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HMG coA reductase

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https://www.readbyqxmd.com/read/28546657/statins-reduce-lipopolysaccharide-induced-cytokine-and-inflammatory-mediator-release-in-an-in-vitro-model-of-microglial-like-cells
#1
A J McFarland, A K Davey, S Anoopkumar-Dukie
The anti-inflammatory effects of statins (HMG-CoA reductase inhibitors) within the cardiovascular system are well-established; however, their neuroinflammatory potential is unclear. It is currently unknown whether statins' neurological effects are lipid-dependent or due to pleiotropic mechanisms. Therefore, the assumption that all statin compounds will have the same effect within the central nervous system is potentially inappropriate, with no studies to date having compared all statins in a single model. Thus, the aim of this study was to compare the effects of the six statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) within a single in vitro model of neuroinflammation...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28542128/hmg-coa-reductase-promotes-protein-prenylation-and-therefore-is-indispensible-for-t-cell-survival
#2
Sonja M Lacher, Julia Bruttger, Bettina Kalt, Jean Berthelet, Krishnaraj Rajalingam, Simone Wörtge, Ari Waisman
Statins are a well-established family of drugs that lower cholesterol levels via the competitive inhibition of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). In addition, the pleiotropic anti-inflammatory effects of statins on T cells make them attractive as therapeutic drugs in T-cell-driven autoimmune disorders. Since statins do not exclusively target HMGCR and thus might have varying effects on different cell types, we generated a new mouse strain allowing for the tissue-specific deletion of HMGCR...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28539592/atorvastatin-promotes-phagocytosis-and-attenuates-pro-inflammatory-response-in-human-retinal-pigment-epithelial-cells
#3
Bo Tian, Ahmad Al-Moujahed, Peggy Bouzika, Yijun Hu, Shoji Notomi, Pavlina Tsoka, Joan W Miller, Haijiang Lin, Demetrios G Vavvas
Phagocytosis of daily shed photoreceptor outer segments is an important function of the retinal pigment epithelium (RPE) and it is essential for retinal homeostasis. RPE dysfunction, especially impairment of its phagocytic ability, plays an essential role in the pathogenesis of age-related macular degeneration (AMD). Statins, or HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, are drugs with multiple properties that have been extensively used to treat hyperlipidemia. However, their effect on RPE cells has not been fully elucidated...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536098/rosuvastatin-and-atorvastatin-are-ligands-of-the-human-car-rxr%C3%AE-complex
#4
Tadeja Rezen, Mateja Hafner, Sandhya Kortagere, Sean Ekins, Vesna Hodnik, Damjana Rozman
Statins are well known lipid lowering agents that inhibit the enzyme HMG-CoA reductase. They also activate drug metabolism but their exact receptor-mediated action has not been proven so far. The aim of this study was to test if atorvastatin and rosuvastatin are direct ligands of human CAR. We measured binding activities of atorvastatin and rosuvastatin to the human CAR/RXRα-LBD heterodimer with surface plasmon resonance (SPR). Additionally, three-dimensional models of CAR/RXRα-LBD were constructed by ligand-based and structure-based in silico modelling...
May 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28533986/atorvastatin-alters-the-expression-of-genes-related-to-bile-acid-metabolism-and-circadian-clock-in-livers-of-mice
#5
Wen-Kai Li, Huan Li, Yuan-Fu Lu, Ying-Ying Li, Zidong Donna Fu, Jie Liu
AIM: Atorvastatin is a HMG-CoA reductase inhibitor used for hyperlipidemia. Atorvastatin is generally safe but may induce cholestasis. The present study aimed to examine the effects of atorvastatin on hepatic gene expression related to bile acid metabolism and homeostasis, as well as the expression of circadian clock genes in livers of mice. METHODS: Adult male mice were given atorvastatin (10, 30, and 100 mg/kg, po) daily for 30 days, and blood biochemistry, histopathology, and gene expression were examined...
2017: PeerJ
https://www.readbyqxmd.com/read/28529486/the-role-of-statins-in-prevention-of-preeclampsia-a-promise-for-the-future
#6
REVIEW
Vasiliki Katsi, Georgios Georgountzos, Manolis S Kallistratos, Ioannis Zerdes, Thomas Makris, Athanasios J Manolis, Petros Nihoyannopoulos, Dimitris Tousoulis
Preeclampsia has been linked to high morbidity and mortality during pregnancy. However, no efficient pharmacological options for the prevention of this condition are currently available. Preeclampsia is thought to share several pathophysiologic mechanisms with cardiovascular disease, which has led to investigations for the potential role of statins (HMG CoA reductase inhibitors) in its prevention and early management. Pravastatin seems to have a safer pharmacokinetic profile compared to other statins, however, the existing preclinical evidence for its effectiveness in preeclampsia treatment has been mostly restricted to animal models...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28527898/triterpenes-and-meroterpenes-from-ganoderma-lucidum-with-inhibitory-activity-against-hmgs-reductase-aldose-reductase-and-%C3%AE-glucosidase
#7
Baosong Chen, Jin Tian, Jinjin Zhang, Kai Wang, Li Liu, Bo Yang, Li Bao, Hongwei Liu
Seven new compounds including four lanostane triterpenoids, lucidenic acids Q-S (1-3) and methyl ganoderate P (4), and three triterpene-farnesyl hydroquinone conjugates, ganolucinins A-C (5-7), one new natural product ganomycin J (8), and 73 known compounds (9-81) were isolated from fruiting bodies of Ganoderma lucidum. The structures of the compounds 1-8 were determined by spectroscopic methods. Bioactivities of compounds isolated were assayed against HMG-CoA reductase, aldose reductase, α-glucosidase, and PTP1B...
May 17, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28511341/in-vivo-and-molecular-docking-studies-using-whole-extract-and-phytocompounds-of-aegle-marmelos-fruit-protective-effects-against-isoproterenol-induced-myocardial-infarction-in-rats
#8
Gadamsetty Saayi Krushna, Vutharadhi Leela Shivaranjani, Jolapuram Umamaheswari, Cheemanapalli Srinivasulu, Shaik Althaf Hussain, Mohammed Abdul Kareem, Vaddi Damodara Reddy, Daoud Ali, Kiran Bharat Lokhande, K Venkateswara Swamy, Lakshmi Devi Kodidhela
Myocardial infarction (MI) is a leading major health problem with increased morbidity and mortality worldwide. The present study investigates isoproterenol (ISO) induced MI and the beneficial role of Aegle marmelos fruit extract (AMFE) in rats. Our results indicated the significant augmentation of plasma nitric oxide (NOx) levels, C-reactive protein (CRP), homocysteine, apolipoprotein B (apo-B), cardiac tissue lipid peroxidation and liver 3-hydroxy-3 methyl glutaryl CoA (HMG-CoA) reductase activity in ISO treated rats (85mg/kg b...
May 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28500274/combined-hmg-coa-reductase-and-prenylation-inhibition-in-treatment-of-ccm
#9
Sayoko Nishimura, Ketu Mishra-Gorur, JinSeok Park, Yulia V Surovtseva, Said M Sebti, Andre Levchenko, Angeliki Louvi, Murat Gunel
Cerebral cavernous malformations (CCMs) are common vascular anomalies that develop in the central nervous system and, more rarely, the retina. The lesions can cause headache, seizures, focal neurological deficits, and hemorrhagic stroke. Symptomatic lesions are treated according to their presentation; however, targeted pharmacological therapies that improve the outcome of CCM disease are currently lacking. We performed a high-throughput screen to identify Food and Drug Administration-approved drugs or other bioactive compounds that could effectively suppress hyperproliferation of mouse brain primary astrocytes deficient for CCM3...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28489008/-do-opioids-sedatives-and-proton-pump-inhibitors-increase-the-risk-of-fractures
#10
Gudlaug Thorsdottir, Elisabet Benedikz, Sigridur A Thorgeirsdottir, Magnus Johannsson
INTRODUCTION: A pharmacoepidemiological study was conducted to analyse the relationship between bone fracture and the use of certain drugs. MATERIAL/METHODS: The study includes patients 40 years and older, diagnosed with bone fractures in the Emergency Department of Landspitali University Hospital in Reykjavik, Iceland, during a 10-year period (2002-2011). Also were included those who picked up from a pharmacy 90 DDD or more per year of the drugs included in the study in the capital region of Iceland during same period...
May 2017: Læknablađiđ
https://www.readbyqxmd.com/read/28484475/de-novo-sequencing-and-transcriptome-analysis-reveal-key-genes-regulating-steroid-metabolism-in-leaves-roots-adventitious-roots-and-calli-of-periploca-sepium-bunge
#11
Jian Zhang, Xinglin Li, Fuping Lu, Shanying Wang, Yunhe An, Xiaoxing Su, Xiankuan Li, Lin Ma, Guangjian Han
Periploca sepium Bunge is a traditional medicinal plant, whose root bark is important for Chinese herbal medicine. Its major bioactive compounds are C21 steroids and periplocin, a kind of cardiac glycoside, which are derived from the steroid synthesis pathway. However, research on P. sepium genome or transcriptomes and their related genes has been lacking for a long time. In this study we estimated this species nuclear genome size at 170 Mb (using flow cytometry). Then, RNA sequencing of four different tissue samples of P...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28481295/inhibiting-hdac1-enhances-the-anti-cancer-effects-of-statins-through-downregulation-of-ggtase-i%C3%AE-expression
#12
Ran Li, Ye-Hua Gan
Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, namely statins, are potential anti-tumor agents. Previously, we showed that a pan-histone deacetylase (HDAC) inhibitor enhances the anti-tumor effects of the HMG-CoA inhibitor. However, the underlying mechanisms were not fully understood. Cancer cell lines (CAL-27 and SACC-83) were exposed to pan-HDAC inhibitor, or HDAC1 inhibitor, or geranylgeranyl transferase type I (GGTase-I) inhibitor alone or in combination with statin. Cell viability, apoptosis, migration, and invasion were assessed by Cell Count Kit-8, 4',6-diamidino-2-phenylindole staining, and transwell assay, respectively...
May 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28476969/preparation-and-characterisation-of-atorvastatin-and-curcumin-loaded-chitosan-nanoformulations-for-oral-delivery-in-atherosclerosis
#13
Varuna Kumara J B, Sistla Ramakrishna, Basavaraj Madhusudhan
Atorvastatin known to be a potential inhibitor of HMG-CoA reductase involved in the synthesis of cholesterol. It is touted as miracle drug due to its profound effect in decreasing the low-density lipoproteins in blood. Unfortunately, the high dosage used poses side-effects relatively in comparison to other statins. On the other hand, curcumin has a diverse therapeutic potential in health and disease. However, the poor aqueous solubility and low bioavailability hinders the therapeutic potential of it when administrated orally...
February 2017: IET Nanobiotechnology
https://www.readbyqxmd.com/read/28462132/spirogyra-neglecta-inhibits-the-absorption-and-synthesis-of-cholesterol-in-vitro
#14
Acharaporn Duangjai, Nanteetip Limpeanchob, Kanittaporn Trisat, Doungporn Amornlerdpison
BACKGROUND: Spirogyra neglecta (SN) has many nutritional benefits and it is commonly used to ameliorate different human conditions including inflammation, gastric ulcer, hyperglycemia, and hyperlipidemia. However, the mechanism of the hypocholesterolemic effect of SN still remains unclear. Therefore, the present study was aimed to evaluate the effect of SN extract particularly on cholesterol absorption and synthesis mechanisms. METHODS: For cholesterol absorption, the uptake of cholesterol was measured by using tritium radiolabeling of cholesterol in Caco-2 cells...
December 2016: Integr Med Res
https://www.readbyqxmd.com/read/28456771/anti-inflammatory-effects-of-simvastatin-in-nonsteroidal-anti-inflammatory-drugs-induced-small-bowel-injury
#15
E K Kim, J H Cho, A R Jeong, E J Kim, D K Park, K A Kwon, J W Chung, K O Kim, J H Kim, J H Kim, Y J Kim
Small bowel injury can occur as the result of a multifaceted process that includes increased acid secretion, generation of reactive oxygen species, and cyclooxygenase inhibition. However, no effective medication for small bowel ulceration is available. Simvastatin is an important lipid-lowering agent with anti-inflammatory activity. We aimed to validate the effects of simvastatin in vitro and in vivo. In presence or absence of simvastatin, IEC-6 small bowel cell line with 50 ng/ml of tumor nectosis factor α (TNF-α) was investigated by western blotting, qRT-PCR, and DCF-DA assay...
February 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28455524/mechanisms-underlying-cognitive-deficits-in-a-mouse-model-for-costello-syndrome-are-distinct-from-other-rasopathy-mouse-models
#16
Jadwiga Schreiber, Laura-Anne Grimbergen, Iris Overwater, Thijs van der Vaart, Jeffrey Stedehouder, Alberto J Schuhmacher, Carmen Guerra, Steven A Kushner, Dick Jaarsma, Ype Elgersma
RASopathies, characterized by germline mutations in genes encoding proteins of the RAS-ERK signaling pathway, show overlapping phenotypes, which manifest themselves with a varying severity of intellectual disability. However, it is unclear to what extent they share the same downstream pathophysiology that underlies the cognitive deficits. Costello syndrome (CS) is a rare RASopathy caused by activating mutations in the HRAS gene. Here we investigated the mechanisms underlying the cognitive deficits of HRas (G12V/G12V) mice...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28454732/fluvastatin-prevents-lung-adenocarcinoma-bone-metastasis-by-triggering-autophagy
#17
Zuozhang Yang, Zhenyi Su, Judy Park DeWitt, Lin Xie, Yongbin Chen, Xiaojuan Li, Lei Han, Dongqi Li, Junfeng Xia, Ya Zhang, Yihao Yang, Congguo Jin, Jing Zhang, Su Li, Kun Li, Zhiping Zhang, Xin Qu, Zewei He, Yanjin Chen, Yan Shen, Mingyan Ren, Zhongqin Yuan
Bone is one of the most preferred sites of metastasis in lung cancer. Currently, bisphosphonates and denosumab are major agents for controlling tumor-associated skeletal-related events (SREs). However, both bisphosphonates and denosumab significantly increase the risk for jaw osteonecrosis. Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and the most frequently prescribed cholesterol-lowering agents, have been reported to inhibit tumor progression and induce autophagy in cancer cells...
April 11, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28445900/central-and-peripheral-glucagon-reduces-hyperlipidemia-in-rats-and-hamsters
#18
Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Hiren M Patel, Dheerendra Pandey, Dipam Patel, Kiran Shah, Rajesh Bahekar, Gaurang B Shah, Mukul R Jain
Increased lipid levels in blood contribute to increasing the risk of diabetic complications. Glucagon exerts lipid lowering effects in diabetic state. However, the mechanism behind the lipid reduction by glucagon independent of glucose homeostasis is not well understood. We assessed the actions of glucagon on lipid modulation in blood and markers in liver in hyperlipidemic hamsters and rats. Male Sprague Dawley rats and Golden Syrian hamsters on a hyperlipidemic diet for 2 weeks were administered a single dose of glucagon by subcutaneous (SC, 150 and 300 µg/kg) or intracerebroventricular (ICV, 15 and 30 µg/animal) route...
April 26, 2017: Drug Research
https://www.readbyqxmd.com/read/28442378/antihyperlipidemic-and-antiapoptotic-potential-of-zingerone-on-alcohol-induced-hepatotoxicity-in-experimental-rats
#19
Vijay Mani, Sivaranjani Arivalagan, Aktarul Islam Siddique, Nalini Namasivayam
The ultimate aim of this present study was to investigate the antihyperlipidemic and antiapoptotic potential of zingerone (ZO) on alcohol induced hepatotoxicity in experimental rats. Male albino wistar rats were divided in four groups. Groups 1 and 2 rats received isocaloric glucose and dimethyl sulphoxide (2% DMSO), liver toxicity was induced in groups 3 and 4 by supplementing 30% ethanol post orally for 60 days. In addition, groups 2 and 4 received zingerone (20 mg/kg body weight in 2% DMSO) daily during the final 30 days of the experimental period...
April 22, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28429814/sulfated-polysaccharides-from-enteromorpha-prolifera-suppress-srebp-2-and-hmg-coa-reductase-expression-and-attenuate-non-alcoholic-fatty-liver-disease-induced-by-a-high-fat-diet
#20
Rendong Ren, Junjie Gong, Yanyan Zhao, Xinyun Zhuang, Yin Ye, Wenting Lin
Non-alcoholic fatty liver disease (NAFLD) is caused by fat accumulation and is associated with abnormal cholesterol metabolism. Previous work indicates that polysaccharides from alga Enteromorpha prolifera improve glucose metabolism and lower cholesterol in diabetic rats. Thus, we studied the possible protective effects of E. prolifera polysaccharides (EP) in the development of NAFLD and underlying mechanisms. EP (200 mg kg(-1)) significantly reduced the liver weight and significantly lowered hepatic HMG-CoA reductase (HMGCR) mRNA protein expression...
May 24, 2017: Food & Function
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