scholarly journals R. verniciflua and E. ulmoides Extract (ILF-RE) Protects against Chronic CCl4-Induced Liver Damage by Enhancing Antioxidation

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 382 ◽  
Author(s):  
Hwa-Young Lee ◽  
Geum-Hwa Lee ◽  
Young Yoon ◽  
Han-Jung Chae
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Liver Damage ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Protective Effects ◽  
Gamma Glutamyl Transpeptidase ◽  
Hepatic Lipid Accumulation ◽  
Lipogenic Genes

This study aimed to characterize the protective effects of R. verniciflua extract (ILF-R) and E. ulmoides extract (ILF-E), the combination called ILF-RE, against chronic CCl4-induced liver oxidative injury in rats, as well as to investigate the mechanism underlying hepatoprotection by ILF-RE against CCl4-induced hepatic dysfunction. Chronic hepatic stress was induced via intraperitoneal (IP) administration of a mixture of CCl4 (0.2 mL/100 g body weight) and olive oil [1:1(v/v)] twice a week for 4 weeks to rats. ILF-RE was administered orally at 40, 80, and 120 mg/kg to rats for 4 weeks. Alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), and lipid peroxidation assays were performed, and total triglyceride, cholesterol, and LDL-cholesterol levels were quantified. Furthermore, ER stress and lipogenesis-related gene expression including sterol regulatory element-binding transcription factor 1 (SREBP-1), fatty acid synthase (FAS), and P-AMPK were assessed. ILF-RE markedly protected against liver damage by inhibiting oxidative stress and increasing antioxidant enzyme activity including glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. Furthermore, hepatic dyslipidemia was regulated after ILF-RE administration. Moreover, hepatic lipid accumulation and its associated lipogenic genes, including those encoding SREBP-1 and FAS, were regulated after ILF-RE administration. This was accompanied by regulation of ER stress response signaling, suggesting a mechanism underlying ILF-RE-mediated hepatoprotection against lipid accumulation. The present results indicate that ILF-RE exerts hepatoprotective effects against chronic CCl4-induced dysfunction by suppressing hepatic oxidative stress and lipogenesis, suggesting that ILF-RE is a potential preventive/therapeutic natural product in treating hepatoxicity and associated dysfunction.

scholarly journals Gentiopicroside Ameliorates Oxidative Stress and Lipid Accumulation through Nuclear Factor Erythroid 2-Related Factor 2 Activation

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Meiyu Jin ◽  
Haihua Feng ◽  
Yue Wang ◽  
Siru Yan ◽  
Bingyu Shen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Regulatory Element ◽  
Cell Counting ◽  
Related Factor ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Akt Inhibitor

The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is closely related to the alleviation of nonalcoholic fatty liver disease (NAFLD) by regulating oxidative stress and lipid homeostasis. Gentiopicroside (GPS), an iridoid glycoside found in the Gentianaceae, possesses anti-inflammatory and antioxidant effects. However, the protective effects of GPS on lipid accumulation and oxidative damage have not been investigated thoroughly in free fatty acid- (FFA-) induced HepG2 cells and tyloxapol- (Ty-) induced hyperlipidemia mice. Cell counting kit-8 assays, Oil Red O staining, Western blotting analysis, extraction of nuclear and cytosolic proteins, and biochemical index assay were employed to explore the mechanisms by which GPS exerts a protective effect on FFA-induced HepG2 cells and Ty-induced hyperlipidemia mouse model. This paper demonstrates that GPS could effectively alleviate NAFLD by elevating cell viability, reducing fatty deposition, downregulating TG, and activating nucleus Nrf2 in FFA-induced HepG2 cells. Meanwhile, GPS significantly regulated the activation of phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, Nrf2 antioxidant pathway, peroxisome proliferator-activated receptor α (PPARα), and GPS-inhibited sterol regulatory element-binding protein-1c (SREBP-1c) expression in FFA-stimulated lipid accumulation of HepG2 cells and Ty-treated mice. Interestingly, we highlight that PI3K/AKT inhibitor (LY294002) markedly increased the expression of Nrf2 antioxidant pathway, PPARα, and downregulated SREBP-1c in FFA-stimulated HepG2 cells. For these reasons, we found that the deletion of Nrf2 could lose the protective effects of GPS on the Nrf2 antioxidant pathway and PPARα activation and SREBP-1c inactivation in FFA-stimulated HepG2 cells and Ty-treated mice. GPS treatment had no effect on abnormal lipogenesis and antioxidant enzymes in Ty-induced Nrf2-/- mice. This work gives a new explanation that GPS may be a useful therapeutic strategy for NAFLD through upregulation of the Nrf2 antioxidant pathway, which can alleviate oxidative damage and lipid accumulation.

miR-23a/b-3p promotes hepatic lipid accumulation by regulating Srebp-1c and Fas

2021 ◽  
Author(s):  
Linfang Li ◽  
Xiaoyi Zhang ◽  
Hangjiang Ren ◽  
Xiuqing Huang ◽  
Tao Shen ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Leptin Receptor ◽  
Regulatory Element ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Protein Levels ◽  
Triglyceride Accumulation ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

miR-23a-3p and miR-23b-3p are members of the miR-23~27~24-2 superfamily. The role of miR-23a/b-3p in regulating hepatic lipid accumulation is still unknown. Here, we found that increased miR-23a-3p and miR-23b-3p levels were accompanied by an increase in the protein levels of the sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) in the steatotic livers of mice fed a high-fat diet (HFD) and leptin-receptor-deficient type 2 diabetic mice (db/db). Importantly, overexpression of miR-23a/b-3p in Hep1-6 cells elevated the intracellular triglyceride level and upregulated the expression of Srebp-1c and Fas. Taken together, these results suggested that miR-23a/b-3p enhanced mRNA stability by binding the 5'-UTR of Srebp-1c and Fas mRNA, thereby promoting triglyceride accumulation in hepatocytes.

scholarly journals Magma Seawater Inhibits Hepatic Lipid Accumulation through Suppression of Lipogenic Enzymes Regulated by SREBPs in Thioacetamide-Injected Rats

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 317 ◽  
Author(s):  
Minji Woo ◽  
Jeong Sook Noh ◽  
Mi Jeong Kim ◽  
Yeong Ok Song ◽  
Hyunjoo Lee
Keyword(s):  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Thiobarbituric Acid ◽  
Control Group ◽  
Chow Diet ◽  
Lipogenic Enzymes ◽  
Hepatic Lipid ◽  
Antioxidative Status ◽  
Hepatic Lipid Accumulation

Thioacetamide (TAA) is known to induce lipid accumulation in the liver. In the present study, we investigated the effects of magma seawater (MS) rich in minerals on hepatic lipid metabolism by evaluating lipogenic enzymes regulated by sterol regulatory element-binding proteins (SREBPs). Rats (n = 10 per group) were intraperitoneally injected with TAA (200 mg/kg bw) thrice a week for seven weeks in combination with a respective experimental diet. Rats in the TAA-treated group received either a chow diet (Control group) or a chow diet containing MS (TMS group, 2.05%) or silymarin (TSM group, 0.05%). Rats in the normal group were injected with PBS as a vehicle and received a chow diet. Rats in the TMS group showed significantly lower hepatic lipid concentrations than rats in the control group (p < 0.05). Hepatic protein expression levels of fatty acid synthase, SREBP-1, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and SREBP-2 were significantly downregulated in the TMS group, whereas carnitine palmitoyltransferase 1 levels were upregulated (p < 0.05). Hepatic thiobarbituric acid reactive substances levels were lower in the TMS group, whereas protein levels of glutathione peroxidase and catalase were elevated (p < 0.05). The effects of MS were comparable to those of silymarin. Our results evidently showed that MS inhibits hepatic lipid accumulation by suppressing lipid synthesis, accompanied by lipid oxidation and elevation of antioxidative status.

scholarly journals Mechanism of the Inhibitory Effects ofEucommia ulmoidesOliv. Cortex Extracts (EUCE) in the CCl4-Induced Acute Liver Lipid Accumulation in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Chang-Feng Jin ◽  
Bo Li ◽  
Shun-Mei Lin ◽  
Raj-Kumar Yadav ◽  
Hyung-Ryong Kim ◽  
...  
Keyword(s):  
Er Stress ◽  
Lipid Accumulation ◽  
Liver Lipid ◽  
Eucommia Ulmoides ◽  
Dependent Manner ◽  
Protective Effects ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Er Stress Response ◽  
Acute Injection

Eucommia ulmoidesOliv. (EU) has been used for treatment of liver diseases. The protective effects ofEucommia UlmoidesOliv. cortex extracts (EUCE) on the carbon tetrachloride- (CCl4-) induced hepatic lipid accumulation were examined in this study. Rats were orally treated with EUCE in different doses prior to an intraperitoneal injection of 1 mg/kg CCl4. Acute injection of CCl4decreased plasma triglyceride but increased hepatic triglyceride and cholesterol as compared to control rats. On the other hand, the pretreatment with EUCE diminished these effects at a dose-dependent manner. CCl4treatment decreased glutathione (GSH) and increased malondialdehyde (MDA) accompanied by activated P450 2E1. The pretreatment with EUCE significantly improved these deleterious effects of CCl4. CCl4treatment increased P450 2E1 activation and ApoB accumulation. Pretreatment with EUCE reversed these effects. ER stress response was significantly increased by CCl4, which was inhibited by EUCE. One of the possible ER stress regulatory mechanisms, lysosomal activity, was examined. CCl4reduced lysosomal enzymes that were reversed with the EUCE. The results indicate that oral pretreatment with EUCE may protect liver against CCl4-induced hepatic lipid accumulation. ER stress and its related ROS regulation are suggested as a possible mechanism in the antidyslipidemic effect of EUCE.

scholarly journals Aqueous Extract of Pepino (Solanum muriactum Ait) Leaves Ameliorate Lipid Accumulation and Oxidative Stress in Alcoholic Fatty Liver Disease

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 931 ◽  
Author(s):  
Jen-Ying Hsu ◽  
Hui-Hsuan Lin ◽  
Cheng-Chin Hsu ◽  
Bing-Chen Chen ◽  
Jing-Hsien Chen
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver ◽  
Aqueous Extract ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Adenosine Monophosphate ◽  
Peroxisome Proliferator ◽  
Alcoholic Fatty Liver ◽  
Anti Inflammatory

Chronic alcohol intake leads to alcoholic fatty liver. The pathogenesis of alcoholic fatty liver is related to abnormal lipid accumulation, oxidative stress, endotoxins, and cytokines. Solanum muricatum Ait. (Pepino) is a plant food commonly cultivated in the Penghu island, Taiwan. Previous studies indicated that the aqueous extract of pepino was able to attenuate diabetic progression via its antioxidative and anti-inflammatory effects. However, the mechanisms of the antioxidative and anti-inflammatory effects of pepino leaf in preventing alcoholic fatty liver remain unknown. In this study, Lieber–DeCarli ethanol-containing liquid diet was used to induce alcoholic hepatic injury in C57BL/6 mice. The hepatoprotective effects and the related mechanisms of aqueous extract of pepino leaf (AEPL) were examined. Our results showed that 2% AEPL treatments protected the liver from ethanol-induced injury through reducing serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and triglyceride (TG) (all p < 0.05). AEPL had the effects in improving the ethanol-induced lipid accumulation in mice under histological examination. Molecular data indicated that the anti-lipid accumulation effect of AEPL might be mediated via inducing hepatic levels of phospho-adenosine monophosphate-activated kinase (p-AMPK) and peroxisome proliferator-activated receptor (PPAR)-α, and reducing the expressions of hepatic lipogenic enzymes, including sterol regulatory element-binding protein (SREBP)-1c, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) (all p < 0.05). AEPL also decreased hepatic levels of thiobarbituric acid relative substances (TBARS), tumor necrosis factor (TNF)-α, and interleukin (IL)-6, as well as the expression of nuclear factor kappa B (NF-κB) (all p < 0.05). Moreover, AEPL significantly elevated the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), and glutathione (GSH) content compared to the ethanol-fed group (all p < 0.05). Our present study suggests that AEPL could protect the liver against ethanol-induced oxidative injury and lipid accumulation.

Treatment with SRT1720, a SIRT1 activator, ameliorates fatty liver with reduced expression of lipogenic enzymes in MSG mice

2009 ◽  
Vol 297 (5) ◽  
pp. E1179-E1186 ◽  
Author(s):  
Yu Yamazaki ◽  
Isao Usui ◽  
Yukiko Kanatani ◽  
Yuji Matsuya ◽  
Koichi Tsuneyama ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Fatty Liver ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Liver Lipid ◽  
Monosodium Glutamate ◽  
Marker Genes ◽  
Lipogenic Genes ◽  
Sirt1 Activator

Nonalcoholic fatty liver disease (NAFLD) is an abnormal liver metabolism often observed with insulin resistance and metabolic syndrome. Calorie restriction is a useful treatment for NAFLD and reportedly prolongs the life spans of several species in which sirtuin plays an important role. In this study, we examined whether the activation of SIRT1, a mammalian ortholog of sirtuin, may ameliorate the development of NAFLD. Monosodium glutamate (MSG) mice, which exhibited obesity and insulin resistance, were treated with SRT1720, a specific SIRT1 activator from the age of 6–16 wk. Sixteen-week-old MSG mice exhibited increased liver triglyceride content and elevated levels of aminotransferase. SRT1720 treatment significantly reduced these levels without affecting body weight or food intake. These results suggested that the administration of SRT1720 ameliorated the development of NAFLD in MSG mice. The expressions of lipogenic genes, such as sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase, and the serum lipid profiles, including free fatty acids, were elevated in MSG mice and were reduced by SRT1720 treatment. SRT1720 treatment also reduced the expressions of lipogenic genes in cultured HepG2 cells. Furthermore, SRT1720 treatment decreased the expressions of marker genes for oxidative stress and inflammatory cytokines in the liver of MSG mice. Taken together, SRT1720 treatment may reduce liver lipid accumulation, at least in part, by directly reducing the expressions of lipogenic genes. The reduction of oxidative stress and inflammation may also be involved in the amelioration of NAFLD.

scholarly journals BL153 Partially Prevents High-Fat Diet Induced Liver Damage Probably via Inhibition of Lipid Accumulation, Inflammation, and Oxidative Stress

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Jian Wang ◽  
Chi Zhang ◽  
Zhiguo Zhang ◽  
Qiang Chen ◽  
Xuemian Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Growth Factor ◽  
Liver Damage ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Liver Weight ◽  
High Fat ◽  
Hepatic Lipid Accumulation ◽  
And Oxidative Stress

The present study was to investigate whether amagnoliaextract, named BL153, can prevent obesity-induced liver damage and identify the possible protective mechanism. To this end, obese mice were induced by feeding with high fat diet (HFD, 60% kcal as fat) and the age-matched control mice were fed with control diet (10% kcal as fat) for 6 months. Simultaneously these mice were treated with or without BL153 daily at 3 dose levels (2.5, 5, and 10 mg/kg) by gavage. HFD feeding significantly increased the body weight and the liver weight. Administration of BL153 significantly reduced the liver weight but without effects on body weight. As a critical step of the development of NAFLD, hepatic fibrosis was induced in the mice fed with HFD, shown by upregulating the expression of connective tissue growth factor and transforming growth factor beta 1, which were significantly attenuated by BL153 in a dose-dependent manner. Mechanism study revealed that BL153 significantly suppressed HFD induced hepatic lipid accumulation and oxidative stress and slightly prevented liver inflammation. These results suggest that HFD induced fibrosis in the liver can be prevented partially by BL153, probably due to reduction of hepatic lipid accumulation, inflammation and oxidative stress.

scholarly journals Oxidative stress and ER stress induce Zidovudine (AZT)‐mediated hepatic lipid accumulation

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Atrayee Banerjee ◽  
Mohamed A Abdelmegeed ◽  
Sehwan Jang ◽  
Byoung Joon Song
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Lipid Accumulation ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation
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