Hylocereus polyrhizus Peel Extract Retards Alcoholic Liver Disease Progression by Modulating Oxidative Stress and Inflammatory Responses in C57BL/6 Mice

Alcoholic liver disease (ALD) has become a health problem as alcohol consumption has increased annually. Hepatic lipid accumulation, oxidative stress, and inflammation are important factors in the progression of ALD. Red pitaya (Hylocereus polyrhizus (Weber) Britt. & Rose) peel is rich in polyphenols and betanins, which possess antioxidative and anti-inflammatory properties. Therefore, the aim of this study was to investigate the effects of red pitaya peel extract (PPE) on ALD and explore the associated mechanisms. C57BL/6 J mice were administered an ethanol liquid diet for 11 weeks with or without two different doses of PPE (500 and 1000 mg/kg BW). PPE treatment significantly ameliorated liver injury and hepatic fat accumulation, and it improved hepatic lipid metabolism via increases in AMPK and PPAR-α protein expression and a decrease in SREBP-1 expression. In addition, PPE inhibited CYP2E1 and Nrf2 protein expression, reduced endotoxin levels in the serum, and decreased TLR4 and MyD88 expression and inflammatory cytokine TNF-α and IL-1β levels in the liver. In conclusion, these findings suggest that PPE may prevent the progression of ALD by modulating lipid metabolism and reducing oxidative stress and inflammatory responses.

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Electromagnetic Fields Ameliorate Hepatic Lipid Accumulation and Oxidative Stress by Activating the CaMKKβ/AMPK/SREBP-1c and Nrf2 Pathways in High-Fat Diet-Fed Mice

10.21203/rs.3.rs-1018391/v1 ◽

2021 ◽

Author(s):

Mingming Zhai ◽

Jinxiu Cui ◽

Chenxu Zhang ◽

Juan Liu ◽

Yuanzhe Li ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Protein Expression ◽

Electromagnetic Fields ◽

High Fat Diet ◽

Lipid Deposition ◽

High Fat ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation ◽

And Oxidative Stress

Abstract Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is related to disturbed lipid metabolism and redox homeostasis. However, a definitive drug treatment has not been approved for this disease. Studies have found that electromagnetic fields (EMFs) can ameliorate hepatic steatosis and oxidative stress. Nevertheless, the mechanism remains unclear.Methods: NAFLD models were established by feeding mice a high-fat diet. Simultaneously, EMF exposure is performed. The effects of the EMF on hepatic lipid deposition and oxidative stress were investigated. Additionally, the AMPK and Nrf2 pathways were analysed to confirm whether they were activated by the EMF.Results: Administration of the EMF decreased the body weight, liver weight and serum triglyceride (TG) levels and restrained the excessive hepatic lipid accumulation caused by feeding the HFD. This EMF function is achieved by boosting CaMKKβ protein expression, activating AMPK phosphorylation and suppressing mature SREBP-1c protein expression. Meanwhile, the activity of GSH-Px was enhanced following an increase in nuclear Nrf2 protein expression by EMF. However, no change was observed in the activities of SOD and CAT. Consequently, EMF reduced hepatic reactive oxygen species (ROS) and MDA levels, which means that EMF relieved liver damage by oxidative stress in HFD-fed mice.Conclusions: EMF can activate the CaMKKβ/AMPK/SREBP-1c and Nrf2 pathways to control hepatic lipid deposition and oxidative stress. This investigation indicates that EMF may be a novel therapeutic method for NAFLD.

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Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

International Journal of Molecular Sciences ◽

10.3390/ijms23020774 ◽

2022 ◽

Vol 23 (2) ◽

pp. 774

Author(s):

Yoon Mee Yang ◽

Ye Eun Cho ◽

Seonghwan Hwang

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Alcoholic Liver Disease ◽

Inflammatory Responses ◽

Tissue Injury ◽

Pathological Features ◽

Excessive Alcohol Consumption ◽

Excessive Alcohol ◽

The Relationship

Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.

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Dietary DHA/EPA Ratio Changes Fatty Acid Composition and Attenuates Diet-Induced Accumulation of Lipid in the Liver of ApoE−/− Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/6256802 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Liang Liu ◽

Qinling Hu ◽

Huihui Wu ◽

Xiujing Wang ◽

Chao Gao ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Lipid Metabolism ◽

Liver Disease ◽

Inflammatory Responses ◽

Elevated Serum ◽

Serum Levels ◽

Hepatic Lipid Metabolism ◽

Hepatic Lipid ◽

Fa Composition

Diets containing various docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) ratios protect against liver damage in mice fed with a high-fat diet (HFD). However, it is unclear whether these beneficial roles of DHA and EPA are associated with alterations of fatty acid (FA) composition in the liver. This study evaluated the positive impacts of n-6/n-3 polyunsaturated fatty acids (PUFAs) containing different DHA/EPA ratios on HFD-induced liver disease and alterations of the hepatic FA composition. ApoE−/− mice were fed with HFDs with various ratios of DHA/EPA (2 : 1, 1 : 1, and 1 : 2) and an n-6/n-3 ratio of 4 : 1 for 12 weeks. After treatment, the serum and hepatic FA compositions, serum biochemical parameters, liver injury, and hepatic lipid metabolism-related gene expression were determined. Our results demonstrated that dietary DHA/EPA changed serum and hepatic FA composition by increasing contents of n-6 and n-3 PUFAs and decreasing amounts of monounsaturated fatty acids (MUFAs) and the n-6/n-3 ratio. Among the three DHA/EPA groups, the DHA/EPA 2 : 1 group tended to raise n-3 PUFAs concentration and lower the n-6/n-3 ratio in the liver, whereas DHA/EPA 1 : 2 tended to raise n-6 PUFAs concentration and improve the n-6/n-3 ratio. DHA/EPA supplementation reduced the hepatic impairment of lipid homeostasis, oxidative stress, and the inflammatory responses in HFD-fed mice. The DHA/EPA 2 : 1 group had lower serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol and higher levels of adiponectin than HFD group. The DHA/EPA 1 : 2 group had elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, without significant change the expression of genes for inflammation or hepatic lipid metabolism among the three DHA/EPA groups. The results suggest that DHA/EPA-enriched diet with an n-6/n-3 ratio of 4 : 1 may reverse HFD-induced nonalcoholic fatty liver disease to some extent by increasing n-6 and n-3 PUFAs and decreasing the amount of MUFAs and the n-6/n-3 ratio.

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Aldose Reductase Inhibitors of Plant Origin in the Prevention and Treatment of Alcoholic Liver Disease: A Minireview

BioMed Research International ◽

10.1155/2019/3808594 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Longxin Qiu ◽

Chang Guo ◽

Baoyu Hua

Keyword(s):

Oxidative Stress ◽

Lipid Metabolism ◽

Liver Disease ◽

Inflammatory Cytokines ◽

Aldose Reductase ◽

Alcoholic Liver Disease ◽

Lipid Synthesis ◽

Plant Origin ◽

Reductase Inhibitors ◽

Natural Medicine

Alcoholic liver disease (ALD) is caused by heavy alcohol consumption over a long period. Acetaldehyde-mediated toxicity, oxidative stress, and imbalance of lipid metabolism are generally considered involved in the initiation of ALD. There is an increasing requirement for alternative and natural medicine to treat ALD. Recently, aldose reductase (AR) has been reported to be involved in the development of ALD by affecting inflammatory cytokines, oxidative stress, and lipid metabolism. Here, we review the effect of plant-derived AR inhibitors on ALD in rodents. And we conclude that AR inhibitors of plant origin may enhance antioxidant capacity, inhibit lipid peroxidation and inflammatory cytokines expression, and activate AMP-activated protein kinase thereby subsequently suppressing alcohol-induced lipid synthesis in liver to achieve ALD protection. This review reveals that natural AR inhibitor may be potential therapeutic agent for ALD.

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Simultaneous co-assembly of fenofibrate and ketoprofen peptide for the dual-targeted treatment of nonalcoholic fatty liver disease (NAFLD)

Chemical Communications ◽

10.1039/d0cc00513d ◽

2020 ◽

Vol 56 (36) ◽

pp. 4922-4925 ◽

Cited By ~ 5

Author(s):

Zhongyan Wang ◽

Chuanrui Ma ◽

Yuna Shang ◽

Lijun Yang ◽

Jing Zhang ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Lipid Accumulation ◽

Fatty Liver Disease ◽

Inflammatory Responses ◽

Targeted Treatment ◽

Nonalcoholic Fatty Liver ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation

An ingenious co-assembled nanosystem based on fenofibrate and ketoprofen peptide for the dual-targeted treatment of NAFLD by reducing hepatic lipid accumulation and inflammatory responses.

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Oxidative Stress and Inflammation: Essential Partners in Alcoholic Liver Disease

International Journal of Hepatology ◽

10.1155/2012/853175 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 92

Author(s):

Aditya Ambade ◽

Pranoti Mandrekar

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Alcoholic Liver Disease ◽

Cytokine Production ◽

Inflammatory Responses ◽

Proinflammatory Cytokine Production ◽

The Past ◽

Proinflammatory Responses ◽

Progression Of Disease ◽

Oxidative Processes

Alcoholic liver disease (ALD) is a multifaceted disease that is characterized by hepatic steatosis or fat deposition and hepatitis or inflammation. Over the past decade, multiple lines of evidence have emerged on the mechanisms associated with ALD. The key mechanisms identified so far are sensitization to gut-derived endotoxin/lipopolysaccharide resulting in proinflammatory cytokine production and cellular stress due to oxidative processes, contributing to the development and progression of disease. While oxidative stress and inflammatory responses are studied independently in ALD, mechanisms linking these two processes play a major role in pathogenesis of disease. Here we review major players of oxidative stress and inflammation and highlight signaling intermediates regulated by oxidative stress that provokes proinflammatory responses in alcoholic liver disease.

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Lingonberry Improves Non-Alcoholic Fatty Liver Disease by Reducing Hepatic Lipid Accumulation, Oxidative Stress and Inflammatory Response

Antioxidants ◽

10.3390/antiox10040565 ◽

2021 ◽

Vol 10 (4) ◽

pp. 565

Author(s):

Susara Madduma Hewage ◽

Suvira Prashar ◽

Karmin O ◽

Yaw L. Siow

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Liver Injury ◽

Lipid Accumulation ◽

Fatty Liver Disease ◽

Inflammatory Cytokine ◽

Alcoholic Fatty Liver ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally and there is a pressing need for effective treatment. Lipotoxicity and oxidative stress are the important mediators in NAFLD pathogenesis. Lingonberry (Vaccinium vitis-idaea L.) is rich in anthocyanins that have antioxidant and anti-inflammatory properties. The present study investigated the effect of lingonberry supplementation on liver injury in C57BL/6J male mice fed a high-fat diet (HFD) for 12 weeks. Mice fed HFD displayed liver injury with steatosis, increased lipid peroxidation and inflammatory cytokine expression in the liver as compared to mice fed a control diet. Lingonberry supplementation for 12 weeks alleviated HFD-induced liver injury, attenuated hepatic lipid accumulation, and inflammatory cytokine expression. Lingonberry supplementation inhibited the expression of sterol regulatory element-binding protein-1c (SREBP-1c) and acetyl-CoA carboxylase-1 (AAC-1) as well as activated AMP-activated protein kinase (AMPK) in the liver. It also decreased HFD-induced hepatic oxidative stress and aggregation of inflammatory foci. This was associated with a restoration of nuclear factor erythroid 2–related factor 2 (Nrf2) and glutathione level in the liver. These results suggest that lingonberry supplementation can protect against HFD-induced liver injury partly through attenuation of hepatic lipid accumulation, oxidative stress, and inflammatory response.

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Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis

Molecules ◽

10.3390/molecules26041156 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1156

Author(s):

Lena Seidemann ◽

Anne Krüger ◽

Victoria Kegel-Hübner ◽

Daniel Seehofer ◽

Georg Damm

Keyword(s):

Lipid Metabolism ◽

Liver Disease ◽

Protein Expression ◽

Hepatic Steatosis ◽

In Vitro Model ◽

Hepatic Lipid Metabolism ◽

Hepatic Lipid ◽

Genistein Treatment ◽

Vitro Model

Nonalcoholic fatty liver disease (NAFLD) is among the leading causes of end-stage liver disease. The impaired hepatic lipid metabolism in NAFLD is exhibited by dysregulated PPARα and SREBP-1c signaling pathways, which are central transcription factors associated with lipid degradation and de novo lipogenesis. Despite the growing prevalence of this disease, current pharmacological treatment options are unsatisfactory. Genistein, a soy isoflavone, has beneficial effects on lipid metabolism and may be a candidate for NAFLD treatment. In an in vitro model of hepatic steatosis, primary human hepatocytes (PHHs) were incubated with free fatty acids (FFAs) and different doses of genistein. Lipid accumulation and the cytotoxic effects of FFAs and genistein treatment were evaluated by colorimetric and enzymatic assays. Changes in lipid homeostasis were examined by RT-qPCR and Western blot analyses. PPARα protein expression was induced in steatotic PHHs, accompanied by an increase in CPT1L and ACSL1 mRNA. Genistein treatment increased PPARα protein expression only in control PHHs, while CPTL1 and ACSL1 were unchanged and PPARα mRNA was reduced. In steatotic PHHs, genistein reversed the increase in activated SREBP-1c protein. The model realistically reflected the molecular changes in hepatic steatosis. Genistein suppressed the activation of SREBP-1c in steatotic hepatocytes, but the genistein-mediated effects on PPARα were abolished by high hepatic lipid levels.

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Alcohol effects on hepatic lipid metabolism

The Journal of Lipid Research ◽

10.1194/jlr.r119000547 ◽

2020 ◽

Vol 61 (4) ◽

pp. 470-479 ◽

Cited By ~ 7

Author(s):

Sookyoung Jeon ◽

Rotonya Carr

Keyword(s):

Lipid Metabolism ◽

Liver Disease ◽

Hepatic Steatosis ◽

De Novo ◽

Lipid Synthesis ◽

Acid Oxidation ◽

Lipid Uptake ◽

Hepatic Lipid Metabolism ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation

Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease with significant morbidity and mortality worldwide. ALD begins with simple hepatic steatosis and progresses to alcoholic steatohepatitis, fibrosis, and cirrhosis. The severity of hepatic steatosis is highly associated with the development of later stages of ALD. This review explores the disturbances of alcohol-induced hepatic lipid metabolism through altered hepatic lipid uptake, de novo lipid synthesis, fatty acid oxidation, hepatic lipid export, and lipid droplet formation and catabolism. In addition, we review emerging data on the contributions of genetics and bioactive lipid metabolism in alcohol-induced hepatic lipid accumulation.

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