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https://www.readbyqxmd.com/read/29670038/taiwanese-green-propolis-ethanol-extract-delays-the-progression-of-type-2-diabetes-mellitus-in-rats-treated-with-streptozotocin-high-fat-diet
#1
Li-Han Chen, Yi-Wen Chien, Mei-Ling Chang, Chia-Chung Hou, Ching-Hung Chan, Hung-Wei Tang, Hui-Yu Huang
Taiwanese green propolis ethanol extract (TGPE) is produced only in Taiwan and has a different composition from other types of propolis. TGPE is known for its anti-inflammation, anti-oxidation, and anti-microbial properties, but the effects and mechanisms of TGPE in the modulation of diabetes are unclear. In this study, we investigated the effects of TGPE on type 2 diabetes mellitus (T2DM) in a streptozotocin/high-fat-diet (STZ/HFD)-induced T2DM rat model. The results revealed that TGPE delayed the development and progression of T2DM and reduced the severity of β-cell failure...
April 18, 2018: Nutrients
https://www.readbyqxmd.com/read/29660435/yangonin-protects-against-cholestasis-and-hepatotoxity-via-activation-of-farnesoid-x-receptor-in-vivo-and-in-vitro
#2
Xiaoguang Gao, Ting Fu, Changyuan Wang, Chenqing Ning, Kexin Liu, Zhihao Liu, Huijun Sun, Xiaodong Ma, Xiaokui Huo, Xiaobo Yang, Ming Zou, Qiang Meng
Cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Recently obeticholic acid (OCA) which is a farnesoid X receptor (FXR) agonist was approved by FDA to treat cholestatic liver diseases, which provided us a newly therapeutic strategy against cholestasis. The purpose of the current study is to screen novel FXR agonists and verify the anti-cholestasis effect of yangonin in vivo and in vitro. The computational strategy of two-dimensional virtual screening was used to search for new FXR agonists, and dual-luciferase reporter gene assay was used to further demonstrate FXR activation by yangonin...
April 13, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29622007/synergistic-effect-of-phytochemicals-on-cholesterol-metabolism-and-lipid-accumulation-in-hepg2-cells
#3
Ennian Leng, Yuan Xiao, Zhentao Mo, Yiqi Li, Yueyue Zhang, Xiaosi Deng, Min Zhou, Chaochao Zhou, Zengxuan He, Jingyi He, Lu Xiao, Junming Li, Wenna Li
BACKGROUND: Crocin (CRO), chlorogenic acid (CGA), geniposide (GEN), and quercetin (QUE) are all natural compounds with anti-obesity properties, in particular, hypolipidemic effects, which have been widely used for the treatment of obesity-related metabolic diseases. However, it is not yet known whether these compounds interact synergistically. Here, we investigated the effects and molecular mechanisms of CRO, CGA, GEN, QUE, and a combination of all four compounds (CCGQ), on lipid accumulation in human hepatoma (HepG2 cells)...
April 5, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29615519/fgf21-acts-as-a-negative-regulator-of-bile-acid-synthesis
#4
Michelle M Chen, Clarence Hale, Shanaka Stanislaus, Jing Xu, Murielle M Véniant
Fibroblast growth factor 21 (FGF21) is a potent regulator of glucose and lipid homeostasis in vivo ; its most closely related subfamily member, FGF19, is known to be a critical negative regulator of bile acid synthesis. To delineate whether FGF21 also plays a functional role in bile acid metabolism, we evaluated the effects of short- and long-term exposure to native FGF21 and long-acting FGF21 analogs on hepatic signal transduction, gene expression and enterohepatic bile acid levels in primary hepatocytes and in rodent and monkey models...
May 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29592890/a-novel-zebrafish-intestinal-tumor-model-reveals-a-role-for-cyp7a1-dependent-tumor-liver-crosstalk-in-tumor-s-adverse-effects-on-host
#5
Sora Enya, Koichi Kawakami, Yutaka Suzuki, Shinpei Kawaoka
The nature of host organs and genes that underlie tumor-induced physiological disruption on host remains ill-defined. Here, we establish a novel zebrafish intestinal tumor model that is suitable for addressing this issue, and find that hepatic cyp7a1 , the rate-limiting factor for synthesizing bile acids, in the case of zebrafish bile alcohol (BA), is such a host gene. Inducing kras G12D by Gal4 specifically expressed in the posterior intestine resulted in formation of intestinal tumor. The local intestinal tumor caused systemic detrimental effects on host including liver inflammation, hepatomegaly, growth defects, and organismal death...
March 28, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29529257/genetic-variants-in-cyp7a1-and-risk-of-myocardial-infarction-and-symptomatic-gallstone-disease
#6
Faiza Qayyum, Bo K Lauridsen, Ruth Frikke-Schmidt, Klaus F Kofoed, Børge G Nordestgaard, Anne Tybjærg-Hansen
Aims: Myocardial infarction (MI) and gallstone disease (GSD) are intrinsically linked via cholesterol metabolism. We tested the hypothesis that genetic variants in the gene encoding cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver, are associated with risk of MI and GSD in the general population. Methods and results: We performed tests of association between lipid levels and eight rare non-synonymous mutations and two common variants, rs2081687 and rs3808607, in CYP7A1 in 100 149 individuals from the general population...
February 23, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29512687/transcriptomic-and-proteomic-analysis-of-potential-therapeutic-target-genes-in-the-liver-of-metformin%C3%A2-treated-sprague%C3%A2-dawley-rats-with-type-2-diabetes-mellitus
#7
Yitao Chen, Yangsheng Wu, Yuanxiao Yang, Zhiwei Xu, Junfeng Tong, Zheming Li, Xiaojie Zhou, Changyu Li
The main actions of metformin are as follows: To reduce hyperglycemia via the suppression of gluconeogenesis, improve glucose uptake and insulin sensitivity, and stimulate activation of adenosine monophosphate‑activated protein kinase during the treatment of diabetes mellitus. It is well known that metformin acts via complex mechanisms, including multitarget and multipathway mechanisms; however, the multitargeted antidiabetic genes of metformin remain obscure. The present study aimed to perform transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformin‑treated Sprague‑Dawley rats with type 2 diabetes mellitus...
March 6, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29499309/relationship-between-the-hippocampal-expression-of-selected-cytochrome-p450-isoforms-and-the-animal-performance-in-the-hippocampus-dependent-learning-task
#8
Sena Gjota-Ergin, Çiğdem Gökçek-Saraç, Orhan Adalı, Ewa Jakubowska-Doğru
Despite very extensive studies on the molecular mechanisms of memory formation, relatively little is known about the molecular correlates of individual variation in the learning skills within a random population of young normal subjects. The role of cytochrome P450 (CYP) enzymes in the brain also remains poorly understood. On the other hand, these enzymes are known to be related to the metabolism of substances important for neural functions including steroids, fatty acids, and retinoic acid. In the present study, we examined the potential correlation between the animals' performance in a place learning task and the levels of selected CYP isoforms (CYP2E1, CYP2D1 and CYP7A1) in the rat hippocampus...
February 27, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29498526/targeted-metabolomics-reveals-a-protective-role-for-basal-ppar%C3%AE-in-cholestasis-induced-by-alpha-naphthylisothiocyanate
#9
Manyun Dai, Huiying Hua, Hante Lin, Gangming Xu, Xiaowei Hu, Fei Li, Frank J Gonzalez, Aiming Liu, Julin Yang
Alpha-naphthylisothiocyanate (ANIT) is an experimental agent used to induce intrahepatic cholestasis. The Ppara-null mouse line is widely employed to explore the physiological and pathological roles of PPARα. However, little is known about how PPARα influences the hepatotoxicity of ANIT. In the present study, wild-type and Ppara-null mice were orally treated with ANIT to induce cholestasis. The serum metabolome of wild-type mice segregated from that of the Ppara-null mice, driven by changes of bile acid (BA) metabolites...
March 2, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29491146/mice-lacking-arv1-have-reduced-signs-of-metabolic-syndrome-and-non-alcoholic-fatty-liver-disease
#10
Christina Gallo-Ebert, Jamie Francisco, Hsing-Yin Liu, Riley Draper, Kinnari Modi, Michael D Hayward, Beverly K Jones, Olesia Buiakova, Virginia McDonough, Joseph T Nickels
MetS syndrome (MetS) is a term used to characterize individuals having at least three of the following diseases: obesity, dyslipidemia, hyperglycemia, insulin resistance, hypertension, and non-alcoholic fatty liver disease (NAFLD).  It is widespread and the number of individuals with MetS is increasing.  However, the events leading to the manifestation of MetS are not well understood.  Here, we show that loss of mARV1 in mice results in resistance to acquiring diseases associated with MetS.   Arv1-/- animals fed a high fat diet were resistant to diet-induced obesity, had lower blood cholesterol and triglycerides levels, and retained glucose tolerance and insulin sensitivity...
February 28, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29488238/potencies-of-vitamin-d-analogs-1%C3%AE-hydroxyvitamin-d-3-1%C3%AE-hydroxyvitamin-d-2-and-25-hydroxyvitamin-d-3-in-lowering-cholesterol-in-hypercholesterolemic-mice-in-vivo
#11
Holly P Quach, Tamara Dzekic, Paola Bukuroshi, K Sandy Pang
Vitamin D3 and the synthetic vitamin D analogs, 1α-hydroxyvitamin D3 [1α(OH)D3 ] and 1α-hydroxyvitamin D2 [1α(OH)D2 ], and 25-hydroxyvitamin D3 [25(OH)D3 ] were appraised for their vitamin D receptor (VDR) associated-potencies as cholesterol lowering agents in mice in vivo. These precursors require activation in vivo: 1α(OH)D3 and 1α(OH)D2 are activated by liver Cyp2r1 and Cyp27a1 to active VDR ligands, 1α,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] and 1α,25-dihydroxyvitamin D2 [1,25(OH)2 D2 ], respectively...
February 27, 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29458450/transcriptomic-and-metabolomic-responses-induced-in-the-livers-of-growing-pigs-by-a-short-term-intravenous-infusion-of-sodium-butyrate
#12
E Ren, X Chen, S Yu, J Xu, Y Su, W Zhu
Previous studies showed that butyrate played benefit roles in the health and metabolism of animals. However, little information on the effects of butyrate on the metabolism of piglets at the extraintestinal level is available. The present study investigated transcriptomic and metabolomic responses in the livers of pigs to evaluate the effects of intravenous sodium butyrate (SB) on the body's metabolism at the extraintestinal level. A total of 12 Duroc×Landrace×Large White growing barrows (60 days of age) fitted with jugular vein cannula were randomly allocated to either the SB group or the control (CO) group...
February 20, 2018: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/29452137/aryl-hydrocarbon-receptor-ahr-mediated-short-term-effects-of-2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-on-bile-acid-homeostasis-in-wild-type-and-ahr-null-mice
#13
Iván L Csanaky, Andrew J Lickteig, Curtis D Klaassen
The effects of the most potent aryl hydrocarbon receptor (AhR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on bile acid (BA) homeostasis was examined in male and female wild-type and AhR-null mice shortly after 4-day exposure, rather than at a later time when secondary non-AhR dependent effects are more likely to occur. TCDD had similar effects on BA homeostasis in male and female mice. TCDD decreased the concentration of total-(Σ) BAs in liver by approximately 50% (all major BA categories except for the non-6,12-OH BAs), without decreasing the expression of the rate limiting BA synthetic enzyme (Cyp7a1) or altering the major BA regulatory pathways (FXR) in liver and intestine...
February 13, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29438852/transcriptome-analysis-to-assess-the-cholestatic-hepatotoxicity-induced-by-polygoni-multiflori-radix-up-regulation-of-key-enzymes-of-cholesterol-and-bile-acid-biosynthesis
#14
Li-Long Jiang, Dong-Sheng Zhao, Ya-Xi Fan, Qiong Yu, Yi-Sheng Lai, Ping Li, Hui-Jun Li
Polygoni Multiflori Radix (PMR) has been commonly used as a tonic in China for centuries. However, PMR-associated hepatotoxicity is becoming a safety issue. Cholestasis often occurs in PMR-induced hepatotoxicity in clinical medicine, but the exact mechanism is not completely understood. An RNA-Seq method was employed, in the present study, to explore the molecular mechanism of cholestatic liver injury induced by PMR, characterized by the hepatic transcriptional response in rats exposed to 1 and 20 g/kg PMR for 90 days...
February 10, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29432567/bile-acid-sequestration-by-cholestyramine-mitigates-fgfr4-inhibition-induced-alt-elevation
#15
Heiko S Schadt, Armin Wolf, Joerg Andreas Mahl, Kuno Wuersch, Philippe Couttet, Marianne Schwald, Audrey Fischer, Mathilde Lienard, Corinne Emotte, Chi-Hse Teng, Elizabeth Skuba, Terrilyn A Richardson, Luigi Manenti, Andreas Weiss, Diana Graus Porta, Robin A Fairhurst, Gerd A Kullak-Ublick, Salah-Dine Chibout, Francois Pognan, William Kluwe, Jacqueline Kinyamu-Akunda
The FGF19-FGFR4-βKlotho (KLB) pathway plays an important role in the regulation of bile acid (BA) homeostasis. Aberrant activation of this pathway has been described in the development and progression of a subset of liver cancers including hepatocellular carcinoma (HCC), establishing FGFR4 as an attractive therapeutic target for such solid tumors. FGF401 is a highly selective FGFR4 kinase inhibitor being developed for HCC, currently in Phase I/II clinical studies. In preclinical studies in mice and dogs, oral administration of FGF401 led to induction of Cyp7a1, elevation of its peripheral marker 7alpha-hydroxy-4-cholesten-3-one (C4), increased BA pool size, decreased serum cholesterol and diarrhea in dogs...
February 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29427579/protective-effects-of-yangonin-from-an-edible-botanical-kava-against-lithocholic-acid-induced-cholestasis-and-hepatotoxicity
#16
Yulong Kong, Xiaoguang Gao, Changyuan Wang, Chenqing Ning, Kexin Liu, Zhihao Liu, Huijun Sun, Xiaodong Ma, Pengyuan Sun, Qiang Meng
Accumulation of toxic bile acids in liver could cause cholestasis and liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of yangonin, a product isolated from an edible botanical Kava against lithocholic acid (LCA)-induced cholestasis, and further to elucidate the involvement of farnesoid X receptor (FXR) in the anticholestatic effect using in vivo and in vitro experiments. The cholestatic liver injury model was established by intraperitoneal injections of LCA in C57BL/6 mice...
February 7, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29425660/cranberry-anthocyanin-as-an-herbal-medicine-lowers-plasma-cholesterol-by-increasing-excretion-of-fecal-sterols
#17
Lijun Wang, Hanyue Zhu, Yimin Zhao, Rui Jiao, Lin Lei, Jingnan Chen, Xiaobo Wang, Zhengnan Zhang, Yu Huang, Tiejie Wang, Zhen-Yu Chen
BACKGROUND: Interest in using herbal medicines to treat the hypercholesterolemia is increasing. Cranberry extract could decrease plasma cholesterol, however, the active ingredients and the underlying mechanisms remain largely unknown. HYPOTHESIS: The present study was to test the hypothesis that cranberry anthocyanins (CrA) were at least one of the active ingredients responsible for the cholesterol-lowering activity of cranberry fruits via a mechanism of increasing fecal sterol excretion...
January 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29409992/the-expression-profiling-and-ontology-analysis-of-non-coding-rnas-in-dexamethasone-induced-steatosis-in-hepatoma-cell
#18
Fengqiong Liu, Ruijie Gong, Xiaofei Lv, Huangyuan Li
Increasing amounts of evidence have indicated that non-coding RNAs (ncRNAs) have important regulatory potential in various biological processes. However, the contribution of ncRNAs, especially long non-coding RNAs (lncRNAs) to drug induced steatosis remain largely unknown. The aim of this study is to investigate miRNA, lncRNA and mRNA expression profiles and their potential roles in the process of drug induced steatosis. Microarray expression profiles of miRNAs, lncRNAs and mRNAs were determined in dexamethasone treated HepG2 cell as well as control cell...
January 31, 2018: Gene
https://www.readbyqxmd.com/read/29404516/deficiency-of-cholesterol-7%C3%AE-hydroxylase-in-bile-acid-synthesis-exacerbates-alcohol-induced-liver-injury-in-mice
#19
Ajay C Donepudi, Jessica M Ferrell, Shannon Boehme, Hueng-Sik Choi, John Y L Chiang
Alcoholic fatty liver disease (AFLD) is a major risk factor for cirrhosis-associated liver diseases. Studies demonstrate that alcohol increases serum bile acids in humans and rodents. AFLD has been linked to cholestasis, although the physiologic relevance of increased bile acids in AFLD and the underlying mechanism of increasing the bile acid pool by alcohol feeding are still unclear. In this study, we used mouse models either deficient of or overexpressing cholesterol 7α-hydroxylase (Cyp7a1), the rate-limiting and key regulatory enzyme in bile acid synthesis, to study the effect of alcohol drinking in liver metabolism and inflammation...
January 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29382564/diabetic-cognitive-dysfunction-is-associated-with-increased-bile-acids-in-liver-and-activation-of-bile-acid-signaling-in-intestine
#20
Xue Wang, Fangyu Wang, Yidan Zhang, Hui Xiong, Yanjun Zhang, Pengwei Zhuang, Youcai Zhang
Impaired regulation of bile acid (BA) homeostasis has been suggested to be associated with adverse metabolic consequences. However, whether BA homeostasis is altered in diabetes-induced cognitive dysfunction (DCD) remains unknown. In the present study, mice were divided into four groups, namely normal control (NC) group, high-fat diet (HFD) group, diabetes without cognitive dysfunction (unDCD) group, and DCD group. Compared to HFD mice, the concentration of total BAs in liver was higher in unDCD and DCD mice, due to increased intestinal BA absorption...
January 27, 2018: Toxicology Letters
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