The Preventive Effects of Xanthohumol on Vascular Calcification Induced by Vitamin D Plus Nicotine.

Vascular calcification (VC) is highly prevalent in patients with atherosclerosis, chronic kidney disease, diabetes mellitus, and hypertension. In blood vessels, VC is associated with major adverse cardiovascular events. Xanthohumol (XN), a main prenylated chalcone found in hops, has antioxidant effects to inhibit VC.

Vasculoprotective effects of , and decoction via the NOXs-ROS-NF-κB pathway in spontaneously hypertensive rats.

Background And Aim: , and decoction (CJID) is efficacious for hypertension. NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (NOX)-induced reactive oxygen species (ROS) generation modulates nuclear factor kappa B (NF-κB) activation and thus mediates hypertension-induced vascular remodeling. This research aims to investigate the anti-remodeling effect of CJID through the mechanism of NOXs-ROS-NF-κB pathway in spontaneously hypertensive rats (SHRs).

B-type natriuretic peptide prevents postnatal closure of ductus arteriosus by both vasodilation and anti-remodeling in neonatal rats.

The physiologic process of postnatal ductus arteriosus (DA) closure consists of vasoconstriction followed by vascular remodeling. We have recently reported that B-type natriuretic peptide (BNP), a potent vasodilator, also has anti-remodeling effects in pulmonary vasculature. However, its effects on DA have not been elucidated.

Gamma-secretase Inhibitor Prevents Proliferation and Migration of Ductus Arteriosus Smooth Muscle Cells through the Notch3-HES1/2/5 Pathway.

Patent ductus arteriosus (PDA) can cause morbidity and mortality in neonates. Vascular remodeling, characterized by proliferation and migration of smooth muscle cells (SMCs), is an essential process for postnatal DA closure. Notch signaling is an important mediator of vascular remodelling but its role in DA is unkonwn.

Activation of endothelial NO synthase by a xanthine derivative ameliorates hypoxia-induced apoptosis in endothelial progenitor cells.

Objectives: Endothelial damage is strongly associated with cardiovascular diseases such as atherosclerosis, thrombosis and hypertension. Endothelial progenitor cells (EPCs) are primitive bone marrow (BM) cells that possess the capacity to mature into endothelial cells and play a role in neovascularization and vascular remodelling. This study aimed to investigate whether KMUP-1, a synthetic xanthine-based derivative, atorvastatin and simvastatin, can prevent endothelial dysfunction and apoptosis induced by hypoxia and to elucidate the underlying mechanisms.

Phosphodiesterase inhibitor KMUP-3 displays cardioprotection via protein kinase G and increases cardiac output via G-protein-coupled receptor agonist activity and Ca(2+) sensitization.

KMUP-3 (7-{2-[4-(4-nitrobenzene) piperazinyl]ethyl}-1, 3-dimethylxanthine) displays cardioprotection and increases cardiac output, and is suggested to increase cardiac performance and improve myocardial infarction. To determine whether KMUP-3 improves outcomes in hypoperfused myocardium by inducing Ca(2+) sensitization to oppose protein kinase (PK)G-mediated Ca(2+) blockade, we measured left ventricular systolic blood pressure, maximal rates of pressure development, mean arterial pressure and heart rate in rats, and measured contractility and expression of PKs/RhoA/Rho kinase (ROCK)II in beating guinea pig left atria. Hemodynamic changes induced by KMUP-3 (0.

KMUP-1 Attenuates Endothelin-1-Induced Cardiomyocyte Hypertrophy through Activation of Heme Oxygenase-1 and Suppression of the Akt/GSK-3β, Calcineurin/NFATc4 and RhoA/ROCK Pathways.

The signaling cascades of the mitogen activated protein kinase (MAPK) family, calcineurin/NFATc4, and PI3K/Akt/GSK3, are believed to participate in endothelin-1 (ET-1)-induced cardiac hypertrophy. The aim of this study was to investigate whether KMUP-1, a synthetic xanthine-based derivative, prevents cardiomyocyte hypertrophy induced by ET-1 and to elucidate the underlying mechanisms. We found that in H9c2 cardiomyocytes, stimulation with ET-1 (100 nM) for 4 days induced cell hypertrophy and enhanced expressions of hypertrophic markers, including atrial natriuretic peptide and brain natriuretic peptide, which were all inhibited by KMUP-1 in a dose-dependent manner.

KMUP-1 Promotes Osteoblast Differentiation Through cAMP and cGMP Pathways and Signaling of BMP-2/Smad1/5/8 and Wnt/β-Catenin.

Phosphodiesterase (PDE) inhibitors have been suggested as a possible candidate for the treatment of osteopenia, including osteoporosis. KMUP-1 is a novel xanthine derivative with inhibitory activities on the PDE 3, 4, and 5 iso-enzymes to suppress the degradation of cAMP and cGMP. This study aimed to investigate the effect of KMUP-1 on osteoblast differentiation and the underlying cellular and molecular mechanisms.

Exogenous heat shock cognate protein 70 pretreatment attenuates cardiac and hepatic dysfunction with associated anti-inflammatory responses in experimental septic shock.

It has been recently demonstrated that intracellular heat shock cognate protein 70 (HSC70) can be released into extracellular space with physiologic effects. However, its extracellular function in sepsis is not clear. In this study, we hypothesize that extracellular HSC70 can protect against lipopolysaccharide (LPS)-induced myocardial and hepatic dysfunction because of its anti-inflammatory actions.

Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways.

Background: Lysophosphatidylcholine (lysoPC), a metabolite from membrane phospholipids, accumulates in the ischemic myocardium and plays an important role in the development of myocardial dysfunction ventricular arrhythmia. In this study, we investigated if baicalein, a major component of Huang Qui, can protect against lysoPC-induced cytotoxicity in rat H9c2 embryonic cardiomyocytes.

Methods: Cell viability was detected by the MTT assay; ROS levels were assessed using DCFH-DA; and intracellular free calcium concentrations were assayed by spectrofluorophotometer.

Baicalein inhibits HMGB1 release and MMP-2/-9 expression in lipopolysaccharide-induced cardiac hypertrophy.

Myocardial dysfunction, a common complication after sepsis, significantly contributes to the death of patients with septic shock. In the search for potentially effective drugs to decrease mortality from sepsis, we investigated the cardioprotective effects of baicalein, a flavonoid present in the root of Scutellaria baicalensis, on lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and matrix metalloproteinase-2 and -9 (MMP-2/-9) expression. We found that baicalein significantly attenuated LPS-induced cardiac hypertrophy and counteracted reactive oxygen species (ROS) generation in neonatal rat cardiomyocytes.

B-type natriuretic peptide inhibits angiotensin II-induced proliferation and migration of pulmonary arterial smooth muscle cells.

Pulmonary vascular remodeling, characterized by disordered proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), is a pathognomonic feature of pulmonary arterial hypertension. Thus, pharmacologic strategy targeting on anti-proliferation and anti-migration of PASMCs may have therapeutic implications for PAH. Here we investigated the effects and underlying mechanisms of B-type natriuretic peptide (BNP) on angiotensin II (Ang II)-induced proliferation and migration of PASMCs.

KMUP-1 suppresses RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss: roles of MAPKs, Akt, NF-κB and calcium/calcineurin/NFATc1 pathways.

Background: KMUP-1 is a xanthine derivative with inhibitory activities on the phosphodiesterase (PDE) 3,4 and 5 isoenzymes to suppress the degradation of cyclic AMP and cyclic GMP. However, the effects of KMUP-1 on osteoclast differentiation are still unclear. In this study, we investigated whether KMUP-1 inhibits osteoclastogenesis induced by RANKL in RAW 264.

Lercanidipine and labedipinedilol--A attenuate lipopolysaccharide/interferon-γ-induced inflammation in rat vascular smooth muscle cells through inhibition of HMGB1 release and MMP-2, 9 activities.

Objective: Inflammation is an important molecular basis of atherosclerosis. Recent studies have shown that dihydropyridine calcium channel blockers (CCBs) can exert potent anti-inflammatory effects in models of vascular dysfunction. The purpose of the present study was to evaluate anti-inflammatory effects and mechanisms of lercanidipine and labedipinedilol-A, new generation dihydropyridine CCBs, in rat vascular smooth muscle cells (VSMCs) exposed to lipopolysaccharide (LPS) and interferon-γ (IFN-γ).

San-Huang-Xie-Xin-Tang protects cardiomyocytes against hypoxia/reoxygenation injury via inhibition of oxidative stress-induced apoptosis.

Oxidative stress has been widely implicated in the pathogenesis of hypoxia/reoxygenation (H/R) injury. San-Huang-Xie-Xin-Tang (SHXT), a widely used traditional Chinese medication, has been shown to possess antioxidant effects. Here, we investigated whether SHXT and its main component baicalin can attenuate oxidative stress induced by H/R injury.

San-Huang-Xie-Xin-Tang Prevents Rat Hearts from Ischemia/Reperfusion-Induced Apoptosis through eNOS and MAPK Pathways.

San-Huang-Xie-Xin-Tang (SHXT) is a traditional Chinese medication consisting of three herbs, namely Coptidis rhizome, Scutellariae radix and Rhei rhizome. This study aimed to examine the cardioprotective effects of SHXT in a rat model of acute myocardial apoptosis induced by ischemia/reperfusion (I/R). Vehicle (intravenous saline) or SHXT (intravenous or oral) was administered prior to I/R (occlusion of left coronary artery for 45 min followed by reperfusion for 2 h).

Labedipinedilol-A prevents lysophosphatidylcholine-induced vascular smooth muscle cell death through reducing reactive oxygen species production and anti-apoptosis.

Objective: Labedipinedilol-A, a novel calcium antagonist, has been previously demonstrated to have pleiotropic protective effects in the cardiovascular system. This study aimed to investigate its cytoprotective effects in rat vascular smooth muscle cells (VSMCs) treated with lysophosphatidylcholine (lysoPC), a key lipid component mediating atherogenesis.

Methods And Results: VSMCs were incubated with lysoPC with or without labedipinedilol-A pretreatment to determine its effects on lysoPC-induced cell death, Ca(2+) influx, oxidative stress, MAPK signaling and apoptosis.

Protective effects of Chlorella-derived peptide on UVB-induced production of MMP-1 and degradation of procollagen genes in human skin fibroblasts.

UV exposure is known to induce premature aging, which is mediated by matrix metalloproteinase-1 (MMP-1) activity. MMP-1 mRNA expression is up-regulated by elevated cysteine-rich 61 (CYR61) and monocyte chemoattractant protein-1 (MCP-1) via action of transcription factor AP-1. Collagen is degraded by MMP-1 activity but synthesized by transforming growth factor-β (TGF-β) signal.

KMUP-1 attenuates isoprenaline-induced cardiac hypertrophy in rats through NO/cGMP/PKG and ERK1/2/calcineurin A pathways.

Background And Purpose: To determine whether KMUP-1, a novel xanthine-based derivative, attenuates isoprenaline (ISO)-induced cardiac hypertrophy in rats, and if so, whether the anti-hypertrophic effect is mediated by the nitric oxide (NO) pathway.

Experimental Approach: In vivo, cardiac hypertrophy was induced by injection of ISO (5 mg.kg(-1).

Inhibition of human prostate cancer cells proliferation by a selective alpha1-adrenoceptor antagonist labedipinedilol-A involves cell cycle arrest and apoptosis.

In this research, we conducted an in vitro analysis to evaluate the prostate cancer cells response to labedipinedilol-A in order to determine the effect of this selective alpha(1)-adrenoceptor antagonist to suppress prostate cancer cell growth by affecting cell proliferation and apoptosis. Here, we report that treatment of androgen-sensitive (LNCaP) and androgen-insensitive (PC-3) prostate cancer cells with labedipinedilol-A inhibited cell proliferation in concentration-dependent and time-dependent manners. Moreover, norepinephrine-stimulated proliferation of both cell lines are markedly inhibited by labedipinedilol-A.

Lercanidipine inhibits vascular smooth muscle cell proliferation and neointimal formation via reducing intracellular reactive oxygen species and inactivating Ras-ERK1/2 signaling.

Lercanidipine, a calcium channel antagonist, is currently employed in the treatment of essential hypertension and angina pectoris. The purpose of this study was to elucidate the anti-proliferative effect of lercanidipine and to investigate the molecular role of this agent. Both in vitro studies and in a balloon injury rat carotid artery model were employed to study the effect of lercanidipine on smooth muscle cell proliferation.

Isoeugenodilol inhibits smooth muscle cell proliferation and neointimal thickening after balloon injury via inactivation of ERK1/2 pathway.

The purpose of this study was to determine the efficacy and the possible mechanism of action of the synthesized drug isoeugenodilol (a new third-generation beta-adrenoceptor blocker) on the growth factor-induced proliferation of cultured rat vascular smooth muscle cells (VSMCs) and neointimal formation in a rat carotid arterial balloon injury model. Isoeugenodilol significantly inhibited 10% FBS, 20 ng/ml PDGF-BB, and 20 ng/ml vascular endothelial growth factor (VEGF)-induced proliferation. In accordance with these findings, isoeugenodilol revealed blocking of the FBS-inducible progression through the G(0)/G(1) to the S phase of the cell cycle in synchronized cells.

Eugenosedin-A amelioration of lipopolysaccharide-induced up-regulation of p38 MAPK, inducible nitric oxide synthase and cyclooxygenase-2.

In this study, we investigate the protective effects of eugenosedin-A on p38 mitogen-activated protein kinase (MAPK), inflammatory nitric oxide (NO) and cyclooxygenase-2 (COX-2) pathways in a rat model of endotoxin shock. Rats were pretreated with eugenosedin-A, trazodone, yohimbine (1 mg kg(-1), i.v.

Inhibition of proinflammatory tumor necrosis factor-{alpha}-induced inducible nitric-oxide synthase by xanthine-based 7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine (KMUP-1) and 7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1, 3-dimethylxanthine (KMUP-3) in rat trachea: The involvement of soluble guanylate cyclase and protein kinase G.

In the study of anti-proinflammation by 7-[2-[4-(2-chlorobenzene)piperazinyl] ethyl]-1,3-dimethylxanthine (KMUP-1) and 7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine (KMUP-3), exposure of rat tracheal smooth muscle cells (TSMCs) to tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, increased the expression of inducible nitric-oxide synthase (iNOS) and NO production and decreased the expression of soluble guanylate cyclase alpha1 (sGCalpha1), soluble guanylate cyclase beta1 (sGCbeta1), protein kinase G (PKG), and the release of cGMP in TSMCs. The cell-permeable cGMP analog 8-Br-cGMP, xanthine-based KMUP-1 and KMUP-3, and the phosphodiesterase 5 inhibitor zaprinast all inhibited TNF-alpha-induced increases of iNOS expression and NO levels and reversed TNF-alpha-induced decreases of sGCalpha1, sGCbeta1, and PKG expression. These results imply that cGMP enhancers could have anti-proinflammatory potential in TSMCs.

Protective effect of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker, on myocardial apoptosis in ischemia-reperfusion injury.

The effects of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker with alpha-/beta-adrenoceptor blocking activities, on myocardial infarct size, apoptosis and necrosis in the rat after myocardial ischemia/reperfusion (45 min/120 min) were investigated. Ten minutes prior to left coronary artery occlusion, rats were treated with vehicle or labedipinedilol-A (0.25 or 0.