Nutrients

Research

18 pages, 4061 KiB

Open AccessArticle

Combination Treatment with Hydroxytyrosol and Vitamin E Improves NAFLD-Related Fibrosis

by Nadia Panera, Maria Rita Braghini, Annalisa Crudele, Antonella Smeriglio, Marzia Bianchi, Angelo Giuseppe Condorelli, Rebecca Nobili, Libenzio Adrian Conti, Cristiano De Stefanis, Gessica Lioci, Fabio Gurrado, Donatella Comparcola, Antonella Mosca, Maria Rita Sartorelli, Vittorio Scoppola, Gianluca Svegliati-Baroni, Domenico Trombetta and Anna Alisi

Nutrients 2022, 14(18), 3791; https://doi.org/10.3390/nu14183791 - 14 Sep 2022

Cited by 16 | Viewed by 3367

Abstract

Non-alcoholic fatty liver disease (NAFLD)-related liver fibrosis results in the encapsulation of injured liver parenchyma by a collagenous scar mainly imputable to hepatic stellate cells’ activation. Approved pharmacological treatments against NAFLD-related fibrosis are still lacking, but natural compounds such as hydroxytyrosol (HXT) and [...] Read more.

Non-alcoholic fatty liver disease (NAFLD)-related liver fibrosis results in the encapsulation of injured liver parenchyma by a collagenous scar mainly imputable to hepatic stellate cells’ activation. Approved pharmacological treatments against NAFLD-related fibrosis are still lacking, but natural compounds such as hydroxytyrosol (HXT) and vitamin E (VitE), are emerging as promising therapeutic opportunities. In this study, the potential anti-fibrotic effect of HXT + VitE combination therapy was investigated in vitro and in vivo. In particular, tumor growth factor (TGF)-β-activated LX-2 cells as an in vitro model, and carbon tetrachloride plus a Western diet as a mice model were employed. The effect of HXT + VitE on fibrosis was also investigated in children with biopsy-proven NAFLD. Our results demonstrated that HXT + VitE caused a reduction of proliferation, migration, contractility, and expression of pro-fibrogenic genes in TGF-β-activated LX-2 cells. HXT + VitE treatment also antagonized TGF-β-dependent upregulation of pro-oxidant NOX2 by interfering with nuclear translocation/activation of SMAD2/3 transcription factors. The mouse model of NAFLD-related fibrosis treated with HXT + VitE showed a marked reduction of fibrosis pattern by histology and gene expression. Accordingly, in children with NAFLD, HXT + VitE treatment caused a decrease of circulating levels of PIIINP and NOX2 that was supported over time. Our study suggests that HXT + VitE supplementation may improve NAFLD-related fibrosis. Full article

(This article belongs to the Special Issue Food Bioactive Compounds and Chronic Liver Diseases)

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15 pages, 952 KiB

Open AccessArticle

Antilipidemic and Hepatoprotective Effects of Ethanol Extract of Justicia spicigera in Streptozotocin Diabetic Rats

by Marina Murillo-Villicaña, Ruth Noriega-Cisneros, Donovan J. Peña-Montes, Maribel Huerta-Cervantes, Asdrubal Aguilera-Méndez, Christian Cortés-Rojo, Rafael Salgado-Garciglia, Rocío Montoya-Pérez, Héctor Riveros-Rosas and Alfredo Saavedra-Molina

Nutrients 2022, 14(9), 1946; https://doi.org/10.3390/nu14091946 - 6 May 2022

Cited by 6 | Viewed by 2539

Abstract

Oxidative stress is a factor that contributes to the development of complications in diabetes; however, its effects can be counteracted using exogenous antioxidants that are found in some plants, which is why people turn to traditional medicines in the search for therapeutic treatment. [...] Read more.

Oxidative stress is a factor that contributes to the development of complications in diabetes; however, its effects can be counteracted using exogenous antioxidants that are found in some plants, which is why people turn to traditional medicines in the search for therapeutic treatment. Justicia spicigera has been demonstrated to have the capacity to reduce glycemic levels; however, its effects on non-insulin-dependent organs such as the liver have not been reported. During 30 days of administration of Justicia spicigera ethanol extract, the blood glucose and weight of rats were measured every 5 days. Once the treatment was concluded, the rats were sacrificed. Corporal weight, blood glucose, cholesterol, very-low-density lipoprotein (VLDL), triglycerides, total lipids, and liver profile were reduced in the diabetic condition and normalized with the application of ethanol extract from J. spicigera (EJS). Additionally, there was a significant increase in catalase and superoxide dismutase activity in the control diabetic rats, a decrease in their activity with the extract administration, and no effect on normoglycemic rats. In conclusion, EJS is considered to be capable of reducing oxidative stress by maintaining diminished lipid and liver function profiles in male Wistar rats with streptozotocin-induced diabetes. Full article

(This article belongs to the Special Issue Food Bioactive Compounds and Chronic Liver Diseases)

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20 pages, 6502 KiB

Open AccessArticle

Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl₄-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses

by Naglaa M. Ammar, Heba A. Hassan, Heba M. I. Abdallah, Sherif M. Afifi, Abdelbaset M. Elgamal, Abdel Razik H. Farrag, Abd El-Nasser G. El-Gendy, Mohamed A. Farag and Abdelsamed I. Elshamy

Nutrients 2022, 14(4), 841; https://doi.org/10.3390/nu14040841 - 17 Feb 2022

Cited by 30 | Viewed by 4038 | Correction

Abstract

Citrus fruits are grown worldwide for their special nutritive and several health benefits. Among citrus bioactives, naringenin, a major flavanone, exhibits a potential hepatoprotective effect that is not fully elucidated. Herein, serum biochemical parameters and histopathological assays were used to estimate the hepatoprotective [...] Read more.

Citrus fruits are grown worldwide for their special nutritive and several health benefits. Among citrus bioactives, naringenin, a major flavanone, exhibits a potential hepatoprotective effect that is not fully elucidated. Herein, serum biochemical parameters and histopathological assays were used to estimate the hepatoprotective activity of naringenin, isolated from Citrus sinensis (var. Valencia) peels, in CCl₄-induced injury in a rat model. Further, GC–MS-based untargeted metabolomics was used to characterize the potential metabolite biomarkers associated with its activity. Present results revealed that naringenin could ameliorate the increases in liver enzymes (ALT and AST) induced by CCl₄ and attenuate the pathological changes in liver tissue. Naringenin decreased urea, creatinine and uric acid levels and improved the kidney tissue architecture, suggesting its role in treating renal disorders. In addition, naringenin increased the expression of the antiapoptoic cell marker, Bcl-2. Significant changes in serum metabolic profiling were noticed in the naringenin-treated group compared to the CCl₄ group, exemplified by increases in palmitic acid, stearic acid, myristic acid and lauric acids and decrease levels of alanine, tryptophan, lactic acid, glucosamine and glucose in CCl₄ model rats. The results suggested that naringenin’s potential hepato- and renoprotective effects could be related to its ability to regulate fatty acids (FAs), amino acids and energy metabolism, which may become effective targets for liver and kidney toxicity management. In conclusion, the current study presents new insights into the hepato- and renoprotective mechanisms of naringenin against CCl₄-induced toxicity. Full article

(This article belongs to the Special Issue Food Bioactive Compounds and Chronic Liver Diseases)

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11 pages, 23357 KiB

Open AccessArticle

Dendropanoxide, a Triterpenoid from Dendropanax morbifera, Ameliorates Hepatic Fibrosis by Inhibiting Activation of Hepatic Stellate Cells through Autophagy Inhibition

by Yong-Joo Park, Dong-Min Kim, Hye-Been Choi, Mi-Ho Jeong, Seung-Hwan Kwon, Ha-Ryong Kim, Jong-Hwan Kwak and Kyu-Hyuck Chung

Nutrients 2022, 14(1), 98; https://doi.org/10.3390/nu14010098 - 27 Dec 2021

Cited by 9 | Viewed by 3049

Abstract

Hepatic fibrosis results from chronic liver damage and is characterized by excessive accumulation of extracellular matrix (ECM). In this study, we showed that dendropanoxide (DPX), isolated from Dendropanax morbifera, had anti-fibrotic effects on hepatic fibrosis by inhibiting hepatic stellate cell (HSC) activation. [...] Read more.

Hepatic fibrosis results from chronic liver damage and is characterized by excessive accumulation of extracellular matrix (ECM). In this study, we showed that dendropanoxide (DPX), isolated from Dendropanax morbifera, had anti-fibrotic effects on hepatic fibrosis by inhibiting hepatic stellate cell (HSC) activation. DPX suppressed mRNA and protein expression of α-SMA, fibronectin, and collagen in activated HSCs. Moreover, DPX (40 mg/kg) treatment significantly lowered levels of liver injury markers (aspartate aminotransferase and alanine transaminase), expression of fibrotic markers, and deposition of ECM in a carbon tetrachloride-induced mouse model. Anti-fibrotic effects of DPX were comparable to those of silymarin in a hepatic fibrosis mouse model. As a possible mechanism of anti-fibrotic effects, we showed that DPX inhibited autophagosome formation (LC3B-II) and degradation of p62, which have important roles in HSC activation. These findings suggest that DPX inhibits HSC activation by inhibiting autophagy and can be utilized in hepatic fibrosis therapy. Full article

(This article belongs to the Special Issue Food Bioactive Compounds and Chronic Liver Diseases)

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18 pages, 4402 KiB

Open AccessArticle

Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis

by Vyacheslav Buko, Ilya Zavodnik, Grażyna Budryn, Małgorzata Zakłos-Szyda, Elena Belonovskaya, Siarhei Kirko, Dorota Żyżelewicz, Agnieszka Zakrzeska, Aliaksei Bakunovich, Viktor Rusin and Valentina Moroz

Nutrients 2021, 13(11), 4155; https://doi.org/10.3390/nu13114155 - 20 Nov 2021

Cited by 17 | Viewed by 3255

Abstract

The aim of this study was to evaluate the therapeutic effects of chlorogenic acid (CGA) in rats with advanced alcoholic steatohepatitis. The rats were fed on a high-fat diet and gavaged with ethanol (4 g/kg) for 8 weeks. The livers of ethanol-treated rats [...] Read more.

The aim of this study was to evaluate the therapeutic effects of chlorogenic acid (CGA) in rats with advanced alcoholic steatohepatitis. The rats were fed on a high-fat diet and gavaged with ethanol (4 g/kg) for 8 weeks. The livers of ethanol-treated rats showed steatosis; necrosis and mononuclear infiltration; and significant upregulation of the mRNA expression of the prooxidant (Cyp2e1, iNos), lipogenic (Srebp1, Acc), proinflammatory (Tlr4, Nf-κb, TnfA, Il-1B, and Il-6), and profibrogenic (TgfB, Col1, VegfA) genes. Simultaneously, a downregulation of level of Sod and Nrf2 was observed, which was accompanied by increased serum transaminase, TnfA, and serum and liver triglycerides levels. CGA administration (40 and 80 mg/kg, 8 weeks) to ethanol-fed group reduced the liver expression levels of Cyp2e1 and iNos, whereas it markedly enhanced the expression of Sod, Nrf2, and Ho-1. CGA at both doses downregulated the expressions of lipogenic, proinflammatory, and profibrogenic genes, while the expression of Tlr4 was lowered only after the higher dose of CGA. The higher dose of CGA efficiently prevented the progression of alcohol-induced steatosis and reduced inflammation through regulation of the expression of genes encoding the proteins involved in the Tlr4/Nf-κB signaling pathway and fibrosis. The study revealed hepatoprotective and anti-inflammatory effects of CGA through the regulation of expression of genes encoding Cyp2e1/Nrf2 involved in oxidative stress modulation. These results demonstrate CGA as a therapeutic candidate for the prevention and treatment of alcoholic steatohepatitis. Full article

(This article belongs to the Special Issue Food Bioactive Compounds and Chronic Liver Diseases)

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Review

Jump to: Research, Other

13 pages, 765 KiB

Open AccessReview

The Role of Phytosterols in Nonalcoholic Fatty Liver Disease

by Otilia Frasinariu, Roxana Serban, Laura Mihaela Trandafir, Ingrith Miron, Magdalena Starcea, Ioana Vasiliu, Anna Alisi and Oana Raluca Temneanu

Nutrients 2022, 14(11), 2187; https://doi.org/10.3390/nu14112187 - 24 May 2022

Cited by 20 | Viewed by 3887

Abstract

Nonalcoholic fatty liver disease is now recognized as the most common cause of chronic liver disease with an increasing prevalence in both adults and children. Although the symptoms are absent or poorly expressed in most cases, some patients may progress to end-stage liver [...] Read more.

Nonalcoholic fatty liver disease is now recognized as the most common cause of chronic liver disease with an increasing prevalence in both adults and children. Although the symptoms are absent or poorly expressed in most cases, some patients may progress to end-stage liver disease. The pathogenesis of NAFLD is known to be multifactorial. Current therapeutic recommendations focus on lifestyle changes in order to reduce the incidence of risk factors and drugs targeting major molecular pathways potentially involved in the development of this disease. Given that a pharmacological treatment, completely safe and effective, is not currently known in recent years more research has been done on the effects that some bio-active natural compounds, derived from plants, have in preventing the onset and progression of NAFLD. Numerous studies, in animals and humans, have shown that phytosterols (PSs) play an important role in this pathology. Phytosterols are natural products that are found naturally in plant. More than 250 phytosterols have been identified, but the most common in the diet are stigmasterol, β-sitosterol, and campesterol. Consumption of dietary PSs can reduce serum cholesterol levels. Due to these properties, most studies have focused on their action on lipid metabolism and the evolution of NAFLD. PSs may reduce steatosis, cytotoxicity oxidative stress, inflammation, and apoptosis. The purpose of this review is to provide an overview of the importance of dietary phytosterols, which are a window of opportunity in the therapeutic management of NAFLD. Full article

(This article belongs to the Special Issue Food Bioactive Compounds and Chronic Liver Diseases)

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13 pages, 2181 KiB

Open AccessReview

Curcumin and Biochemical Parameters in Metabolic-Associated Fatty Liver Disease (MAFLD)—A Review

by Gracjan Różański, Sławomir Kujawski, Julia L. Newton, Paweł Zalewski and Joanna Słomko

Nutrients 2021, 13(8), 2654; https://doi.org/10.3390/nu13082654 - 30 Jul 2021

Cited by 17 | Viewed by 4527

Abstract

Metabolic-associated fatty liver disease (MAFLD), formerly non-alcoholic fatty liver disease (NAFLD), is characterized by excessive fat accumulation in hepatocytes. It is the most common chronic liver disease worldwide and is a significant public health problem. In the absence of pharmacological therapy, other treatments [...] Read more.

Metabolic-associated fatty liver disease (MAFLD), formerly non-alcoholic fatty liver disease (NAFLD), is characterized by excessive fat accumulation in hepatocytes. It is the most common chronic liver disease worldwide and is a significant public health problem. In the absence of pharmacological therapy, other treatments such as diet, physical activity, or supplementation are sought. Non-pharmacological therapies may include curcumin supplementation, which has been shown to have many health-promoting properties, including antioxidant, anti-inflammatory, and anti-cancer effects. For this reason, we reviewed available databases to analyze publications describing the effect of curcumin supplementation on biochemical parameters in MAFLD. Nine studies (eight RCTs and one CT) based solely on supplementation of patients with curcumin were included in this review. The results from the individual trials were varied and did not allow clear conclusions. Although they suggest that curcumin shows some potential in the treatment of MAFLD, further research is needed. Full article

(This article belongs to the Special Issue Food Bioactive Compounds and Chronic Liver Diseases)

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3 pages, 2426 KiB

Open AccessCorrection

Correction: Ammar et al. Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl₄-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses. Nutrients 2022, 14, 841

by Naglaa M. Ammar, Heba A. Hassan, Heba M. I. Abdallah, Sherif M. Afifi, Abdelbaset M. Elgamal, Abdel Razik H. Farrag, Abd El-Nasser G. El-Gendy, Mohamed A. Farag and Abdelsamed I. Elshamy

Nutrients 2024, 16(3), 394; https://doi.org/10.3390/nu16030394 - 30 Jan 2024

Viewed by 847

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Food Bioactive Compounds and Chronic Liver Diseases)

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