Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation

Liu, Liang; Gao, Chao; Yao, Ping; Gong, Zhiyong

doi:10.1155/2015/607531

Cited by 44 publications

(31 citation statements)

References 50 publications

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“…Thus, regulating lipid metabolism could be an important means to manage the disease. Clinically, TC, TG, and LDL-C all increase in NASH patients [21]. Our experimental results are consistent with the clinical observations and there were significant differences in serum FFA, TC, TG, and LDL-C between the HFD model group and the control group.…”

Section: Discussionsupporting

confidence: 89%

Shugan Xiaozhi Decoction Attenuates Nonalcoholic Steatohepatitis by Enhancing PPARαand L-FABP Expressions in High-Fat-Fed Rats

Xing

Zhang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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This study aimed to investigate the effects of Shugan Xiaozhi decoction (SX) on nonalcoholic steatohepatitis (NASH) induced by high-fat diet in rats. The rats were randomly divided into 6 groups, namely, control, model, fenofibrate, and three different dosage of SX (10, 20, and 40 g/kg/day, p.o.). After establishing the NASH model, at 8 weeks of the experiment, treatments were administrated intragastrically to the fenofibrate and SX groups. All rats were killed after 4 weeks of treatment. Compared with the model group, alanine aminotransferase (ALT), aspartate aminotransferase (AST), free fatty acid (FFA), total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL) serum in the serum were significantly reduced in all SX treatment groups in a dose-dependent manner. Evidence showed that SX could protect the liver by upregulating the gene and protein expressions of peroxisome proliferator-activated receptor alpha (PPARα) and liver fatty acid binding protein (L-FABP) in a dose-dependent manner. Chemical constituents of SX were further analyzed by ultraperformance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC-ESI-MS) and 30 chemicals in the ethanolic extract were tentatively identified. To conclude, our results clearly indicated that SX could protect liver functions and relieve hepatic steatosis and inflammation.

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Section: Discussionsupporting

confidence: 89%

Shugan Xiaozhi Decoction Attenuates Nonalcoholic Steatohepatitis by Enhancing PPARαand L-FABP Expressions in High-Fat-Fed Rats

Xing

Zhang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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“…Luteolin could attenuate NAFLD by blocking the expression of liver X receptor and SERBP-1c [43]. Quercetin has also been confirmed to alleviate oxidized LDL levels in the liver and decrease hepatic steatosis in HFD-induced obese mice [44]. In this current study, fisetin effectively alleviated body weight and epididymal adipose tissue weight.…”

Section: Fig 10supporting

confidence: 50%

“…In addition, Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry appropriate diet could regulate the liver lipid metabolism and attenuate the development of NAFLD. Previous studies found that quercetin not only inhibits the differentiation of adipocytes and lipid synthesis, but also enhances the decomposition of lipids in obese mice [44]. Quercetin has also been shown to promote lipolysis in the livers of NAFLD mice.…”

Section: Fig 10mentioning

confidence: 95%

Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

Liou

Wei

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway.

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“…One flavonoid found in plant-based food with potential health benefits is quercetin. Quercetin has been reported to have a role in prevention of diseases such as liver disease [12], pulmonary hypertension [13], and other cardiovascular diseases [14]. Furthermore, quercetin exhibits anti-inflammatory [15], anticancer [16], and antioxidant [17, 18] effects.…”

Section: Introductionmentioning

confidence: 99%

Mechanistically elucidating the in vitro safety and efficacy of a novel doxorubicin derivative

Alrushaid

Zhao

Sayre

et al. 2017

Drug Deliv. and Transl. Res.

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Doxorubicin is an effective anticancer drug; however, it is cardiotoxic and has poor oral bioavazilability. Quercetin is a plant-based flavonoid with inhibitory effects on P-glycoprotein (P-gp) and CYP3A4 and also antioxidant properties. To mitigate these therapeutic barriers, DoxQ, a novel derivative of doxorubicin, was synthesized by conjugating quercetin to doxorubicin. The purpose of this study is to mechanistically elucidate the in vitro safety and efficacy of DoxQ. Drug release in vitro and cellular uptake by multidrug-resistant canine kidney (MDCK-MDR) cells were quantified by HPLC. Antioxidant activity, CYP3A4 inhibition, and P-gp inhibitory effects were examined using commercial assay kits. Drug potency was assessed utilizing triple-negative murine breast cancer cells, and cardiotoxicity was assessed utilizing adult rat and human cardiomyocytes (RL-14). Levels of reactive oxygen species and gene expression of cardiotoxicity markers, oxidative stress markers, and CYP1B1 were determined in RL-14. DoxQ was less cytotoxic to both rat and human cardiomyocytes and retained anticancer activity. Levels of ROS and markers of oxidative stress demonstrate lower oxidative damage induced by DoxQ compared to doxorubicin. DoxQ also inhibited the expression and catalytic activity of CYP1B1. Additionally, DoxQ inhibited CYP3A4 and demonstrated higher cellular uptake by MDCK-MDR cells than doxorubicin. DoxQ provides a novel therapeutic approach to mitigate the cardiotoxicity and poor oral bioavailability of doxorubicin. The cardioprotective mechanism of DoxQ likely involves scavenging ROS and CYP1B1 inhibition, while the mechanism of improving the poor oral bioavailability of doxorubicin is likely related to inhibiting CYP3A4 and P-gp.

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Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation

Cited by 44 publications

References 50 publications

Shugan Xiaozhi Decoction Attenuates Nonalcoholic Steatohepatitis by Enhancing PPARαand L-FABP Expressions in High-Fat-Fed Rats

Shugan Xiaozhi Decoction Attenuates Nonalcoholic Steatohepatitis by Enhancing PPARαand L-FABP Expressions in High-Fat-Fed Rats

Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

Mechanistically elucidating the in vitro safety and efficacy of a novel doxorubicin derivative

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