmacology Authors: Io T, Saunders R, Pesic M, Petersen KU, Stoehr T Tags: Eur J Pharmacol Source Type: research

Gypenoside XVII alleviates early diabetic retinopathy by regulating M üller cell apoptosis and autophagy in db/db mice.
This study explored the effect of Gyp-17 on early DR and Müller cell injury in db/db mice. Blood glucose and blood lipids were measured. Optical coherence tomography and fundus fluorescein angiography were applied to detect retinal thickness and vascular leakage, respectively. Hematoxylin eosin staining assessed the pathological changes of the retina. Retinal oxidative environment and cell apoptosis and autophagy were monitored using commercial kits, immunofluorescence, and Western blot assays. Results showed that Gyp-17 exerted no significant effect on blood glucose and lipid levels but maintained normal retinal perm...
Source: European Journal of Pharmacology - January 22, 2021 Category: Drugs & Pharmacology Authors: Luo Y, Dong X, Lu S, Gao Y, Sun G, Sun X Tags: Eur J Pharmacol Source Type: research

Therapeutic targets of rosuvastatin on heart failure and associated biological mechanisms: A study of network pharmacology and experimental validation.
Abstract To explore the potential targets underlying the effect of rosuvastatin on heart failure (HF) by utilizing a network pharmacology approach and experiments to identify the results. PharmMapper and other databases were mined for information relevant to the prediction of rosuvastatin targets and HF-related targets. Then, the rosuvastatin-HF target gene networks were created in Cytoscape software. Eventually, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Furthermore, we constructed an HF animal model and use...
Source: European Journal of Pharmacology - January 22, 2021 Category: Drugs & Pharmacology Authors: Lian Z, Song JX, Yu SR, Su LN, Cui YX, Li SF, Lee CY, Liang HZ, Chen H Tags: Eur J Pharmacol Source Type: research

T1143 Essential for CaV1.2 Inhibition by Diltiazem.
Abstract Careful analysis of previously published reports and some new insights into the structure activity studies revealed an important role of Threonine 1143 in drug binding. Substituting T1143 by alanine and other residues significantly reduced channel inhibition by qDil and Dil. Mutation T1143A did not affect channel activation or inactivation while almost completely diminishing channel block by Dil or qDil. These findings support the view that T1143 serves as drug binding determinant. Other mutations in this position than T1143A (T1143L/Y/S/N/C/V/E) diminished channel inhibition by qDil but additionally affe...
Source: European Journal of Pharmacology - January 19, 2021 Category: Drugs & Pharmacology Authors: Shabbir W Tags: Eur J Pharmacol Source Type: research

MiR-874-3p plays a protective role in intervertebral disc degeneration by suppressing MMP2 and MMP3.
In this study, using quantitative reverse transcription PCR, luciferase reporter assay, Western blotting, immunofluorescence, flow cytometry, and Cell Counting Kit-8 assay, we found that the miR-874-3p expression level was significantly decreased in IDD patients. MiR-874-3p could target and repress MMP2 and MMP3 expression in nucleus pulposus cells. These results could improve the understanding of IDD and provide a possible diagnostic marker and treatment candidate for IDD. The miR-874-3p/MMP2/MMP3 axis might also provide direction for future cancer and inflammation investigations. PMID: 33482178 [PubMed - as supplied...
Source: European Journal of Pharmacology - January 19, 2021 Category: Drugs & Pharmacology Authors: Song Q, Zhang F, Wang K, Chen Z, Li Q, Liu Z, Shen H Tags: Eur J Pharmacol Source Type: research

Aldose reductase regulates doxorubicin-induced immune and inflammatory responses by activating mitochondrial biogenesis.
In this study, we examined the immunomodulatory effects of fidarestat in combination with Dox in vivo and in vitro. We observed that fidarestat decreased Dox-induced upregulation of CD11b in THP-1 monocytes. Fidarestat further attenuated Dox-induced upregulation of IL-6, IL-1β, and Nos2 in murine BMDMs. Fidarestat also attenuated Dox-induced activation and infiltration of multiple subsets of inflammatory immune cells identified by expression of markers CD11b+, CD11b+F4/80+, Ly6C+CCR2high, and Ly6C+CD11b+ in the mouse spleen and liver. Furthermore, significant upregulation of markers of mitochondrial biogenesis PGC-1&a...
Source: European Journal of Pharmacology - January 19, 2021 Category: Drugs & Pharmacology Authors: Sonowal H, Saxena A, Qiu S, Srivastava S, Ramana KV Tags: Eur J Pharmacol Source Type: research

Fabry disease-associated globotriaosylceramide induces mechanical allodynia via activation of signaling through proNGF-p75NTR but not mature NGF-TrkA.
Abstract Fabry disease (FD) is an X-linked metabolic storage disorder arising from the deficiency of lysosomal α-galactosidase A, which leads to the gradual accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3), throughout the body. Pain in the extremities is an early symptom of FD; however, the underlying pathophysiological mechanisms remain unknown. α-Galactosidase A knockout animals exhibit nociceptive behaviors, with enhanced expression levels of several ion channels. These characteristics are observed in animals treated with nerve growth factor (NGF). Here, we aimed to elucidate t...
Source: European Journal of Pharmacology - January 19, 2021 Category: Drugs & Pharmacology Authors: Sugimoto J, Satoyoshi H, Takahata K, Muraoka S Tags: Eur J Pharmacol Source Type: research

A review of potential suggested drugs for coronavirus disease (COVID-19) treatment.
This article summarizes clinical investigations of potential therapeutic drugs used as COVID-19 therapy. Subsequently, it prepares a pattern of results and therapeutic targets to help further experiment designs. We have investigated drugs as classified in the following three groups; 1) The drugs which computationally showed effectiveness (in silico) but needed further lab confirmations; 2) Emetine, Teicoplanin, and Nelfinavir have shown effectiveness in vitro; 3) The drugs currently under clinical trial. PMID: 33482181 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - January 19, 2021 Category: Drugs & Pharmacology Authors: Tarighi P, Eftekhari S, Chizari M, Sabernavaei M, Jafari D, Mirzabeigi P Tags: Eur J Pharmacol Source Type: research

Berberine inhibits chemotherapy-exacerbated ovarian cancer stem cell-like characteristics and metastasis through GLI1.
Abstract Despite the remarkable clinical response in ovarian cancer therapy, the distinctively high metastasis rate is still a barrier to achieve satisfying prognosis. Our study aimed to decipher the role of berberine in inhibiting chemotherapy-exacerbated ovarian cancer metastasis. We found that chemotherapy exacerbated the migration and cancer stem cell (CSC)-like characteristics through transcriptional factor GLI1, which regulated the pluripotency-associated gene BMI1 and the epithelial-mesenchymal transition (EMT) markers Vimentin and Snail. Berberine could not only down-regulate CSC-like characteristics but a...
Source: European Journal of Pharmacology - January 19, 2021 Category: Drugs & Pharmacology Authors: Zhao Y, Yang X, Zhao J, Gao M, Zhang M, Shi T, Zhang F, Zheng X, Pan Y, Shao D, Li J, He K, Chen L Tags: Eur J Pharmacol Source Type: research

The relevance of DHA with modulating of host-gut microbiome signatures alterations and repairing of lipids metabolism shifts.
In conclusion, we considered that DHA repaired lipid metabolism by modulating gut microbiome and regulating fatty acids metabolism pathway. PMID: 33482183 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - January 19, 2021 Category: Drugs & Pharmacology Authors: Yu H, Fang C, Li P, Wu M, Shen S Tags: Eur J Pharmacol Source Type: research

Inhibitors of angiotensin I converting enzyme potentiate fibromyalgia-like pain symptoms via kinin receptors in mice.
ra SM Abstract Fibromyalgia is a potentially disabling chronic disease, characterized by widespread pain and a range of comorbidities such as hypertension. Among the mechanisms involved in fibromyalgia-like pain symptoms are kinins and their B1 and B2 receptors. Moreover, angiotensin I converting enzyme (ACE) inhibitors, commonly used as antihypertensive drugs, can enhance pain by blocking the degradation of peptides such as substance P and bradykinin, besides enhancing kinin receptors signalling. We investigated the effect of ACE inhibitors on reserpine-induced fibromyalgia-like pain symptoms and the involvement ...
Source: European Journal of Pharmacology - January 18, 2021 Category: Drugs & Pharmacology Authors: Brusco I, Justino AB, Silva CR, Scussel R, Machado-de-Ávila RA, Oliveira SM Tags: Eur J Pharmacol Source Type: research

JTP-117968, a novel selective glucocorticoid receptor modulator, exhibits significant anti-inflammatory effect while maintaining bone mineral density in mice.
In this study, we investigated the anti-inflammatory effect of JTP-117968 on a lipopolysaccharide (LPS) challenge model and collagen-induced arthritis (CIA) model in mice. Meanwhile, we tested the effect of JTP-117968 on the bone mineral density (BMD) in mouse femur to evaluate the side effect. Based on the evaluation, JTP-117968 reduced the plasma levels of tumor necrosis factor α induced by LPS challenge in mice significantly. Remarkably, CIA development was suppressed by JTP-117968 comparably with prednisolone and PF-802, an active form of fosdagrocorat that has been developed clinically as an orally available SGR...
Source: European Journal of Pharmacology - January 18, 2021 Category: Drugs & Pharmacology Authors: Kurimoto T, Tamai I, Nakagawa T, Miyai A, Yamamoto Y, Kosugi Y, Deai K, Hata T, Ohta T, Matsushita M, Yamada T Tags: Eur J Pharmacol Source Type: research

Volume-regulated chloride channel regulates cell proliferation and is involved in the possible interaction between TMEM16A and LRRC8A in human metastatic oral squamous cell carcinoma cells.
CONCLUSIONS: We have found that VRAC acts to regulate the proliferation of human metastatic OSCC cells and the composition of VRAC may involve in the interactions between TMEM16A and LRRC8A in HST-1 cells. PMID: 33476655 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - January 18, 2021 Category: Drugs & Pharmacology Authors: Yoshimoto S, Matsuda M, Kato K, Jimi E, Takeuchi H, Nakano S, Kajioka S, Matsuzaki E, Hirofuji T, Inoue R, Hirata M, Morita H Tags: Eur J Pharmacol Source Type: research

TBC1D16 predicts chemosensitivity and prognosis in adult acute myeloid leukemia (AML) patients.
Abstract Acute myeloid leukemia (AML) is a hematopoietic disease with poor survival. Chemotherapy resistance is one of the determinant factors influencing AML prognosis. To identify genes possibly affecting the drug responses in AML, the Illumina Infinium MethylationEPIC (850K) was used to screen for differential DNA methylation loci between patients achieved complete remission (CR) or not (non-CR) after induction therapy in 37 AML patients. Then, 32 differentially methylated sites (DMS) were selected for replication in another 86 AML patients by next-generation sequencing. Nine sites including cg03988660, cg16804...
Source: European Journal of Pharmacology - January 18, 2021 Category: Drugs & Pharmacology Authors: Liu H, Chen P, Yang YL, Zhu KW, Wang T, Tang L, Liu YL, Cao S, Zhou G, Zeng H, Zhao XL, Zhang W, Chen XP Tags: Eur J Pharmacol Source Type: research

Role of pERK1/2-NF κB signaling in the neuroprotective effect of Thalidomide against cerebral ischemia reperfusion injury in rats.
Role of pERK1/2-NFκB signaling in the neuroprotective effect of Thalidomide against cerebral ischemia reperfusion injury in rats. Eur J Pharmacol. 2021 Jan 16;:173872 Authors: Mohammed RA, El-Yamany MF, Abdel-Rahman AA, Nassar NN, Al-Shorbagy MY Abstract In the present investigation, we tested the hypothesis that suppression of the phospho-extracellular signal regulated kinase (pERK1/2)-nuclear factor kappa (NFκ)-B signaling, subsequent to tumor necrosis factor-α (TNF-α) inhibition, underlies thalidomide (TLM) mediated neuroprotection. Male Wistar rats (250 - 280 g) were divide...
Source: European Journal of Pharmacology - January 16, 2021 Category: Drugs & Pharmacology Authors: Mohammed RA, El-Yamany MF, Abdel-Rahman AA, Nassar NN, Al-Shorbagy MY Tags: Eur J Pharmacol Source Type: research

GR/NF- κB signaling pathway regulates hippocampal inflammatory responses in diabetic rats with chronic unpredictable mild stress.
GR/NF-κB signaling pathway regulates hippocampal inflammatory responses in diabetic rats with chronic unpredictable mild stress. Eur J Pharmacol. 2021 Jan 16;:173861 Authors: Li ZR, Han YS, Liu Z, Zhao HQ, Liu J, Yang H, Wang YH Abstract Clinical studies have shown that diabetes can present with underlying depression, and a combination of the two can lead to emotional, memory and cognitive disorders, closely associated with hippocampal neuroinflammation. However, the mechanism underlying the development of hippocampal neuroinflammation under the above condition remains elusive. The aims of this ...
Source: European Journal of Pharmacology - January 16, 2021 Category: Drugs & Pharmacology Authors: Li ZR, Han YS, Liu Z, Zhao HQ, Liu J, Yang H, Wang YH Tags: Eur J Pharmacol Source Type: research

Suppression of Nanog inhibited cell migration and increased the sensitivity of colorectal cancer cells to 5-fluorouracil.
In conclusion, our results indicated that Nanog may play an important role in the drug sensitivity, migration, and self-renewal of CRC cells; suggesting Nanog as a promising target in combination with 5-FU for the development of new therapeutic approaches for CRC. PMID: 33460610 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Authors: Khosravi N, Shahgoli VK, Amini M, Safaeai S, Mokhtarzadeh A, Mansoori B, Derakhshani A, Baghbanzadeh A, Baradaran B Tags: Eur J Pharmacol Source Type: research

Apoptotic neurons and amyloid-beta clearance by phagocytosis in Alzheimer's disease: Pathological mechanisms and therapeutic outlooks.
kar A Abstract Neuronal survival and axonal renewal following central nervous system damage and in neurodegenerative illnesses, such as Alzheimer's disease (AD), can be enhanced by fast clearance of neuronal apoptotic debris, as well as the removal of amyloid beta (Aβ) by phagocytic cells through the process of efferocytosis. This process quickly inhibits the release of proinflammatory and antigenic autoimmune constituents, enhancing the formation of a microenvironment vital for neuronal survival and axonal regeneration. Therefore, the detrimental features associated with microglial phagocytosis uncoupling, s...
Source: European Journal of Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Authors: Tajbakhsh A, Read M, Barreto GE, Ávila-Rodriguez M, Gheibi-Hayat SM, Sahebkar A Tags: Eur J Pharmacol Source Type: research

Analogues of cannabinoids as multitarget drugs in the treatment of Alzheimer's disease.
z J, Egea J, Martín MI, Girón R Abstract Given that neuronal degeneration in Alzheimer's disease (AD) is caused by the combination of multiple neurotoxic insults, current directions in the research of novel therapies to treat this disease attempts to design multitarget strategies that could be more effective than the simply use of acetylcholinesterase inhibitors; currently, the most used therapy for AD. One option, explored recently, is the synthesis of new analogues of cannabinoids that could competitively inhibit the acetylcholinesterase (AChE) enzyme and showing the classic neuroprotective profile...
Source: European Journal of Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Authors: Sánchez Montero JM, Agis-Torres A, Solano D, Söllhuber M, Fernandez M, Villaro W, Gómez-Cañas M, García-Arencibia M, Fernández-Ruiz J, Egea J, Martín MI, Girón R Tags: Eur J Pharmacol Source Type: research

Inhibition of platelet-derived growth factor C and their receptors additionally increases doxorubicin effects in triple-negative breast cancer cells.
Abstract Complex of platelet-derived growth factor (PDGF) isoforms and PDGF receptors have important functions in the regulation of growth and survival of various cell types. Herein, it was found that aberrant PDGFC expression is closely associated with survival rates in triple-negative breast cancer (TNBC) patients. In addition, PDGFC expression was identified to be significantly increased in TNBC cells unlike other subtypes such as PDGFA, PDGFB, and PDGFD. Apparently, the effects of specific PDGF receptor (PDGFR) inhibitors such as sunitinib and ponatinib on HCC1806 and Hs578T TNBC cells were investigated. Both ...
Source: European Journal of Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Authors: Kim S, You D, Jeong Y, Yoon SY, Kim SA, Lee JE Tags: Eur J Pharmacol Source Type: research

16-Substituted steroids alleviate LPS-induced neurodegenerative disorders in rats.
Abstract The neuroprotective effects of some 16-substituted steroidal derivatives against the locomotive impairment and cognitive deficits in the lipopolysaccharide (LPS)-induced neuroinflammation model of rats have been investigated. The in vivo and in vitro evaluations include behavioural tests (actophotometer, block tests, Morris water maize and elevated plus maize), estimation of the biochemical parameters such as acetylcholinesterase, lipid peroxide, reactive oxygen, and nitric oxide species and molecular assays for the key proinflammatory mediators like Tumour Necrosis Factor alpha (TNF-α) and Interleu...
Source: European Journal of Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Authors: Singh R, Bansal R Tags: Eur J Pharmacol Source Type: research

Gliclazide alters macrophages polarization state in diabetic atherosclerosis in vitro via blocking AGE-RAGE/TLR4-reactive oxygen species-activated NF-k β nexus.
Gliclazide alters macrophages polarization state in diabetic atherosclerosis in vitro via blocking AGE-RAGE/TLR4-reactive oxygen species-activated NF-kβ nexus. Eur J Pharmacol. 2021 Jan 15;:173874 Authors: Jahan H, Choudhary MI Abstract Hyperglycemic milieu in diabetes mellitus stimulates macrophages for exaggerated pro-inflammatory cytokine response, particularly IL-1β, IL-6, and TNF-α. Although hyperglycemia causes macrophages to produce pro-inflammatory cytokines, AGEs (advanced glycation end products) produced as a result of chronic hyperglycemia, as active inflammation inducers ca...
Source: European Journal of Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Authors: Jahan H, Choudhary MI Tags: Eur J Pharmacol Source Type: research

Organelle dynamics of endothelial mitochondria in diabetic angiopathy.
Abstract Diabetes, a chronic non-communicable disease, has become one of the most serious and critical public health problems with increasing incidence trends. Chronic vascular complications are the major causes of disability and death in diabetic patients with endothelial dysfunction. Diabetes is intimately associated with endothelial mitochondrial dysfunction, indicated by increased oxidative stress, decreased biogenesis, increased DNA damage, and weakened autophagy in mitochondria. All these morphological and functional changes of mitochondria play important roles in diabetic endothelial dysfunction. Herein, we...
Source: European Journal of Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Authors: Xiang H, Song R, Ouyang J, Zhu R, Shu Z, Liu Y, Wang X, Zhang D, Zhao J, Lu H Tags: Eur J Pharmacol Source Type: research

The recent advances of PD-1 and PD-L1 checkpoint signaling inhibition for breast cancer immunotherapy.
Abstract Over the past decade, there has been sustained research activity on programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors for breast cancer (BC) immunotherapy. Several clinical studies have demonstrated the anti-tumor efficacy of monotherapy drugs targeting PD-1 and PD-L1 checkpoint signaling in BC. Besides, the combination of anti-PD-1/PD-L1 agents with other inhibitors, including poly-adenosine diphosphate-ribose polymerase (PARP) inhibitors, vaccines, mitogen-activated protein kinase (MEK) inhibitors, and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors a...
Source: European Journal of Pharmacology - January 15, 2021 Category: Drugs & Pharmacology Authors: Patience S, Chang X, Liu Z, Wu Y, Zuo D Tags: Eur J Pharmacol Source Type: research

Synergistic interaction between matrine and paracetamol in the acetic acid writhing test in mice.
Abstract The purpose of this study was to investigate the analgesic interaction between matrine and paracetamol in an acetic acid-induced writhing model in mice. Fifty percent effective dose (ED50) values of the individual drugs were determined, and the different proportions of matrine and paracetamol were assayed using the isobolographic method. Our study demonstrated that both of matrine and paracetamol dose-dependently inhibited the writhing response evoked by acetic acid, and the ED50 values and their 95% confidence intervals against these tonic pain were 21.10 (17.86-24.92) mg/kg and 61.30 (50.71-74.10) mg/kg...
Source: European Journal of Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Authors: Dai G, Li B, Xu Y, Li Z, Mo F, Wei C Tags: Eur J Pharmacol Source Type: research

PEG-GO@XN nanocomposite suppresses breast cancer metastasis via inhibition of mitochondrial oxidative phosphorylation and blockade of epithelial-to-mesenchymal transition.
Abstract Metastatic breast cancer is a significant contributor to mortality among women, but its complex regulation represents a barrier to precision targeting. In the present study, a graphene-based nanocomposite which probes and selectively inhibits cancer cell motility is described. By controllable coupling of prenylated chalcone xanthohumol, an efficient inhibitor of mitochondrial electron transport chain complex I, with PEGylated graphene oxide nanosheet, a PEG-GO@XN nanocomposite with good stability and biocompatibility is synthesized. PEG-GO@XN is capable of inhibiting mitochondrial oxidative phosphorylatio...
Source: European Journal of Pharmacology - January 14, 2021 Category: Drugs & Pharmacology Authors: Zhang J, Yan L, Wei P, Zhou R, Hua C, Xiao M, Tu Y, Gu Z, Wei T Tags: Eur J Pharmacol Source Type: research

Isorhamnetin promotes functional recovery in rats with spinal cord injury by abating oxidative stress and modulating M2 macrophages/microglia polarization.
In conclusions, ISO treatment promotes functional recovery in rats with SCI by abating oxidative stress and modulating M1/M2 macrophage polarization. PMID: 33453223 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Authors: Chen F, Hu M, Zhu W, Cao A, Shen Y, Ni B, Qian J, Yang J Tags: Eur J Pharmacol Source Type: research

β-lactam antibiotics to tame down molecular pathways of Alzheimer's disease.
β-lactam antibiotics to tame down molecular pathways of Alzheimer's disease. Eur J Pharmacol. 2021 Jan 13;:173877 Authors: Kumari S, Deshmukh R Abstract Alzheimer's disease is a multifactorial disorder characterized by extracellular accumulation of amyloid-β (Aβ) and intracellular accumulations of neurofibrillary tangles. Numerous drug targets have been explored for therapeutic efficacy but failed to deliver successful treatments clinically. However, over the years our understanding of the disease pathophysiology increased significantly. Many of the novel targets which can cure or modif...
Source: European Journal of Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Authors: Kumari S, Deshmukh R Tags: Eur J Pharmacol Source Type: research

Parkinson's disease in Women: Mechanisms underlying sex differences.
Abstract Parkinson's disease is a neurodegenerative disease which is associated with different motor, cognitive and mood-related problems. Though it has been established that Parkinson's disease is less prevalent in women in comparison to men, the differences tend to diminish with the advancing age. Different genetic, hormonal, neuroendocrinal and molecular players contribute towards the differences in the Parkinson's disease pathogenesis. Furthermore, data available with respect to the therapeutic management of Parkinson's disease in females is limited; women often tend to suffer more from the side effects of the...
Source: European Journal of Pharmacology - January 12, 2021 Category: Drugs & Pharmacology Authors: Vaidya B, Dhamija K, Guru P, Sharma SS Tags: Eur J Pharmacol Source Type: research

Dexamethasone: Therapeutic potential, risks, and future projection during COVID-19 pandemic.
Abstract The current outbreak of novel COVID-19 challenges the development of an efficient treatment plan as soon as possible. Several promising treatment options stand out as potential therapy of COVID-19, including plasma-derived drugs, monoclonal antibodies, antivirals, antimalarial, cell therapy, and corticosteroids. Dexamethasone an approved corticosteroid medication, acting as an anti-inflammatory and immunosuppressant agent. In the current pandemic, dexamethasone is declared a "major development" in the fight against COVID-19. Steroidal dexamethasone was presented as the recent advancement that si...
Source: European Journal of Pharmacology - January 8, 2021 Category: Drugs & Pharmacology Authors: Noreen S, Maqbool I, Madni A Tags: Eur J Pharmacol Source Type: research

Antiproliferative effect, alteration of cancer cell cycle progression and potential MET kinase inhibition induced by 3,4-dihydropyrimidin-2(1H)-one C5 amide derivatives.
In this study, twenty-seven 3,4-dihydropyrimidin-2(1H)-one C5 amide derivatives were synthesized and their cancer cell growth inhibitory activity was examined in MCF-7, HT-29 and MOLT-4 cells and also NIH/3T3 non-cancer cells by MTT assay. The antiproliferative effect of the most potent derivatives were tested against MET-dependent EBC-1 and MKN-45, lung and gastric cancer cell lines, respectively. MET kinase inhibition was measured by a Homogenous Time Resolved Fluorescence (HTRF®) Assay. The influence of the test compounds on cell cycle was examined by RNase/PI flow cytometric assay. A number of compounds exhibited c...
Source: European Journal of Pharmacology - January 8, 2021 Category: Drugs & Pharmacology Authors: Moosavi F, Ebadi A, Mohabbati M, Damghani T, Mortazavi M, Miri R, Firuzi O Tags: Eur J Pharmacol Source Type: research

Protective effect of a novel phosphodiesterase 4 selective inhibitor, compound A, in diabetic nephropathy model mice.
Abstract Phosphodiesterase subtype 4 (PDE4) hydrolyzes cyclic AMP (cAMP), a secondary messenger that mediates intracellular signaling, and plays key roles in inflammatory and profibrotic responses. Clinical benefits of pentoxifylline, a non-selective PDE inhibitor, have been reported in patients with kidney disease. Here, we identified compound A as a potent and selective PDE4 inhibitor and evaluated its potential as a novel therapeutic agent for diabetic nephropathy (DN). To determine its in vivo efficacy on DN, uninephrectomized (UNx-) db/db mice and KKAy mice were used as DN mice models. Eight-week repeated dos...
Source: European Journal of Pharmacology - January 7, 2021 Category: Drugs & Pharmacology Authors: Ookawara M, Nio Y, Yamasaki M, Kuniyeda K, Hanauer G, Tohyama K, Hazama M, Matsuo T Tags: Eur J Pharmacol Source Type: research

Synthetic cyclopenta[b]indoles exhibit antineoplastic activity by targeting microtubule dynamics in acute myeloid leukemia cells.
Abstract Acute promyelocytic leukemia (APL) is associated with PML-RARα oncogene, which is treated using all-trans retinoic acid (ATRA)-based chemotherapy. However, chemoresistance is observed in 20-30% of treated patients and represents a clinical challenge, raising the importance of the development of new therapeutic options. In the present study, the effects of three synthetic cyclopenta[b]indoles on the leukemia phenotype were investigated using NB4 (ATRA-sensitive) and NB4-R2 (ATRA-resistant) cells. Among the tested synthetic cyclopenta[b]indoles, compound 2, which contains a heterocyclic nucleus, was t...
Source: European Journal of Pharmacology - January 7, 2021 Category: Drugs & Pharmacology Authors: Vicari HP, Lima K, da Costa Gomes R, Fernandes DC, Lipreri da Silva JC, Rodrigues Junior MT, Barroso de Oliveira AS, Nascimento Dos Santos R, Andricopulo AD, Coelho F, Costa-Lotufo LV, Machado-Neto JA Tags: Eur J Pharmacol Source Type: research

Do neprilysin inhibitors walk the line? Heart ameliorative but brain threatening!
This article reviewed data reported by experimental and clinical studies that examined NEP inhibitors and their dementia-related side effects. Based on the literature, LCZ696 increases the risk of memory and cognitive dysfunctions, and clinical trials failed to show compelling evidence for LCZ696 safety for the brain. Together, it was concluded that more experimental and clinical studies with particular focus on LCZ696 side effects on β-amyloid (Aβ) degradation are needed to assess LCZ696 safety for the cognitive function, especially in case of long-term administration. PMID: 33422508 [PubMed - as supplied b...
Source: European Journal of Pharmacology - January 7, 2021 Category: Drugs & Pharmacology Authors: Poorgolizadeh E, Moghadam FH, Dormiani K, Rezaei N, Nasr-Esfahani MH Tags: Eur J Pharmacol Source Type: research

Unraveling the mechanism of arbidol binding and inhibition of SARS-CoV-2: Insights from atomistic simulations.
Abstract The COVID-19 pandemic has spread rapidly and posed an unprecedented threat to the global economy and human health. Broad-spectrum antivirals are currently being administered to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). China's prevention and treatment guidelines suggest the use of an antiinfluenza drug, arbidol, for the clinical treatment of COVID-19. Reports indicate that arbidol could neutralize SARS-CoV-2. Monotherapy with arbidol is found to be superior to lopinavir-ritonavir or favipiravir for treating COVID-19. In SARS-CoV-2 infection, arbidol acts by interfering with viral...
Source: European Journal of Pharmacology - December 30, 2020 Category: Drugs & Pharmacology Authors: Padhi AK, Seal A, Khan JM, Ahamed M, Tripathi T Tags: Eur J Pharmacol Source Type: research

Ginsenoside Rb1 protected PC12  cells from Aβ25-35-induced cytotoxicity via PPARγ activation and cholesterol reduction.
Ginsenoside Rb1 protected PC12 cells from Aβ25-35-induced cytotoxicity via PPARγ activation and cholesterol reduction. Eur J Pharmacol. 2020 Dec 24;893:173835 Authors: Changhong K, Peng Y, Yuan Z, Cai J Abstract Accumulating evidences suggest that amyloid β (Aβ)-peptide plays a key role in pathogenesis of Alzheimer's disease (AD) through aggregation and deposition into plaques in neuronal cells. Membrane components such as cholesterol and gangliosides not only enhance the production of amyloidogenic Aβ fragments, but also appear to strengthen Aβ-membrane interaction...
Source: European Journal of Pharmacology - December 24, 2020 Category: Drugs & Pharmacology Authors: Changhong K, Peng Y, Yuan Z, Cai J Tags: Eur J Pharmacol Source Type: research

A direct thrombin inhibitor, dabigatran etexilate protects from renal fibrosis by inhibiting protease activated receptor-1.
Abstract Chronic kidney disease (CKD) involves interstitial fibrosis as an influential underlying pathological process associated with compromised renal function regardless of etiological cause of the injury. The tubulointerstitial fibrosis is found to be well correlated with declining renal function and its subsequent culmination into renal failure. Given the prominent role of thrombin in multiple diseases, it was tempting for us to investigate the outcome of a direct thrombin inhibitor in renal injury. We investigated the involvement of thrombin in renal injury and fibrosis by using an FDA approved orally active...
Source: European Journal of Pharmacology - December 24, 2020 Category: Drugs & Pharmacology Authors: Saifi MA, Annaldas S, Godugu C Tags: Eur J Pharmacol Source Type: research

Neuropharmacological potentials of β-Carboline Alkaloids for neuropsychiatric disorders - A review.
Neuropharmacological potentials of β-Carboline Alkaloids for neuropsychiatric disorders - A review. Eur J Pharmacol. 2020 Dec 24;:173837 Authors: Ayipo YO, Mordi MN, Mustapha M, Damodaran T Abstract Neuropsychiatric disorders are diseases of the central nervous system (CNS) which are characterised by complex pathomechanisms that including homeostatic failure, malfunction, atrophy, pathology remodelling and reactivity anomaly of the neuronal system where treatment options remain challenging. β-Carboline (βC) alkaloids are scaffolds of structurally diverse tricyclic pyrido[3,4-b]indole al...
Source: European Journal of Pharmacology - December 24, 2020 Category: Drugs & Pharmacology Authors: Ayipo YO, Mordi MN, Mustapha M, Damodaran T Tags: Eur J Pharmacol Source Type: research

A comprehensive understanding about the pharmacological effect of diallyl disulfide other than its anti-carcinogenic activities.
Abstract Diallyl disulfide (DADS), an oil-soluble sulfur compound that is responsible for the biological effects of garlic, displays numerous biological activities, among which its anti-cancer activities are the most famous ones. In recent years, the pharmacological effects of DADS other than its anti-carcinogenic activities have attracted numerous attentions. For example, it has been reported that DADS can prevent the microglia-mediated neuroinflammatory response and depression-like behaviors in mice. In the cardiovascular system, DADS administration was found to ameliorate the isoproterenol- or streptozotocin-in...
Source: European Journal of Pharmacology - December 24, 2020 Category: Drugs & Pharmacology Authors: He H, Ma Y, Huang H, Huang C, Chen Z, Chen D, Gu Y, Wang X, Chen J Tags: Eur J Pharmacol Source Type: research

Effects of atorvastatin in combination with celecoxib and tipifarnib on proliferation and apoptosis in pancreatic cancer sphere-forming cells.
Abstract Cancer stem cell (CSC) plays an important role in pancreatic cancer pathogenesis and treatment failure. CSCs are characterized by their ability to form tumor spheres in serum-free medium and expression of CSC related markers. In the present study, we investigated the effect atorvastatin, celecoxib and tipifarnib in combination on proliferation and apoptosis in Panc-1 sphere-forming cells. The sphere-forming cells were isolated from Panc-1 cells by sphere-forming method. These sphere-forming cells showed CSC properties. The levels of CD44, CD133 and ALDH1A1 in the sphere-forming cells were increased. Mor...
Source: European Journal of Pharmacology - December 24, 2020 Category: Drugs & Pharmacology Authors: Xu XT, Chen J, Ren X, Ma YR, Wang X, Ma YY, Zhao DG, Zhou RP, Zhang K, Goodin S, Li DL, Zheng X Tags: Eur J Pharmacol Source Type: research

Glucocorticoids impair type I IFN signalling and enhance rhinovirus replication.
ari R Abstract Inhaled corticosteroids (ICS) are recommended treatments for all degrees of asthma severity and in combination with bronchodilators are indicated for COPD patients with a history of frequent exacerbations. However, the long-term side effects of glucocorticoids (GCs) may include increased risk of respiratory infections, including viral triggered exacerbations. Rhinovirus (RV) infection is the main trigger of asthma and COPD exacerbations. Thus, we sought to explore the influence of GCs on viral replication. We demonstrate the ICS fluticasone propionate (FP) and two selective non-steroidal (GRT7) and ...
Source: European Journal of Pharmacology - December 24, 2020 Category: Drugs & Pharmacology Authors: Marcellini A, Swieboda D, Guedán A, Farrow SN, Casolari P, Contoli M, Johnston SL, Papi A, Solari R Tags: Eur J Pharmacol Source Type: research

Quinazoline alpha-adrenoreceptor blockers as an adjunct cancer treatment: From bench to bedside.
Abstract Drug repurposing has been increasingly used by both researchers and clinicians to identify new cancer treatments. The alpha-1 adrenoreceptor blockers are a class of drugs that have been used for many years in the treatment of hypertension and benign prostatic hyperplasia. Some of the drugs in this class, notably the quinazoline derivatives, have been found to display cytotoxic properties, identifying them as potential options in the treatment of cancer. This review will examine the currently available evidence that investigates the cytotoxic and anti-cancer properties of these agents, the mechanisms behin...
Source: European Journal of Pharmacology - December 23, 2020 Category: Drugs & Pharmacology Authors: King L, Christie D, Dare W, Bernaitis N, Chess-Williams R, McDermott C, Forbes A, Anoopkumar-Dukie S Tags: Eur J Pharmacol Source Type: research

Corrigendum to "Essential role of Cav3.2 T-type calcium channels in butyrate-induced colonic pain and nociceptor hypersensitivity in mice" [Eur. J. Pharmacol. 887 (2020) 173576].
Corrigendum to "Essential role of Cav3.2 T-type calcium channels in butyrate-induced colonic pain and nociceptor hypersensitivity in mice" [Eur. J. Pharmacol. 887 (2020) 173576]. Eur J Pharmacol. 2020 Dec 22;:173795 Authors: Tsubota M, Matsui K, Nakano M, Kajitani R, Ishii Y, Tomochika K, Nishikawa Y, Fukushi S, Yamagata A, Sekiguchi F, Okada T, Toyooka N, Kawabata A PMID: 33358247 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - December 22, 2020 Category: Drugs & Pharmacology Authors: Tsubota M, Matsui K, Nakano M, Kajitani R, Ishii Y, Tomochika K, Nishikawa Y, Fukushi S, Yamagata A, Sekiguchi F, Okada T, Toyooka N, Kawabata A Tags: Eur J Pharmacol Source Type: research

Common Targets for a deadly duo of diabetes mellitus and colon cancer: Catching two fish with one worm.
Abstract Colon cancer is a major health issue and number of cases are increasing every year. Diabetes mellitus is also a significant health issue that is growing day by day worldwide having negative influences on the survival of individuals. Research has shown a strong relationship between the two malignant diseases. The risk of colon cancer with patients who have type 2 diabetes mellitus has spiked by 30%. The scientific research suggests insulin has a major role in the spread of cancer and the condition unifying between the two diseases is hyperinsulinemia. Several anti-diabetic agents are used for the treatment...
Source: European Journal of Pharmacology - December 22, 2020 Category: Drugs & Pharmacology Authors: Gajjar S, Patel BM Tags: Eur J Pharmacol Source Type: research

Preconditioning and anti-apoptotic effects of Metformin and Cyclosporine-A in an Isolated bile duct-ligated rat heart.
Abstract Despite all previous studies relating to the mechanism of cirrhotic cardiomyopathy (CCM), the role of cirrhosis on Ischemic Preconditioning (IPC) has not yet been explored. The present study strives to assess the cardioprotective role of IPC in bile duct ligated (BDL) rats as well as the cardioprotective role of Cyclosporin-A (CsA) and Metformin (Met) in CCM. Cirrhosis was induced by bile duct ligation (BDL). Rats' hearts were isolated and attached to a Langendorff Apparatus. The pharmacological preconditioning with Met and CsA was done before the main ischemia. Myocardial infarct size, hemodynamic and el...
Source: European Journal of Pharmacology - December 22, 2020 Category: Drugs & Pharmacology Authors: Moheimani HR, Amiriani T, Alizadeh AM, Jand Y, Shakiba D, Ensan PS, Jafarzadeh F, Rajaei M, Enayati A, Pourabouk M, Aliazadeh S, Pourkhani AH, Mazaheri Z, Zeyghami MA, Dehpour A, Khori V Tags: Eur J Pharmacol Source Type: research

Advantages and Challenges in nanomedicines for chronic liver diseases: a hepatologist's perspectives.
Abstract Chronic liver disease (CLD) is responsible for significant morbidity and mortality worldwide. CLD patients are at a high risk of developing progressive liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and subsequent liver failure. To date, there is no specific and effective therapies exist for patients with various forms of CLD. The application of nanotechnology has emerged as a rapidly developing area of interest for the safe and target-specific delivery of poorly aqueous soluble hepatoprotective agents and nucleic acids (siRNA/miRNAs) in CLD. The nanoparticle combination improves bioavailabili...
Source: European Journal of Pharmacology - December 21, 2020 Category: Drugs & Pharmacology Authors: Ezhilarasan D Tags: Eur J Pharmacol Source Type: research

Enhanced targeting of 3D pancreatic cancer spheroids by aptamer-conjugated polymeric micelles with deep tumor penetration.
Abstract Pancreatic cancer is a high degree malignant tumor which makes its diagnosis and treatment highly critical. The effect of conventional chemotherapy for pancreatic cancer is quite poor due to the low accumulation of the chemotherapeutic drugs at the tumor site. Therefore, enhancing the targeting efficiency and accumulation of the drug carrier at tumor site with subsequent release of drug within the effective time period is one of the key factors for successful targeted chemotherapy of pancreatic cancer. Our previous studies have demonstrated that aptamer can be a valid targeting moiety to guide the chemoth...
Source: European Journal of Pharmacology - December 19, 2020 Category: Drugs & Pharmacology Authors: Tian L, Pei R, Zhong L, Ji Y, Zhou D, Zhou S Tags: Eur J Pharmacol Source Type: research

The effects of glucagon-like peptide-1 receptor agonists on glycemic control and anthropometric profiles among diabetic patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials.
This study was undertaken to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs), mainly liraglutide and exenatide, on glycemic control and anthropometric profiles to see if they are effective in treating patients with non-alcoholic fatty liver disease (NAFLD) and type-2 diabetes mellitus (T2DM). We searched PubMed, Embase, Scopus, Web of Science (WOS), and Cochrane Library databases to identify all the randomized clinical trials (RCTs) up to 23 August 2020. Heterogeneity of the included studies was evaluated using Cochrane's Q test and the I2 statistic. Moreover, a random-effects model was used to p...
Source: European Journal of Pharmacology - December 19, 2020 Category: Drugs & Pharmacology Authors: Nowrouzi-Sohrabi P, Rezaei S, Jalali M, Ashourpour M, Ahmadipour A, Keshavarz P, Akbari H Tags: Eur J Pharmacol Source Type: research

Haloperidol potentiates antinociceptive effects of morphine and disrupt opioid tolerance.
In conclusion, haloperidol enhances the antinociceptive effects of morphine without significant adverse effects, as it is able to disrupt or delay the morphine-tolerance in neuropathic pain. PMID: 33347818 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - December 18, 2020 Category: Drugs & Pharmacology Authors: Mena-Valdés LC, Blanco-Hernández Y, Espinosa-Juárez JV, López-Muñoz FJ Tags: Eur J Pharmacol Source Type: research

Impact of epicatechin on fibrin clot structure.
Abstract Fibrin clot structure and function are major determinants of thromboembolic diseases. The study aim was to determine the impact of epicatechin (a flavonoid with cardiovascular protective effects) on fibrin clot structure and permeability. Plasma samples from 12 healthy subjects were incubated with increasing concentrations of epicatechin. Turbidity of fibrin clot was analyzed by absorbance measurement at 405nm. The fibrin clot nanostructure was determined by scanning spectrometry (wavelength from 500 to 800nm) and fibrin fiber size by electron microscopy. Permeability was analyzed to assess the fibrin clo...
Source: European Journal of Pharmacology - December 18, 2020 Category: Drugs & Pharmacology Authors: Sinegre T, Milenkovic D, Teissandier D, Fully P, Bourdin J, Morand C, Lebreton A Tags: Eur J Pharmacol Source Type: research