Effect of CAPE-pNO2 against type 2 diabetes mellitus via the AMPK/GLUT4/ GSK3 β/PPARα pathway in HFD/STZ-induced diabetic mice.
Effect of CAPE-pNO2 against type 2 diabetes mellitus via the AMPK/GLUT4/ GSK3β/PPARα pathway in HFD/STZ-induced diabetic mice. Eur J Pharmacol. 2019 Mar 15;: Authors: Li S, Huang Q, Zhang L, Qiao X, Zhang Y, Tang F, Li Z Abstract CAPE-pNO2, a para-nitro derivative of caffeic acid phenethyl ester (CAPE), has been proved to exert stronger effects on diabetic complications in diabetic mice. The present study aimed at probing into the effect and potential mechanism of CAPE-pNO2 in type 2 diabetes mellitus (T2DM) compared with CAPE on model animal. Diabetic model was established by feeding one m...
Source: European Journal of Pharmacology - March 15, 2019 Category: Drugs & Pharmacology Authors: Li S, Huang Q, Zhang L, Qiao X, Zhang Y, Tang F, Li Z Tags: Eur J Pharmacol Source Type: research

Chiral ruthenium(II) complex Δ-[Ru(bpy)2(o-FMPIP)] (bpy = bipyridine, o-FMPIP = 2-(2'-trifluoromethyphenyl) imidazo[4,5-f][1,10]phenanthroline) as potential apoptosis inducer viaDNA damage.
Chiral ruthenium(II) complex Δ-[Ru(bpy)2(o-FMPIP)] (bpy = bipyridine, o-FMPIP = 2-(2'-trifluoromethyphenyl) imidazo[4,5-f][1,10]phenanthroline) as potential apoptosis inducer viaDNA damage. Eur J Pharmacol. 2019 Mar 14;: Authors: Bai M, Pan T, Yu G, Xie Q, Zeng Z, Zhang Y, Zhu D, Mu L, Qian J, Chang B, Mei WJ, Guan S Abstract Chiral ruthenium(II) complexes have long been considered as potential anticancer agents. Herein, in vivo inhibitory activity of a chiral ruthenium(II) complex coordinated by ligand 2-(2'-trifluoromethyphenyl) imidazo [4,5-f][1,10]phenanthroline, Δ-[Ru(bpy)2(o-FMPIP)] ...
Source: European Journal of Pharmacology - March 14, 2019 Category: Drugs & Pharmacology Authors: Bai M, Pan T, Yu G, Xie Q, Zeng Z, Zhang Y, Zhu D, Mu L, Qian J, Chang B, Mei WJ, Guan S Tags: Eur J Pharmacol Source Type: research

Paeoniflorin protects pancreatic β cells from STZ-induced damage through inhibition of the p38 MAPK and JNK signaling pathways.
Paeoniflorin protects pancreatic β cells from STZ-induced damage through inhibition of the p38 MAPK and JNK signaling pathways. Eur J Pharmacol. 2019 Mar 14;: Authors: Liu Y, Han J, Zhou Z, Li D Abstract Pancreatic β-cells are responsible for insulin secretion and control of plasma glucose levels. Accumulating evidences indicate a relationship between β-cell dysfunction/death and diabetes onset. Paeoniflorin (PF), a natural glycoside, has antihyperglycemic effect. However, the role of PF in pancreatic β-cells has not been examined. The aim of this study was to evaluate the protecti...
Source: European Journal of Pharmacology - March 14, 2019 Category: Drugs & Pharmacology Authors: Liu Y, Han J, Zhou Z, Li D Tags: Eur J Pharmacol Source Type: research

Bupivacaine-induced contraction is attenuated by endothelial nitric oxide release modulated by activation of both stimulatory and inhibitory phosphorylation (Ser1177 and Thr495) of endothelial nitric oxide synthase.
This study examined the mechanism associated with the endothelium-dependent attenuation of vasoconstriction induced by bupivacaine (BPV), with a particular focus on the upstream cellular signaling pathway of endothelial nitric oxide synthase (eNOS) phosphorylation induced by BPV in human umbilical vein endothelial cells (HUVECs). BPV concentration-response curves were investigated in the isolated rat aorta. The effects of Nω-nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), methylene blue, calmidazolium, the Src kinase inhibitor 4-amino-3-(4-chlorophenyl)-1-(t-butyl)-1H-pyrazo...
Source: European Journal of Pharmacology - March 14, 2019 Category: Drugs & Pharmacology Authors: Lee SH, Park CS, Ok SH, Kim D, Kim KN, Hong JM, Kim JY, Bae SI, An S, Sohn JT Tags: Eur J Pharmacol Source Type: research

A novel, highly-water-soluble apigenin derivative provides neuroprotection following ischemia in male rats by regulating the ERK/Nrf2/HO-1 pathway.
Abstract 6"-O-succinylapigenin [apigenin-7-O-(6''-O-succinyl)-glucoside], a novel compound, is identified in chamomile. Although it is highly produced by Bacillus amyloliquefaciens FJ18, its bioactivity remains unknown. The neuroprotective effects and antioxidative mechanism of 6''-O-succcinylapigenin in the middle cerebral artery occlusion model in male rats was investigated in this study. The structure of this compound was determined by spectroscopic data analysis. After 2h of occlusion and 24h of reperfusion, magnetic resonance imaging and assessed neurological scores following middle cerebral artery occlu...
Source: European Journal of Pharmacology - March 14, 2019 Category: Drugs & Pharmacology Authors: Zhang S, Xu S, Duan H, Zhu Z, Yang Z, Cao J, Zhao Y, Huang Z, Wu Q, Duan J Tags: Eur J Pharmacol Source Type: research

Comparative study of carvedilol and quinidine for inhibiting hKv4.3 channel stably expressed in HEK 293 cells.
Abstract The inhibition of transient outward potassium current (Ito) is the major ionic mechanism for quinidine to treat Brugada syndrome; however, quinidine is inaccessible in many countries. The present study compared the inhibitory effect of the nonselective β-adrenergic blocker carvedilol with quinidine on human Kv4.3 (hKv4.3, encoding for Ito) channel and action potential notch using a whole-cell patch technique in HEK 293 cell line expressing KCND3 as well as in ventricular epicardial myocytes of rabbit hearts. It was found that carvedilol and quinidine inhibited hKv4.3 current in a concentration-depend...
Source: European Journal of Pharmacology - March 14, 2019 Category: Drugs & Pharmacology Authors: Zhang R, Jie LJ, Wu WY, Wang ZQ, Sun HY, Xiao GS, Wang Y, Li YG, Li GR Tags: Eur J Pharmacol Source Type: research

Rutaecarpine prevented ox-LDL-induced VSMCs dysfunction through inhibiting overexpression of connexin 43.
In conclusion, this study demonstrated that rutaecarpine inhibited Cx43 overexpression through TRPV1/[Ca2+]i/CaM/NF-κB signal pathway, thereby preventing VSMCs dysfunction induced by ox-LDL. Our study provides a novel mechanism by which rutaecarpine modulate Cx43 expression and VSMC function. PMID: 30880182 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - March 14, 2019 Category: Drugs & Pharmacology Authors: Wang M, Wu Y, Yu Y, Fu Y, Yan H, Wang X, Li T, Peng W, Luo D Tags: Eur J Pharmacol Source Type: research

SGL5213, a novel and potent intestinal SGLT1 inhibitor, suppresses intestinal glucose absorption and enhances plasma GLP-1 and GLP-2 secretion in rats.
This study characterizes the pharmacological profiles of SGL5213 in rodents. Orally administered SGL5213 was hardly absorbed and its distribution was restricted to the gastrointestinal lumen. SGL5213 significantly improved post-prandial hyperglycemia in streptozotocin (STZ)-induced diabetic rats at doses of 1mg/kg or more. After the oral administration of starch, SGL5213 increased the amount of residual glucose in the small intestine at 1-3h and in the cecum and colon at 3-9h by inhibiting glucose absorption and allowing the unabsorbed glucose to be delivered into the lower-gastrointestinal tract. In the vehicle group, the...
Source: European Journal of Pharmacology - March 13, 2019 Category: Drugs & Pharmacology Authors: Io F, Gunji E, Koretsune H, Kato K, Sugisaki-Kitano M, Okumura-Kitajima L, Kimura K, Uchida S, Yamamoto K Tags: Eur J Pharmacol Source Type: research

EPA:DHA 6:1 is a superior omega-3 PUFAs formulation attenuating platelets-induced contractile responses in porcine coronary and human internal mammary artery by targeting the serotonin pathway via an increased endothelial formation of nitric oxide.
This study evaluated whether omega-3 polyunsaturated fatty acids (PUFAs), known to protect the vascular system, are able to prevent platelets-induced contractile responses in isolated arteries and, if so, to investigate the underlying mechanism and the importance of the omega-3 PUFAs formulation. Porcine coronary arteries (PCA), human internal mammary arteries (IMA) and washed human platelets were prepared and vascular reactivity was studied in organ chambers. In PCA rings, aggregating platelets caused concentration-dependent contractions that were significantly inhibited by the 5-HT2A receptor antagonist ketanserin, and b...
Source: European Journal of Pharmacology - March 13, 2019 Category: Drugs & Pharmacology Authors: Zgheel F, Perrier S, Remila L, Houngue U, Mazzucotelli JP, Morel O, Auger C, Schini-Kerth VB Tags: Eur J Pharmacol Source Type: research

Tanshinone I inhibits vascular smooth muscle cell proliferation by targeting insulin-like growth factor-1 receptor/phosphatidylinositol-3-kinase signaling pathway.
In this study, we investigated the effects of tanshinone I on VSMC proliferation, as well as the underlying mechanisms. We found that this compound inhibited the proliferation of VSMCs in a dose-dependent manner, based on 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Western blotting demonstrated that tanshinone I inhibited the expression of proliferation-related proteins, including cyclin-dependent kinase 4 (CDK4), cyclin D3, and cyclin D1, in a dose-dependent manner. Molecular docking showed that this compound docked to the ...
Source: European Journal of Pharmacology - March 13, 2019 Category: Drugs & Pharmacology Authors: Wu YT, Bi YM, Tan ZB, Xie LP, Xu HL, Fan HJ, Chen HM, Li J, Liu B, Zhou YC Tags: Eur J Pharmacol Source Type: research

Atrasentan alleviates high glucose-induced podocyte injury by the microRNA-21/forkhead box O1 axis.
Abstract Diabetic nephropathy (DN) is the most common complication of diabetes mellitus. Atrasentan (Atr) has potential therapeutic values for DN. MicroRNAs (miRNAs) function as vital regulators in the pathophysiology of kidney diseases including DN. Our present study aimed to further explore whether Atr could alleviate kidney injury by regulating microRNA-21(miR-21)/forkhead box O1 (FOXO1) in DN mouse models and cell models. Blood glucose concentration and ACR ratio were determined by matching commercial kits. MiR-21 and FOXO1 mRNA level was measured by RT-qPCR assay. Protein levels of FOXO1, LC3Ⅰ, LC3Ⅱ and p...
Source: European Journal of Pharmacology - March 12, 2019 Category: Drugs & Pharmacology Authors: Wang J, Shen L, Hong H, Li J, Wang H, Li X Tags: Eur J Pharmacol Source Type: research

DNA polymerase- γ hypothesis in nucleoside reverse transcriptase-induced mitochondrial toxicity revisited: a potentially protective role for citrus fruit-derived naringenin?
DNA polymerase-γ hypothesis in nucleoside reverse transcriptase-induced mitochondrial toxicity revisited: a potentially protective role for citrus fruit-derived naringenin? Eur J Pharmacol. 2019 Mar 12;: Authors: Lutu MR, Nzuza S, Mofo Mato PE, Govender K, Gumede LM, Kumalo SI, Mlambo NN, Hurchund R, Oroma Owira PM Abstract Nucleoside reverse transcriptase inhibitors (NRTIs) form the backbone in combination antiretroviral therapy (cARVs). They halt chain elongation of the viral cDNA by acting as false substrates in counterfeit incorporation mechanism to viral RNA-dependent DNA polymerase. In the...
Source: European Journal of Pharmacology - March 12, 2019 Category: Drugs & Pharmacology Authors: Lutu MR, Nzuza S, Mofo Mato PE, Govender K, Gumede LM, Kumalo SI, Mlambo NN, Hurchund R, Oroma Owira PM Tags: Eur J Pharmacol Source Type: research

D2-like receptor agonist synergizes the μ-opioid agonist spinal antinociception in nociceptive, inflammatory and neuropathic models of pain in the rat.
D2-like receptor agonist synergizes the μ-opioid agonist spinal antinociception in nociceptive, inflammatory and neuropathic models of pain in the rat. Eur J Pharmacol. 2019 Mar 12;: Authors: Mercado-Reyes J, Almanza A, Segura-Chama P, Pellicer F, Mercado F Abstract Opioids are potent analgesic drugs, but their use has been limited due to their side effects. Antinociceptive effects of D2-like receptor agonists such as quinpirole have been shown at the spinal cord level; however, their efficacy is not as high as that of opioids. Dopaminergic agonists are long-prescribed and well-tolerated drugs that...
Source: European Journal of Pharmacology - March 12, 2019 Category: Drugs & Pharmacology Authors: Mercado-Reyes J, Almanza A, Segura-Chama P, Pellicer F, Mercado F Tags: Eur J Pharmacol Source Type: research

Visfatin promotes the malignancy of human acute myeloid leukemia cells via regulation of IL-17.
Abstract Understanding the mechanisms of malignancy in acute myeloid leukemia (AML) cell is important for the targeted treatment and drug development. We found that visfatin, a 52-kDa adipokine, can positively regulate the proliferation of AML cells. Targeted inhibition of visfatin via its specific siRNAs or inhibitor can suppress the proliferation of AML cells. Further, knockdown of visfatin can increase the doxorubicin (Dox) and cisplatin (CDDP) sensitivity of AML cells. Among the tested six cytokines, si-visfatin can decrease the expression of interleukin-17 (IL-17). Over expression of IL-17 can reverse si-visf...
Source: European Journal of Pharmacology - March 12, 2019 Category: Drugs & Pharmacology Authors: Hui Z, Liu Z, He A, Chen Y, Zhang P, Lei B, Yao H, Yu Y, Liang R, Li Z, Zhang W Tags: Eur J Pharmacol Source Type: research

Potassium channels contribute to the increased sensitivity of the rabbit carotid artery to hydrogen sulfide in diabetes.
Miranda FJ Abstract Hydrogen sulfide (H2S) is a potential endothelium-derived hyperpolarizing factor (EDHF) and adventitium- or adipocyte-derived relaxing factor (ADRF) which vasorelaxant action is mediated by potassium channels. H2S could also play an important role in the pathophysiology of diabetic cardiovascular complications. The present study has investigated the influence of alloxan-induced diabetes on the role of potassium channels mediating the relaxant response of the rabbit carotid artery to NaHS, a donor of H2S. NaHS (10-8-3×10-5 M) relaxed phenylephrine-precontracted carotid arteries, with high...
Source: European Journal of Pharmacology - March 12, 2019 Category: Drugs & Pharmacology Authors: Centeno JM, López-Morales MA, Aliena-Valero A, Jover-Mengual T, Burguete MC, Castelló-Ruiz M, Miranda FJ Tags: Eur J Pharmacol Source Type: research

Vitexin protects against ischemia/reperfusion-induced brain endothelial permeability.
In this study, the effects of Vitexin on endothelial permeability and the underlying mechanisms in human brain microvascular endothelial cells (HBMEc) I/R injury model were investigated. Cell viability, lactate dehydrogenase (LDH), inflammation and apoptosis were detected. The effects of Vitexin on BBB integrity tight junction, matrix metalloproteinases (MMP) were also investigated. The mechanism was confirmed by PI3K inhibitor and NOS inhibitor in normal or eNOS siRNA transfection HBMEc. Vitexin significantly reduced LDH, Caspase 3 level, alleviated inflammation, also could maintain BBB integrity, increased tight junction...
Source: European Journal of Pharmacology - March 12, 2019 Category: Drugs & Pharmacology Authors: Cui YH, Zhang XQ, Wang ND, Zheng MD, Yan J Tags: Eur J Pharmacol Source Type: research

BRD4 promotes the stemness of gastric cancer cells via attenuating miR-216a-3p-mediated inhibition of Wnt/ β-catenin signaling.
BRD4 promotes the stemness of gastric cancer cells via attenuating miR-216a-3p-mediated inhibition of Wnt/β-catenin signaling. Eur J Pharmacol. 2019 Mar 12;: Authors: Song H, Shi L, Xu Y, Xu T, Fan R, Cao M, Xu W, Song J Abstract The bromodomain and extra-terminal domain (BET) protein BRD4 is emerging as a potential target for cancer therapy. However, BRD4 roles in regulating the stemness of gastric cancer cells are unclear. Here, we demonstrated that BRD4 expression was significantly increased in gastric cancer tissues, cell spheroids, and BRD4 knockdown attenuated the stemness of gastric cancer...
Source: European Journal of Pharmacology - March 12, 2019 Category: Drugs & Pharmacology Authors: Song H, Shi L, Xu Y, Xu T, Fan R, Cao M, Xu W, Song J Tags: Eur J Pharmacol Source Type: research

Protective effect of [Pyr1]-apelin-13 on oxidative stress-induced apoptosis in hair cell -like cells derived from bone marrow mesenchymal stem cells.
Abstract Oxidative stress plays an important role in auditory dysfunction. Exogenous cell therapy has brought new hopes for repairing mammalian inner ear hair cells. However, poor cell viability of transplanted cells under oxidative stress conditions has limited their therapeutic potential. The adipocytokine apelin-13 was isolated from a bovine stomach. Apelin-13 might protect oxidative stress-induced hair cell damage was raised considering other oxidative stress-induced injury, including brain ischemia-induced cell death. Therefore, we evaluated the protective effects of apelin- 13 on the damage induced by hydrog...
Source: European Journal of Pharmacology - March 12, 2019 Category: Drugs & Pharmacology Authors: Niknazar S, Abbaszadeh HA, Peyvandi H, Rezaei O, Forooghirad H, Khoshsirat S, Peyvandi AA Tags: Eur J Pharmacol Source Type: research

Dihydromyricetin ameliorates memory impairment induced by acute sleep deprivation.
Abstract Dihydromyricetin (DHM), the major bioactive flavonoid ingredient extracted from the leaves of Ampelopsis grossedentata (Hand.-Mazz) W.T. Wang displays multiple pharmacological activities, including oxidation resistance, anti-tumour properties and free radical scavenging capacities. However, the role of DHM in sleep deprivation (SD)-induced memory impairments and its underlying molecular mechanisms are unclear. The aim of the present study was to evaluate the effects of DHM on oxidative stress and its role in ameliorating memory impairment induced by acute SD. DHM (100, 50, 25mg/kg) and melatonin (10mg/kg)...
Source: European Journal of Pharmacology - March 12, 2019 Category: Drugs & Pharmacology Authors: Li H, Yu F, Sun X, Xu L, Miu J, Xiao P Tags: Eur J Pharmacol Source Type: research

Effects of sulforaphane in the central nervous system.
Abstract Sulforaphane (SFN) is an active component extracted from vegetables like cauliflower and broccoli. Activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling is a common mechanism for the anti-oxidative and anti-inflammatory activity of some herb-derived compounds, such as icariin and berberine. However, due to its peculiar ability in Nrf2 activation, SFN is recognized as an activator of Nrf2 and recommended as a supplementation for prevention and/or treatment of disorders like neoplasm and heart failure. In the central nervous system (CNS), the prophylactic and/or therapeutic effects ...
Source: European Journal of Pharmacology - March 8, 2019 Category: Drugs & Pharmacology Authors: Chen D, Huang C, Jin J, Wu Y, Chen Z Tags: Eur J Pharmacol Source Type: research

Modulation of urinary frequency via type 1 lysophosphatidic acid receptors: effect of the novel antagonist ASP6432 in conscious rats.
Abstract Bladder dysfunctions associated with benign prostatic hyperplasia are not sufficiently alleviated by current pharmacotherapies. Lysophosphatidic acid (LPA) is a phospholipid with diverse biological effects. LPA modulates prostate and urethral contraction via the type 1 LPA (LPA1) receptor, suggesting the potential of the LPA1 receptor as a therapeutic target. However, the role of LPA and the LPA1 receptor in bladder function has not been studied in vivo. We investigated the effects of LPA and the novel LPA1 receptor antagonist ASP6432 (potassium 1-(2-{[3,5-dimethoxy-4-methyl-N-(3-phenylpropyl)benzamido]me...
Source: European Journal of Pharmacology - March 7, 2019 Category: Drugs & Pharmacology Authors: Sakamoto K, Noguchi Y, Ueshima K, Ohtake A, Sato S, Imazumi K, Takeda M, Masuda N Tags: Eur J Pharmacol Source Type: research

Protocatechuic acid exerts protective effects via suppression of the P38/JNK- NF- κB signalling pathway in an experimental mouse model of intracerebral haemorrhage.
In conclusion, PCA effectively improves prognosis of ICH mice by inhibiting oxidative stress, inflammation and apoptosis. The mechanism possibly results of downregulating of P38/JNK-NF-κB pathway, and PCA can be a potential therapeutic agent for ICH. PMID: 30853532 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - March 7, 2019 Category: Drugs & Pharmacology Authors: Xi Z, Hu X, Chen X, Yang Y, Ren J, Wang B, Zhong Z, Sun Y, Yang G, Sun Q, Bian L Tags: Eur J Pharmacol Source Type: research

MicroRNA-34a-5p suppresses tumorigenesis and progression of glioma and potentiates Temozolomide-induced cytotoxicity for glioma cells by targeting HMGA2.
Abstract Glioma is a frequently diagnosed brain tumors and Temozolomide (TMZ) is a common chemotherapeutic drug for glioma. High mobility group AT-hook 2 (HMGA2) was reported to be linked with glioma pathogenesis and Temozolomide (TMZ)-induced cytotoxicity. Our present study aimed to further search for the upstream regulatory microRNAs (miRNAs) of HMGA2 in glioma. RT-qPCR assay was conducted to measure the expression of HMGA2 mRNA and microRNA-34a-5p (miR-34a-5p). HMGA2 protein expression was examined by western blot assay. Cell proliferative ability and cell viability was assessed by CCK-8 assay. Cell migratory a...
Source: European Journal of Pharmacology - March 6, 2019 Category: Drugs & Pharmacology Authors: Ma S, Fu T, Zhao S, Gao M Tags: Eur J Pharmacol Source Type: research

Death-associated protein kinase 3 deficiency alleviates vascular calcification via AMPK-mediated inhibition of endoplasmic reticulum stress.
Abstract Vascular calcification (VC) is a critical feature of chronic kidney disease (CKD), diabetes, hypertension, and atherosclerosis. Death-associated protein kinase 3 (DAPK3) is involved in vascular remodeling in hypertension. However, it remains to be clarified whether DAPK3 controls vascular smooth muscle cell (VSMC) phenotypic transition into an osteogenic cell phenotype, which is an important process for VC. In vivo VC was induced in rats by vitamin D3 and nicotine. VSMCs were incubated with calcifying media containing β-glycerophosphate and Ca2+ to induce VC in vitro. Herein, we demonstrated increase...
Source: European Journal of Pharmacology - March 6, 2019 Category: Drugs & Pharmacology Authors: Li KX, Du Q, Wang HP, Sun HJ Tags: Eur J Pharmacol Source Type: research

Metformin reduced NLRP3 inflammasome activity in Ox-LDL stimulated macrophages through adenosine monophosphate activated protein kinase and protein phosphatase 2A.
Abstract Metformin has been suggested to have cardiovascular protective effects. Previous researches showed that metformin activates Adenosine Monophosphate Activated Protein Kinase (AMPK) and Protein Phosphatase 2A (PP2A). This research aimed to elucidate whether and how metformin affects NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activity in oxidized low-density lipoprotein (ox-LDL) stimulated macrophages. Macrophages were treated with ox-LDL and metformin in a continuous manner, and NLRP3 inflammasome activation was evaluated by detecting IL-1β and caspase-1 p10 release by ELISA and western ...
Source: European Journal of Pharmacology - March 6, 2019 Category: Drugs & Pharmacology Authors: Zhang L, Lu L, Zhong X, Yue Y, Hong Y, Li Y, Li Y Tags: Eur J Pharmacol Source Type: research

Adapalene suppressed the proliferation of melanoma cells by S-phase arrest and subsequent apoptosis via induction of DNA damage.
Abstract Malignant melanoma was the leading cause of mortality among the skin-associated cancer owing to its highly metastatic feature, increasing incidence and drug resistance requirement. Retinoids played important roles in the treatment of cancer via the activation of retinoid acid receptor (RAR) or retinoid X receptor (RXR). Our present study showed that the third-generation retinoid adapalene exhibited strong inhibitory effects on the proliferation of melanoma cells than other retinoids, such as all-trans-retinoic acid (ATRA), isotretinoin, acitretin and bexarotene, and adapalene exerted significant inhibitor...
Source: European Journal of Pharmacology - March 2, 2019 Category: Drugs & Pharmacology Authors: Li H, Wang C, Li L, Bu W, Zhang M, Wei J, Tao L, Qian K, Ma P Tags: Eur J Pharmacol Source Type: research

Therapeutic effects of the rhSOD2-Hirudin fusion protein on bleomycin-induced pulmonary fibrosis in mice.
In conclusion, rhSOD2-Hirudin protein can effectively attenuate pulmonary fibrosis in vitro and in vivo, mainly by inhibiting the activity of thrombin meanwhile increasing SOD2 levels prevent cells from being damaged by reactive oxygen species, thereby mitigating IPF progression. This study provided important information on the feasibility and efficacy of rhSOD2-Hirudin protein as a novel therapeutic agent for IPF. PMID: 30831079 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - March 1, 2019 Category: Drugs & Pharmacology Authors: Shen L, Lei S, Huang L, Li S, Yi S, Breitzig M, Huang M, Mo X, Sun H, Zheng Q, Tian J, Czachor A, Wang F Tags: Eur J Pharmacol Source Type: research

LncRNA FAM83H-AS1 contributes to the radioresistance, proliferation, and metastasis in ovarian cancer through stabilizing HuR protein.
In conclusion, present study proved that FAM83H-AS1 contributes to the radioresistance and cell metastasis in ovarian cancer through stabilizing HuR protein. PMID: 30831080 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - March 1, 2019 Category: Drugs & Pharmacology Authors: Dou Q, Xu Y, Zhu Y, Hu Y, Yan Y, Yan H Tags: Eur J Pharmacol Source Type: research

New insight into NANOG: A novel therapeutic target for ovarian cancer (OC).
Abstract Cancer incidence, metastasis, drug resistance and recurrence are still the critical issues of oncological diseases especially Ovarian cancer (OC). It has been suggested that drug resistance and disease relapse are the main causes for the aggressive nature of OC. There is an immediate need to develop novel strategies to understand the mechanism to overcome chemoresistance. Nanog has been found to regulate stemness like cells inside the cancer cells that are termed as Cancer Stem Cells (CSCs). These cells show high self-renewal capacity with a peculiar potential in tumour initiation, heterogeneity, progress...
Source: European Journal of Pharmacology - March 1, 2019 Category: Drugs & Pharmacology Authors: Mahalaxmi I, Devi SM, Kaavya J, Arul S, Balachandar V, Santhy KS Tags: Eur J Pharmacol Source Type: research

The cordycepin derivative IMM-H007 improves endothelial dysfunction by suppressing vascular inflammation and promoting AMPK-dependent eNOS activation in high-fat diet-fed ApoE knockout mice.
Abstract 2',3',5'-Tri-O-acetyl-N6-(3-hydroxyphenyl) adenosine, a cordycepin derivative that is also known as IMM-H007, is a new adenosine analogue and anti-hyperlipidaemic drug that was developed in our laboratory. It has been previously reported to alleviate atherosclerosis by regulating blood lipid levels. The purpose of the current study was to determine the protective effects of IMM-H007 on endothelial function and vascular inflammation independent of its lipid-lowering effect. Vascular reactivity was determined using a pressure myography system-120CP. Vascular inflammation was assessed to quantify leukocyte-e...
Source: European Journal of Pharmacology - February 28, 2019 Category: Drugs & Pharmacology Authors: Wang MJ, Peng XY, Lian ZQ, Zhu HB Tags: Eur J Pharmacol Source Type: research

Amniotic cells share clusters of differentiation of fibroblasts and keratinocytes, influencing their ability to proliferate and aid in wound healing while impairing their angiogenesis capability.
Abstract An alternative to cultured skin cell grafts usage in burn treatment is the graft of allogenic stem cells. We verified whether amniotic stem cells are better than the present therapeutic standard: grafts of autologous keratinocytes and fibroblasts along with autologous adipose-derived stem cells, and whether amniotic stem cells can support the growth of autologous keratinocytes and fibroblasts in the culture. The study was performed on the material from 18 amnia. Skin cells were obtained from 3 patients. In order to assess the influence of stem cells on keratinocytes and fibroblasts, the following experime...
Source: European Journal of Pharmacology - February 28, 2019 Category: Drugs & Pharmacology Authors: Kitala D, Klama-Baryła A, Łabuś W, Ples M, Misiuga M, Kraut M, Szapski M, Bobiński R, Pielesz A, Łos MJ, Kucharzewski M Tags: Eur J Pharmacol Source Type: research

Role of brown adipose tissue in modulating adipose tissue inflammation and insulin resistance in high-fat diet fed mice.
Abstract Obesity results in the chronic activation of innate immune system and subsequently sets in diabetes. Aim of the study was to investigate the immunometabolic role of brown adipose tissue (BAT) in the obesity. We performed both BAT transplantation as well as extirpation experiments in the mouse model of high-fat diet (HFD)-induced obesity. We carried out immune cell profiling in the stromal vascular fraction (SVF) isolated from epididymal white adipose tissue (eWAT). BAT transplantation reversed HFD-induced increase in body weight gain and insulin resistance without altering diet intake. Importantly, BAT tr...
Source: European Journal of Pharmacology - February 26, 2019 Category: Drugs & Pharmacology Authors: Shankar K, Kumar D, Gupta S, Varshney S, Rajan S, Srivastava A, Gupta A, Gupta AP, Vishwakarma AL, Gayen JR, Gaikwad AN Tags: Eur J Pharmacol Source Type: research

Targeted regulation of Rell2 by microRNA-18a is implicated in the anti-metastatic effect of polyphyllin VI in breast cancer cells.
Abstract Polyphyllin VI (PP-VI) is one of the major saponins present in Paris polyphylla Sm., a medicinal plant primarily used for cancer treatment in China and India. However, its anti-metastatic activity remains largely unknown. The current study thus investigated the anti-metastatic activity of PP-VI in mouse mammary carcinoma 4T1 and human breast cancer MDA-MB-231 cells. The anti-metastatic effect of PP-VI was investigated at a sub-cytotoxic dose in migration and invasion assays in vitro. Experimental metastasis mouse model was used to examine the anti-metastatic effect of PP-VI in vivo. Additionally, target p...
Source: European Journal of Pharmacology - February 25, 2019 Category: Drugs & Pharmacology Authors: Wang P, Yang Q, Du X, Chen Y, Zhang T Tags: Eur J Pharmacol Source Type: research

Modulation of Na+/K+- ATPase activityby triterpene 3 β, 6β, 16β-trihidroxilup-20 (29)-ene (TTHL) limits the long-term secondary degeneration after traumatic brain injury in mice.
Modulation of Na+/K+- ATPase activityby triterpene 3β, 6β, 16β-trihidroxilup-20 (29)-ene (TTHL) limits the long-term secondary degeneration after traumatic brain injury in mice. Eur J Pharmacol. 2019 Feb 23;: Authors: Della-Pace ID, Lopes T, Grauncke ACB, Rambo LM, Ribeiro LR, Cipolatto RP, Severo L, Papalia WL, Santos ARS, Facundo VA, Oliveria MS, Furian AF, Fighera MR, Royes LFF Abstract Traumatic brain injury (TBI) is a public health problem characterized by a combination of immediate mechanical dysfunction of the brain tissue, and secondary damage. Based on the hypothesis that selec...
Source: European Journal of Pharmacology - February 23, 2019 Category: Drugs & Pharmacology Authors: Della-Pace ID, Lopes T, Grauncke ACB, Rambo LM, Ribeiro LR, Cipolatto RP, Severo L, Papalia WL, Santos ARS, Facundo VA, Oliveria MS, Furian AF, Fighera MR, Royes LFF Tags: Eur J Pharmacol Source Type: research

Protective effects of Hesperetin on Lipopolysaccharide-induced acute lung injury by targeting MD2.
Abstract Inflammation plays an important role in acute lung injury (ALI). Hesperetin (HES), a natural flavanone and an aglycone of hesperidin, has established potent anti-inflammatory activity. The aim of this study was to evaluate the potential protective effect of HES on lipopolysaccharide (LPS)-induced ALI in mice and to illuminate its possible directly target. Results indicated that HES pretreatment significantly attenuated LPS-induced pulmonary pathological injury, total protein concentration, markedly decreased the number of neutrophils and the levels of inflammatory cytokines, TNF-α and IL-6, in ALI m...
Source: European Journal of Pharmacology - February 23, 2019 Category: Drugs & Pharmacology Authors: Ye J, Guan M, Lu Y, Zhang D, Li C, Li Y, Zhou C Tags: Eur J Pharmacol Source Type: research

Dihydromyricetin attenuates hypertrophic scar formation by targeting activin receptor-like kinase 5.
Abstract Hypertrophic scar (HPS) is a manifestation of abnormal tissue repair, representing excessive extracellular matrix production and abnormal function of fibroblasts, for which no satisfactory treatment is available at present. Here we identified a natural product of flavonoid, dihydromyricetin, could effectively attenuate HPS formation. We showed that local intradermal injection of dihydromyricetin (50μM) reduced the gross scar area, cross-sectional size of the scar and the scar elevation index in a mechanical load-induced mouse model. In addition, dihydromyricetin treatment also markedly decreased collag...
Source: European Journal of Pharmacology - February 23, 2019 Category: Drugs & Pharmacology Authors: Ye X, Pang Z, Zhu N Tags: Eur J Pharmacol Source Type: research

Stearoyl lysophosphatidylcholine inhibits LPS-induced extracellular release of HMGB1 through the G2A/ calcium/ CaMKK β/ AMPK pathway.
This study investigated the mechanism by which sLPC inhibits lipopolysaccharide (LPS)-induced extracellular secretion of HMGB1 after the onset of sepsis. sLPC increased AMPK phosphorylation and the binding of AMPK to calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ), one of the upstream signals of AMPK. Inhibition of CaMKKβ activity decreased sLPC-mediated inhibition of HMGB1 release, and sLPC increased the concentration of intracellular calcium. Blocking of the macrophage G protein-coupled receptor G2A (G2A) suppressed AMPK phosphorylation, suppressed increases in the intracellular levels of cal...
Source: European Journal of Pharmacology - February 21, 2019 Category: Drugs & Pharmacology Authors: Quan H, Bae HB, Hur YH, Lee KH, Lee CH, Jang EA, Jeong S Tags: Eur J Pharmacol Source Type: research

Suppressive effects of type I angiotensin receptor antagonists, candesartan and irbesartan on allergic asthma.
Abstract The effects of candesartan and irbesartan, antagonists of the type I angiotensin II receptor, were investigated on allergic asthma. The antigen-induced degranulation was measured by evaluating β-hexosaminidase activity in vitro. Additionally, a murine ovalbumin-induced allergic asthma model was used to test the in vivo efficacy. It was observed that while candesartan inhibited the antigen-induced degranulation in rat RBL-2H3 mast cells, irbesartan did not. Administration of candesartan and irbesartan decreased the number of immune cells in the bronchoalveolar lavage fluid and reduced the expression o...
Source: European Journal of Pharmacology - February 21, 2019 Category: Drugs & Pharmacology Authors: Kim MJ, Im DS Tags: Eur J Pharmacol Source Type: research

Rosiglitazone attenuates paraquat-induced lung fibrosis in rats in a PPAR gamma-dependent manner.
Abstract Rosiglitazone, a PPAR-γ agonist, possesses anti-fibritic effect; however, its inhibitory effect on paraquat (PQ)-induced pulmonary fibrosis is not completely understood. Here, we investigated the inhibitory effect of rosiglitazone on PQ-induced acute pulmonary fibrosis in rats and its underlying mechanism. Male Sprague-Dawly rats were administered a single intraperitoneal injection of 30 mg/kg PQ and euthanised 7, 14, 21, and 28 days after PQ poisoning.PQ-induced pulmonary fibrosis was most obvious on day 28. Male Sprague-Dawly rats were exposed either against distilled water as a control group or P...
Source: European Journal of Pharmacology - February 21, 2019 Category: Drugs & Pharmacology Authors: Zhang H, You L, Zhao M Tags: Eur J Pharmacol Source Type: research

Positive allosteric modulation of native and recombinant GABAA receptors by hops prenylflavonoids.
Abstract Hops are a major component of beer that is added during brewing. In addition to its wide range of bioactivity, it exhibits neuroactive properties as a sedative and sleeping aid. The compounds responsible for this activity are yet to be revealed and understood in terms of their pharmacological properties. Here we evaluated the potential of several hops flavonoids in modulating the GABAergic activity and assessed their selectivity to GABAA receptors subtypes. GABA-potentiating effects were measured using [3H]ethynylbicycloorthobenzoate (EBOB) radioligand binding assay in native and recombinant α1&beta...
Source: European Journal of Pharmacology - February 21, 2019 Category: Drugs & Pharmacology Authors: Benkherouf AY, Soini SL, Stompor M, Uusi-Oukari M Tags: Eur J Pharmacol Source Type: research

Aspirin eugenol ester inhibits agonist-induced platelet aggregation in vitro by regulating PI3K/Akt, MAPK and Sirt 1/CD40L pathways.
Abstract Aspirin eugenol ester (AEE) was a promising drug candidate for treating inflammation, pain and fever and preventing cardiovascular diseases with fewer side effects than its precursors. Previous researches indicated that AEE could markedly inhibit agonist-induced platelet aggregation in vitro and ex vivo, however, the anti-platelet aggregation mechanisms of AEE remain to be defined. Here, AEE in vitro effects on agonist-induced granule-secretion, intercellular Ca2+ mobilization and thromboxane A2 (TXA2) generation were examined. Vasodilator-stimulated phosphoprotein (VASP), mitogen-activated protein kinase...
Source: European Journal of Pharmacology - February 21, 2019 Category: Drugs & Pharmacology Authors: Shen DS, Yang YJ, Kong XJ, Ma N, Liu XW, Li SH, Jiao ZH, Qin Z, Huang MZ, Li JY Tags: Eur J Pharmacol Source Type: research

Anti-oxidant and anti-inflammatory effects of Cinnamaldehyde and Eugenol on mononuclear cells of rheumatoid arthritis patients.
Abstract Rheumatoid arthritis (RA) is an autoimmune disorder affecting joints and frequently characterized by initial local and later systemic inflammation. The present study was conducted with the aim to determine the anti-inflammatory and antioxidant effects of cinnamaldehyde and eugenol in the peripheral blood mononuclear cells (PBMC) of RA patients. PBMCs obtained from RA patients were treated with varying concentrations of cinnamaldehyde and eugenol. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were monitored in the 24-hours culture supernatant of PBMCs. Reactive oxygen s...
Source: European Journal of Pharmacology - February 20, 2019 Category: Drugs & Pharmacology Authors: Mateen S, Rehman MT, Shahzad S, Naeem SS, Faizy AF, Khan AQ, Khan MS, Husain FM, Moin S Tags: Eur J Pharmacol Source Type: research

Diabetes-induced damage of gastric nitric oxide neurons mediated by P2X7R in diabetic mice.
Abstract It is generally considered that enteric neuropathy is one of the causative factors in diabetic gastroparesis. Our previous study demonstrated that there is a loss of NOS neurons in diabetic mice. However, the underlying mechanism remains unclear. The present study was designed to clarify the relationship between neuronal P2X7R and NOS neuron damage. The effect of P2X7R on diabetes-induced gastric NOS neurons damage and its mechanism were investigated by using quantitative RT-PCR,immunofluorescence, western blot, isometric force recording, intracellular calcium ([Ca2+]i) measurement and whole-cell patch ...
Source: European Journal of Pharmacology - February 20, 2019 Category: Drugs & Pharmacology Authors: Zhang CM, Huang X, Lu HL, Meng XM, Song NN, Chen L, Kim YC, Chen J, Xu WX Tags: Eur J Pharmacol Source Type: research

Berberine attenuates arthritis in adjuvant-induced arthritic rats associated with regulating polarization of macrophages through AMPK/NF- кB pathway.
This study aimed to investigate the anti-arthritic effects of BBR in adjuvant arthritis (AA) in rats and its regulatory role in the polarization of macrophages. Rats were immunized with Complete Freund's Adjuvant (CFA), and then BBR (40, 80, 160mg/kg) was administered orally for 14 days. BBR significantly reduced paw swelling and arthritis global assessment as well as alleviated joint destruction and inflammatory cell infiltration. The index of the thymus and thymocyte proliferation were significantly reduced by BBR. Moreover, BBR treatment restrained the phagocytic function of macrophages and restored the balance of M1/M2...
Source: European Journal of Pharmacology - February 20, 2019 Category: Drugs & Pharmacology Authors: Zhou J, Yu Y, Yang X, Wang Y, Song Y, Wang Q, Chen Z, Zong S, Fan M, Meng X, Xie C, Zhou F, Liu H, Wei F Tags: Eur J Pharmacol Source Type: research

Ginsenoside Rg1 attenuates protein aggregation and inflammatory Response following cerebral ischemia and reperfusion injury.
Abstract Ginsenoside Rg1 (GS Rg1) is a glycosylated triterpenoid saponin extracted from Panax ginseng. We aim to investigate the impact of GS Rg1 on protein aggregation and inflammatory response in a cerebral ischemia/reperfusion (I/R) injury model. Rats were administered different doses of GS Rg1 (10, 20, or 40mg/kg/day) or nimodipine (1mg/kg/day) for 5 consecutive days. Cerebral I/R injury was induced by middle cerebral artery occlusion for 2h followed by a 22h reperfusion period. Next, we examined the differences in infarct volume and neurological deficit via TTC staining and Longa's scoring, respectively. Furt...
Source: European Journal of Pharmacology - February 19, 2019 Category: Drugs & Pharmacology Authors: Zheng T, Jiang H, Jin R, Zhao Y, Bai Y, Xu H, Chen Y Tags: Eur J Pharmacol Source Type: research

Characterization of novel kainic acid analogs as inhibitors of select microglial functions.
Abstract Alzheimer's disease (AD) is characterized by abnormal accumulation of extracellular amyloid beta protein (Aβ) plaques and intracellular neurofibrillary tangles, as well as by a state of chronic inflammation in the central nervous system (CNS). Adverse activation of microglia, the brain immune cells, is believed to contribute to AD pathology including excessive neuronal death. Thus, normalizing immune functions of microglia could slow neurodegeneration, and identification of novel compounds capable of modifying microglial functions is an important goal. Since kainic acid (KA) has been shown to modulat...
Source: European Journal of Pharmacology - February 18, 2019 Category: Drugs & Pharmacology Authors: Alford MA, Tian Z, Menard F, Klegeris A Tags: Eur J Pharmacol Source Type: research

Triptolide prevents proliferation and migration of Esophageal Squamous Cell Cancer via MAPK/ERK signaling pathway.
Abstract Triptolide, the component of traditional Chinese herb, has been used as an inflammatory medicine and reported to be anti-tumor for various cancers recently. However, the effect of triptolide on Esophageal Squamous Cell Cancer (ESCC) has not yet been elucidated. In the study, we found that triptolide significantly inhibited cell proliferation, invasion, migration and survivability of ESCC cells. Moreover, we observed that triptolide induced ESCC cell cycle arrest at the G1/S phase and apoptosis through cyclin D1-CDK4/6 regulation and caspases activation. In addition, we revealed that triptolide regulates c...
Source: European Journal of Pharmacology - February 16, 2019 Category: Drugs & Pharmacology Authors: Yanchun M, Yi W, Lu W, Yu Q, Jian Y, Pengzhou K, Ting Y, Hongyi L, Fang W, Xiaolong C, Yongping C Tags: Eur J Pharmacol Source Type: research

Vaccarin ameliorates insulin resistance and steatosis by activating the AMPK signaling pathway.
In this study, glucosamine (GlcN) and free fatty acids (FFAs, oleate/palmitate, 2:1 ratio) were applied to mimic insulin resistance and lipid deposition in HepG2 cells, respectively. Type 2 diabetic mice were induced using a high-fat diet (HFD) together with streptozotocin (STZ). GlcN stimulation was found to upregulate glucose production and gluconeogenesis but downregulate glycogen synthesis and phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in HepG2 cells, abnormal changes that were reversed by vaccarin. Furthermore, lipid accumulation was enhanced, but AMPK was inactivated in FFAs-e...
Source: European Journal of Pharmacology - February 16, 2019 Category: Drugs & Pharmacology Authors: Lei Y, Gong L, Tan F, Liu Y, Li S, Shen H, Zhu M, Cai W, Xu F, Hou B, Zhou Y, Han H, Qiu L, Sun H Tags: Eur J Pharmacol Source Type: research

Berberine promotes osteogenic differentiation of mesenchymal stem cells with therapeutic potential in periodontal regeneration.
In this study, we found that berberine, a benzylisoquinoline plant alkaloid from Coptidis Rhizoma, strongly inhibited the growth of Porphyromonas gingivalis. Gingipain is the most important virulence factor of Porphyromonas gingivalis in the process of periodontal tissue destruction. Berberine also had an inhibitory effect on gingipain activity in a concentration dependent manner. Remarkably, berberine restored the downregulation of osteogenesis-related genes expression in bone mesenchymal stem cells (BMSCs) induced by Porphyromonas gingivalis infection, and significantly increased the expression of osteogenesis-related ge...
Source: European Journal of Pharmacology - February 15, 2019 Category: Drugs & Pharmacology Authors: Zhang R, Yang J, Wu J, Xiao L, Miao L, Qi X, Li Y, Sun W Tags: Eur J Pharmacol Source Type: research

MicroRNA-30c abrogation protects against spinal cord ischemia reperfusion injury through modulating SIRT1.
In this study, I/R surgery or oxygen-glucose deprivation (OGD) were performed to establish SCI model in vivo or in vitro, respectively. Basso, Beattie and Bresnahan (BBB) score, spinal cord infarct, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining, flow cytometry and enzyme linked immunosorbent assays (ELISA) were used to investigate SCI. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the abundances of miR-30c and sirtuin 1 (SIRT1) either in spinal cord or PC12 cells. Luciferase assay and RNA immunoprecipitation (RIP) were performed to probe the int...
Source: European Journal of Pharmacology - February 15, 2019 Category: Drugs & Pharmacology Authors: Wang X, Su X, Gong F, Yin J, Sun Q, Zeyi LV, Liu B Tags: Eur J Pharmacol Source Type: research