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https://www.readbyqxmd.com/read/28327628/corrigendum-pregnane-x-receptor-regulates-pathogen-induced-inflammation-and-host-defense-against-an-intracellular-bacterial-infection-through-toll-like-receptor-4
#1
Zhijuan Qiu, Jorge L Cervantes, Basak B Cicek, Subhajit Mukherjee, Madhukumar Venkatesh, Leigh A Maher, Juan C Salazar, Sridhar Mani, Kamal M Khanna
No abstract text is available yet for this article.
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28320072/constitutive-androstane-receptor-regulates-the-intestinal-mucosal-response-to-injury
#2
Grace M Hudson, Kyle L Flannigan, Sarah L Erickson, Fernando A Vicentini, Alexandra Zamponi, Christina L Hirota, Laurie Alston, Christophe Altier, Subrata Ghosh, Kevin P Rioux, Sridhar Mani, Thomas K Chang, Simon A Hirota
BACKGROUND AND PURPOSE: The pathogenesis of the inflammatory bowel diseases(IBD), composed of Crohn's disease(CD) and ulcerative colitis(UC), involves aberrant interactions between a genetically susceptible individual, their microbiota and environmental factors. Alterations in xenobiotic receptor expression and function are associated with increased risk for IBD. In the current study, we assessed the role of the constitutive androstane receptor(CAR), a xenobiotic receptor closely related to the pregnane X receptor, in the regulation of intestinal mucosal homeostasis...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28318987/a-clinical-evaluation-of-the-pharmacokinetics-and-pharmacodynamics-of-intravenous-alfaxalone-in-cyclodextrin-in-male-and-female-rats-following-a-loading-dose-and-constant-rate-infusion
#3
Kate L White, Stuart Paine, John Harris
OBJECTIVE: To characterise, as a clinical study, the pharmacokinetics and pharmacodynamics and describe the hypnotic effect of the neurosteroid alfaxalone (3α-hydroxy-5 α-pregnane-11, 20-dione) formulated with 2-hydroxypropyl-β-cyclodextrin in male and female rats. STUDY DESIGN: Prospective, experimental laboratory study. ANIMALS: A total of 12 (six male and six female) adult, aged-matched Sprague Dawley rats. METHODS: Surgery and instrumentation was performed under isoflurane anaesthesia in an oxygen/nitrous oxide mixture (1:2) and local anaesthetic infiltration...
February 1, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/28315689/in-silico-prediction-of-hpxr-activators-using-structure-based-pharmacophore-modeling
#4
Nao Torimoto-Katori, Ruili Huang, Harutoshi Kato, Rikiya Ohashi, Menghang Xia
The activation of pregnane X receptor (PXR), a member of the nuclear receptor superfamily, can mediate potential drug-drug interactions by regulating the expression of several drug- mediated enzymes and transporters, resulting in reduced therapeutic efficacy or increased toxicity by producing reactive metabolites. Therefore, in the early stage of drug development, it is important to predict these risks using an in silico approach. We constructed a human PXR (hPXR) pharmacophore model based on known structural information of compounds that activate PXR...
March 15, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28303499/pregnane-x-receptor-not-nuclear-factor-kappa-b-up-regulates-p-glycoprotein-expression-in-the-brain-of-chronic-epileptic-rats-induced-by-kainic-acid
#5
Nian Yu, Yan-Fang Zhang, Kang Zhang, Yong-Fei Cheng, Hai-Yan Ma, Qing Di
Drug-resistance epilepsy (DRE) is attributed to the brain P-glycoprotein (P-gp) overexpression. We previously reported that nuclear factor-kappa B (NF-κB) played a critical role in regulating P-gp expression at the brain of the acute seizure rats. This study was extended further to investigate the interaction effect of NF-κB and pregnane X receptor (PXR) on P-gp expression at the brain of chronic epileptic rats treated with carbamazepine (CBZ). The chronic epileptic models were induced by the micro-injection of kainic acid (KA) into rats' hippocampus...
March 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28300701/novel-immunosuppressive-pregnane-glycosides-from-the-leaves-of-epigynum-auritum
#6
Fei Gao, Yuan Cheng Yao, Sheng-Bao Cai, Tian-Rui Zhao, Xiao-Yan Yang, Jian Fan, Xiao-Nian Li, Jian-Xin Cao, Gui-Guang Cheng
Phytochemical investigation on the leaves of Epigynum auritum led to the isolation of three novel C21 pregnane glycosides, epigynosides, E-G (1-3), together with two known pregnane glycosides, epigynosides A (4) and C (5). Their structures were elucidated based on extensive spectroscopic data (MS, IR, 1D and 2D NMR) analysis, as well as comparison with the reported data. The immunological activities of the new compounds was evaluated against concanavalin A (Con A)-stimulated proliferation of mice splenocyte in vitro...
March 11, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28294615/absolute-configuration-of-periplosides-c-and-f-and-isolation-of-minor-spiro-orthoester-group-containing-pregnane-type-steroidal-glycosides-from-periploca-sepium-and-their-t-lymphocyte-proliferation-inhibitory-activities
#7
Luo-Yi Wang, Jun-Jun Qin, Zhen-Hua Chen, Yu Zhou, Wei Tang, Jian-Ping Zuo, Wei-Min Zhao
Further phytochemical investigation of the root bark of Periploca sepium afforded nine new spiro-orthoester group-containing pregnane-type glycosides termed periplosides O-V and 3-O-formyl-periploside A. The structures of these glycosides along with the absolute configuration of the unique seven-membered formyl acetal-bridged spiro-orthoester function and the 4,6-dideoxy-3-O-methyl-Δ(3)-2-hexosulosyl moiety were elucidated on the basis of spectroscopic data interpretation and chemical transformation. The absolute configurations of the major compounds periplosides C and F were established by single-crystal X-ray diffraction analysis...
March 15, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28289823/human-pregnane-x-receptor-is-activated-by-dibenzazepine-carbamate-based-inhibitors-of-constitutive-androstane-receptor
#8
Judith Jeske, Björn Windshügel, Wolfgang E Thasler, Matthias Schwab, Oliver Burk
Unintentional activation of xenosensing nuclear receptors pregnane X receptor (PXR) and/or constitutive androstane receptor (CAR) by clinical drug use is known to produce severe side effects in patients, which may be overcome by co-administering antagonists. However, especially antagonizing CAR is hampered by the lack of specific inhibitors, which do not activate PXR. Recently, compounds based on a dibenzazepine carbamate scaffold were identified as potent CAR inhibitors. However, their potential to activate PXR was not thoroughly investigated, even if the lead compound was named "CAR inhibitor not PXR activator 1" (CINPA1)...
March 13, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28288941/differential-activation-of-pregnane-x-receptor-by-carnosic-acid-carnosol-ursolic-acid-and-rosmarinic-acid
#9
Chun Ling Seow, Aik Jiang Lau
Pregnane X receptor (PXR) regulates the expression of many genes, including those involved in drug metabolism and transport, and has been linked to various diseases, including inflammatory bowel disease. In the present study, we determined whether carnosic acid and other chemicals in rosemary extract (carnosol, ursolic acid, and rosmarinic acid) are PXR activators. As assessed in dual-luciferase reporter gene assays, carnosic acid, carnosol, and ursolic acid, but not rosmarinic acid, activated human PXR (hPXR) and mouse PXR (mPXR), whereas carnosol and ursolic acid, but not carnosic acid or rosmarinic acid, activated rat PXR (rPXR)...
March 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28284564/14-15-secopregnane-type-c21-steriosides-from-the-roots-of-cynanchum-stauntonii
#10
Jin-Qian Yu, Ming-Bao Lin, An-Jun Deng, Qi Hou, Jin-Ye Bai, Zhi-Hong Li, Lin Ma, Zhi-Hui Zhang, Shao-Peng Yuan, Ren-Tao Jiang, Hai-Lin Qin
Nine 14,15-secopregnane-type C21-steriosides, stauntosides U, V, V1-V3, W and C1-C3, as well as two known C21-steriosides, were isolated from the roots of Cynanchum stauntonii. Stauntosides U, V and V1-V3 share the same basic structural features of 8α:14α,14:16,15:20,18:20-tetraepoxy-14,15-secopregn-6-ene-3β,5α,9α-triol, with the numbering system following that of C21-pregnanes. The aglycones of stauntosides U, V and V1-V3 are classified into two subcategories, the 5,9-dihydroxy groups and 5α:9α-peroxy bridge, according to the oxidative states of the two hydroxy groups at the C-5 and C-9 positions...
March 8, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28270768/extracts-of-immature-orange-aurantii-fructus-immaturus-and-citrus-unshiu-peel-citri-unshiu-pericarpium-induce-p-glycoprotein-and-cytochrome-p450-3a4-expression-via-upregulation-of-pregnane-x-receptor
#11
Naoto Okada, Aki Murakami, Shiori Urushizaki, Misa Matsuda, Kazuyoshi Kawazoe, Keisuke Ishizawa
P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) are expressed in the intestine and are associated with drug absorption and metabolism. Pregnane X receptor (PXR) is the key molecule that regulates the expression of P-gp and CYP3A4. Given that PXR activity is regulated by a variety of compounds, it is possible that unknown PXR activators exist among known medicines. Kampo is a Japanese traditional medicine composed of various natural compounds. In particular, immature orange [Aurantii fructus immaturus (IO)] and citrus unshiu peel [Citri unshiu pericarpium (CP)] are common ingredients of kampo...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28259787/development-of-a-common-carp-cyprinus-carpio-pregnane-x-receptor-cpxr-transactivation-reporter-assay-and-its-activation-by-azole-fungicides-and-pharmaceutical-chemicals
#12
Anke Lange, Jenna Corcoran, Shinichi Miyagawa, Taisen Iguchi, Matthew J Winter, Charles R Tyler
In mammals, the pregnane X receptor (PXR) is a transcription factor with a key role in regulating expression of several genes involved in drug biotransformation. PXR is present in fish and some genes known to be under its control can be up-regulated by mammalian PXR ligands. Despite this, direct involvement of PXR in drug biotransformation in fish has yet to be established. Here, the full length PXR sequence was cloned from carp (Cyprinus carpio) and used in a luciferase reporter assay to elucidate its role in xenobiotic metabolism in fish...
March 1, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28257661/alisol-b-23-acetate-from-the-rhizomes-of-alisma-orientale-is-a-natural-agonist-of-the-human-pregnane-x-receptor
#13
Yuichiro Kanno, Tomofumi Yatsu, Naoya Yamashita, Shuai Zhao, Wei Li, Miyuki Imai, Manami Kashima, Yoshio Inouye, Kiyomitsu Nemoto, Kazuo Koike
BACKGROUND: Pregnane X receptor (PXR) is a key regulator of the induction of drug metabolizing enzymes. PXR has been studied for its importance in drug-drug or herb-drug interactions, and it is also a molecular target for the treatment of inflammatory and metabolic diseases. PURPOSE: This study aims to determine new natural PXR-ligands from traditional plant medicines. METHODS: The PXR activation activity was measured by a mammalian one hybrid assay of PXR...
March 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28238946/involvement-of-pregnane-x-receptor-in-the-suppression-of-carboxylesterases-by-metformin-in-vivo-and-in-vitro-mediated-by-the-activation-of-ampk-and-jnk-signaling-pathway
#14
Enfang Shan, Zhu Zhu, Shuangcheng He, Dongbao Chu, Dinghao Ge, Yunran Zhan, Wei Liu, Jian Yang, Jing Xiong
Type 2 diabetes mellitus (T2D) is a complex metabolic disorder requiring polypharmacy treatment in clinic, with metformin being widely used antihyperglycemic drug. However, the mechanisms of metformin as a perpetrator inducing potential drug-drug interactions and adverse drug reactions are scarcely known to date. Carboxylesterases (CESs) are major hydrolytic enzymes highly expressed in the liver, including mouse carboxylesterase 1d (Ces1d) and Ces1e. In the present study, experiments are designed to investigate the effects and mechanisms of metformin on Ces1d and Ces1e in vivo and in vitro...
February 24, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28237809/pregnenolone-16%C3%AE-carbonitrile-ameliorates-concanavalin-a-induced-liver-injury-in-mice-independent-of-the-nuclear-receptor-pxr-activation
#15
Susumu Kodama, Takuto Shimura, Hideaki Kuribayashi, Taiki Abe, Kouichi Yoshinari
The pregnane X receptor (PXR) is well-known as a key regulator of drug/xenobiotic clearance. Upon activation by ligand, PXR transcriptionally upregulates the expression of drug-metabolizing enzymes and drug transporters. Recent studies have revealed that PXR also plays a role in regulating immune/inflammatory responses. Specific PXR activators, including synthetic ligands and phytochemicals, have been shown to ameliorate chemically induced colitis in mice. In this study, we investigated an anti-inflammatory effect of pregnenolone 16α-carbonitrile (PCN), a prototypical activator for rodent PXR, in concanavalin A (Con A)-induced liver injury, a model of immune-mediated liver injury, using wild-type and Pxr(-/-) mice...
February 22, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28218408/toxaphene-induced-mouse-liver-tumorigenesis-is-mediated-by-the-constitutive-androstane-receptor
#16
Zemin Wang, Xilin Li, Qiangen Wu, James C Lamb, James E Klaunig
Toxaphene was shown to increase liver tumor incidence in B6C3F1 mice following chronic dietary exposure. Preliminary evidence supported a role for the constitutive androstane receptor (CAR) in the mode of action of toxaphene-induced mouse liver tumors. However, these results could not rule out a role for the pregnane X receptor (PXR) in liver tumor formation. To define further the nuclear receptors involved in this study, we utilized CAR, PXR and PXR/CAR knockout mice (CAR(-/-) , PXR(-/-) and PXR(-/-) /CAR(-/-) ) along with the wild-type C57BL/6...
February 20, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28216505/-effect-of-hypoxia-on-expression-of-multidrug-resistance-protein-2-and-its-regulation-mechanism
#17
Bingfeng Luo, Wenbin Li, Rong Wang, Hui Lu, Tao Yang, Zhengping Jia
Drug efflux transporters plays a key role in pharmacokinetics parameters changes. In recent years, in addition to P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), MRP2 has become an advanced research hotspot. Several signaling pathways andtranscription factors have been reported to be involved in regulation of MRP2 expression in hypoxic microenvironment of tumor, such as peroxisome proliferators-activated receptors (PPARα), nuclear factor κB (NF-κB), pregnane X receptor (PXR), farnesoid X receptor (FXR), constitutive androstane receptor (CAR) and microRNA...
January 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28207286/lc-ms-ms-simultaneous-analysis-of-allopregnanolone-epiallopregnanolone-pregnanolone-dehydroepiandrosterone-and-dehydroepiandrosterone-3-sulfate-in-human-plasma
#18
Luana Lionetto, Fernando De Andrés, Matilde Capi, Martina Curto, Donata Sabato, Maurizio Simmaco, Paola Bossù, Eleonora Sacchinelli, Maria Donata Orfei, Federica Piras, Nerisa Banaj, Gianfranco Spalletta
AIM: Several neuropsychopharmacological properties have been attributed to the 3α-reduced pregnane steroids, allopregnanolone and pregnanolone, as well as to dehydroepiandrosterone sulfate because of their ability to modulate γ-aminobutyric acid (GABAA) receptors in the CNS. In order to understand better their role in several mechanisms in CNS, a new methodology is proposed to monitor these compounds in human plasma. Methodology & results: The analytes were first derivatized with 2-hydrazinopyridine and extracted from plasma using SPE...
March 2017: Bioanalysis
https://www.readbyqxmd.com/read/28199000/overexpression-of-pregnane-x-and-glucocorticoid-receptors-and-the-regulation-of-cytochrome-p450-in-human-epileptic-brain-endothelial-cells
#19
Chaitali Ghosh, Mohammed Hossain, Jesal Solanki, Imad M Najm, Nicola Marchi, Damir Janigro
OBJECTIVE: Recent evidence suggests a metabolic contribution of cytochrome P450 enzymes (CYPs) to the drug-resistant phenotype in human epilepsy. However, the upstream molecular regulators of CYP in the epileptic brain remain understudied. We therefore investigated the expression and function of pregnane xenobiotic (PXR) and glucocorticoid (GR) nuclear receptors in endothelial cells established from post-epilepsy surgery brain samples. METHODS: PXR/GR localization was evaluated by immunohistochemistry in specimens from subjects who underwent temporal lobe resections to relieve drug-resistant seizures...
February 15, 2017: Epilepsia
https://www.readbyqxmd.com/read/28198586/influence-of-a-critical-single-nucleotide-polymorphism-on-nuclear-receptor-pxr-promoter-function
#20
Manjul Rana, Poonam Coshic, Ravinder Goswami, Rakesh K Tyagi
The Pregnane and Xenobiotic Receptor (PXR; NR1I2), is a ligand-modulated transcription factor that belongs to the nuclear receptor superfamily. It is expressed at higher levels primarily in liver and intestine as compared to the levels in several other organs. It is activated by a broad spectrum of xenobiotics and endobiotics. The primary function of PXR is to regulate the expression of drug metabolizing enzymes and transporters and prevent the accumulation of toxic chemicals in the body, thereby maintaining body's homeostasis...
February 15, 2017: Cell Biology International
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