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Lovastatin

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https://www.readbyqxmd.com/read/29132077/lovastatin-analogues-and-other-metabolites-from-soil-derived-aspergillus-terreus-yim-ph30711
#1
Qiang Wang, Ya-Bin Yang, Xue-Qiong Yang, Cui-Ping Miao, Yi-Qing Li, Shi-Xi Liu, Na Luo, Zhong-Tao Ding, Li-Xing Zhao
Eight previously undescribed metabolites including of lovastatin analogues, a pair of diastereoisomers, a cyclopentenone dimer, and three polyketides were isolated from the culture of Aspergillus terreus YIM PH30711. Two types of unprecedented skeletons, benzene-cyclopentanone complex and linear polyketide, and an unusual dimer structure were determined by spectral analysis. Compound, 3α-hydroxy-3,5-dihydromonacolin L showed moderate activity against HMG-CoA reductase, with an inhibition ratio of 34% at the concentration of 50 μM, while lovastatin and dihydromonacolin K ethyl ester presented much stronger activity against HMGR with inhibition rates of 85% and 90% at the concentration of 50 μM, respectively...
November 10, 2017: Phytochemistry
https://www.readbyqxmd.com/read/29107672/lovastatin-inhibits-visceral-allodynia-and-increased-colonic-permeability-induced-by-lipopolysaccharide-or-repeated-water-avoidance-stress-in-rats
#2
Tsukasa Nozu, Saori Miyagishi, Shima Kumei, Rintaro Nozu, Kaoru Takakusaki, Toshikatsu Okumura
Statins have been reported to block inflammatory somatic pain and have an anti-cytokine property. Lipopolysaccharide (LPS) or repeated water avoidance stress (WAS) induces visceral hypersensitivity and increases gut permeability in rats, which are mediated through proinflammatory cytokine-dependent pathways. Since visceral hypersensitivity with increased gut permeability plays a crucial role in the pathophysiology of irritable bowel syndrome (IBS), these above animal models are considered to simulate IBS. We hypothesized that lovastatin improves symptoms in the patients with IBS by attenuating these visceral changes...
October 28, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29097328/lovastatin-suppresses-hyperexcitability-and-seizure-in-angelman-syndrome-model
#3
Leeyup Chung, Alexandra L Bey, Aaron J Towers, Xinyu Cao, Il Hwan Kim, Yong-Hui Jiang
Epilepsy is prevalent and often medically intractable in Angelman syndrome (AS). AS mouse model (Ube3a(m-/p+)) shows reduced excitatory neurotransmission but lower seizure threshold. The neural mechanism linking the synaptic dysfunction to the seizure remains elusive. We show that the local circuits of Ube3a(m-/p+)in vitro are hyperexcitable and display a unique epileptiform activity, a phenomenon that is reminiscent of the finding in fragile X syndrome (FXS) mouse model. Similar to the FXS model, lovastatin suppressed the epileptiform activity and audiogenic seizures in Ube3a(m-/p+)...
October 31, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29092018/the-function-of-hdl-and-ldl-in-the-maintenance-of-mouse-ovarian-steroid-balance
#4
Xin-Lian Chang, Lisheng Liu, Naiqiang Wang, Zi-Jiang Chen, Cong Zhang
The membrane proteins, low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SR-BI, gene name Scarb1), are lipoprotein receptors that play central roles in lipoprotein metabolism. Cholesterol bound in high-density lipoprotein (HDL) and LDL is transported into cells mainly by SR-BI and LDLR. The relative contribution of LDL and HDL to the steroidogenic cholesterol pool varies among species and may vary among tissues within one species. To investigate which of these pathways is more important in the supply of cholesterol in mouse ovary, we utilized immunohistochemistry, western blotting, RNAi and RT-PCR as well as Ldlr-/- mice to explore the uptake of HDL and LDL in the ovary...
October 30, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29069775/drug-repositioning-of-mevalonate-pathway-inhibitors-as-antitumor-agents-for-ovarian-cancer
#5
Yusuke Kobayashi, Hiroyasu Kashima, Yohan Suryo Rahmanto, Kouji Banno, Yu Yu, Yusuke Matoba, Keiko Watanabe, Moito Iijima, Takashi Takeda, Haruko Kunitomi, Miho Iida, Masataka Adachi, Kanako Nakamura, Kosuke Tsuji, Kenta Masuda, Hiroyuki Nomura, Eiichiro Tominaga, Daisuke Aoki
Drug repositioning is an alternative strategy redirecting existing drugs for new disease. We have previously reported an antitumor effect of statins, antidyslipidemic drugs, on ovarian cancer in vitro and in vivo. In this study, we investigated the antitumor effects of other mevalonate pathway inhibitors and the mechanism of the antitumor effect from a metabolic perspective. The effects of inhibitors of the mevalonate pathway on tumor cell growth were evaluated in vitro. Bisphosphonates that inhibit this pathway are commonly used as antiosteoporotic drugs, and antitumor effects of the bisphosphonate were examined in vitro and in vivo...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29067253/evidence-based-review-of-statin-use-in-patients-with-hiv-on-antiretroviral-therapy
#6
REVIEW
Daniel B Chastain, Kayla R Stover, Daniel M Riche
INTRODUCTION: As a result of improved safe and effective therapeutic options for human immunodeficiency virus (HIV), life expectancy of those living with HIV is increasing leading to new challenges (e.g., management of chronic diseases). Some chronic diseases (e.g., cardiovascular disease [CVD]), are up to two times more prevalent in patients with HIV. Statins are a mainstay of therapy for prevention of CVD; but, clinicians should be aware that not all statins are appropriate for use in the HIV population, especially those receiving antiretroviral therapy (ART)...
June 2017: Journal of Clinical & Translational Endocrinology
https://www.readbyqxmd.com/read/29018905/cyp109e1-is-a-novel-versatile-statin-and-terpene-oxidase-from-bacillus-megaterium
#7
Natalia Putkaradze, Martin Litzenburger, Ammar Abdulmughni, Mohammed Milhim, Elisa Brill, Frank Hannemann, Rita Bernhardt
CYP109E1 is a cytochrome P450 monooxygenase from Bacillus megaterium with a hydroxylation activity for testosterone and vitamin D3. This study reports the screening of a focused library of statins, terpene-derived and steroidal compounds to explore the substrate spectrum of this enzyme. Catalytic activity of CYP109E1 towards the statin drug-precursor compactin and the prodrugs lovastatin and simvastatin as well as biotechnologically relevant terpene compounds including ionones, nootkatone, isolongifolen-9-one, damascones, and β-damascenone was found in vitro...
October 11, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28990114/clinical-guidance-for-managing-statin-and-antimicrobial-drug-drug-interactions
#8
REVIEW
Leigh Anne Hylton Gravatt, Rachel W Flurie, Estela Lajthia, Dave L Dixon
PURPOSE OF REVIEW: This review discusses potential drug-drug interactions between statins and antimicrobials and provides clinician's guidance on how to manage these interactions. RECENT FINDINGS: In addition to statin utilization increasing in recent years, there is greater emphasis on using moderate to high-intensity statin doses. Statin-related adverse effects are often dose-dependent; therefore, patients may be at increased risk. Antimicrobial use has also increased in recent years, and various efforts have been implemented to ensure appropriate use of antimicrobials...
October 9, 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28989013/development-of-a-modified-release-formulation-of-lovastatin-targeted-to-intestinal-methanogens-implicated-in-irritable-bowel-syndrome-with-constipation
#9
Steven Hubert, Alan Chadwick, Vince Wacher, Olivia Coughlin, John Kokai-Kun, Andrew Bristol
There is growing evidence that methane production, predominantly by Methanobrevibacter smithii, in the intestines is a cause of constipation, pain, and bloating in irritable bowel syndrome with constipation (IBS-C). M smithii resides primarily in the large intestine but can also colonize the small intestine. In vitro studies found that the prodrug lactone form of lovastatin, found in cholesterol-lowering drugs, inhibited methane production in stool samples from patients with IBS-C. However, the cholesterol-lowering lovastatin β-hydroxyacid was ineffective at inhibiting methane production in this system...
October 6, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28987600/lipid-lowering-agents-of-natural-origin-an-account-of-some-promising-chemotypes
#10
REVIEW
Suriya P Singh, Koneni V Sashidhara
The role of natural products in the drug development and discovery has been phenomenal. There has been an enormous interest in exploring all possible natural sources to identify structures exhibiting pronounced hypolipidemic activity albeit with no toxicity. The present review describes the profile of some interesting naturally occurring compounds and their derivatives as potential hypolipidemic agents. Some of the interesting natural chemotypes that can control the increased levels of plasma lipids and discussed in this review are compactin, lovastatin, gugglesterone, berberine, lupeol, phytol, polyprenol, aegeline, 4-hydroxyisoleucine, α-asarone, resveratrol, esculeoside A, swertiamarin, rutin, saucerneol B, curcumin and a clerodane diterpene...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28971147/statins-decrease-vascular-epithelial-growth-factor-expression-via-down-regulation-of-receptor-for-advanced-glycation-end-products
#11
Hiroki Tsujinaka, Asako Itaya-Hironaka, Akiyo Yamauchi, Sumiyo Sakuramoto-Tsuchida, Ryogo Shobatake, Mai Makino, Naonori Masuda, Hiromasa Hirai, Shin Takasawa, Nahoko Ogata
AIMS: Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, possess pleiotropic effects that have been extended to modulation of various cellular behaviors. This study aimed to examine whether statins modulate vascular endothelial growth factor A (VEGF-A) expression in human retinal pigment epithelium (RPE) cells. MAIN METHODS: Human RPE cells (h1RPE7), damaged by hydroquinone (HQ) + advanced glycation endproducts (AGE) in an in vitro AMD model, were treated with atorvastatin or lovastatin for 24 h...
September 2017: Heliyon
https://www.readbyqxmd.com/read/28968593/gsk3%C3%AE-%C3%AE-a-novel-therapeutic-target-for-neuroendocrine-tumors
#12
Elke Tatjana Aristizabal Prada, Carla Weis, Michael Orth, Michael Lauseker, Gerald Spoettl, Julian Maurer, Ashley Grossman, Christoph Josef Auernhammer, Svenja Nölting, Patricia Grabowski
<br>Introduction: GSK3α/β is a serine/threonine-kinase that plays a critical role in cancer. AIM(S): In this study, we evaluated the effects of the specific GSK3α/β inhibitor AR-A014418 in vitro to gain novel insights into GSK3α/β signaling in NETs. MATERIALS AND METHODS: Human NET cell lines (BON1, QGP1, H727 and GOT1) were treated with different concentrations of AR-A014418 alone and in combination with lovastatin, everolimus, 5-fluorouracil (5-FU) and γ-irradiation...
October 2, 2017: Neuroendocrinology
https://www.readbyqxmd.com/read/28962550/a-transcriptome-based-protein-network-that-identifies-new-therapeutic-targets-in-colorectal-cancer
#13
Stéphanie Durand, Killian Trillet, Arnaud Uguen, Aude Saint-Pierre, Catherine Le Jossic-Corcos, Laurent Corcos
BACKGROUND: Colon cancer occurrence is increasing worldwide, making it the third most frequent cancer. Although many therapeutic options are available and quite efficient at the early stages, survival is strongly decreased when the disease has spread to other organs. The identification of molecular markers of colon cancer is likely to help understanding its course and, eventually, to uncover novel genes to be targeted by drugs. In this study, we compared gene expression in a set of 95 human colon cancer samples to that in 19 normal colon mucosae, focusing on 401 genes from 5 selected pathways (Apoptosis, Cancer, Cholesterol metabolism and lipoprotein signaling, Drug metabolism, Wnt/beta-catenin)...
September 30, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28944737/alginate-gelatin-formulation-to-modify-lovastatin-release-profile-from-red-yeast-rice-for-hypercholesterolemia-therapy
#14
Gemma Leone, Marco Consumi, Simone Pepi, Stefania Lamponi, Claudia Bonechi, Gabriella Tamasi, Alessandro Donati, Claudio Rossi, Agnese Magnani
AIM: The preparation of a delivery system able to guarantee a delayed release of lovastatin from red yeast rice (RYR) is mandatory to counteract cholesterol biosynthesis effectively. MATERIALS & METHODS: Polymeric formulations were prepared mixing alginate and gelatin, in different ratios, with RYR. The effect of different composition on stiffness, viscosity, swelling behavior and mesostructure of matrices was analyzed. RESULTS: Formulations obtained combining polymers in comparable amount (i...
October 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28919704/secondary-prevention-of-major-cerebrovascular-events-with-seven-different-statins-a-multi-treatment-meta-analysis
#15
Ping Zhong, Danhong Wu, Xiaofei Ye, Ying Wu, Tuming Li, Shuwen Tong, Xueyuan Liu
BACKGROUND: Statins have been recommended for the use in atherosclerotic cardiovascular diseases, but different statins have distinct pharmacological characteristics. This multi-treatment meta-analysis aimed to evaluate the efficacy of seven statins in the secondary prevention of major cerebrovascular events (CVEs). METHODS AND ANALYSES: The PubMed, Embase, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials were searched to identify studies published between January 1, 2011, and June 30, 2016...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28918367/25-hydroxycholesterol-and-inflammation-in-lovastatin-deregulated-mevalonate-pathway
#16
Paola Maura Tricarico, Rossella Gratton, Luca Braga, Fulvio Celsi, Sergio Crovella
Mevalonate pathway deregulation has been observed in several diseases, including Mevalonate kinase deficiency (MKD). MKD is a hereditary auto-inflammatory disorder, due to mutations at mevalonate kinase gene (MVK), encoding mevalonate kinase (MK) enzyme. MVK mutations have been reported as associated with impairment of mevalonate pathway with consequent decrease of protein prenylation levels, defective autophagy and increase of IL-1β secretion, followed by cell death. Since 25-hydroxycholesterol (25-HC), a metabolite of cholesterol, can suppress IL-1β production, thus reducing inflammation, we evaluated the effect of 25-HC in an in vitro model of mevalonate pathway alteration, obtained using Lovastatin...
September 14, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28879627/the-effect-of-viscosity-friction-and-sonication-on-the-morphology-and-metabolite-production-from-aspergillus-terreus-atcc-20542
#17
Muhamad Hafiz Abd Rahim, Hanan Hasan, Hanis H Harith, Ali Abbas
This study investigates the effects of viscosity, friction, and sonication on the morphology and the production of lovastatin, (+)-geodin, and sulochrin by Aspergillus terreus ATCC 20542. Sodium alginate and gelatine were used to protect the fungal pellet from mechanical force by increasing the media viscosity. Sodium alginate stimulated the production of lovastatin by up to 329.0% and sulochrin by 128.7%, with inhibitory effect on (+)-geodin production at all concentrations used. However, the use of gelatine to increase viscosity significantly suppressed lovastatin, (+)-geodin, and sulochrin's production (maximum reduction at day 9 of 42...
September 6, 2017: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/28879444/comparative-study-on-whole-genome-sequences-of-aspergillus-terreus-soil-fungus-and-diaporthe-ampelina-endophytic-fungus-with-reference-to-lovastatin-production
#18
S D Bhargavi, V K Praveen, M Anil Kumar, J Savitha
Lovastatin is a competitive inhibitor of the enzyme hydroxymethyl glutaryl coenzyme A reductase (HMGR) in cholesterol biosynthetic pathway and hence used in the treatment of hyperlipidemia. In a previous study, we report a tropical soil isolate, Aspergillus terreus (KM017963), which produces ample amount of lovastatin than its counterpart that are endophytic in origin. Bioinformatic analysis of whole genome sequence of A. terreus (AH007774.1), a soil isolate revealed the presence of gene cluster (AF141924.1 & AF141925...
September 6, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28847079/gentamicin-degradation-and-changes-in-fungal-diversity-and-physicochemical-properties-during-composting-of-gentamicin-production-residue
#19
Yuanwang Liu, Yao Feng, Dengmiao Cheng, Jianming Xue, Steve A Wakelin, Haiyan Hu, Zhaojun Li
An indoor co-composting of gentamicin fermentation residues (GFR) and lovastatin fermentation residues (LFR) inoculated with gentamicin-degrading Aspergillus terreus FZC3 was conducted to remove gentamicin residues. The results showed that treatment MFZC3, consisting of a 10:1 blend of GFR and LFR (w/w), had the longest thermophilic phase (7days), quickest gentamicin degradation (t½=4.4days), and relatively higher gentamicin degradation percentage (96.7%) at the end of composting. Addition of Aspergillus terreus FZC3 affected fungal diversity of the compost and improved the removal of gentamicin during composting of the 15:1 GFR:LFR blend...
November 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28829786/tramesan-a-novel-polysaccharide-from-trametes-versicolor-structural-characterization-and-biological-effects
#20
Marzia Scarpari, Massimo Reverberi, Alessia Parroni, Valeria Scala, Corrado Fanelli, Chiara Pietricola, Slaven Zjalic, Vittoria Maresca, Agostino Tafuri, Maria R Ricciardi, Roberto Licchetta, Simone Mirabilii, Aris Sveronis, Paola Cescutti, Roberto Rizzo
Mushrooms represent a formidable source of bioactive compounds. Some of these may be considered as biological response modifiers; these include compounds with a specific biological function: antibiotics (e.g. plectasin), immune system stimulator (e,g, lentinan), antitumor agents (e.g. krestin, PSK) and hypolipidemic agents (e.g. lovastatin) inter alia. In this study, we focused on the Chinese medicinal mushroom "yun zhi", Trametes versicolor, traditionally used for (cit.) "replenish essence and qi (vital energy)"...
2017: PloS One
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