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Su Chui Len Candyrine, Mazrul Fahmi Mahadzir, Sani Garba, Mohammad Faseleh Jahromi, Mahdi Ebrahimi, Yong Meng Goh, Anjas Asmara Samsudin, Awis Qurni Sazili, Wei Li Chen, Siva Ganesh, Ron Ronimus, Stefan Muetzel, Juan Boo Liang
Twenty male Saanen goats were randomly assigned to four levels of lovastatin supplementation and used to determine the optimal dosage and sustainability of naturally produced lovastatin from fermentation of palm kernel cake (PKC) with Aspergillus terreus on enteric methane (CH4) mitigation. The effects on ruminal microbiota, rumen fermentation, feed digestibility and health of animal were determined over three measuring periods (4-, 8- and 12-weeks) and the accumulation of lovastatin in tissues was determined at the end of the experiment...
2018: PloS One
Claudia Villani, Giuseppina Sacchetti, Renzo Bagnati, Alice Passoni, Federica Fusco, Mirjana Carli, Roberto William Invernizzi
No abstract text is available yet for this article.
June 29, 2018: ELife
Chintan V Dave, Almut G Winterstein, Haesuk Park, Robert L Cook, Abraham G Hartzema
OBJECTIVES: To evaluate the risk of new-onset depression in a cohort of US adult patients initiating lipophilic statin therapy compared to hydrophilic statin therapy. DESIGN: Retrospective cohort study. SETTING: Large US commercial claims database PARTICIPANTS: 1:1 propensity score matched cohort of lipophilic (atorvastatin, lovastatin and simvastatin) and hydrophilic (pravastatin and rosuvastatin) statin initiators between January 2009 to June 2015...
June 15, 2018: Journal of Affective Disorders
Wen-Bin Zhong, Yuan-Chin Tsai, Li-Han Chin, Jen-Ho Tseng, Li-Wen Tang, Steve Horng, Yu-Ching Fan, Sung-Po Hsu
Anaplastic thyroid cancer (ATC) is a malignant subtype of thyroid cancers and its mechanism of development remains inconclusive. Importantly, there is no effective strategy for treatment since ATC is not responsive to conventional therapies, including radioactive iodine therapy and thyroid-stimulating hormone suppression. Here, we report that a combinational approach consisting of drugs designed for targeting lipid metabolism, lovastatin (an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, HMGCR) and troglitazone (an agonist of peroxisome proliferator-activated receptor gamma, PPARγ), exhibits anti-proliferation in cell culture systems and leads to tumor regression in a mouse xenograft model...
June 22, 2018: International Journal of Molecular Sciences
Suthipong Chujan, Tawit Suriyo, Teerapat Ungtrakul, Yotsawat Pomyen, Jutamaad Satayavivad
Cholangiocarcinoma (CCA) remains to be a major health problem in several Asian countries including Thailand. The molecular mechanism of CCA is poorly understood. Early diagnosis is difficult, and at present, no effective therapeutic drug is available. The present study aimed to identify the molecular mechanism of CCA by gene expression profile analysis and to search for current approved drugs which may interact with the upregulated genes in CCA. Gene Expression Omnibus (GEO) was used to analyze the gene expression profiles of CCA patients and normal subjects...
July 2018: Biomedical Reports
Junyu Zhao, Chunmei Xu, Jinming Yao, Changzhen Yu, Lin Liao, Jianjun Dong
BACKGROUND/AIMS: Experimental studies have reported the antineoplastic effects of statins in thyroid carcinoma; however, observational studies suggested that statins might increase the risk of thyroid carcinoma. Therefore, this study evaluated the antineoplastic effects of statins in both in vitro studies and animal models, as well as the epidemiological evidence. METHODS: Databases-PubMed, Cochrane Library, SinoMed, CNKI, Wanfang, and clinical trial registries- were searched...
June 19, 2018: Cellular Physiology and Biochemistry
Dong Feng, Chun Ge, Zhao-Yi Tan, Jian-Guo Sun, Yuan Xie, Lan Yao, Cai-Xia Yan, Ji-Ye Aa, Guang-Ji Wang
Xuezhikang capsule (XZK) is a traditional Chinese medicine that contains lovastatin (Lv) for hyperlipidemia treatment, although it has fewer side effects than Lv. However, the pharmacokinetic mechanisms contributing to its distinct efficacy and low side effects are unclear. Mice were fed a high-fat diet (HFD) for 6 weeks to induce hyperlipidemia. We first conducted the pharmacokinetic studies in HFD mice following oral administration of Lv (10 mg/kg, i.g.) and found that HFD remarkably decreased the active form of Lv (the lovastatin acid, LvA) exposure in the circulation system, especially in the targeting organ liver, with a declined conversion from Lv to LvA, whereas the Lv (responsible for myotoxicity) exposure in muscle markedly increased...
June 19, 2018: Acta Pharmacologica Sinica
Hiromi Shiratori, Carmen Feinweber, Sonja Luckhardt, Nadja Wallner, Gerd Geisslinger, Andreas Weigert, Michael J Parnham
Macrophages undergo activation by pathophysiological stimuli to pro-inflammatory and bactericidal, or wound-healing and anti-inflammatory phenotypes, termed M1 or M2, respectively. Dysregulation of the M1-M2 balance is often associated with inflammatory diseases. Therefore, mechanisms of macrophage polarization may reveal new drug targets. We profiled six compounds with claimed modulatory effects on macrophage polarization using peripheral blood monocyte-derived macrophages. Based on the distinct mRNA or protein expression in macrophages stimulated either with M1 [lipopolysaccharide (LPS) + interferon-γ, IFNγ] or M2 interleukin-4 (IL-4) stimuli, we selected a combination of M1 (IL1β, tumor necrosis factor-α,TNFα, CC chemokine receptor 7, CCR7 and CD80) and M2 (chemokine (C-C motif) ligand 22, CCL22, CD200R and mannose receptor C type 1, MRC1) markers to monitor drug effects on "M1 polarization" or cells "pre-polarized to M1"...
June 18, 2018: European Journal of Pharmacology
Shuzo Urata, Yukiko Uno, Yohei Kurosaki, Jiro Yasuda
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a high mortality rate. Currently, no licensed vaccines or therapeutic agents have been approved for use against SFTSV infection. Here, we report that the cholesterol, fatty acid, and triglyceride synthesis pathways regulated by S1P is involved in SFTSV replication, using CHO-K1 cell line (SRD-12B) that is deficient in site 1 protease (S1P) enzymatic activity, PF-429242, a small compound targeting S1P enzymatic activity, and Fenofibrate and Lovastatin, which inhibit triglyceride and cholesterol synthesis, respectively...
June 12, 2018: Biochemical and Biophysical Research Communications
Yu-Jia Zhai, Bing-Chen Liu, Shi-Peng Wei, Chu-Fang Chou, Ming-Ming Wu, Bin-Lin Song, Valerie A Linck, Li Zou, Shuai Zhang, Xue-Qi Li, Zhi-Ren Zhang, He-Ping Ma
BACKGROUND/AIMS: The epithelial sodium channel (ENaC) in cortical collecting duct (CCD) principal cells plays a critical role in regulating systemic blood pressure. We have previously shown that cholesterol (Cho) in the apical cell membrane regulates ENaC; however, the underlying mechanism remains unclear. METHODS: Patch-clamp technique and confocal microscopy were used to evaluate ENaC activity and density. RESULTS: Here we show that extraction of membrane Cho with methyl-β-cyclodextrin (MβCD) significantly reduced amiloride-sensitive current and ENaC single-channel activity...
May 24, 2018: Cellular Physiology and Biochemistry
Leonardo Di Donna, Lucia Bartella, Anna Napoli, Giovanni Sindona, Fabio Mazzotti
Monacolin K, the active ingredient present in dietary supplement, is a nutraceutical whose health benefits have been widely documented. A fast approach for the assay of lovastatin in both form, lactone and acid, by mass spectrometry is presented. The quantitative assay is carried out by HPLC-MS/MS using the multiple reaction monitoring (MRM) mode and simvastatin and pravastatin as internal standards. The accuracy values ranged from 97 to 101%; the analytical parameters values of LOQ, LOD, recovery and reproducibility, were calculated analyzing fortified samples, confirming the reliability of the proposed approach...
May 16, 2018: Journal of Mass Spectrometry: JMS
Jae H Chang, Xiaolin Zhang, Kirsten Messick, Yi-Chen Chen, Eugene Chen, Jonathan Cheong, Justin Ly
1. Oatp inhibitors have been shown to significantly increase the plasma exposure of statins. However, understanding alterations of liver concentration is also important. While modeling has simulated liver concentration changes, availability of experimental data is limited, especially when concerning drug-drug interactions (DDI). The objective of this work was to determine blood and liver concentrations of fluvastatin, lovastatin and pitavastatin, when blocking uptake transporters. 2. In wild-type mouse, rifampin pre-treatment decreased the unbound liver-to-plasma ratio (Kp,uu ) of fluvastatin by 4...
June 6, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Daniel Fabio Kawano, Marcelo Rodrigues de Carvalho, Mauricio Ferreira Marcondes Machado, Adriana Karaoglanovic Carmona, Gilberto Ubida Leite Braga, Ivone Carvalho
BACKGROUND: Fungal secondary metabolites are important sources for the discovery of new pharmaceuticals, as exemplified by penicillin, lovastatin and cyclosporine. Searching for secondary metabolites of the fungi Metarhizium ssp., we previously identified tyrosine betaine as a major constituent. METHODS: Because of the structural similarity with other inhibitors of neprilysin (NEP), an enzyme explored for the treatment of heart failure, we devised the synthesis of tyrosine betaine and three analogues to be subjected to in vitro NEP inhibition assays and to molecular modeling studies...
May 14, 2018: Current Pharmaceutical Design
Yun Yang, Ji Wang, Hongliang He, Wenli Zhang, Yuansheng Zhang, Jianping Liu
PURPOSE: Spherical reconstituted high density lipoprotein (rHDL) can target atherosclerotic lesions by the very low density lipoprotein (VLDL) receptor, which is seldom expressed in liver. By promoting this pathway, the targeting efficiency was hyphothesized to be improved due to avoiding undesired uptake in liver mediated by the scavenger receptor class B type I (SR-BI). In this study, how fatty acid modification in spherical rHDL influenced the VLDL receptor-mediated endocytosis pathway was investigated...
May 7, 2018: Pharmaceutical Research
Hanan Hasan, Muhammad Hafiz Abd Rahim, Leona Campbell, Dee Carter, Ali Abbas, Alejandro Montoya
The present work describes the application of homologous recombination techniques in a wild-type Aspergillus terreus (ATCC 20542) strain to increase the flow of precursors towards the lovastatin biosynthesis pathway. A new strain was generated to overexpress acetyl-CoA carboxylase (ACCase) by replacing the native ACCase promoter with a strong constitutive PadhA promoter from Aspergillus nidulans. Glycerol and a mixture of lactose and glycerol were used independently as the carbon feedstock to determine the degree of response by the A...
September 25, 2018: New Biotechnology
Shinji Yamazaki
A general objective of drug-drug interaction (DDI) studies is to determine whether potential interactions of new molecular entities with concomitantly administered other drugs exist and, if DDIs occur, whether dosage adjustments are required. A typical end point for DDI evaluations is the ratio of area under the plasma concentration-time curve (AUC) of substrate drugs (AUCR), whereas the ratios of maximal plasma concentration (Cmax ) and terminal half-life (t1/2 ) are also important to understand DDI mechanisms (Cmax R and t1/2 R, respectively)...
May 3, 2018: Journal of Clinical Pharmacology
Punya Shrivastava-Ranjan, Mike Flint, Éric Bergeron, Anita K McElroy, Payel Chatterjee, César G Albariño, Stuart T Nichol, Christina F Spiropoulou
Ebola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments. Statins, widely used cholesterol-lowering drugs, have pleiotropic mechanisms of action and were suggested as potential adjunct therapy for Ebola virus disease (EVD) during the 2013-2016 outbreak in West Africa. Here, we evaluated the antiviral effects of statin (lovastatin) on EBOV infection in vitro Statin treatment decreased infectious EBOV production in primary human monocyte-derived macrophages and in the hepatic cell line Huh7...
May 1, 2018: MBio
Yujie Zhou, Hong Yang, Xuedong Zhou, Hongke Luo, Fan Tang, Jin Yang, Gil Alterovitz, Lei Cheng, Biao Ren
The increase of fungal infectious diseases and lack of safe and efficacious antifungal drugs result in the urgent need of new therapeutic strategies. Here, we repurposed the lovastatin (LOV) as a synergistic antifungal potentiator to itraconazole (ITZ) against Candida albicans planktonic cells and biofilms in vitro for the first time. Mutants from ergosterol biosynthesis pathway were employed and key gene expression profiles of ergosterol pathway were also measured. LOV single treatment was unable to inhibit C...
June 2018: Applied Microbiology and Biotechnology
Nkiruka Arinze, Alik Farber, Teviah Sachs, Gregory Patts, Jeffrey Kalish, Angela Kuhnen, George Kasotakis, Jeffrey J Siracuse
OBJECTIVE: Statin use in patients with cerebrovascular disease undergoing carotid endarterectomy (CEA) has been advocated for prevention of stroke and cardiovascular events. However, the effect of statin therapy on long-term outcomes after CEA still needs to be delineated. METHODS: OptumLabs Data Warehouse, a comprehensive, longitudinal, real-world dataset with deidentified lives across claims and clinical information, was used to analyze the rates of stroke, myocardial infarction (MI), and statin use after CEA...
April 20, 2018: Journal of Vascular Surgery
Yuanwang Liu, Yao Feng, Dengmiao Cheng, Jianming Xue, Steven Wakelin, Zhaojun Li
Dynamics in bacterial community composition, along with 13 antibiotic resistance genes (ARGs) and eight mobile genetic elements (MGEs), were assessed during co-composting with gentamicin and lovastatin fermentation residue (GFR and LFR, respectively). Using next generation sequencing, the key bacterial taxa associated with the different stages of composting were identified. Most importantly, Bacillus, belonging to Phylum Firmicutes, was associated with enhanced degradation of gentamicin, decomposition of organic matter (OM) and dissolved organic carbon (DOC), and also extension of the thermophilic phase of the composting cycle...
August 2018: Bioresource Technology
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