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Berberine Promotes OATP1B1 Expression and Rosuvastatin Uptake by Inducing Nuclear Translocation of FXR and LXR α
In conclusion, berberine-induced nuclear translocation of FXR and LXRα could activate OATP1B1 promoter, resulting in enhanced expression of OATP1B1 and increased uptake of rosuvastatin.
Source: Frontiers in Pharmacology - March 26, 2020 Category: Drugs & Pharmacology Source Type: research

Small Interfering RNA Therapeutic Inclisiran: A New Approach to Targeting PCSK9
AbstractHypercholesterolemia is a leading cause of cardiovascular disease and mortality in men and women throughout the USA and abroad. The development of statins (HMG-CoA reductase inhibitors) to lower plasma atherogenic cholesterol levels and improve cardiovascular outcomes represents one of the greatest contributions to clinical science in the twentieth century, although residual risk remains even among statin-treated patients. Our understanding of lipid metabolism took a giant leap forward in 2003 with the discovery of proprotein convertase subtilsin/kexin type  9 (PCSK9), a low abundance circulating protein with an o...
Source: BioDrugs - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

Ability to Suppress TGF- β-Activated Myofibroblast Differentiation Distinguishes the Anti-pulmonary Fibrosis Efficacy of Two Danshen-Containing Chinese Herbal Medicine Prescriptions
Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of “removing both phlegm and blood stasis” will better achieve co-protection of heart and lung in PHD. Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic ...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Geranylgeraniol prevents the simvastatin-induced PCSK9 expression: Role of the small G protein Rac1
Publication date: August 2017 Source:Pharmacological Research, Volume 122 Author(s): Nicola Ferri, Silvia Marchianò, Maria Giovanna Lupo, Annalisa Trenti, Giuseppe Biondo, Paola Castaldello, Alberto Corsini Statins are known to increase the plasma levels of proprotein convertase subtilisin kexin type 9 (PCSK9) through the activation of the sterol responsive element binding protein (SREBP) pathway due to the inhibition of cholesterol biosynthesis. In the present study, we explore a possible role of the prenylated proteins on the statin-mediated PCSK9 induction in Caco-2 cells. Simvastatin (40μM) induced both PCSK9 mRNA (...
Source: Pharmacological Research - June 10, 2017 Category: Drugs & Pharmacology Source Type: research

Pitavastatin Suppresses Hyperglycemia-induced Podocyte Injury via Bone Morphogenetic Protein-7 Preservation.
CONCLUSION: Pitavastatin attenuates hyperglycemia-induced podocyte injury via Rho-Rho kinase-dependent BMP-7 preservation. This article is protected by copyright. All rights reserved. PMID: 27997722 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Pharmacology and Physiology - December 19, 2016 Category: Drugs & Pharmacology Authors: Ohigashi M, Kobara M, Takahashi T, Toba H, Wada T, Nakata T Tags: Clin Exp Pharmacol Physiol Source Type: research

Involvement of Pregnane X Receptor in the Impaired Glucose Utilization Induced by Atorvastatin in Hepatocytes.
In conclusion, atorvastatin impaired glucose utilization in hepatocytes via repressing GLUT2 and GCK expressions, which may be partly due to PXR activation. PMID: 26616219 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - November 23, 2015 Category: Drugs & Pharmacology Authors: Ling Z, Shu N, Xu P, Wang F, Zhong Z, Sun B, Li F, Zhang M, Zhao K, Tang X, Wang Z, Zhu L, Liu L, Liu X Tags: Biochem Pharmacol Source Type: research

Estrogen receptor mediates simvastatin-stimulated osteogenic effects in bone marrow mesenchymal stem cells.
In this study, we hypothesize that the estrogen receptor (ER) mediates simvastatin-induced osteogenic differentiation. ER antagonists and siRNA were used to determine the involvement of the ER in simvastatin-induced osteogenesis in mouse bone marrow mesenchymal stem cells (D1 cells). Osteogenesis was evaluated by mRNA expression, protein level/activity of osteogenic markers, and mineralization. The estrogen response element (ERE) promoter activity and the ER-simvastatin binding affinity were examined. Our results showed that the simvastatin-induced osteogenic effects were decreased by treatment with ERα antagonists and ER...
Source: Biochemical Pharmacology - September 24, 2015 Category: Drugs & Pharmacology Authors: Chuang SC, Chen CH, Fu YC, Tai IC, Li CJ, Chang LF, Ho ML, Chang JK Tags: Biochem Pharmacol Source Type: research

Atorvastatin-induced endothelial nitric oxide synthase expression in endothelial cells is mediated by endoglin.
Authors: Zemankova L, Varejckova M, Dolezalova E, Fikrova P, Jezkova K, Rathouska J, Cerveny L, Botella LM, Bernabeu C, Nemeckova I, Nachtigal P Abstract Endoglin, a transforming growth factor β (TGF-β) receptor type III, is co-expressed with endothelial nitric oxide synthase (eNOS) in aortic endothelium in atherosclerotic plaques of mice. Interestingly, atorvastatin (ATV) is able to increase both endoglin and eNOS expression and reduce plaque size beyond its lipid lowering effects but by unknown mechanisms. We hypothesized whether inflammation modulates ATV-dependent induction of endoglin and eNOS expression in ...
Source: Journal of Physiology and Pharmacology - June 20, 2015 Category: Drugs & Pharmacology Tags: J Physiol Pharmacol Source Type: research

Atorvastatin attenuates homocysteine-induced migration of smooth muscle cells through mevalonate pathway involving reactive oxygen species and p38 MAPK.
This article is protected by copyright. All rights reserved. PMID: 26041506 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Pharmacology and Physiology - June 4, 2015 Category: Drugs & Pharmacology Authors: Bao XM, Zheng H Tags: Clin Exp Pharmacol Physiol Source Type: research

Atorvastatin reduces long pentraxin 3 expression in vascular cells by inhibiting protein geranylgeranylation.
CONCLUSIONS: Results suggest that statins may interfere with PTX3 expression in vascular cells via inhibition of protein geranylgeranylation. Since PTX3 is increasingly regarded as an important mediator of the inflammatory response underlying atherosclerosis and its complications, these results highlight the need for further studies of the role of PTX3 and its potential pharmacological modulation in cardiovascular disease. PMID: 25849951 [PubMed - as supplied by publisher]
Source: Vascular Pharmacology - April 4, 2015 Category: Drugs & Pharmacology Authors: Baetta R, Lento S, Ghilardi S, Barbati E, Corsini A, Tremoli E, Banfi C Tags: Vascul Pharmacol Source Type: research

Autocrine secretion of 15d‐PGJ2 mediates simvastatin‐induced apoptotic burst in human metastatic melanoma cells
Conclusions and ImplicationsWe characterized simvastatin‐induced activation of the 15d‐PGJ2/FABP5 signalling cascades, which triggered an apoptotic burst in melanoma cells but did not affect primary human melanocytes. These data support the rationale for the pharmacological targeting of 15d‐PGJ2 in metastatic melanoma.
Source: British Journal of Pharmacology - December 1, 2014 Category: Drugs & Pharmacology Authors: Christine Wasinger, Martin Künzl, Christoph Minichsdorfer, Christoph Höller, Maria Zellner, Martin Hohenegger Tags: RESEARCH PAPER Source Type: research

Statins upregulate cystathionine γ-lyase transcription and H2S generation via activating Akt signaling in macrophage
In this study, we examined the effects of three different statins (fluvastatin, atorvastatin and pravastatin) on H2S formation in raw264.7 macrophages. There was a remarkable rise in H2S level in fluvastatin- and atorvastatin-stimulated macrophages, while pravastatin failed to show any significant effect on it. Moreover, fluvastatin and atorvastatin enhanced the mRNA and protein expression of cystathionine γ-lyase (CSE) in dose- and time-dependent manners. Fluvastatin also markedly enhanced the CSE activity. However, fluvastatin did not alter the mRNA or protein expression of another H2S-producing enzyme 3-mercaptopyruvat...
Source: Pharmacological Research - November 6, 2014 Category: Drugs & Pharmacology Source Type: research

Simvastatin induces NFκB/p65 down-regulation and JNK1/c-Jun/ATF-2 activation, leading to matrix metalloproteinase-9 (MMP-9) but not MMP-2 down-regulation in human leukemia cells.
Abstract The aim of the present study was to explore the signaling pathways associated with the effect of simvastatin on matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia K562 cells. In sharp contrast to its insignificant effect on MMP-2, simvastatin down-regulated MMP-9 protein expression and mRNA levels in K562 cells. Simvastatin-induced Pin1 down-regulation evoked NFκB/p65 degradation. Meanwhile, simvastatin induced JNK-mediated c-Jun and ATF-2 activation. Over-expression of Pin1 suppressed simvastatin-induced MMP-9 down-regulation. Treatment with SP600125 (a JNK inhibitor) or knock-down of...
Source: Biochemical Pharmacology - October 11, 2014 Category: Drugs & Pharmacology Authors: Chen YJ, Chang LS Tags: Biochem Pharmacol Source Type: research

Autocrine secretion of 15d‐PGJ2 mediates simvastatin induced apoptotic burst in human metastatic melanoma cells
ConclusionWe here delineate simvastatin induced activation of the 15d‐PGJ2/FABP5 signalling cascades, which trigger an apoptotic burst in melanoma cells, while primary human melanocytes were unaffected. These data support new rational ground for pharmacological targeting of 15d‐PGJ2 in metastatic melanoma.
Source: British Journal of Pharmacology - August 4, 2014 Category: Drugs & Pharmacology Authors: Christine Wasinger, Martin Künzl, Christoph Minichsdorfer, Christoph Höller, Maria Zellner, Martin Hohenegger Tags: Research Paper Source Type: research

Rosuvastatin inhibits pressure-induced fibrotic responses via the expression regulation of prostacyclin and prostaglandin E(2) in rat renal tubular cells.
In conclusion, rosuvastatin reduces pressure-induced fibrotic responses in renal tubular cells by enhancing the PGI(2)-peroxisome proliferator-activated receptor α pathway and reducing PGE(2) generation. PMID: 23276663 [PubMed - as supplied by publisher]
Source: European Journal of Pharmacology - December 28, 2012 Category: Drugs & Pharmacology Authors: Chen CH, Cheng CY, Chen YC, Sue YM, Hsu YH, Tsai WL, Chen TH Tags: Eur J Pharmacol Source Type: research

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