Plant-Based Foods and Their Bioactive Compounds on Fatty Liver Disease: Effects, Mechanisms, and Clinical Application

Fatty liver disease (FLD), including nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), is a serious chronic metabolic disease that affects a wide range of people. Lipid accumulation accompanied by oxidative stress and inflammation in the liver is the most important pathogenesis of FLD. The plant-based, high-fiber, and low-fat diet has been recommended to manage FLD for a long time. This review discusses the current state of the art into the effects, mechanisms, and clinical application of plant-based foods in NAFLD and AFLD, with highlighting related molecular mechanisms. Epidemiological evidence revealed that the consumption of several plant-based foods was beneficial to alleviating FLD. Further experimental studies found out that fruits, spices, teas, coffee, and other plants, as well as their bioactive compounds, such as resveratrol, anthocyanin, curcumin, and tea polyphenols, could alleviate FLD by ameliorating hepatic steatosis, oxidative stress, inflammation, gut dysbiosis, and apoptosis, as well as regulating autophagy and ethanol metabolism. More importantly, clinical trials confirmed the beneficial effects of plant-based foods on patients with fatty liver. However, several issues need to be further studied especially the safety and effective doses of plant-based foods and their bioactive compounds. Overall, certain plant-based foods are promising natural sources of bioactive compounds to prevent and alleviate fatty liver disease.

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Sex differences in non-alcoholic fatty liver disease: hints for future management of the disease

10.37349/emed.2020.00005 ◽

2020 ◽

Vol 1 (2) ◽

pp. 51-74 ◽

Cited By ~ 1

Author(s):

Noel C. Salvoza ◽

Pablo J. Giraudi ◽

Claudio Tiribelli ◽

Natalia Rosso

Keyword(s):

Oxidative Stress ◽

Sex Differences ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Molecular Mechanisms ◽

Protective Effects ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) remains a major cause of chronic liver disease worldwide. Despite extensive studies, the heterogeneity of the risk factors as well as different disease mechanisms complicate the goals toward effective diagnosis and management. Recently, it has been shown that sex differences play a role in the prevalence and progression of NAFLD. In vitro, in vivo, and clinical studies revealed that the lower prevalence of NAFLD in premenopausal as compared to postmenopausal women and men is mainly due to the protective effects of estrogen and body fat distribution. It has been also described that males and females present differential pathogenic features in terms of biochemical profiles and histological characteristics. However, the exact molecular mechanisms for the gender differences that exist in the pathogenesis of NAFLD are still elusive. Lipogenesis, oxidative stress, and inflammation play a key role in the progression of NAFLD. For NAFLD, only a few studies characterized these mechanisms at the molecular level. Therefore, we aim to review the reported differential molecular mechanisms that trigger such different pathogenesis in both sexes. Differences in lipid metabolism, glucose homeostasis, oxidative stress, inflammation, and fibrosis were discussed based on the evidence reported in recent publications. In conclusion, with this review, we hope to provide a new perspective for the development of future practice guidelines as well as a new avenue for the management of the disease.

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Serum and hepatic sphingolipids relate to insulin resistance, hepatic mitochondrial capacity and oxidative stress in non-alcoholic fatty liver disease

Diabetologie und Stoffwechsel ◽

10.1055/s-0037-1601637 ◽

2017 ◽

Vol 12 (S 01) ◽

pp. S1-S84

Author(s):

M Apostolopoulou ◽

R Gordillo ◽

C Koliaki ◽

S Gancheva ◽

T Jelenik ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

And Oxidative Stress ◽

Alcoholic Fatty Liver Disease ◽

Mitochondrial Capacity

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New therapy for fatty liver

Thai Journal of Hepatology ◽

10.30856/th.jhep2018vol1iss2_06 ◽

2018 ◽

Vol 1 (2) ◽

pp. 24-28

Author(s):

Tanita Suttichaimongkol

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Lifestyle Modifications ◽

Alcoholic Fatty Liver ◽

Nonalcoholic Fatty Liver ◽

Liver Insulin Resistance ◽

Alcoholic Fatty Liver Disease ◽

Related Mortality

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of death from liver cirrhosis, endstage liver disease, and hepatocellular carcinoma. It is also associated with increased cardiovasculardisease and cancer related mortality. While lifestyle modifications are the mainstay of treatment,only a proportion of patients are able to make due to difficult to achieve and maintain, and so moretreatment options are required such as pharmacotherapy. This review presents the drugs used inmanaging NAFLD and their pharmacologic targets. Therapies are currently directed towards improvingthe metabolic status of the liver, insulin resistance, cell oxidative stress, apoptosis, inflammation orfibrosis. Several agents are now in large clinical trials and within the next few years, the availability oftherapeutic options for NAFLD will be approved. Keywords: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, fibrosis, cirrhosis

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Natural Aldose Reductase Inhibitor: A Potential Therapeutic Agent for Non-alcoholic Fatty Liver Disease

Current Drug Targets ◽

10.2174/1389450120666191007111712 ◽

2020 ◽

Vol 21 (6) ◽

pp. 599-609 ◽

Cited By ~ 3

Author(s):

Longxin Qiu ◽

Chang Guo

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Aldose Reductase ◽

Fatty Liver Disease ◽

Acid Oxidation ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Alcoholic Fatty Liver ◽

Nonalcoholic Fatty Liver

Aldose reductase (AR) has been reported to be involved in the development of nonalcoholic fatty liver disease (NAFLD). Hepatic AR is induced under hyperglycemia condition and converts excess glucose to lipogenic fructose, which contributes in part to the accumulation of fat in the liver cells of diabetes rodents. In addition, the hyperglycemia-induced AR or nutrition-induced AR causes suppression of the transcriptional activity of peroxisome proliferator-activated receptor (PPAR) α and reduced lipolysis in the liver, which also contribute to the development of NAFLD. Moreover, AR induction in non-alcoholic steatohepatitis (NASH) may aggravate oxidative stress and the expression of inflammatory cytokines in the liver. Here, we summarize the knowledge on AR inhibitors of plant origin and review the effect of some plant-derived AR inhibitors on NAFLD/NASH in rodents. Natural AR inhibitors may improve NAFLD at least in part through attenuating oxidative stress and inflammatory cytokine expression. Some of the natural AR inhibitors have been reported to attenuate hepatic steatosis through the regulation of PPARα-mediated fatty acid oxidation. In this review, we propose that the natural AR inhibitors are potential therapeutic agents for NAFLD.

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Paraoxonase 1 and Non-Alcoholic Fatty Liver Disease: A Meta-Analysis

Molecules ◽

10.3390/molecules26082323 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2323

Author(s):

Kazuhiko Kotani ◽

Jun Watanabe ◽

Kouichi Miura ◽

Alejandro Gugliucci

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Meta Analysis ◽

Laboratory Data ◽

Paraoxonase 1 ◽

Mixed Data ◽

Alcoholic Fatty Liver ◽

Paraoxonase Activity

Oxidative stress is involved in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). However, reliable biomarkers of NAFLD in relation to oxidative stress are not available. While paraoxonase 1 (PON1) is an antioxidant biomarker, there appears to be mixed data on PON-1 in patients with NAFLD. The aim of this meta-analysis was to assess the current data on PON1 activity (i.e., paraoxonase and arylesterase) in patients with NAFLD. A PubMed, CENTRAL, and Embase search identified 12 eligible articles. In the meta-analysis, the paraoxonase activity was low in patients with NAFLD (mean difference (MD) −27.17 U/L; 95% confidence interval (CI) −37.31 to −17.03). No difference was noted in the arylesterase activity (MD 2.45 U/L; 95% CI −39.83 to 44.74). In a subgroup analysis, the paraoxonase activity was low in biopsy-proven nonalcoholic steatohepatitis (MD −92.11 U/L; 95% CI −115.11 to −69.11), while the activity in NAFLD as diagnosed by ultrasonography or laboratory data was similar (MD −2.91 U/L; 95% CI −11.63 to 5.80) to that of non-NAFLD. In summary, the PON1, especially paraoxonase, activity could be a useful biomarker of NAFLD. Further studies are warranted to ascertain the relevance of PON1 measurements in patients with NAFLD.

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The Role of Oxidative Stress in NAFLD–NASH–HCC Transition—Focus on NADPH Oxidases

Biomedicines ◽

10.3390/biomedicines9060687 ◽

2021 ◽

Vol 9 (6) ◽

pp. 687

Author(s):

Daniela Gabbia ◽

Luana Cannella ◽

Sara De De Martin

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Current Knowledge ◽

Mechanisms Of Action ◽

Nadph Oxidases ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

A peculiar role for oxidative stress in non-alcoholic fatty liver disease (NAFLD) and its transition to the inflammatory complication non-alcoholic steatohepatitis (NASH), as well as in its threatening evolution to hepatocellular carcinoma (HCC), is supported by numerous experimental and clinical studies. NADPH oxidases (NOXs) are enzymes producing reactive oxygen species (ROS), whose abundance in liver cells is closely related to inflammation and immune responses. Here, we reviewed recent findings regarding this topic, focusing on the role of NOXs in the different stages of fatty liver disease and describing the current knowledge about their mechanisms of action. We conclude that, although there is a consensus that NOX-produced ROS are toxic in non-neoplastic conditions due to their role in the inflammatory vicious cycle sustaining the transition of NAFLD to NASH, their effect is controversial in the neoplastic transition towards HCC. In this regard, there are indications of a differential effect of NOX isoforms, since NOX1 and NOX2 play a detrimental role, whereas increased NOX4 expression appears to be correlated with better HCC prognosis in some studies. Further studies are needed to fully unravel the mechanisms of action of NOXs and their relationships with the signaling pathways modulating steatosis and liver cancer development.

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Addressing the liver progenitor cell response and hepatic oxidative stress in experimental non-alcoholic fatty liver disease/non-alcoholic steatohepatitis using amniotic epithelial cells

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02476-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Mihiri Goonetilleke ◽

Nathan Kuk ◽

Jeanne Correia ◽

Alex Hodge ◽

Gregory Moore ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Epithelial Cells ◽

Fatty Liver ◽

Progenitor Cells ◽

Fatty Liver Disease ◽

Hepatic Inflammation ◽

Alcoholic Fatty Liver ◽

And Oxidative Stress ◽

Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease is the most common liver disease globally and in its inflammatory form, non-alcoholic steatohepatitis (NASH), can progress to cirrhosis and hepatocellular carcinoma (HCC). Currently, patient education and lifestyle changes are the major tools to prevent the continued progression of NASH. Emerging therapies in NASH target known pathological processes involved in the progression of the disease including inflammation, fibrosis, oxidative stress and hepatocyte apoptosis. Human amniotic epithelial cells (hAECs) were previously shown to be beneficial in experimental models of chronic liver injury, reducing hepatic inflammation and fibrosis. Previous studies have shown that liver progenitor cells (LPCs) response plays a significant role in the development of fibrosis and HCC in mouse models of fatty liver disease. In this study, we examined the effect hAECs have on the LPC response and hepatic oxidative stress in an experimental model of NASH. Methods Experimental NASH was induced in C57BL/6 J male mice using a high-fat, high fructose diet for 42 weeks. Mice received either a single intraperitoneal injection of 2 × 106 hAECs at week 34 or an additional hAEC dose at week 38. Changes to the LPC response and oxidative stress regulators were measured. Results hAEC administration significantly reduced the expansion of LPCs and their mitogens, IL-6, IFNγ and TWEAK. hAEC administration also reduced neutrophil infiltration and myeloperoxidase production with a concurrent increase in heme oxygenase-1 production. These observations were accompanied by a significant increase in total levels of anti-fibrotic IFNβ in mice treated with a single dose of hAECs, which appeared to be independent of c-GAS-STING activation. Conclusions Expansion of liver progenitor cells, hepatic inflammation and oxidative stress associated with experimental NASH were attenuated by hAEC administration. Given that repeated doses did not significantly increase efficacy, future studies assessing the impact of dose escalation and/or timing of dose may provide insights into clinical translation.

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