Olmesartan attenuates type 2 diabetes-associated liver injury: Cross-talk of AGE/RAGE/JNK, STAT3/SCOS3 and RAS signaling pathways.
In conclusion, OLM and its combination with PIO enhanced insulin sensitivity and guarded against hepatic complications associated with type 2 diabetes probably via modulating various inter-related pathways; namely, metabolic alteration, renin-angiotensin system, inflammatory trajectories, as well as oxidative stress. This study manifests the potential synergistic effects of OLM as an adjuvant therapy to the conventional antidiabetic therapies. PMID: 32067934 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Authors: Abo El-Nasr NME, Saleh DO, Mahmoud SS, Nofal SM, Abdel Salam RM, Safar MM, El-Abhar H Tags: Eur J Pharmacol Source Type: research

In vitro investigation of the effect of mesalazine on amyloid fibril formation of hen egg-white lysozyme and defibrillation lysozyme fibrils.
In this study, we investigated the in vitro effects of mesalazine drug on both preventions of lysozyme aggregation and the removal of lysozyme fibrils. With this regard, hen egg-white lysozyme (HEWL) was incubated in the absence and presence of mesalazine in high temperature and acidic pH conditions. The influence of mesalazine was surveyed by Congo red (CR) absorbance, Circular dichroism spectroscopy (CD), Thioflavin T (ThT) fluorescence assay, 1-anilinonaphthalene-8-sulfonic acid (ANS) fluorescence test, and Field-emission scanning electron microscopy (FE-SEM). Our results demonstrate that mesalazine, in all concentratio...
Source: European Journal of Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Authors: Faramarzian M, Bahramikia S, Dehghan Shasaltaneh M Tags: Eur J Pharmacol Source Type: research

Therapeutic drugs modulate ATP-Binding cassette transporter-mediated transport of amyloid beta(1-42) in brain microvascular endothelial cells.
Abstract Deposition of amyloid-β peptide (Aβ(1-42)) is a hallmark of Alzheimer's disease. Clearance of Aβ(1-42), across the blood-brain barrier (BBB), is mediated by ATP-binding Cassette (ABC) efflux transporters. Many therapeutic drugs inhibit ABC transporters, but little is known of the effect of therapeutic drugs on Aβ(1-42) transport across BBB endothelial cells. The effects of selected, widely prescribed, therapeutic drugs on ABCB1, ABCC5 and ABCG2 activities were determined by measuring intracellular levels of calcein, GS-MF, and Hoechst 33342 respectively in primary porcine brain endothe...
Source: European Journal of Pharmacology - February 13, 2020 Category: Drugs & Pharmacology Authors: Shubbar MH, Penny JI Tags: Eur J Pharmacol Source Type: research

Dipyrone is locally hydrolyzed to 4-methylaminoantipyrine and its antihyperalgesic effect depends on CB2 and kappa-opioid receptors activation.
In conclusion, the analgesic effect of dipyrone may involve a possible interaction between the cannabinoid and opioid system in peripheral tissue. PMID: 32057719 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - February 11, 2020 Category: Drugs & Pharmacology Authors: Gonçalves Dos Santos G, Vieira WF, Vendramini PH, Bassani da Silva B, Magalhães SF, Tambeli CH, Parada CA Tags: Eur J Pharmacol Source Type: research

Osthole inhibits ovarian carcinoma cells through LC3-mediated autophagy and GSDME-dependent pyroptosis except for apoptosis.
In this study, we aim to evaluate the mechanism of osthole against OC cells. Methodologically, Cell Counting Kit-8 (CCK-8) and LIVE/DEAD™ Cell Imaging experiments were employed to assess cell viability. 2',7'-Dichlorofluorescin diacetate (DCFH-DA) staining, flow cytometry, Hoechst staining, JC-1 staining assay and western blotting were performed to study apoptosis. Transmission electron microscopy, western blotting and monodansyl cadaverine (MDC) staining assay were used to study autophagy. Western blotting and microscopy image were employed to determine pyroptosis. Our results demonstrated that osthole could signifi...
Source: European Journal of Pharmacology - February 10, 2020 Category: Drugs & Pharmacology Authors: Liang J, Zhou J, Xu Y, Huang X, Wang X, Huang W, Li H Tags: Eur J Pharmacol Source Type: research

Diosmin enhances the anti-angiogenic activity of sildenafil and pentoxifylline against hepatopulmonary syndrome via regulation of TNF- α/VEGF, IGF-1/PI3K/AKT, and FGF-1/ANG-2 signaling pathways.
In this study, we aimed to investigate the regulatory effects of diosmin (DS) on selected phosphodiesterase inhibitors against chronic bile duct ligation (CBDL)-induced HPS. Experimentally, Wistar Albino rats were used and HPS was induced by CBDL for 28 days. DS (100 mg/kg, daily, P.O.), sildenafil (Sild; 10 mg/kg, twice daily, P.O.), and pentoxifylline (PTX; 50 mg/kg, daily, P.O.) were evaluated either alone or in combinations for their anti-angiogenic activity. CBDL significantly altered oxidative stress biomarkers and up-regulated pulmonary mRNA expressions of VEGF, IGF-1, ET-1, iNOS, eNOS, and ANG-2 as well as th...
Source: European Journal of Pharmacology - February 9, 2020 Category: Drugs & Pharmacology Authors: Bakr AG, El-Bahrawy AH, Taha HH, Ali FEM Tags: Eur J Pharmacol Source Type: research

Naringin inhibits autophagy mediated by PI3K-Akt-mTOR pathway to ameliorate endothelial cell dysfunction induced by high glucose/high fat stress.
In conclusion, Nar improves the function of HUVECs under HG/HF stress through activating the PI3K-Akt-mTOR pathway to inhibit autophagy. The findings offer an insight into HG/HF stress-induced autophagy and indicate that Nar might have potential to prevent and treat the diabetic angiopathy. PMID: 32045600 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - February 8, 2020 Category: Drugs & Pharmacology Authors: Wang K, Peng S, Xiong S, Niu A, Xia M, Xiong X, Zeng G, Huang Q Tags: Eur J Pharmacol Source Type: research

Modulation of the hepatic expression of miR-33 and miR-34a possibly mediates the metabolic effects of estrogen in ovariectomized female rats.
In conclusion, estrogen replacement therapy in OVX females significantly ameliorated the metabolic derangements of insulin resistance, dyslipidemia and hepatic fat accumulation possibly via corrections of hepatic expression of miR-33 and miR-34a; effects that were mediated through the receptor-mediated signaling of ERs as confirmed by fulvestrant. PMID: 32045601 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - February 8, 2020 Category: Drugs & Pharmacology Authors: Ali MA, Kamel MA Tags: Eur J Pharmacol Source Type: research

Vitexin protects against ethanol-induced liver injury through Sirt1/p53 signaling pathway.
Abstract In the present study, we aimed to investigate the therapeutic effect of Vitexin on inhibiting ethanol-induced liver damage and explore the underling mechanism. In vitro, the injury was induced in LO2 cell by 100 mM ethanol. Cell viability, AST, oxidative stress, inflammation, apoptosis rate, and related gene and protein expressions were assessed. Alcoholic liver injury model was made by intragastric infusion of alcohol for 4 weeks on male KM mice. Liver index, AST, ALT, TC, TG, TP, TBIL in serum and liver pathology were evaluated. Meanwhile, the level of SOD, MDA and TNF-α also were detected by Ki...
Source: European Journal of Pharmacology - February 8, 2020 Category: Drugs & Pharmacology Authors: Yuan H, Duan S, Guan T, Yuan X, Lin J, Hou S, Lai X, Huang S, Du X, Chen S Tags: Eur J Pharmacol Source Type: research

Beta-sitosterol attenuates insulin resistance in adipose tissue via IRS-1/Akt mediated insulin signaling in high fat diet and sucrose induced type-2 diabetic rats.
Abstract In our previous study, we have shown that β-sitosterol (SIT) enhances glycemic control by increasing the activation of insulin receptor (IR) and glucose transporter 4 (GLUT4) proteins in adipose tissue. However, the possible role of SIT on the regulation of post-receptor insulin signal transduction is not known. Hence, the study was aimed to assess the effects of SIT on IRS-1/Akt mediated insulin signaling molecules in high-fat diet and sucrose induced type-2 diabetic rats. An oral effective dose of SIT (20 mg/kg b.wt) was given for 30 days to high fat-fed type-2 diabetic rats to find out whether S...
Source: European Journal of Pharmacology - February 8, 2020 Category: Drugs & Pharmacology Authors: Babu S, Krishnan M, Rajagopal P, Periyasamy V, Veeraraghavan V, Govindan R, Jayaraman S Tags: Eur J Pharmacol Source Type: research

Exposure to the cannabinoid agonist WIN 55, 212-2 in adolescent rats causes sleep alterations that persist until adulthood.
illo-Rodríguez E Abstract Cannabis and, to a lesser extent, synthetic cannabinoids are used during adolescence, a period in which multiple brain areas are still undergoing development. Among such areas is the hypothalamus, which is implicated in the control of sleep-wake cycle. In the present report, we show that exposing adolescent rats to the cannabinoid receptor agonist WIN 55, 212-2 (0.1, 0.3 or 1.0 mg/kg, i.p) for 14 days during adolescence (i.e., from post-natal day 30-44) resulted in significant sleep disturbances when the animals became adult (post-natal day 80). These included decreased wakefulne...
Source: European Journal of Pharmacology - February 8, 2020 Category: Drugs & Pharmacology Authors: Macías-Triana L, Romero-Cordero K, Tatum-Kuri A, Vera-Barrón A, Millán-Aldaco D, Arankowsky-Sandoval G, Piomelli D, Murillo-Rodríguez E Tags: Eur J Pharmacol Source Type: research

YC-1 potentiates the antitumor activity of gefitinib by inhibiting HIF-1 α and promoting the endocytic trafficking and degradation of EGFR in gefitinib-resistant non-small-cell lung cancer cells.
YC-1 potentiates the antitumor activity of gefitinib by inhibiting HIF-1α and promoting the endocytic trafficking and degradation of EGFR in gefitinib-resistant non-small-cell lung cancer cells. Eur J Pharmacol. 2020 Feb 07;:172961 Authors: Hu H, Miao XK, Li JY, Zhang XW, Xu JJ, Zhang JY, Zhou TX, Hu MN, Yang WL, Mou LY Abstract The tyrosine kinase inhibitor (TKI) gefitinib exerts good therapeutic effect on NSCLC patients with sensitive EGFR-activating mutations. However, most patients ultimately relapse due to the development of drug resistance after 6-12 months of treatment. Here, we showed th...
Source: European Journal of Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Authors: Hu H, Miao XK, Li JY, Zhang XW, Xu JJ, Zhang JY, Zhou TX, Hu MN, Yang WL, Mou LY Tags: Eur J Pharmacol Source Type: research

Mesenchymal stem cells as carriers for systemic delivery of oncolytic viruses.
Abstract Progress in genetic engineering led to the emergence of some viruses as potent anticancer therapeutics. These oncolytic viruses combine self-amplification with dual antitumor action: oncolytic (destruction of cancer cells) and immunostimulatory (eliciting acquired antitumor response against cancer epitopes). As any other viruses, they trigger antiviral response upon systemic administration. Mesenchymal stem cells are immature cells capable of self-renewing and differentiating into many cell types that belong to three germinal layers. Due to their inherent tumor tropism mesenchymal stem cells loaded with o...
Source: European Journal of Pharmacology - February 7, 2020 Category: Drugs & Pharmacology Authors: Hadryś A, Sochanik A, McFadden G, Jazowiecka-Rakus J Tags: Eur J Pharmacol Source Type: research

Hesperetin ameliorates DSS-induced colitis by maintaining the epithelial barrier via blocking RIPK3/MLKL necroptosis signaling.
This study aimed to investigate the protective effects and mechanisms of hesperetin on dextran sodium sulfate (DSS) -induced colitis. Our results showed that hesperetin significantly relieved the symptoms of DSS -induced colitis and increased the expressions of zonula occludens-1 (ZO-1), occludin and mucin2 (MUC-2) as well as the decrease of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-18, HMGB1 and IL-6. Of note, results from immunohistochemistry (IHC) and western blotting indicated that hesperetin inhibited the expressions of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kin...
Source: European Journal of Pharmacology - February 5, 2020 Category: Drugs & Pharmacology Authors: Zhang J, Lei H, Hu X, Dong W Tags: Eur J Pharmacol Source Type: research

4-Octyl itaconate protects against renal fibrosis via inhibiting TGF- β/Smad pathway, autophagy and reducing generation of reactive oxygen species.
This study reports for the first time that OI ameliorated renal fibrosis by suppressing the activation of TGF-β/Smad and nuclear factor kappa B (NF-κB) pathways, reducing generation of reactive oxygen species and inhibiting autophagy. These results clearly suggest that OI has great clinical potential for managing renal fibrosis. PMID: 32032597 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Authors: Tian F, Wang Z, He J, Zhang Z, Tan N Tags: Eur J Pharmacol Source Type: research

κ-opioid receptor activation promotes mitochondrial fusion and enhances myocardial resistance to ischemia and reperfusion injury via STAT3-OPA1 pathway.
This study aims to investigate the effect of κ-opioid receptor activation on the pathogenesis of MI/R and its underlying mechanisms. MI/R mouse model and hypoxia-reoxygenation cardiomyocyte model were established in this study. Mitochondrial dynamics were analyzed with transmission electron microscopy in vivo and confocal microscopy in vitro. STAT3 phosphorylation and OPA1 expression were detected by Western blotting. We show here that κ-opioid receptor activation with its selective receptor agonist U50,488H promoted mitochondrial fusion and enhanced myocardial resistance to MI/R injury, while these protective ...
Source: European Journal of Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Authors: Wang K, Liu Z, Zhao M, Zhang F, Wang K, Feng N, Fu F, Li J, Li J, Liu Y, Zhang S, Fan R, Guo H, Pei J Tags: Eur J Pharmacol Source Type: research

Withaferin A alleviates traumatic brain injury induced secondary brain injury via suppressing apoptosis in endothelia cells and modulating activation in the microglia.
Abstract Traumatic brain injury (TBI) is a major public health concern with high rates of morbidity and mortality worldwide. Currently used medications, though effective, are also associated with several adverse effects. Development of effective neuroprotective agents with fewer side-effects would be of clinical value. Previous studies have shown that withaferin compounds have a potential neuroprotective effect in nervous system disorders. However, the effect of withaferin compounds, especially withaferin A (WFA), on traumatic brain injury is unclear. In the present study, both in vivo and in vitro models were use...
Source: European Journal of Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Authors: Zhou Z, Xiang W, Jiang Y, Tian N, Wei Z, Wen X, Wang W, Liao W, Xia X, Li Q, Liao R Tags: Eur J Pharmacol Source Type: research

Differential effects of aminochlorin derivatives on the phagocytic and inflammatory potentials of mammalian macrophages.
Abstract Chlorin derivatives have been known for their biological activities. Especially due to their advanced electron transfer capacity they have been used as photodynamic therapy agent both at clinical and laboratory scales. Photodynamic therapy (PDT) against cancer or an infectious disease aims the development of less side effect on the patient since the activation of the inert drug molecule will start only after the light treatment. In order to increase our library of photodynamic therapy agents, we generated a set of chlorin derivatives and tested their PDT potential on the immune system cells; macrophages. ...
Source: European Journal of Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Authors: Ayaz F, Ocakoglu K Tags: Eur J Pharmacol Source Type: research

Antidiarrheal activity of farnesol in rodents: Pharmacological actions and molecular docking.
The objective of this study was to evaluate the antidiarrheal activity of Farnesol (FOH). Initially, FOH activity was evaluated in models of diarrhea and enteropooling induced by castor oil and PGE2. To evaluate motility, the opioid and cholinergic pathways were studied. In addition, the effect of FOH was investigated in the secretion model in intestinal loops treated with cholera toxin. FOH was evaluated for the ability to absorb fluids in intestinal loops and interact with GM1 receptors using the ELISA method and molecular docking. The dose of 50 mg/kg of FOH showed the best results in all antidiarrheal activity tests ...
Source: European Journal of Pharmacology - February 4, 2020 Category: Drugs & Pharmacology Authors: da Costa DS, Negreiros PDS, da Silva VG, Nunes DB, Acha BT, Quintans-Junior LJ, Antunes de Souza Júnior A, Araújo TSL, Sousa FBM, Medeiros JVR, Lima FDCA, da Silva FI, Magalhães Costa RK, Santos RFD, Oliveira RCM Tags: Eur J Pharmacol Source Type: research

Gabapentin attenuates intestinal inflammation: Role of PPAR-gamma receptor.
Barbosa AL Abstract Gabapentin is an anticonvulsant drug that is also used for post-herpetic neuralgia and neuropathic pain. Recently, gabapentin showed anti-inflammatory effect. Nuclear factor kappa B (NFκB) is a regulator of the inflammatory process, and Peroxisome Proliferator-activated Receptor gamma (PPAR-gamma) is an important receptor involved in NFκB regulation. The aim of the present work was to study the potential role of PPAR-gamma receptor in gabapentin-mediated anti-inflammatory effects in a colitis experimental model. We induced colitis in rats using trinitrobenzenosulfonic acid and trea...
Source: European Journal of Pharmacology - February 3, 2020 Category: Drugs & Pharmacology Authors: de Brito TV, Júnior GJD, da Cruz Júnior JS, Silva RO, da Silva Monteiro CE, Franco AX, Vasconcelos DFP, de Oliveira JS, da Silva Costa DV, Carneiro TB, Gomes Duarte AS, de Souza MHLP, Soares PMG, Dos Reis Barbosa AL Tags: Eur J Pharmacol Source Type: research

Onvansertib, a polo-like kinase 1 inhibitor, inhibits prostate stromal cell growth and prostate smooth muscle contraction, which is additive to inhibition by α1-blockers.
Onvansertib, a polo-like kinase 1 inhibitor, inhibits prostate stromal cell growth and prostate smooth muscle contraction, which is additive to inhibition by α1-blockers. Eur J Pharmacol. 2020 Feb 01;:172985 Authors: Wang X, Li B, Ciotkowska A, Rutz B, Erlander MG, Ridinger M, Wang R, Tamalunas A, Waidelich R, Stief CG, Hennenberg M Abstract Prostate smooth muscle contraction and prostate enlargement contribute to lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Recent evidence demonstrated that inhibitors for polo-like kinases (PLKs) inhibit smooth muscle contraction of ...
Source: European Journal of Pharmacology - February 1, 2020 Category: Drugs & Pharmacology Authors: Wang X, Li B, Ciotkowska A, Rutz B, Erlander MG, Ridinger M, Wang R, Tamalunas A, Waidelich R, Stief CG, Hennenberg M Tags: Eur J Pharmacol Source Type: research

Targeting Keap1/Nrf2/ARE signaling pathway in multiple sclerosis.
te; NK, Slanař O Abstract Multiple sclerosis (MS) is a neurologic autoimmune disorder featured by chronic inflammation of the central nervous system, demyelination and axonal damage. Recently, the term "oxinflammation" has been proposed to depict the vicious circle of chronic inflammation and oxidative stress (OS). OS promotes demyelination and neurodegeneration directly, by oxidation of lipids, proteins, and DNA but also indirectly, by inducing a dysregulation of the immunity and favoring the state of pro-inflammatory response. Many of the actors of this delicately tuned network are controlled by Keap1...
Source: European Journal of Pharmacology - February 1, 2020 Category: Drugs & Pharmacology Authors: Michaličková D, Hrnčíř T, Canová NK, Slanař O Tags: Eur J Pharmacol Source Type: research

The effects of gasotransmitters on bronchopulmonary dysplasia.
Abstract Bronchopulmonary dysplasia (BPD), which remains a major clinical problem for preterm infants, is caused mainly by hyperoxia, mechanical ventilation and inflammation. Many approaches have been developed with the aim of decreasing the incidence of or alleviating BPD, but effective methods are still lacking. Gasotransmitters, a type of small gas molecule that can be generated endogenously, exert a protective effect against BPD-associated lung injury; nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) are three such gasotransmitters. The protective effects of NO have been extensively studied i...
Source: European Journal of Pharmacology - February 1, 2020 Category: Drugs & Pharmacology Authors: Lin H, Wang X Tags: Eur J Pharmacol Source Type: research

An investigation into the pleiotropic activity of metformin. A glimpse of haemostasis.
Abstract The most characteristic features of type 2 diabetes mellitus (T2DM) are hyperglycaemia and insulin resistance, however, patients with T2DM are at higher risk of cardiovascular disease (CVD) and atherosclerosis. Diabetes, frequently related to metabolic and vascular impairments, is also associated with thrombosis, increased blood coagulation and an imbalance between coagulation and fibrinolysis. Metformin is the most often used oral glucose-lowering agent; its beneficial properties include lowering insulin resistance, weight reduction and cardioprotection. Available data suggest that the advantageous prope...
Source: European Journal of Pharmacology - February 1, 2020 Category: Drugs & Pharmacology Authors: Markowicz-Piasecka M, Sadkowska A, Huttunen KM, Podsiedlik M, Mikiciuk-Olasik E, Sikora J Tags: Eur J Pharmacol Source Type: research

Long non-coding RNA ROR confers arsenic trioxide resistance to HepG2 cells by inhibiting p53 expression.
In this study, We found that cellular apoptosis was increased by arsenic trioxide in liver cancer HepG2 cells; P53 expression was also increased by arsenic trioxide at both mRNA level and protein level, indicating that P53-dependent apoptosis is the main mechanism for arsenic trioxide to induce cytotoxicity in liver cancer HepG2 cells. Meanwhile, we found an obvious increase in the level of long non-coding RNA ROR in arsenic trioxide-treated HepG2 cells. By measuring the level of reactive oxygen species, glutathione, superoxide dismutase, and malondialdehyde, the product of lipid peroxidation, we further demonstrated that ...
Source: European Journal of Pharmacology - February 1, 2020 Category: Drugs & Pharmacology Authors: Li X, Sun D, Zhao T, Zhang Z Tags: Eur J Pharmacol Source Type: research

Toll-like receptor 4: A promising crossroads in the diagnosis and treatment of several pathologies.
ual D Abstract Toll-like receptor 4 (TLR4) is expressed in a wide variety of cells and is the central component of the mammalian innate immune system. Since its discovery in 1997, TLR4 has been assigned an ever-increasing number of functions that extend from pathogen recognition to tissue damage identification and promotion of the intrinsic "damage repair response" in pain, intestinal, respiratory and vascular disorders. Precisely, the finding of conserved sequence homology among species along with the molecular and functional characterisation of the TLR4 gene enabled researchers to envisage a common ope...
Source: European Journal of Pharmacology - February 1, 2020 Category: Drugs & Pharmacology Authors: Garcia MM, Goicoechea C, Molina-Álvarez M, Pascual D Tags: Eur J Pharmacol Source Type: research

In vitro benchmarking of NF- κB inhibitors.
In vitro benchmarking of NF-κB inhibitors. Eur J Pharmacol. 2020 Jan 31;:172981 Authors: Harrold AP, Cleary MM, Bharathy N, Lathara M, Berlow NE, Foreman NK, Donson AM, Amani V, Zuercher WJ, Keller C Abstract Dysregulated activity of the transcription factors of the nuclear factor κb (NF-κB) family has been implicated in numerous cancer types, inflammatory diseases, autoimmune disease, and other disorders. As such, selective NF-κB pathway inhibition is an attractive target to researchers for preclinical and clinical drug development. A plethora of commercially and clinically av...
Source: European Journal of Pharmacology - January 31, 2020 Category: Drugs & Pharmacology Authors: Harrold AP, Cleary MM, Bharathy N, Lathara M, Berlow NE, Foreman NK, Donson AM, Amani V, Zuercher WJ, Keller C Tags: Eur J Pharmacol Source Type: research

Atypical antipsychotic drug modulates early life infection induced impairment of hypothalamic-pituitary-adrenal axis: An age related study in mice.
Abstract Evidences from human and animal studies indicate that exposure to infection during early life act as a stressor to impair the hypothalamic-pituitary-adrenal (HPA) axis and may be one of the contributing factors of mental illness of later life. Several atypical antipsychotic drugs (AAPDs) proved to be effective in alleviating psychiatric illness through normalization of HPA axis. However, AAPD are least tried to evaluate their efficacy in modulation of HPA axis impaired under infection. The present study elucidated that the treatment with AAPD paliperidone (PAL: 0.025 mg/kg/bw and 0.05 mg/kg/bw) during...
Source: European Journal of Pharmacology - January 31, 2020 Category: Drugs & Pharmacology Authors: Gupta P, Mohanty B Tags: Eur J Pharmacol Source Type: research

Vasoactive intestinal peptide infusion reverses existing renal interstitial fibrosis via a blood pressure independent mechanism in the rat.
Abstract Dialysis requiring renal failure is a silent epidemic. Despite an annual mortality of 24% the dialysis population has increased by 1-4% per annum. Regardless of the initial injury, tubulointerstitial fibrosis is a feature of the renal pathology and it inversely correlates with declining renal function. Current agents display little efficacy against tubulointerstitial fibrosis. Clearly, therapies effective against tubulointerstitial fibrosis and able to preserve kidney function are needed. Vasoactive intestinal peptide (VIP) has been shown to reverse pre-existing cardiac fibrosis. We sought to determine wh...
Source: European Journal of Pharmacology - January 31, 2020 Category: Drugs & Pharmacology Authors: Duggan KA, Hodge G, Chen J, Trajanovska S, Hunter T Tags: Eur J Pharmacol Source Type: research

SNHG9, delivered by adipocyte-derived exosomes, alleviates inflammation and apoptosis of endothelial cells through suppressing TRADD expression.
In this study, we proved that adipocytes-derived exosomal SNHG9 were downregulated in obese persons and further decreased in obese individuals with endothelial dysfunction. Functional experimentations demonstrated that adipocytes-derived exosomal SNHG9 alleviated inflammation and apoptosis in endothelial cells. Bioinformatic analysis revealed that there was a potential interaction between SNHG9 and the TNF receptor type 1-associated death domain protein (TRADD) mRNA. Then, RNA-binding protein immunoprecipitation assay based on Ago2 antibody and ribonuclease protection assay demonstrated that exosomal SNHG9 directly bound t...
Source: European Journal of Pharmacology - January 30, 2020 Category: Drugs & Pharmacology Authors: Song Y, Li H, Ren X, Li H, Feng C Tags: Eur J Pharmacol Source Type: research

Antidepressants induce profibrotic responses via the lysophosphatidic acid receptor LPA1.
Abstract Preclinical and clinical studies have indicated that antidepressants can promote inflammation and fibrogenesis, particularly in the lung, by mechanisms not fully elucidated. We have previously shown that different classes of antidepressants can activate the lysophosphatidic acid (LPA) receptor LPA1, a major pathogenetic mediator of tissue fibrosis. The aim of the present study was to investigate whether in cultured human dermal and lung fibroblasts antidepressants could trigger LPA1-mediated profibrotic responses. In both cell types amitriptyline, clomipramine and mianserin mimicked the ability of LPA to ...
Source: European Journal of Pharmacology - January 30, 2020 Category: Drugs & Pharmacology Authors: Olianas MC, Dedoni S, Onali P Tags: Eur J Pharmacol Source Type: research

6-Methoxyflavanone abate cisplatin-induced neuropathic pain apropos anti-inflammatory mechanisms: A behavioral and molecular simulation study.
Abstract Cisplatin is used as a first line therapy in treating cancers. However, its use is often accompanied with the development of peripheral neuropathy. 6-Methoxyflavanone (6-MeOF) is a positive allosteric modulator at GABAA receptors and is known for attenuating diabetes-induced neuropathic pain. Neuropathy was induced in male Sprague-Dawley rats (150-250 g), via intraperitoneal injection of cisplatin (3 mg/kg) once a week for four consecutive weeks. 6-MeOF (25, 50 and 75 mg/kg, i.p) and gabapentin (75 mg/kg, i.p) were administered 30 min before each cisplatin injection. Static and dynamic allodynia...
Source: European Journal of Pharmacology - January 29, 2020 Category: Drugs & Pharmacology Authors: Akbar S, Subhan F, Shahid M, Wadood A, Shahbaz N, Farooq U, Ayaz M, Raziq N Tags: Eur J Pharmacol Source Type: research

Denatonium enhanced the tone of denuded rat aorta via bitter taste receptor and phosphodiesterase activation.
Abstract Bitter taste receptors (Tas2rs) initiate a bitter taste signaling involving the activation of taste-specific G protein gustducin and phosphodiesterases (PDEs); it leads to the decrease of cytosolic level of cyclic adenosine monophosphate (cAMP) in taste cells. Recent studies have identified the expression of Tas2rs in a variety of non-lingual tissues including vascular smooth muscle (VSM), pulmonary smooth muscle and airway smooth muscle. The current study aims to determine the expression of Tas2rs and gustducin in rat aortic smooth muscle tissue and to investigate the effect of Tas2rs agonist denatonium ...
Source: European Journal of Pharmacology - January 29, 2020 Category: Drugs & Pharmacology Authors: Liu M, Qian W, Subramaniyam S, Liu S, Xin W Tags: Eur J Pharmacol Source Type: research

Novel anti-inflammatory and chondroprotective effects of the human melanocortin MC1 receptor agonist BMS-470539 dihydrochloride and human melanocortin MC3 receptor agonist PG-990 on lipopolysaccharide activated chondrocytes.
Abstract Human melanocortin MC1 and MC3 receptors expressed on C-20/A4 chondrocytes exhibit chondroprotective and anti-inflammatory effects when activated by melanocortin peptides. Nearly 9 million people in the UK suffer from osteoarthritis, and bacterial infections play a role in its development. Here, we evaluate the effect of a panel of melanocortin peptides with different selectivity for human melanocortin MC1 (α-MSH, BMS-470539 dihydrochloride) and MC3 receptors ([DTrp8]-γ-MSH, PG-990) and C-terminal peptide α-MSH11-13(KPV), on inhibiting LPS-induced chondrocyte death, pro-inflammatory medi...
Source: European Journal of Pharmacology - January 28, 2020 Category: Drugs & Pharmacology Authors: Can VC, Locke IC, Kaneva MK, Kerrigan MJP, Merlino F, De Pascale C, Grieco P, Getting SJ Tags: Eur J Pharmacol Source Type: research

Selective metabotropic glutamate receptor 2 positive allosteric modulation alleviates L-DOPA-induced psychosis-like behaviours and dyskinesia in the MPTP-lesioned marmoset.
uot P Abstract Psychosis and dyskinesia significantly diminish the quality of life of patients with advanced Parkinson's disease (PD). Available treatment options are unfortunately few and their use is limited by adverse effects. We have recently shown that activation of metabotropic glutamate 2 and 3 (mGlu2/3) receptors produced significant relief of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced psychosis-like behaviours (PLBs) and dyskinesia in experimental models of PD. Here, using the highly-selective mGlu2 positive allosteric modulator (PAM) LY-487,379, we seek to determine the contribution of selective mGlu2...
Source: European Journal of Pharmacology - January 28, 2020 Category: Drugs & Pharmacology Authors: Sid-Otmane L, Hamadjida A, Nuara SG, Bédard D, Gaudette F, Gourdon JC, Michaud V, Beaudry F, Panisset M, Huot P Tags: Eur J Pharmacol Source Type: research

Infliximab ameliorates tumor necrosis factor-alpha exacerbated renal insulin resistance induced in rats by regulating insulin signaling pathway.
In conclusion, MET and IFX ameliorated the TNF-α worsening effect on IR in rat renal tissues by regulating insulin signaling. Interestingly, infliximab was superior to metformin in regulating insulin signaling pathway. Therefore, infliximab could be used as an adjuvant therapy in improving renal IR. PMID: 32004528 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - January 28, 2020 Category: Drugs & Pharmacology Authors: Mohamad HE, Asker ME, Keshawy MM, Abdel Aal SM, Mahmoud YK Tags: Eur J Pharmacol Source Type: research

Highly bioavailable berberine formulation ameliorates diabetic nephropathy through the inhibition of glomerular mesangial matrix expansion and the activation of autophagy.
Abstract Glomerular mesangial matrix expansion and cell autophagy are the most important factors in the development of kidney damage under diabetic conditions. The activation of AMPK might be an important treatment target for diabetic nephropathy. Berberine has multiple effects on all types of diabetic complications as an activator of AMPK. However, the poor bioavailability of berberine limits its clinical applications. Huang-Gui Solid Dispersion (HGSD), a new formulation of berberine developed in our lab, has 4-fold greater bioavailability than berberine. However, its therapeutic application and mechanism still n...
Source: European Journal of Pharmacology - January 27, 2020 Category: Drugs & Pharmacology Authors: Zhang M, Zhang Y, Xiao D, Zhang J, Wang X, Guan F, Zhang M, Chen L Tags: Eur J Pharmacol Source Type: research

Effect of levosimendan, an inodilator, on streptozotocin-induced diabetic nephropathy in rats.
This study examined the effect of levosimendan on streptozotocin-induced early diabetic nephropathy. Rats were distributed into four groups and treated for six weeks. The first and third group received either vehicle or levosimendan (1 mg/kg/day) for the last three weeks, respectively. The second and fourth groups were rendered diabetic by a single intraperitoneal injection of streptozotocin (60 mg/kg) and were treated as the first and third groups, respectively. In the untreated diabetic group, there was a significant decrease in body weight, polyuria and hyperglycemia as well as, increased urinary albumin/creatinine ...
Source: European Journal of Pharmacology - January 27, 2020 Category: Drugs & Pharmacology Authors: Abdelrahman AM, Al Salam S, Al Sulemani Y, Ashique M, Manoj P, Ali BH Tags: Eur J Pharmacol Source Type: research

Hops compounds modulatory effects and 6-prenylnaringenin dual mode of action on GABAA receptors.
ari M Abstract Hops (Humulus lupulus L.), a major component of beer, contain potentially neuroactive compounds that made it useful in traditional medicine as a sleeping aid. The present study aims to investigate the individual components in hops acting as allosteric modulators in GABAA receptors and bring further insight into the mode of action behind the sedative properties of hops. GABA-potentiating effects were measured using [3H]ethynylbicycloorthobenzoate (EBOB) radioligand binding assay in native GABAA receptors. Flumazenil sensitivity of GABA-potentiating effects, [3H]Ro 15-4513, and [3H]flunitrazepam bindi...
Source: European Journal of Pharmacology - January 27, 2020 Category: Drugs & Pharmacology Authors: Benkherouf AY, Logrén N, Somborac T, Kortesniemi M, Soini SL, Yang B, Salo-Ahen OMH, Laaksonen O, Uusi-Oukari M Tags: Eur J Pharmacol Source Type: research

Mechanisms for pituitary adenylate cyclase-activating polypeptide-induced increase in excitability in guinea-pig and mouse adrenal medullary cells.
Abstract Pituitary adenylate cyclase-activating polypeptide (PACAP) acts on adrenal medullary (AM) cells as a neurotransmitter of the sympathetic preganglionic nerve. In guinea-pig AM cells, PACAP induces little catecholamine secretion, but enhances secretion evoked by stimulants, whereas in other animals, such as mouse, PACAP itself induces depolarization and/or catecholamine secretion. The present studies aim to explore the physiological implication of these species differences in PACAP actions, the ion channel mechanism for PACAP-induced depolarization, and the mechanism for facilitation of muscarinic receptor-...
Source: European Journal of Pharmacology - January 27, 2020 Category: Drugs & Pharmacology Authors: Inoue M, Harada K, Matsuoka H Tags: Eur J Pharmacol Source Type: research

Epigallocatechin-3-gallate protects Wharton's jelly derived mesenchymal stem cells against in vitro heat stress.
Abstract The deteriorating effects of heat stress abrogate the therapeutic implications of human Wharton's jelly derived mesenchymal stem cells (hWJMSCs) transplanted in burn wounds. Topically applied green tea extract comprising epigallocatechin-3-gallate (EGCG) is known to repair burn wounds. Here, we investigated the protective role of EGCG priming of hWJMSCs against heat-induced stress in vitro along with the involved underlying mechanism. EGCG ameliorated heat-induced injuries as demonstrated by significantly improved cell morphology, viability, triggered cell migration and enhanced expression of heat shock p...
Source: European Journal of Pharmacology - January 27, 2020 Category: Drugs & Pharmacology Authors: Butt H, Mehmood A, Ejaz A, Humayun S, Riazuddin S Tags: Eur J Pharmacol Source Type: research

Evaluation of artesunate for the treatment of adult T-cell leukemia/lymphoma.
Abstract Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by infection with human T-cell leukemia virus type 1 (HTLV-1). Successful treatment is limited by resistance to chemotherapies. Therefore, there is an urgent need to develop novel effective strategies. Artesunate (ART), a widely used antimalarial compound, has been shown to exert cytotoxicity. Here, we aimed to assess the anti-ATLL activities of ART and to elucidate the possible molecular mechanisms involved in this effect. Compared with uninfected T cells, HTLV-1-infected T-cell lines were sensitive to ART-induced cytotoxicity. ART cau...
Source: European Journal of Pharmacology - January 26, 2020 Category: Drugs & Pharmacology Authors: Ishikawa C, Senba M, Mori N Tags: Eur J Pharmacol Source Type: research

Evaluating the mucoprotective effect of polydeoxyribonucleotide against indomethacin-induced gastropathy via the MAPK/NF- κB signaling pathway in rats.
In this study, we evaluated the efficacy of PDRN in the initial treatment of gastropathy against that of ecabet sodium and irsoglandin maleate, which are commonly used medications. The rats were administrated indomethacin once a day for 7 days after 24 h of fasting to induce gastropathy. Rats in the drug-treated groups were orally administrated 500 μL of distilled water containing the drug once daily for 7 days 1 h after indomethacin administration. Indomethacin administration caused mucosal damage and increased pro-inflammatory cytokine release. Both NF-κB and MAPK cascade factors were increased by indometh...
Source: European Journal of Pharmacology - January 26, 2020 Category: Drugs & Pharmacology Authors: Ko IG, Jin JJ, Hwang L, Kim SH, Kim CJ, Han JH, Kwak MS, Yoon JY, Jeon JW Tags: Eur J Pharmacol Source Type: research

Platycodin D alleviates liver fibrosis and activation of hepatic stellate cells by regulating JNK/c-JUN signal pathway.
Abstract Liver fibrosis is involved in the progression of most chronic liver diseases. Even though we have made a huge progress in order to understand the pathogenesis of liver fibrosis, however, there is still a lack of productive treatments. Being a traditional Chinese medicine, Platycodin D (PD), an oleanane kind of triterpenoid saponin has been put to extensive use for treating different kinds of illnesses that include not just anti-nociceptive, but also antiviral, anti-inflammatory, and anti-cancer for thousands of years. Nonetheless, there has been no clarification made for its effects on the progression of ...
Source: European Journal of Pharmacology - January 26, 2020 Category: Drugs & Pharmacology Authors: Liu YM, Cong S, Cheng Z, Hu YX, Lei Y, Zhu LL, Zhao XK, Mu M, Zhang BF, Fan LD, Yu L, Cheng ML Tags: Eur J Pharmacol Source Type: research

Effect of spinal angiotensin-converting enzyme 2 activation on the formalin-induced nociceptive response in mice.
Abstract We have previously demonstrated that the phosphorylation of p38 MAPK, through spinal AT1 receptor activation, is involved in formalin-induced nociception and follows accompanied by the increase in spinal angiotensin (Ang) II levels. We have also found that Ang (1-7), an N-terminal fragment of Ang II generated by ACE2, prevents the Ang II-induced nociceptive behavior via spinal MAS1 and the inhibition of p38 MAPK phosphorylation. Here, we examined whether the ACE2 activator diminazene aceturate (DIZE) can prevent the formalin-induced nociception in mice. The i.t. administration of DIZE attenuated the secon...
Source: European Journal of Pharmacology - January 25, 2020 Category: Drugs & Pharmacology Authors: Nemoto W, Yamagata R, Nakagawasai O, Nakagawa K, Hung WY, Fujita M, Tadano T, Tan-No K Tags: Eur J Pharmacol Source Type: research

In vitro profiling of opioid ligands using the cAMP formation inhibition assay and the β-arrestin2 recruitment assay: No two ligands have the same profile.
In vitro profiling of opioid ligands using the cAMP formation inhibition assay and the β-arrestin2 recruitment assay: No two ligands have the same profile. Eur J Pharmacol. 2020 Jan 25;:172947 Authors: Kuo A, Magiera J, Rethwan N, Andersson Å, Leen Lam A, Wyse B, Meutermans W, Lewis R, Smith M Abstract Previously, we showed that no two of seven opioids administered by the intracerebroventricular route had the same potency rank order for evoking antinociception, constipation and respiratory depression in rats. To gain insight at the cellular level, this study was designed to systematically i...
Source: European Journal of Pharmacology - January 25, 2020 Category: Drugs & Pharmacology Authors: Kuo A, Magiera J, Rethwan N, Andersson Å, Leen Lam A, Wyse B, Meutermans W, Lewis R, Smith M Tags: Eur J Pharmacol Source Type: research

Behavioral effects of the kappa opioid receptor partial agonist nalmefene in tests relevant to depression.
Abstract Compounds with high affinity at kappa and mu opioid receptors may have clinical utility in treating major depressive disorder. Nalmefene (NMF) is a partial kappa opioid receptor agonist and potent mu opioid receptor antagonist, but there has been no preclinical evaluation of NMF in rodent tests relevant to depression and anxiety. To address this, we examined the effects of NMF on neurochemical and behavioral endpoints in C57BL/6J mice and contrasted the behavioral effects with a structurally related analog, naltrexone (NTX). To confirm that NMF exerts kappa opioid receptor agonist activity, we demonstrate...
Source: European Journal of Pharmacology - January 25, 2020 Category: Drugs & Pharmacology Authors: Browne CA, Smith T, Lucki I Tags: Eur J Pharmacol Source Type: research

Morroniside enhances angiogenesis and improves cardiac function following acute myocardial infarction in rats.
This study aimed to investigate the effects of morroniside on angiogenesis after AMI and explored associated proangiogenic mechanisms. A rat model of AMI was established by ligation of the left anterior descending coronary artery followed by administration of three doses of morroniside. Immunofluorescence staining was performed to identify newly generated endothelial cells and arterioles. The protein expression levels associated with angiogenesis were examined by western blots. Echocardiography was used to examine cardiac function. Our data revealed that morroniside promoted angiogenesis and improved cardiac function in ra...
Source: European Journal of Pharmacology - January 25, 2020 Category: Drugs & Pharmacology Authors: Liu T, Sun F, Cui J, Zheng S, Li Z, Guo D, Tian X, Zhu Z, Zheng W, Wang Y, Wang W Tags: Eur J Pharmacol Source Type: research

Intrathecally administered perampanel alleviates neuropathic and inflammatory pain in rats.
Abstract Chronic pain conditions such as neuropathic pain and persistent inflammatory pain are difficult to manage. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors modulate nociceptive processing at the spinal dorsal horn. Previous studies have shown that intrathecal AMPA receptor antagonists exert antinociception in various pain states. Perampanel is a selective, noncompetitive inhibitor of the AMPA receptor and used clinically as an antiepileptic drug. Little is known about antinociceptive action of perampanel in the spinal cord. Here, we explored whether intrathecal perampanel attenuat...
Source: European Journal of Pharmacology - January 25, 2020 Category: Drugs & Pharmacology Authors: Hara K, Haranishi Y, Terada T Tags: Eur J Pharmacol Source Type: research

Targets and pathways involved in the antitumor activity of citral and its stereo-isomers.
Abstract This review provides a comprehensive analysis of the anticancer potential of the natural product citral (CIT) found in many plants and essential oils, and extensively used in the food and cosmetic industry. CIT is composed of two stereoisomers, the trans-isomer geranial being a more potent anticancer compound than the cis-isomer neral. CIT inhibits cancer cell proliferation and induces cancer cell apoptosis. Its pluri-factorial mechanism of anticancer activity is essentially based on three pillars: (i) a drug-induced accumulation of reactive oxygen species in cancer cells leading to an oxidative burst and...
Source: European Journal of Pharmacology - January 22, 2020 Category: Drugs & Pharmacology Authors: Bailly C Tags: Eur J Pharmacol Source Type: research