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Sun L, He Z, Li Y, Huo Z, Liu L. The relationship between nutrient intake, lifestyle, and non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus: Results from the National Health and Nutrition Examination Surveys 2007-2018. Clin Nutr ESPEN 2025; 66:446-453. [PMID: 39993562 DOI: 10.1016/j.clnesp.2025.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 01/24/2025] [Accepted: 02/10/2025] [Indexed: 02/26/2025]
Abstract
OBJECTIVE More than half of the individuals with type 2 diabetes mellitus (T2DM) are accompanied by Non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the relationship between nutrient intake, lifestyle, and the risk NAFLD in patients with T2DM. METHODS This study comprised 2110 adult patients with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. We employed weighted logistic regression to assess the associations between nutrient intake, lifestyle and NAFLD, while exploring potential non-linear relationships using restrictive cubic spline analysis. Additionally, we validated our findings through subgroup analyses and sensitivity analyses to ensure the robustness and reliability of our results. RESULT Out of 2110 diabetes patients, 1743 were diagnosed with NAFLD, and 53.43 % of them were male. After adjusting for potential confounders, we found a negative correlation between Vitamin K intake and the occurrence of NAFLD in patients with T2DM (OR = 0.885 [0.829, 0.959]). This dose-response relationship was further validated through stratification analysis by tertiles of vitamin K intake. Lycopene intake is identified as a risk factor for NAFLD in patients with T2DM. Specifically, for every 100 μg of lycopene ingested, there was a 0.2 % higher likelihood of NAFLD (OR = 1.002 [1.0001, 1.005], p < 0.05). Conversely, a 0.5 % reduction in NAFLD risk was observed with the same amount of lutein intake (OR = 0.995 [0.992, 0.999], p < 0.05). Furthermore, we also found that a high-quality diet can reduce the risk of NAFLD in patients with T2DM, with an odds ratio of 0.208 (0.101, 0.430). CONCLUSION Increasing intake of Vitamin K and lutein, reducing intake of lycopene, and improving dietary quality may lower the risk of NAFLD in patients with T2DM.
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Affiliation(s)
- Liangyuanhui Sun
- Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China; Department of Gastroenterology, Fourth Affiliated Hospital of Guangxi Medical University/Liuzhou Worker's Hospital, Liuzhou 545000, Guangxi, China.
| | - Zhiqing He
- Department of Otolaryngology-Head and Neck Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 519041, Guangdong, China.
| | - Yanbin Li
- Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
| | - Zijun Huo
- Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
| | - Liehua Liu
- Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
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Fu Y, Jiang C, Li Z, Shi X, Lv P, Zhang J. Association between the composite dietary antioxidant index and non-alcoholic fatty liver disease: evidence from National Health and Nutrition Examination Survey 2005-2016. Front Nutr 2025; 12:1473487. [PMID: 39917746 PMCID: PMC11798779 DOI: 10.3389/fnut.2025.1473487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 01/06/2025] [Indexed: 02/09/2025] Open
Abstract
Importance Oxidative stress contributes to the progression of non-alcoholic fatty liver disease (NAFLD). Antioxidants from food can reduce NAFLD incidence, and the Composite Dietary Antioxidant Index (CDAI) measures total antioxidant capacity (TAC). However, the relationship between CDAI and NAFLD in the US adult population remains unclear. Objective To assess whether CDAI is associated with NAFLD in US adults. Design setting and participants This population-based cross-sectional study used data on US adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2016 cycles. Data were analyzed from January to February 2024. Exposures CDAI obtained from the dietary intake questionnaire. Main outcomes and measures The main outcome was NAFLD which defined by the US fatty liver score (USFLI) ≥30. Sampling weights were calculated according to NHANES guidelines. Results Among 9,746 adults included in this study [mean age, 48.3 years; 4,662 (47.6%) males], 3,324 (33.0%) were classified as having NAFLD using USFLI. In the fully adjusted of multivariable logistic regression, CDAI was negatively associated with NAFLD (odds ratio [OR], 0.95; 95% CI, 0.93-0.98). Furthermore, individuals in the highest quartile of CDAI were 34% less likely to have NAFLD compared to those in the lowest quartile (OR, 0.66; 95% CI, 0.52-0.85). In subgroup analyses, CDAI was inversely associated with NAFLD among participants with a BMI <25 (OR, 0.89; 95% CI, 0.83-0.95) and without metabolic syndrome (OR, 0.93; 95% CI, 0.91-0.96). The interaction tests revealed significant differences in these subgroups (P for interaction = 0.04 for BMI and 0.003 for metabolic syndrome). Sensitivity analyses confirmed this association using the hepatic steatosis index (HSI) to define NAFLD, applying unweighted logistic regression, adjusting for physical activity or after excluding non-Hispanic Black participants, and after excluding medications known for their potential hepatotoxic effects. Conclusions and relevance In this cross-sectional study based on six cycles (2005-2016) of the NHANES, CDAI was negatively associated with NAFLD in US adult population. This association highlights the potential for dietary interventions to reduce NAFLD incidence and underscores the need for future research, including clinical trials and mechanistic studies, to further explore the role of dietary antioxidants in NAFLD prevention and management.
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Affiliation(s)
- Yidian Fu
- Graduate School of Hebei Medical University, Shijiazhuang, Hebei, China
- Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, China
| | - Chao Jiang
- Department of Psychosomatic Medicine, Hebei General Hospital, Shijiazhuang, Hebei, China
| | - Zonglin Li
- Department of Medical Laboratory, Liaocheng Hospital of Traditional Chinese Medicine, Liaocheng, Shandong, China
| | - Xiangyun Shi
- College of Geography and Resources, Sichuan Normal University, Chengdu, China
| | - Peiyuan Lv
- Graduate School of Hebei Medical University, Shijiazhuang, Hebei, China
- Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, China
| | - Jingbo Zhang
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Claria B, Espinosa A, Rodríguez A, Dovale-Rosabal G, Bucarey JL, Pando ME, Romero N, Reinoso F, Sánchez C, Valenzuela R, Ribeiro CH, Aubourg SP. Cold-Pressed Aristotelia chilensis (Mol.) Stuntz Seed Oil Prevents Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD) in a High-Fat-Diet-Induced Obesity Murine Model. Antioxidants (Basel) 2024; 13:1384. [PMID: 39594526 PMCID: PMC11590904 DOI: 10.3390/antiox13111384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/08/2024] [Accepted: 11/11/2024] [Indexed: 11/28/2024] Open
Abstract
This study evaluated the effects of cold-pressed maqui (Aristotelia chilensis (Mol.) Stuntz) seed oil (MO) on liver metabolism and biochemical markers in a high-fat diet (HFD) murine model. In it, the fatty acid profile, tocopherol and tocotrienol contents, and antioxidant capacity of MO were analyzed. Male C57BL/6 mice were divided into four groups (i.e., a, b, c, and d groups) and supplemented for 12 weeks according to the following distribution: (a) control diet (CD)-sunflower oil (SO), (b) CD+MO, (c) HFD+SO, and (d) HFD+MO. Total body and organ weights, serum markers, and liver fat infiltration were assessed. MO contained 32.31% oleic acid, 46.41% linoleic acid, and 10.83% α-linolenic acid; additionally, α- and γ-tocopherol levels were 339.09 ± 5.15 and 135.52 ± 38.03 mg/kg, respectively, while β-, δ-tocopherol, and α-tocotrienol were present in trace amounts and the antioxidant capacity measured was 6.66 ± 0.19 μmol Trolox equivalent/g. MO supplementation significantly reduced the visceral fat (0.76 ± 0.06 g vs. 1.32 ± 0.04 g) and GPT (glutamate pyruvate transaminase) levels (71.8 ± 5.0 vs. 35.2 ± 2.6 U/L), and the liver fat infiltration score (6 vs. 3) in the HFD+MO group compared to HFD+SO. It is suggested that MO may effectively prevent fatty liver disease, warranting further research on its potential benefits for human health.
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Affiliation(s)
- Benjamín Claria
- Department of Food Science and Chemical Technology, Faculty of Chemical and Pharmaceutical Sciences, Dr. Carlos Lorca Tobar 964, University of Chile, Santiago 8380494, Chile; (B.C.); (G.D.-R.); (N.R.); (F.R.); (C.S.)
- Department of Medical Technology, Faculty of Medicine, University of Chile, Santiago 8380000, Chile;
| | - Alejandra Espinosa
- Department of Medical Technology, Faculty of Medicine, University of Chile, Santiago 8380000, Chile;
- School of Medicine, Faculty of Medicine, Universidad de Valparaíso, San Felipe 2172972, Chile;
- Center of Interdisciplinary Biomedical and Engineering Research for Health, Universidad de Valparaíso, San Felipe 2172972, Chile
| | - Alicia Rodríguez
- Department of Food Science and Chemical Technology, Faculty of Chemical and Pharmaceutical Sciences, Dr. Carlos Lorca Tobar 964, University of Chile, Santiago 8380494, Chile; (B.C.); (G.D.-R.); (N.R.); (F.R.); (C.S.)
| | - Gretel Dovale-Rosabal
- Department of Food Science and Chemical Technology, Faculty of Chemical and Pharmaceutical Sciences, Dr. Carlos Lorca Tobar 964, University of Chile, Santiago 8380494, Chile; (B.C.); (G.D.-R.); (N.R.); (F.R.); (C.S.)
| | - José Luis Bucarey
- School of Medicine, Faculty of Medicine, Universidad de Valparaíso, San Felipe 2172972, Chile;
| | - María Elsa Pando
- Department of Nutrition, Faculty of Medicine, University of Chile, Santiago 8380000, Chile; (M.E.P.); (R.V.)
| | - Nalda Romero
- Department of Food Science and Chemical Technology, Faculty of Chemical and Pharmaceutical Sciences, Dr. Carlos Lorca Tobar 964, University of Chile, Santiago 8380494, Chile; (B.C.); (G.D.-R.); (N.R.); (F.R.); (C.S.)
| | - Francisca Reinoso
- Department of Food Science and Chemical Technology, Faculty of Chemical and Pharmaceutical Sciences, Dr. Carlos Lorca Tobar 964, University of Chile, Santiago 8380494, Chile; (B.C.); (G.D.-R.); (N.R.); (F.R.); (C.S.)
| | - Camila Sánchez
- Department of Food Science and Chemical Technology, Faculty of Chemical and Pharmaceutical Sciences, Dr. Carlos Lorca Tobar 964, University of Chile, Santiago 8380494, Chile; (B.C.); (G.D.-R.); (N.R.); (F.R.); (C.S.)
| | - Rodrigo Valenzuela
- Department of Nutrition, Faculty of Medicine, University of Chile, Santiago 8380000, Chile; (M.E.P.); (R.V.)
| | - Carolina H. Ribeiro
- Immunology Program, Biomedical Sciences Institute (ICBM), Faculty of Medicine, University of Chile, Santiago 8380000, Chile;
| | - Santiago P. Aubourg
- Department of Food Technology, Marine Research Institute (CSIC), Eduardo Cabello 6, 36208 Vigo, Spain
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He YX, Liu MN, Wu H, Lan Q, Liu H, Mazhar M, Xue JY, Zhou X, Chen H, Li Z. Puerarin: a hepatoprotective drug from bench to bedside. Chin Med 2024; 19:139. [PMID: 39380120 PMCID: PMC11460048 DOI: 10.1186/s13020-024-01011-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 09/22/2024] [Indexed: 10/10/2024] Open
Abstract
Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases.
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Affiliation(s)
- Yi-Xiang He
- The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou City, Affiliated Traditional Medicine Hospital of Southwest Medical University, Luzhou, 646000, China
- Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Meng-Nan Liu
- Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Hao Wu
- Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Qi Lan
- Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Hao Liu
- Department of Pediatrics, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Maryam Mazhar
- Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Jin-Yi Xue
- Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Xin Zhou
- The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou City, Affiliated Traditional Medicine Hospital of Southwest Medical University, Luzhou, 646000, China.
- Department of Spleen and Stomach Diseases, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
- Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China.
| | - Hui Chen
- The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou City, Affiliated Traditional Medicine Hospital of Southwest Medical University, Luzhou, 646000, China.
- Department of Spleen and Stomach Diseases, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
- Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China.
| | - Zhi Li
- The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou City, Affiliated Traditional Medicine Hospital of Southwest Medical University, Luzhou, 646000, China.
- Department of Spleen and Stomach Diseases, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
- Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China.
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Minetti ET, Hamburg NM, Matsui R. Drivers of cardiovascular disease in metabolic dysfunction-associated steatotic liver disease: the threats of oxidative stress. Front Cardiovasc Med 2024; 11:1469492. [PMID: 39411175 PMCID: PMC11473390 DOI: 10.3389/fcvm.2024.1469492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 08/30/2024] [Indexed: 10/19/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), now known as metabolic-associated steatotic liver disease (MASLD), is the most common liver disease worldwide, with a prevalence of 38%. In these patients, cardiovascular disease (CVD) is the number one cause of mortality rather than liver disease. Liver abnormalities per se due to MASLD contribute to risk factors such as dyslipidemia and obesity and increase CVD incidents. In this review we discuss hepatic pathophysiological changes the liver of MASLD leading to cardiovascular risks, including liver sinusoidal endothelial cells, insulin resistance, and oxidative stress with a focus on glutathione metabolism and function. In an era where there is an increasingly robust recognition of what causes CVD, such as the factors included by the American Heart Association in the recently developed PREVENT equation, the inclusion of liver disease may open doors to how we approach treatment for MASLD patients who are at risk of CVD.
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Affiliation(s)
| | | | - Reiko Matsui
- Whitaker Cardiovascular Institute, Section of Vascular Biology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States
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Assalve G, Lunetti P, Zara V, Ferramosca A. In Vivo Antioxidant Activity of Common Dietary Flavonoids: Insights from the Yeast Model Saccharomyces cerevisiae. Antioxidants (Basel) 2024; 13:1103. [PMID: 39334762 PMCID: PMC11429029 DOI: 10.3390/antiox13091103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 09/05/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Oxidative stress, associated with diseases and aging, underscores the therapeutic potential of natural antioxidants. Flavonoids, known for scavenging free radicals and modulating cell signaling, offer significant health benefits and contribute to longevity. To explore their in vivo effects, we investigated the antioxidant activity of quercetin, apigenin, luteolin, naringenin, and genistein, using Saccharomyces cerevisiae as a model organism. METHODS We performed viability assays to evaluate the effects of these compounds on cell growth, both in the presence and absence of H2O2. Additional assays, including spot assays, drug drop tests, and colony-forming unit assays, were also conducted. RESULTS Viability assays indicated that the tested compounds are non-toxic. H2O2 reduced yeast viability, but flavonoid-treated cells showed increased resistance, confirming their protective effect. Polyphenols scavenged intracellular reactive oxygen species (ROS) and protected cells from oxidative damage. Investigations into defense systems revealed that H2O2 induced catalase activity and oxidized glutathione accumulation, both of which were reduced by polyphenol treatment. CONCLUSIONS The tested natural compounds enhance cell viability and reduce oxidative damage by scavenging ROS and modulating antioxidant defenses. These results suggest their potential as supplements and pave the way for further research.
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Pezzino S, Sofia M, Mazzone C, Litrico G, Greco LP, Gallo L, La Greca G, Latteri S. Innovative treatments for obesity and NAFLD: A bibliometric study on antioxidants, herbs, phytochemicals, and natural compounds. Heliyon 2024; 10:e35498. [PMID: 39220898 PMCID: PMC11365328 DOI: 10.1016/j.heliyon.2024.e35498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 07/19/2024] [Accepted: 07/30/2024] [Indexed: 09/04/2024] Open
Abstract
The increasing scientific interest in antioxidants and naturally derived compounds as potential remedies for obesity and non-alcoholic fatty liver disease (NAFLD) has led to extensive research. The objective of this bibliometric analysis is to present an updated perspective on the topic of antioxidants, herbs, phytochemicals, and natural compounds, in the control of obesity and NAFLD, to identify new areas for future research. Publications from the years 2012-2022 were retrieved using the Scopus database. The research trends were analyzed using the Biblioshiny and VOSviewer tools. The field has seen a significant increase in research activity, as indicated by an annual growth rate of 10 % in the number of published manuscripts. China, Korea, and the USA emerged as the most prominent contributors in this specific field, supported by their notable volumes of publications and citations. The density analysis revealed that the most frequently occurring authors' keywords related to herbal species are, in rank order, Camelia sinensis, Momordica charantia, Curcuma longa, Ilex paraguariensis, Panax ginseng, Moringa oleifera, Garcinia cambogia, Garcinia mangostana, Zingiber officinale, and Cinnamomum verum. In the group of antioxidants, phytochemicals, and natural compounds, the top 10 were resveratrol, curcumin, quercetin, vitamin E, alpha-lipoic acid, vitamin C, chlorogenic acid, lycopene, fucoxanthin, and berberine. The co-occurrence analysis unveiled significant themes and potential trends, including a notable interest in the impact of herbal species, antioxidants, phytochemicals, and natural compounds on obesity and NAFLD through the modulation of the gut microbiome. Another recurring theme that arises, is the ongoing investigation of molecular targets that demonstrate anti-adipogenesis properties. The analysis presented in this study provides valuable insights for researchers investigating the efficacy of antioxidants, herbs, phytochemicals, and natural compounds in addressing obesity and NAFLD. Through the use of bibliometric methods, the study offers a comprehensive overview. Furthermore, the findings of this analysis can serve as a foundation for future research in this specific domain.
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Affiliation(s)
- Salvatore Pezzino
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Maria Sofia
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Chiara Mazzone
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Giorgia Litrico
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Luigi Piero Greco
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Luisa Gallo
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Gaetano La Greca
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
| | - Saverio Latteri
- Department of Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Cannizzaro Hospital, University of Catania, 95123, Catania, Italy
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Hefer M, Petrovic A, Roguljic LK, Kolaric TO, Kizivat T, Wu CH, Tabll AA, Smolic R, Vcev A, Smolic M. Green Tea Polyphenol (-)-Epicatechin Pretreatment Mitigates Hepatic Steatosis in an In Vitro MASLD Model. Curr Issues Mol Biol 2024; 46:8981-8994. [PMID: 39194748 DOI: 10.3390/cimb46080531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/06/2024] [Accepted: 08/13/2024] [Indexed: 08/29/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is becoming more prominent globally due to an increase in the prevalence of obesity, dyslipidemia, and type 2 diabetes. A great deal of studies have proposed potential treatments for MASLD, with few of them demonstrating promising results. The aim of this study was to investigate the potential effects of (-)-epicatechin (EPI) on the development of MASLD in an in vitro model using the HepG2 cell line by determining the metabolic viability of the cells and the levels of PPARα, PPARγ, and GSH. HepG2 cells were pretreated with 10, 30, 50, and 100 μM EPI for 4 h to assess the potential effects of EPI on lipid metabolism. A MASLD cell culture model was established using HepG2 hepatocytes which were exposed to 1.5 mM oleic acid (OA) for 24 h. Moreover, colorimetric MTS assay was used in order to determine the metabolic viability of the cells, PPARα and PPARγ protein levels were determined using enzyme-linked immunosorbent assay (ELISA), and lipid accumulation was visualized using the Oil Red O Staining method. Also, the levels of intracellular glutathione (GSH) were measured to determine the level of oxidative stress. EPI was shown to increase the metabolic viability of the cells treated with OA. The metabolic viability of HepG2 cells, after 24 h incubation with OA, was significantly decreased, with a metabolic viability of 71%, compared to the cells pretreated with EPI, where the metabolic viability was 74-86% with respect to the concentration of EPI used in the experiment. Furthermore, the levels of PPARα, PPARγ, and GSH exhibited a decrease in response to increasing EPI concentrations. Pretreatment with EPI has demonstrated a great effect on the levels of PPARα, PPARγ, and GSH in vitro. Therefore, considering that EPI mediates lipid metabolism in MASLD, it should be considered a promising hepatoprotective agent in future research.
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Affiliation(s)
- Marija Hefer
- Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Ana Petrovic
- Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Lucija Kuna Roguljic
- Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Tea Omanovic Kolaric
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Tomislav Kizivat
- Department of Nuclear Medicine and Oncology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Catherine H Wu
- Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Ashraf A Tabll
- Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Robert Smolic
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Aleksandar Vcev
- Department of Integrative Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Martina Smolic
- Department of Translational Medicine, Faculty of Dental Medicine and Health Osijek, J. J. Strossmayer University of Osijek, 31000 Osijek, Croatia
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Yahya MA, Alshammari GM, Osman MA, Al-Harbi LN, Yagoub AEA, AlSedairy SA. Liquorice root extract and isoliquiritigenin attenuate high-fat diet-induced hepatic steatosis and damage in rats by regulating AMPK. Arch Physiol Biochem 2024; 130:385-400. [PMID: 36121371 DOI: 10.1080/13813455.2022.2102654] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 07/05/2022] [Accepted: 07/08/2022] [Indexed: 11/11/2022]
Abstract
Objective: This study compared the ability of Liquorice roots aqueous extract (LRE) and its ingredient, isoliquiritigenin (ISL), in alleviating high-fat diet (HFD)-induced hepatic steatosis and examined if this effect involves activation of AMPK.Materials and methods: Control or HFD-fed rats were treated with the vehicle, LRE (200 mg/kg), or ISL (30 mg/kg) for 8 weeks orally.Results: ISL and LRE reduced HFD-induced hyperglycaemia, improved liver structure, lowered serum and hepatic lipids, and attenuated hepatic oxidative stress and inflammation. In the control and HFD-fed rats, ISL and LRE significantly stimulated the muscular and hepatic mRNA and protein levels of AMPK, improved oral glucose tolerance, reduced hepatic mRNA levels of SREBP1/2, and upregulated hepatic levels of PPARα and Bcl2. These effects were comparable for ISL and LRE and were prevented by co-administration of compound C, an AMPK inhibitor.Discussion and conclusion: ISL and LRE provide an effective theory to alleviate hepatic steatosis through activating AMPK.
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Affiliation(s)
- Mohammed Abdo Yahya
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Ghedeir M Alshammari
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Magdi A Osman
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Laila Naif Al-Harbi
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Abu ElGasim A Yagoub
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Sahar Abdulaziz AlSedairy
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia
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10
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Unagolla JM, Das S, Flanagan R, Oehler M, Menon JU. Targeting chronic liver diseases: Molecular markers, drug delivery strategies and future perspectives. Int J Pharm 2024; 660:124381. [PMID: 38917958 PMCID: PMC11246230 DOI: 10.1016/j.ijpharm.2024.124381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 06/10/2024] [Accepted: 06/22/2024] [Indexed: 06/27/2024]
Abstract
Chronic liver inflammation, a pervasive global health issue, results in millions of annual deaths due to its progression from fibrosis to the more severe forms of cirrhosis and hepatocellular carcinoma (HCC). This insidious condition stems from diverse factors such as obesity, genetic conditions, alcohol abuse, viral infections, autoimmune diseases, and toxic accumulation, manifesting as chronic liver diseases (CLDs) such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), alcoholic liver disease (ALD), viral hepatitis, drug-induced liver injury, and autoimmune hepatitis. Late detection of CLDs necessitates effective treatments to inhibit and potentially reverse disease progression. However, current therapies exhibit limitations in consistency and safety. A potential breakthrough lies in nanoparticle-based drug delivery strategies, offering targeted delivery to specific liver cell types, such as hepatocytes, Kupffer cells, and hepatic stellate cells. This review explores molecular targets for CLD treatment, ongoing clinical trials, recent advances in nanoparticle-based drug delivery, and the future outlook of this research field. Early intervention is crucial for chronic liver disease. Having a comprehensive understanding of current treatments, molecular biomarkers and novel nanoparticle-based drug delivery strategies can have enormous impact in guiding future strategies for the prevention and treatment of CLDs.
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Affiliation(s)
- Janitha M Unagolla
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
| | - Subarna Das
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
| | - Riley Flanagan
- Department of Chemical Engineering, University of Rhode Island, Kingston, RI 02881, USA
| | - Marin Oehler
- Department of Biomedical Engineering, College of Engineering, University of Rhode Island, Kingston, RI 02881, USA
| | - Jyothi U Menon
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA; Department of Chemical Engineering, University of Rhode Island, Kingston, RI 02881, USA.
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11
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Balboa E, Saud F, Parra-Ruiz C, de la Fuente M, Landskron G, Zanlungo S. Exploring the lutein therapeutic potential in steatotic liver disease: mechanistic insights and future directions. Front Pharmacol 2024; 15:1406784. [PMID: 38978979 PMCID: PMC11228318 DOI: 10.3389/fphar.2024.1406784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 06/03/2024] [Indexed: 07/10/2024] Open
Abstract
The global prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is increasing, now affecting 25%-30% of the population worldwide. MASLD, characterized by hepatic steatosis, results from an imbalance in lipid metabolism, leading to oxidative stress, lipoperoxidation, and inflammation. The activation of autophagy, particularly lipophagy, alleviates hepatic steatosis by regulating intracellular lipid levels. Lutein, a carotenoid with antioxidant and anti-inflammatory properties, protects against liver damage, and individuals who consume high amounts of lutein have a lower risk of developing MASLD. Evidence suggests that lutein could modulate autophagy-related signaling pathways, such as the transcription factor EB (TFEB). TFEB plays a crucial role in regulating lipid homeostasis by linking autophagy to energy metabolism at the transcriptional level, making TFEB a potential target against MASLD. STARD3, a transmembrane protein that binds and transports cholesterol and sphingosine from lysosomes to the endoplasmic reticulum and mitochondria, has been shown to transport and bind lutein with high affinity. This protein may play a crucial role in the uptake and transport of lutein in the liver, contributing to the decrease in hepatic steatosis and the regulation of oxidative stress and inflammation. This review summarizes current knowledge on the role of lutein in lipophagy, the pathways it is involved in, its relationship with STARD3, and its potential as a pharmacological strategy to treat hepatic steatosis.
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Affiliation(s)
- Elisa Balboa
- Center for Biomedical Research, Universidad Finis Terrae, Santiago, Chile
| | - Faride Saud
- Center for Biomedical Research, Universidad Finis Terrae, Santiago, Chile
| | - Claudia Parra-Ruiz
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Glauben Landskron
- Center for Biomedical Research, Universidad Finis Terrae, Santiago, Chile
| | - Silvana Zanlungo
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
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12
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Yang Z, Song S, Li L, Yuan Z, Li Y. Association between the composite dietary antioxidant index and metabolic dysfunction-associated steatotic liver disease in adults: a cross-sectional study from NHANES 2017-2020. Sci Rep 2024; 14:13801. [PMID: 38877074 PMCID: PMC11178812 DOI: 10.1038/s41598-024-63965-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 06/04/2024] [Indexed: 06/16/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a predominant liver disease worldwide, lacking approved drugs for clinical intervention at present. The composite dietary antioxidant index (CDAI) is used to assess the anti-inflammatory properties of diets, with higher CDAI indicating greater exposure to antioxidants. Therefore, our study aimed to explore the relationship between CDAI and MASLD in order to identify potential therapeutic approaches. We collected data from 12,286 participants in the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2020 for analysis. The correlation between CDAI and MASLD status, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) was evaluated by adjusting for confounding variables using weighted binary logistic regression model, linear regression model, and restricted cubic spline (RCS) regression. The median CDAI in this study was - 0.3055 (interquartile range [IQR], - 2.299 to 2.290). The CDAI was higher in the population characterized by being young, female, higher income, absence of diabetes, and non-MASLD. After multivariable adjustment, the results of the weighted linear regression model suggested that higher CDAI may be associated with a decrease in CAP values; the results of the RCS regression model indicated significant non-linear relationships between MASLD status, CAP, LSM, and CDAI. The CDAI corresponding to the inflection points of the relationship curves between MASLD status, CAP, LSM, and CDAI were 0.349, 0.699, and 0.174, respectively. After further stratification by gender, we found that the relationship between MASLD status, CAP, and CDAI was significantly linear for females, whereas for males, it was non-linear, and the CDAI values corresponding to the inflection points in the curves for males were 1.325 and 0.985, respectively. We found that higher CDAI may be associated with decreased CAP values, particularly significant in females, suggesting that the intake of complex dietary antioxidants may ameliorate hepatic steatosis and reduce the occurrence of MASLD. Therefore, promoting dietary patterns rich in antioxidants may be an appropriate strategy to reduce the incidence of MASLD.
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Affiliation(s)
- Zheng Yang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Department of Infectious Disease, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
| | - Shupeng Song
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lufeng Li
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhe Yuan
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Yongguo Li
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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13
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Ma K, Yi X, Yang ST, Zhu H, Liu TY, Jia SS, Fan JH, Hu DJ, Lv GP, Huang H. Isolation, purification, and structural characterization of polysaccharides from Codonopsis pilosula and its therapeutic effects on non-alcoholic fatty liver disease in vitro and in vivo. Int J Biol Macromol 2024; 265:130988. [PMID: 38518942 DOI: 10.1016/j.ijbiomac.2024.130988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 03/01/2024] [Accepted: 03/16/2024] [Indexed: 03/24/2024]
Abstract
Codonopsis pilosula is a famous edible and medicinal plants, in which polysaccharides are recognized as one of the important active ingredients. A neutral polysaccharide (CPP-1) was purified from C. pilosula. The structure was characterized by HPSEC-MALLS-RID, UV, FT-IR, GC-MS, methylation analysis, and NMR. The results showed that CPP-1 was a homogeneous pure polysaccharide, mainly containing fructose and glucose, and a small amount of arabinose. Methylation analysis showed that CPP-1 composed of →1)-Fruf-(2→, Fruf-(1→ and Glcp-(1→ residues. Combined the NMR results the structure of CPP-1 was confirmed as α-D-Glcp-(1 → [2)-β-D-Fruf-(1 → 2)-β-D-Fruf-(1]26 → 2)-β-D-Fruf with the molecular weight of 4.890 × 103 Da. The model of AML12 hepatocyte fat damage was established in vitro. The results showed that CPP-1 could increase the activity of SOD and CAT antioxidant enzymes and reduce the content of MDA, thus protecting cells from oxidative damage. Subsequently, the liver protective effect of CPP-1 was studied in the mouse model of nonalcoholic fatty liver disease (NAFLD) induced by the high-fat diet. The results showed that CPP-1 significantly reduced the body weight, liver index, and body fat index of NAFLD mice, and significantly improved liver function. Therefore, CPP-1 should be a potential candidate for the treatment of NAFLD.
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Affiliation(s)
- Kai Ma
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, PR China
| | - Xin Yi
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, PR China
| | - Shu-Ting Yang
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, PR China
| | - Hua Zhu
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, PR China
| | - Tian-Yu Liu
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, PR China
| | - Si-Si Jia
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, PR China
| | - Jia-Hao Fan
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, PR China
| | - De-Jun Hu
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China
| | - Guang-Ping Lv
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, PR China.
| | - He Huang
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, PR China
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14
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Arai T, Kawasumi K. Natural products exhibiting antiobesity effects in dogs and cats. STUDIES IN NATURAL PRODUCTS CHEMISTRY 2024:293-304. [DOI: 10.1016/b978-0-443-22214-6.00007-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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15
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Guariglia M, Saba F, Rosso C, Bugianesi E. Molecular Mechanisms of Curcumin in the Pathogenesis of Metabolic Dysfunction Associated Steatotic Liver Disease. Nutrients 2023; 15:5053. [PMID: 38140312 PMCID: PMC10745597 DOI: 10.3390/nu15245053] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 11/23/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial condition characterized by insulin resistance, oxidative stress, chronic low-grade inflammation, and sometimes fibrosis. To date, no effective pharmacological therapy has been approved for the treatment of metabolic-associated steatohepatitis (MASH), the progressive form of MASLD. Recently, numerous in vitro and in vivo studies have described the efficacy of nutraceutical compounds in the diet has been tested. Among them, curcumin is the most widely used polyphenol in the diet showing potent anti-inflammatory and antifibrotic activities. This review aims to summarize the most important basic studies (in vitro and animal models studies), describing the molecular mechanisms by which curcumin acts in the context of MASLD, providing the rationale for its effective translational use in humans.
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Affiliation(s)
| | | | - Chiara Rosso
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (M.G.); (F.S.)
| | - Elisabetta Bugianesi
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (M.G.); (F.S.)
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16
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Al Jadani JM, Albadr NA, Alshammari GM, Almasri SA, Alfayez FF, Yahya MA. Esculeogenin A, a Glycan from Tomato, Alleviates Nonalcoholic Fatty Liver Disease in Rats through Hypolipidemic, Antioxidant, and Anti-Inflammatory Effects. Nutrients 2023; 15:4755. [PMID: 38004149 PMCID: PMC10675668 DOI: 10.3390/nu15224755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 11/09/2023] [Accepted: 11/10/2023] [Indexed: 11/26/2023] Open
Abstract
This study examined the preventative effects of esculeogenin A (ESGA), a newly discovered glycan from tomato, on liver damage and hepatic steatosis in high-fat-diet (HFD)-fed male rats. The animals were divided into six groups (each of eight rats): a control group fed a normal diet, control + ESGA (200 mg/kg), HFD, and HFD + ESAG in 3 doses (50, 100, and 200 mg/kg). Feeding and treatments were conducted for 12 weeks. Treatment with ESGA did not affect gains in the body or fat weight nor increases in fasting glucose, insulin, and HOMA-IR or serum levels of free fatty acids (FFAs), tumor-necrosis factor-α, and interleukin-6 (IL-6). On the contrary, it significantly reduced the serum levels of gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein cholesterol (LDL-c) in the HFD-fed rats. In addition, it improved the liver structure, attenuating the increase in fat vacuoles; reduced levels of TGs and CHOL, and the mRNA levels of SREBP1 and acetyl CoA carboxylase (ACC); and upregulated the mRNA levels of proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase I (CPT I) in HFD-fed rats. These effects were concomitant with increases in the mRNA, cytoplasmic, and nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO); a reduction in the nuclear activity of nuclear factor-kappa beta (NF-κB); and inhibition of the activity of nuclear factor kappa B kinase subunit beta (IKKβ). All of these effects were dose-dependent effects in which a normal liver structure and normal levels of all measured parameters were seen in HFD + ESGA (200 mg/kg)-treated rats. In conclusion, ESGA prevents NAFLD in HFD-fed rats by attenuating hyperlipidemia, hepatic steatosis, oxidative stress, and inflammation by acting locally on Nrf2, NF-κB, SREBP1, and PPARα transcription factors.
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Affiliation(s)
- Jwharah M. Al Jadani
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia; (J.M.A.J.); (G.M.A.); (S.A.A.); (M.A.Y.)
| | - Nawal A. Albadr
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia; (J.M.A.J.); (G.M.A.); (S.A.A.); (M.A.Y.)
| | - Ghedeir M. Alshammari
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia; (J.M.A.J.); (G.M.A.); (S.A.A.); (M.A.Y.)
| | - Soheir A. Almasri
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia; (J.M.A.J.); (G.M.A.); (S.A.A.); (M.A.Y.)
| | - Farah Fayez Alfayez
- Department of Medicine and Surgery, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia;
| | - Mohammed Abdo Yahya
- Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia; (J.M.A.J.); (G.M.A.); (S.A.A.); (M.A.Y.)
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17
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Shit A, Park S, Lee Y, Ryplida B, Morgan N, Jang YC, Jin EJ, Park SY. Stimuli-responsive pressure-strain sensor-based conductive hydrogel for alleviated non-alcoholic fatty liver disease by scavenging reactive oxygen species in adipose tissue. Acta Biomater 2023; 171:406-416. [PMID: 37739252 DOI: 10.1016/j.actbio.2023.09.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/28/2023] [Accepted: 09/17/2023] [Indexed: 09/24/2023]
Abstract
A visible light- and reactive oxygen species (ROS)-responsive pressure/strain sensor based on carbon dot (CD)-loaded conductive hydrogel was developed for detecting high-fat diet (HFD) and preventing the risk of non-alcoholic fatty liver disease. The designed nanoparticle consisted of a diselenide polymer dot (dsPD) loaded with a visible light-responsive CD to form dsPD@CD (DSCD). The influence of visible light irradiation and ROS on DSCD facilitated the electron transport, enhancing the conductivity of DSCD-embedded hydrogel (DSCD hydrogel) from 1.3 to 35.9 mS/m. Alternatively, the tensile modulus of the DSCD hydrogel enhanced to 223 % after light-induced ROS treatment, which simultaneously impacted the capacitive response (120 %). The hydrogel implantation into inguinal white adipose tissue of HFD mice showed 82 % higher conductivity and 83 % enhanced pressure sensing response to HFD-generated high ROS levels compared with the normal diet-fed mice. Additionally, the ROS scavenging activity of DSCD hydrogel was confirmed by the downregulation of ROS-responsive genes, such as Sod2, Nrf2, and catalase (Cat) in murine primary hepatocytes isolated from fatty liver-induced mice. In addition, in vivo animal studies also confirmed the suppression of hepatic lipogenesis, as shown by decreased Pparγ and Fasn expression and hypertrophy of adipocytes in HFD mice. The distinguishable real-time wireless resistance response observed with pressure sensing indicates the potential application of the device for monitoring the risk of non-alcoholic fatty liver disease. STATEMENT OF SIGNIFICANCE: A visible-light-induced ROS-responsive carbon dot-loaded conductive hydrogel was developed for the detection of HFD-induced alterations in ROS levels by evaluating the conductivity and electrochemical responses with applied pressure/strain. The implanted hydrogel facilitates the recovery of the inflated adipocytes induced by NAFLD, which reduces fat accumulation in the liver, preventing the risk of NAFLD. Real-time detection based on the resistance response during local compression of the hydrogel is possibly performed utilizing a wireless sensing device, demonstrating the ease of NAFLD monitoring.
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Affiliation(s)
- Arnab Shit
- Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju 27469, Republic of Korea
| | - Sujeong Park
- Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk 54538, Republic of Korea
| | - Yunki Lee
- Department of Orthopaedics, Emory Musculoskeletal Institute, Emory University School of Medicine, Atlanta, GA, USA
| | - Benny Ryplida
- Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju 27469, Republic of Korea
| | - Nyssa Morgan
- School of Biological Science, Wallace H. Coulter Department of Biomedical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
| | - Young C Jang
- Department of Orthopaedics, Emory Musculoskeletal Institute, Emory University School of Medicine, Atlanta, GA, USA; School of Biological Science, Wallace H. Coulter Department of Biomedical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
| | - Eun-Jung Jin
- Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk 54538, Republic of Korea.
| | - Sung Young Park
- Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju 27469, Republic of Korea; Department of IT and Energy Convergence (BK21 FOUR), Korea National University of Transportation, Chungju 27469, Republic of Korea.
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18
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Myint M, Oppedisano F, De Giorgi V, Kim BM, Marincola FM, Alter HJ, Nesci S. Inflammatory signaling in NASH driven by hepatocyte mitochondrial dysfunctions. J Transl Med 2023; 21:757. [PMID: 37884933 PMCID: PMC10605416 DOI: 10.1186/s12967-023-04627-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 10/14/2023] [Indexed: 10/28/2023] Open
Abstract
Liver steatosis, inflammation, and variable degrees of fibrosis are the pathological manifestations of nonalcoholic steatohepatitis (NASH), an aggressive presentation of the most prevalent chronic liver disease in the Western world known as nonalcoholic fatty liver (NAFL). Mitochondrial hepatocyte dysfunction is a primary event that triggers inflammation, affecting Kupffer and hepatic stellate cell behaviour. Here, we consider the role of impaired mitochondrial function caused by lipotoxicity during oxidative stress in hepatocytes. Dysfunction in oxidative phosphorylation and mitochondrial ROS production cause the release of damage-associated molecular patterns from dying hepatocytes, leading to activation of innate immunity and trans-differentiation of hepatic stellate cells, thereby driving fibrosis in NASH.
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Affiliation(s)
| | - Francesca Oppedisano
- Department of Health Sciences, Institute of Research for Food Safety and Health, University "Magna Græcia" of Catanzaro, Catanzaro, Italy
| | - Valeria De Giorgi
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, USA
| | | | | | - Harvey J Alter
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, USA
| | - Salvatore Nesci
- Department of Veterinary Medical Sciences, University of Bologna, Ozzano Emilia, Italy.
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19
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Wang L, Yan Y, Wu L, Peng J. Natural products in non-alcoholic fatty liver disease (NAFLD): Novel lead discovery for drug development. Pharmacol Res 2023; 196:106925. [PMID: 37714392 DOI: 10.1016/j.phrs.2023.106925] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 09/06/2023] [Accepted: 09/12/2023] [Indexed: 09/17/2023]
Abstract
With changing lifestyles, non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide. A substantial increase in the incidence, mortality, and associated burden of NAFLD-related advanced liver disease is expected. Currently, the initial diagnosis of NAFLD is still based on ultrasound and there is no approved treatment method. Lipid-lowering drugs, vitamin supplementation, and lifestyle improvement treatments are commonly used in clinical practice. However, most lipid-lowering drugs can produce poor patient compliance and specific adverse effects. Therefore, the exploration of bio-diagnostic markers and active lead compounds for the development of innovative drugs is urgently needed. More and more studies have reported the anti-NAFLD effects and mechanisms of natural products (NPs), which have become an important source for new drug development to treat NAFLD due to their high activity and low side effects. At present, berberine and silymarin have been approved by the US FDA to enter clinical phase IV studies, demonstrating the potential of NPs against NAFLD. Studies have found that the regulation of lipid metabolism, insulin resistance, oxidative stress, and inflammation-related pathways may play important roles in the process. With the continuous updating of technical means and scientific theories, in-depth research on the targets and mechanisms of NPs against NAFLD can provide new possibilities to find bio-diagnostic markers and innovative drugs. As we know, FXR agonists, PPARα agonists, and dual CCR2/5 inhibitors are gradually coming on stage for the treatment of NAFLD. Whether NPs can exert anti-NAFLD effects by regulating these targets or some unknown targets remains to be further studied. Therefore, the study reviewed the potential anti-NAFLD NPs and their targets. Some works on the discovery of new targets and the docking of active lead compounds were also discussed. It is hoped that this review can provide some reference values for the development of non-invasive diagnostic markers and new drugs against NAFLD in the clinic.
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Affiliation(s)
- Lu Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China
| | - Yonghuan Yan
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China
| | - Linfang Wu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China
| | - Jinyong Peng
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
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20
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Cortés-Espinar AJ, Ibarz-Blanch N, Soliz-Rueda JR, Bonafos B, Feillet-Coudray C, Casas F, Bravo FI, Calvo E, Ávila-Román J, Mulero M. Rhythm and ROS: Hepatic Chronotherapeutic Features of Grape Seed Proanthocyanidin Extract Treatment in Cafeteria Diet-Fed Rats. Antioxidants (Basel) 2023; 12:1606. [PMID: 37627601 PMCID: PMC10452039 DOI: 10.3390/antiox12081606] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 08/02/2023] [Accepted: 08/09/2023] [Indexed: 08/27/2023] Open
Abstract
Polyphenols play a key role in the modulation of circadian rhythms, while the cafeteria diet (CAF) is able to perturb the hepatic biological rhythm and induce important ROS production. Consequently, we aimed to elucidate whether grape seed proanthocyanidin extract (GSPE) administration recovers the CAF-induced hepatic antioxidant (AOX) misalignment and characterize the chronotherapeutic properties of GSPE. For this purpose, Fischer 344 rats were fed a standard diet (STD) or a CAF and concomitantly treated with GSPE at two time-points (ZT0 vs. ZT12). Animals were euthanized every 6 h and the diurnal rhythms of hepatic ROS-related biomarkers, hepatic metabolites, and AOX gene expression were examined. Interestingly, GSPE treatment was able to recover the diurnal rhythm lost due to the CAF. Moreover, GSPE treatment also increased the acrophase of Sod1, as well as bringing the peak closer to that of the STD group. GSPE also corrected some hepatic metabolites altered by the CAF. Importantly, the differences observed at ZT0 vs. ZT12 due to the time of GSPE administration highlight a chronotherapeutic profile on the proanthocyanin effect. Finally, GSPE could also reduce diet-induced hepatic oxidative stress not only by its ROS-scavenging properties but also by retraining the circadian rhythm of AOX enzymes.
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Affiliation(s)
- Antonio J. Cortés-Espinar
- Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain; (A.J.C.-E.); (N.I.-B.); (J.R.S.-R.); (F.I.B.); (E.C.)
- Nutrigenomics Research Group, Institut d’Investigació Sanitària Pere Virgili, 43007 Tarragona, Spain
- DMEM, EMN, UMR 866, INRAe, Université de Montpellier, 34090 Montpellier, France; (B.B.); (C.F.-C.); (F.C.)
| | - Néstor Ibarz-Blanch
- Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain; (A.J.C.-E.); (N.I.-B.); (J.R.S.-R.); (F.I.B.); (E.C.)
- Nutrigenomics Research Group, Institut d’Investigació Sanitària Pere Virgili, 43007 Tarragona, Spain
| | - Jorge R. Soliz-Rueda
- Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain; (A.J.C.-E.); (N.I.-B.); (J.R.S.-R.); (F.I.B.); (E.C.)
- Nutrigenomics Research Group, Institut d’Investigació Sanitària Pere Virgili, 43007 Tarragona, Spain
| | - Béatrice Bonafos
- DMEM, EMN, UMR 866, INRAe, Université de Montpellier, 34090 Montpellier, France; (B.B.); (C.F.-C.); (F.C.)
| | - Christine Feillet-Coudray
- DMEM, EMN, UMR 866, INRAe, Université de Montpellier, 34090 Montpellier, France; (B.B.); (C.F.-C.); (F.C.)
| | - François Casas
- DMEM, EMN, UMR 866, INRAe, Université de Montpellier, 34090 Montpellier, France; (B.B.); (C.F.-C.); (F.C.)
| | - Francisca Isabel Bravo
- Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain; (A.J.C.-E.); (N.I.-B.); (J.R.S.-R.); (F.I.B.); (E.C.)
- Nutrigenomics Research Group, Institut d’Investigació Sanitària Pere Virgili, 43007 Tarragona, Spain
| | - Enrique Calvo
- Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain; (A.J.C.-E.); (N.I.-B.); (J.R.S.-R.); (F.I.B.); (E.C.)
- Nutrigenomics Research Group, Institut d’Investigació Sanitària Pere Virgili, 43007 Tarragona, Spain
| | - Javier Ávila-Román
- Molecular and Applied Pharmacology Group (FARMOLAP), Department of Pharmacology, Universidad de Sevilla, 41012 Sevilla, Spain
| | - Miquel Mulero
- Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain; (A.J.C.-E.); (N.I.-B.); (J.R.S.-R.); (F.I.B.); (E.C.)
- Nutrigenomics Research Group, Institut d’Investigació Sanitària Pere Virgili, 43007 Tarragona, Spain
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21
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Atwaa ESH, Shahein MR, Raya-Álvarez E, Abd El-Sattar ES, Hassan MAA, Hashim MA, Dahran N, El-Khadragy MF, Agil A, Elmahallawy EK. Assessment of the physicochemical and sensory characteristics of fermented camel milk fortified with Cordia myxa and its biological effects against oxidative stress and hyperlipidemia in rats. Front Nutr 2023; 10:1130224. [PMID: 37229477 PMCID: PMC10203225 DOI: 10.3389/fnut.2023.1130224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 04/17/2023] [Indexed: 05/27/2023] Open
Abstract
Natural feed additives and their potential benefits in production of safe and highly nutritious food have gained the attention of many researchers the last decades. Cordia myxa is a nutrient-dense food with various health benefits. Despite this fact, very limited studied investigated the physicochemical and sensory impacts of incorporation of fermented camel milk with Cordia myxa and its biological effects. The current study aimed to assess the physical, chemical, and sensory characteristics of fermented camel milk (FCM) fortified with 5, 10, and 15% Cordia myxa pulp. The study demonstrated that fortification of camel milk efficiently enhanced protein, total solids, ash, fiber, phenolic substance, and antioxidant activity. When compared to other treatments, FCM supplemented with 10% Cordia myxa pulp had the best sensory features. In addition, FCM fortified with 10% Cordia myxa pulp was investigated as a potential inhibitor of hypercholesterolemia agents in obese rats. Thirty-two male Wistar rats were split into two main groups including normal pellet group (n = 8) served as negative control group (G1) and a group of hyperlipidemic animals (n = 24) were feed on a high-fat diet (HFD). Hyperlipidemic rats group (n = 24) were then divided into three subgroups (8 per each); second group or positive control (G2) which include hyperlipidemic rats received distilled water (1 mL/day), the third group (G3) involved hyperlipidemic rats feed on FCM (10 g/day) and the fourth group (G4) included hyperlipidemic animals feed on 10 g/day FCM fortified with 10% of Cordia myxa pulp by oral treatment via an intestinal tube for another 4 weeks. In contrast to the positive control group, G4 treated with Cordia myxa showed a substantial decrease in malondialdehyde, LDL, cholesterol, triglycerides, AST, ALT, creatinine, and urea levels, while a significant increase in HDL, albumin, and total protein concentrations. The number of large adipocytes decreased while the number of small adipocytes increased after consumption of fortified FCM. The results indicated that fermented milk fortified with Cordia myxa pulp improved the functions of the liver and kidney in hyperlipidemic rats. These results demonstrated the protective effects of camel milk and Cordia myxa pulp against hyperlipidemia in rats.
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Affiliation(s)
- El Sayed Hassan Atwaa
- Department of Food Science, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
| | - Magdy Ramadan Shahein
- Department of Food Science and Technology, Faculty of Agriculture, Tanta University, Tanta, Egypt
| | | | - El Sayed Abd El-Sattar
- Department of Food and Dairy Technology, Faculty of Technology and Development, Zagazig University, Zagazig, Egypt
| | - Moustafa A. A. Hassan
- Department of Food Science, Faculty of Agriculture, Ain Shams University, Cairo, Egypt
| | - Madeha Ahmed Hashim
- Department of Histology, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt
| | - Naief Dahran
- Department of Anatomy, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia
| | - Manal F. El-Khadragy
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Ahmad Agil
- Department of Pharmacology, Biohealth Institute Granada (IBs Granada) and Neuroscience Institute, School of Medicine, University of Granada, Granada, Spain
| | - Ehab Kotb Elmahallawy
- Department of Zoonoses, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt
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22
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Zhong L, Lyu W, Lin Z, Lu J, Geng Y, Song L, Zhang H. Quinoa Ameliorates Hepatic Steatosis, Oxidative Stress, Inflammation and Regulates the Gut Microbiota in Nonalcoholic Fatty Liver Disease Rats. Foods 2023; 12:foods12091780. [PMID: 37174318 PMCID: PMC10178724 DOI: 10.3390/foods12091780] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/23/2023] [Accepted: 03/25/2023] [Indexed: 05/15/2023] Open
Abstract
A long-term high-fat diet causes hepatic steatosis, which further leads to oxidative stress and inflammation. In this study, we firstly investigated the regulation effects of different amounts of quinoa on hepatic steatosis, oxidative stress, and inflammation of rats fed a high-fat diet, then the gut microbiota was dynamically determined. Sprague-Dawley (SD, male) rats were randomized into four groups: normal controls (NC, fed standard chow), model groups (HF, fed a high-fat diet), low quinoa intake (HF + LQ), and high quinoa intake (HF + HQ) groups, which were supplemented with 9% and 27% quinoa in the high-fat feed (equivalent to 100 g/day and 300 g/day human intake, respectively). The results showed that quinoa intake significantly inhibited the hepatomegaly and splenomegaly, ameliorated hepatic steatosis pathologically; effectively rescued the decrease in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) and the increase in malondialdehyde (MDA). The levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and leptin in rats of two quinoa groups were close to those of the NC group. Besides, high quinoa intake significantly increased the relative abundance of Akkermansia, and low quinoa intake significantly increased the relative abundance of Blautia at the genus level. The relative abundances of Blautia and Dorea in rats in the HF + HQ group were lower than those in rats in the HF + LQ group. In addition, the relative abundances of Clostridium and Turicibacter of rats in the two quinoa intervention groups were lower than those of rats in the HF group after 12 weeks of intervention. In summary, quinoa exhibits a series of beneficial effects in the prevention of nonalcoholic fatty liver disease (NAFLD) and is suggested to be a component of a daily diet for the prevention of NAFLD.
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Affiliation(s)
- Lingyue Zhong
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Wei Lyu
- National Semi-Arid Agriculture Engineering Technology Research Center, Shijiazhuang 050051, China
| | - Zihan Lin
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Jun Lu
- CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai 201602, China
| | - Yanlou Geng
- National Semi-Arid Agriculture Engineering Technology Research Center, Shijiazhuang 050051, China
| | - Lihua Song
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Heng Zhang
- CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai 201602, China
- School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
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23
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Farage AE, Abdo W, Osman A, Abdel-Kareem MA, Hakami ZH, Alsulimani A, Bin-Ammar A, Alanazi AS, Alsuwayt B, Alanazi MM, Antar SA, Kamel EM, Mahmoud AM. Betulin prevents high fat diet-induced non-alcoholic fatty liver disease by mitigating oxidative stress and upregulating Nrf2 and SIRT1 in rats. Life Sci 2023; 322:121688. [PMID: 37030617 DOI: 10.1016/j.lfs.2023.121688] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 04/04/2023] [Accepted: 04/05/2023] [Indexed: 04/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common chronic hepatic disorder characterized by hepatic lipid accumulation. This study explored the effect of betulin (BE), a terpenoid with promising antioxidant, anti-inflammatory and insulin sensitizing effects, on NAFLD induced by high fat diet (HFD). Rats received HFD and BE (15 and 30 mg/kg) for 12 weeks and blood and liver samples were collected for analyses. HFD caused hyperlipidemia, cholesterol and triglycerides accumulation in the liver, hepatocellular ballooning, fibrosis, insulin resistance (IR), lipid peroxidation (LPO), and NF-kB p65 upregulation. BE ameliorated serum and liver lipids, blood glucose, and insulin, liver LPO, prevented steatosis and fibrosis, suppressed NF-kB p65 and enhanced antioxidants in HFD-fed rats. BE downregulated ACC1 and FAS, and upregulated Nrf2, HO-1 and SIRT1 in the liver of HFD-fed rats. In silico investigations revealed the binding affinity of BE towards NF-kB, Keap1, HO-1 and SIRT1. In conclusion, BE attenuated HFD-induced NAFLD by ameliorating hyperlipidemia, IR, lipogenesis, liver lipid accumulation, and oxidative stress. The protective effect of BE was associated with enhanced Nrf2/HO-1 signaling and SIRT1.
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Al-Hussan R, Albadr NA, Alshammari GM, Almasri SA, Yahya MA. Phloretamide Prevent Hepatic and Pancreatic Damage in Diabetic Male Rats by Modulating Nrf2 and NF-κB. Nutrients 2023; 15:nu15061456. [PMID: 36986192 PMCID: PMC10059022 DOI: 10.3390/nu15061456] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/07/2023] [Accepted: 03/14/2023] [Indexed: 03/22/2023] Open
Abstract
This study examined the effect of phloretamide, a metabolite of phloretin, on liver damage and steatosis in streptozotocin-induced diabetes mellitus (DM) in rats. Adult male rats were divided into two groups: control (nondiabetic) and STZ-treated rats, each of which was further treated orally with the vehicle phloretamide 100 mg or 200 mg. Treatments were conducted for 12 weeks. Phloretamide, at both doses, significantly attenuated STZ-mediated pancreatic β-cell damage, reduced fasting glucose, and stimulated fasting insulin levels in STZ-treated rats. It also increased the levels of hexokinase, which coincided with a significant reduction in glucose-6 phosphatase (G-6-Pase), and fructose-1,6-bisphosphatase 1 (PBP1) in the livers of these diabetic rats. Concomitantly, both doses of phloretamide reduced hepatic and serum levels of triglycerides (TGs) and cholesterol (CHOL), serum levels of low-density lipoprotein cholesterol (LDL-c), and hepatic ballooning. Furthermore, they reduced levels of lipid peroxidation, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), mRNA, and total and nuclear levels of NF-κB p65, but increased mRNA levels, total and nuclear levels of Nrf2, as well as levels of reduced glutathione (GSH), superoxide dismutase (SOD-1), catalase (CAT), and heme-oxygenase-1 (HO-1) in the livers of diabetic rats. All of these effects were dose-dependent. In conclusion, phloretamide is a novel drug that could ameliorate DM-associated hepatic steatosis via its powerful antioxidant and anti-inflammatory effects. Mechanisms of protection involve improving the β-cell structure and hepatic insulin action, suppressing hepatic NF-κB, and stimulating hepatic Nrf2.
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Martin-Grau M, Monleon D. Sex dimorphism and metabolic profiles in management of metabolic-associated fatty liver disease. World J Clin Cases 2023; 11:1236-1244. [PMID: 36926130 PMCID: PMC10013124 DOI: 10.12998/wjcc.v11.i6.1236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/30/2022] [Accepted: 02/02/2023] [Indexed: 02/23/2023] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) refers to the build-up of fat in the liver associated with metabolic dysfunction and has been estimated to affect a quarter of the population worldwide. Although metabolism is highly influenced by the effects of sex hormones, studies of sex differences in the incidence and progression of MAFLD are scarce. Metabolomics represents a powerful approach to studying these differences and identifying potential biomarkers and putative mechanisms. First, metabolomics makes it possible to obtain the molecular phenotype of the individual at a given time. Second, metabolomics may be a helpful tool for classifying patients according to the severity of the disease and obtaining diagnostic biomarkers. Some studies demonstrate associations between circulating metabolites and early and established MAFLD, but little is known about how metabolites relate to and encompass sex differences in disease progression and risk management. In this review, we will discuss the epidemiological metabolomic studies for sex differences in the development and progression of MAFLD, the role of metabolic profiles in understanding mechanisms and identifying sex-dependent biomarkers, and how this evidence may help in the future management of the disease.
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Affiliation(s)
- Maria Martin-Grau
- Department of Pathology, University of Valencia, Valencia 46010, Spain
| | - Daniel Monleon
- Department of Pathology, University of Valencia, Valencia 46010, Spain
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26
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The Effects of Probiotics on Small Intestinal Microbiota Composition, Inflammatory Cytokines and Intestinal Permeability in Patients with Non-Alcoholic Fatty Liver Disease. Biomedicines 2023; 11:biomedicines11020640. [PMID: 36831176 PMCID: PMC9953317 DOI: 10.3390/biomedicines11020640] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/02/2023] [Accepted: 02/13/2023] [Indexed: 02/22/2023] Open
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) has soared globally. As our understanding of the disease grows, the role of the gut-liver axis (GLA) in NAFLD pathophysiology becomes more apparent. Hence, we focused mainly on the small intestinal area to explore the role of GLA. We looked at how multi-strain probiotics (MCP® BCMC® strains) containing six different Lactobacillus and Bifidobacterium species affected the small intestinal gut microbiota, inflammatory cytokines, and permeability in NAFLD patients. After six months of supplementation, biochemical blood analysis did not show any discernible alterations in either group. Five predominant phyla known as Actinobacteria, Proteobacteria, Firmicutes, Bacteroidota and Fusobacteria were found in NAFLD patients. The probiotics group demonstrated a significant cluster formation of microbiota composition through beta-diversity analysis (p < 0.05). This group significantly reduced three unclassifiable species: unclassified_Proteobacteria, unclassified_Streptococcus, and unclassified_Stenotrophomonas. In contrast, the placebo group showed a significant increase in Prevotella_melaninogenica and Rothia_mucilaginosa, which were classified as pathogens. Real-time quantitative PCR analysis of small intestinal mucosal inflammatory cytokines revealed a significant decrease in IFN-γ (-7.9 ± 0.44, p < 0.0001) and TNF-α (-0.96 ± 0.25, p < 0.0033) in the probiotics group but an increase in IL-6 (12.79 ± 2.24, p < 0.0001). In terms of small intestinal permeability analysis, the probiotics group, unfortunately, did not show any positive changes through ELISA analysis. Both probiotics and placebo groups exhibited a significant increase in the level of circulating zonulin (probiotics: 107.6 ng/mL ± 124.7, p = 0.005 vs. placebo: 106.9 ng/mL ± 101.3, p = 0.0002) and a significant decrease in circulating zonula occluden-1 (ZO-1) (probiotics: -34.51 ng/mL ± 18.38, p < 0.0001 vs. placebo: -33.34 ng/mL ± 16.62, p = 0.0001). The consumption of Lactobacillus and Bifidobacterium suggested the presence of a well-balanced gut microbiota composition. Probiotic supplementation improves dysbiosis in NAFLD patients. This eventually stabilised the expression of inflammatory cytokines and mucosal immune function. To summarise, more research on probiotic supplementation as a supplement to a healthy diet and lifestyle is required to address NAFLD and its underlying causes.
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Yoshikawa S, Taniguchi K, Sawamura H, Ikeda Y, Asai T, Tsuji A, Matsuda S. Metabolic Associated Fatty Liver Disease as a Risk Factor for the Development of Central Nervous System Disorders. LIVERS 2023; 3:21-32. [DOI: 10.3390/livers3010002] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
MAFLD/NAFLD is the most ordinary liver disease categorized by hepatic steatosis with the increase of surplus fat in the liver and metabolic liver dysfunction, which is associated with bigger mortality and a high medical burden. An association between MAFLD/NAFLD and central nervous system disorders including psychological disorders has been demonstrated. Additionally, MAFLD/NAFLD has been correlated with various types of neurodegenerative disorders such as amyotrophic lateral sclerosis or Parkinson’s disease. Contrasted to healthy controls, patients with MAFLD/NAFLD have a greater prevalence risk of extrahepatic complications within multiple organs. Dietary interventions have emerged as effective strategies for MAFLD/NAFLD. The PI3K/AKT/mTOR signaling pathway involved in the regulation of Th17/Treg balance might promote the pathogenesis of several diseases including MAFLD/NAFLD. As extrahepatic complications may happen across various organs including CNS, cooperative care with individual experts is also necessary for managing patients with MAFLD/NAFLD.
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Affiliation(s)
- Sayuri Yoshikawa
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Kurumi Taniguchi
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Haruka Sawamura
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Yuka Ikeda
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Tomoko Asai
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Ai Tsuji
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Satoru Matsuda
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
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28
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Abulikemu A, Zhao X, Xu H, Li Y, Ma R, Yao Q, Wang J, Sun Z, Li Y, Guo C. Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress. Redox Biol 2022; 59:102569. [PMID: 36512914 PMCID: PMC9763688 DOI: 10.1016/j.redox.2022.102569] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
The metabolic associated fatty liver disease (MAFLD) is a public health challenge, leading to a global increase in chronic liver disease. The respiratory exposure of silica nanoparticles (SiNPs) has revealed to induce hepatotoxicity. However, its role in the pathogenesis and progression of MAFLD was severely under-studied. In this context, the hepatic impacts of SiNPs were investigated in vivo and in vitro through using ApoE-/- mice and free fatty acid (FFA)-treated L02 hepatocytes. Histopathological examinations and biochemical analysis showed SiNPs exposure via intratracheal instillation aggravated hepatic steatosis, lipid vacuolation, inflammatory infiltration and even collagen deposition in ApoE-/- mice, companied with increased hepatic ALT, AST and LDH levels. The enhanced fatty acid synthesis and inhibited fatty acid β-oxidation and lipid efflux may account for the increased hepatic TC/TG by SiNPs. Consistently, SiNPs induced lipid deposition and elevated TC in FFA-treated L02 cells. Further, the activation of hepatic oxidative stress was detected in vivo and in vitro, as evidenced by ROS accumulation, elevated MDA, declined GSH/GSSG and down-regulated Nrf2 signaling. Endoplasmic reticulum (ER) stress was also triggered in response to SiNPs-induced lipid accumulation, as reflecting by the remarkable ER expansion and increased BIP expression. More importantly, an UPLC-MS-based metabolomics analysis revealed that SiNPs disturbed the hepatic metabolic profile in ApoE-/- mice, prominently on amino acids and lipid metabolisms. In particular, the identified differential metabolites were strongly correlated to the activation of oxidative stress and ensuing hepatic TC/TG accumulation and liver injuries, contributing to the progression of liver diseases. Taken together, our study showed SiNPs promoted hepatic steatosis and liver damage, resulting in the aggravation of MAFLD progression. More importantly, the disturbed amino acids and lipid metabolisms-mediated oxidative stress was a key contributor to this phenomenon from a metabolic perspective.
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Affiliation(s)
- Alimire Abulikemu
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China,Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Xinying Zhao
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China,Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China
| | - Hailin Xu
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China,Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China
| | - Yan Li
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China,Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Ru Ma
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China,Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Qing Yao
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China,Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China
| | - Ji Wang
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China,Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China
| | - Zhiwei Sun
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China,Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China
| | - Yanbo Li
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.
| | - Caixia Guo
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
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29
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Citrus Bergamia and Cynara Cardunculus Reduce Serum Uric Acid in Individuals with Non-Alcoholic Fatty Liver Disease. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58121728. [PMID: 36556930 PMCID: PMC9784233 DOI: 10.3390/medicina58121728] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/16/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022]
Abstract
Background and Objectives: Hyperuricemia and liver steatosis are risk factors for cardiovascular diseases and mortality. The use of natural compounds could be a safe and effective alternative to drugs for the treatment of fatty liver and hyperuricemia. Polyphenolic fraction of Citrus Bergamia in association with the extract of Cynara Cardunculus, as nutraceutical, is able to reduce body weight, hepatic steatosis and markers of oxidative stress. Then, we performed a secondary analysis of a double-blind placebo-controlled trial to examine the effects of this nutraceutical on serum uric acid levels in adults with fatty liver. Materials and Methods: The study included 94 individuals with hepatic steatosis. For six weeks, the intervention group was given a nutraceutical (300 mg/day) comprising a Bergamot polyphenol fraction and Cynara Cardunculus extract. The control group received a daily pill of placebo. Serum uric acid, lipids, glucose and anthropometric parameters were assessed at baseline and after 6 weeks. Results: We found a greater reduction in serum uric acid in the participants taking the nutraceutical rather than placebo (−0.1 ± 0.7 mg/dL vs. 0.3 ± 0.7 mg/dL, p = 0.004), and especially in those with moderate/severe hepatic steatosis also after adjustment for confounding variables. In addition, we analysed the two groups according to tertiles of uric acid concentration. Among participants taking the nutraceutical, we found in those with the highest baseline serum uric acid (>5.4 mg/dL) the greater reduction compared to the lowest baseline uric acid (−7.8% vs. +4.9%; adjusted p = 0.04). The stepwise multivariable analysis confirmed the association between the absolute serum uric acid change and nutraceutical treatment (B = −0.43; p = 0.004). Conclusions: A nutraceutical containing bioactive components from bergamot and wild cardoon reduced serum uric acid during 6 weeks in adults with fatty liver. Future investigations are needed to evaluate the efficacy of this nutraceutical in the treatment of hyperuricaemia.
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Shi Z, Zhang C, Lei H, Chen C, Cao Z, Song Y, Chen G, Wu F, Zhou J, Lu Y, Zhang L. Structural Insights into Amelioration Effects of Quercetin and Its Glycoside Derivatives on NAFLD in Mice by Modulating the Gut Microbiota and Host Metabolism. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:14732-14743. [PMID: 36351282 DOI: 10.1021/acs.jafc.2c06212] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
The sugar moieties of natural flavonoids determine their absorption, bioavailability, and bioactivity in humans. To explore structure-dependent bioactivities of quercetin, isoquercetin, and rutin, which have the same basic skeleton linking different sugar moieties, we systemically investigated the ameliorative effects of dietary these flavonoids on high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) of mice. Our results revealed that isoquercetin exhibits the strongest capability in improving NAFLD phenotypes of mice, including body and liver weight gain, glucose intolerance, and systemic inflammation in comparison with quercetin and rutin. At the molecular level, dietary isoquercetin markedly ameliorated liver dysfunction and host metabolic disorders in mice with NAFLD. At the microbial level, the three flavonoids compounds, especially isoquercetin, can effectively regulate the gut microbiota composition, such as genera Akkermansia, Bifidobacterium, and Lactobacillus, which were significantly disrupted in NAFLD mice. These comparative findings offer new insights into the structure-dependent activities of natural flavonoids for NAFLD treatment.
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Affiliation(s)
- Zunji Shi
- State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China
- State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, China
| | - Ce Zhang
- State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Hehua Lei
- State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China
| | - Chuan Chen
- State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Zheng Cao
- State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yuchen Song
- State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Gui Chen
- State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Fang Wu
- State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jinlin Zhou
- Engineering Research Academy of High Value Utilization of Green Plants, Meizhou 514021, China
- Golden Health (Guangdong) Biotechnology Co., Ltd, Foshan 528225, China
| | - Yujing Lu
- School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
- Engineering Research Academy of High Value Utilization of Green Plants, Meizhou 514021, China
| | - Limin Zhang
- State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China
- University of Chinese Academy of Sciences, Beijing 100049, China
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Jiang S, Uddin MJ, Yu X, Piao L, Dorotea D, Oh GT, Ha H. Peroxisomal Fitness: A Potential Protective Mechanism of Fenofibrate against High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice. Diabetes Metab J 2022; 46:829-842. [PMID: 35746892 PMCID: PMC9723204 DOI: 10.4093/dmj.2021.0274] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 03/15/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has been increasing in association with the epidemic of obesity and diabetes. Peroxisomes are single membrane-enclosed organelles that play a role in the metabolism of lipid and reactive oxygen species. The present study examined the role of peroxisomes in high-fat diet (HFD)-induced NAFLD using fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist. METHODS Eight-week-old male C57BL/6J mice were fed either a normal diet or HFD for 12 weeks, and fenofibrate (50 mg/kg/day) was orally administered along with the initiation of HFD. RESULTS HFD-induced liver injury as measured by increased alanine aminotransferase, inflammation, oxidative stress, and lipid accumulation was effectively prevented by fenofibrate. Fenofibrate significantly increased the expression of peroxisomal genes and proteins involved in peroxisomal biogenesis and function. HFD-induced attenuation of peroxisomal fatty acid oxidation was also significantly restored by fenofibrate, demonstrating the functional significance of peroxisomal fatty acid oxidation. In Ppara deficient mice, fenofibrate failed to maintain peroxisomal biogenesis and function in HFD-induced liver injury. CONCLUSION The present data highlight the importance of PPARα-mediated peroxisomal fitness in the protective effect of fenofibrate against NAFLD.
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Affiliation(s)
- Songling Jiang
- Graduate School of Pharmaceutical Sciences, Ewha Womans University, College of Pharmacy, Seoul, Korea
| | - Md Jamal Uddin
- Graduate School of Pharmaceutical Sciences, Ewha Womans University, College of Pharmacy, Seoul, Korea
| | - Xiaoying Yu
- Graduate School of Pharmaceutical Sciences, Ewha Womans University, College of Pharmacy, Seoul, Korea
| | - Lingjuan Piao
- Graduate School of Pharmaceutical Sciences, Ewha Womans University, College of Pharmacy, Seoul, Korea
| | - Debra Dorotea
- Graduate School of Pharmaceutical Sciences, Ewha Womans University, College of Pharmacy, Seoul, Korea
| | - Goo Taeg Oh
- Department of Life Sciences, Ewha Womans University, Seoul, Korea
| | - Hunjoo Ha
- Graduate School of Pharmaceutical Sciences, Ewha Womans University, College of Pharmacy, Seoul, Korea
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Lyu X, Yan K, Wang X, Xu H, Guo X, Zhu H, Pan H, Wang L, Yang H, Gong F. A novel anti-obesity mechanism for liraglutide by improving adipose tissue leptin resistance in high-fat diet-fed obese mice. Endocr J 2022; 69:1233-1244. [PMID: 35705299 DOI: 10.1507/endocrj.ej21-0802] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Liraglutide has been approved for the treatment of obesity in the past few years. Both oxidative stress and leptin resistance are the critical drivers of obesity. The present study investigated the mechanism of liraglutide protection against obesity by ameliorating leptin resistance and oxidative stress. Male C57BL/6J mice were fed a high-fat diet (HFD) and subcutaneously injected with 200 μg/kg/d liraglutide for 20 weeks. Body weight, fat mass, serum levels of leptin, insulin, and superoxide dismutase (SOD) activities were measured. In addition, glucose and insulin tolerance tests were performed. The expressions of leptin, its signaling genes, and antioxidant enzymes were detected using RT-qPCR and western blot methods in liver and white adipose tissue (WAT) of mice. The results depicted that liraglutide treatment significantly slowed weight gain of body, reduced the fat mass, ameliorated glucose and lipid metabolism, and hepatic steatosis in HFD-fed obese mice. Further study demonstrated that liraglutide treatment resulted in decreased serum levels and the transcript levels of leptin as well as leptin signaling inhibitory regulators. However, it increased leptin receptor expression and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) in WAT (p < 0.05). In addition, the antioxidant enzyme expression was elevated in both liver and WAT of liraglutide-treated mice (p < 0.05). In conclusion, liraglutide conspicuously prevented obesity and ameliorated glucose and lipid metabolism in obese mice through a novel mechanism that improves peripheral leptin resistance in WAT and enhance the antioxidant enzyme expression in both liver and WAT.
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Affiliation(s)
- Xiaorui Lyu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Kemin Yan
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Xin Wang
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Hanyuan Xu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Xiaonan Guo
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Huijuan Zhu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Hui Pan
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Linjie Wang
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Hongbo Yang
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Fengying Gong
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
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Shan Q, Zhang Y, Zhang X, Wang W, Liang Z. The Effect of Coumestrol on Hub Genes in Lung Squamous Cell Carcinoma Based on Bioinformatic Strategy. Nat Prod Commun 2022. [DOI: 10.1177/1934578x221127960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Purpose There is limited treatment for lung squamous cell carcinoma (LUSC), so there is an urgent need to find new antitumor drugs. Materials and Methods We downloaded datasets from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas databases. We used GEO2R and the “limma” package to screen differentially expressed genes. We used the Cytoscape software to screen out hub genes. We screened herbs that act on hub genes on the Chinese medicine website. We then studied the effect of coumestrol (CM) on the hub genes in the H226 cell line. Results Seven hub genes were screened, namely CCNB2, CENPF, KIF11, MELK, nucleolar and spindle-associated protein 1 (NUSAP1), PBK, and RRM2. We observed that CM had a tumor-inhibiting effect on H226 cells by inhibiting the expression of CCNB2, KIF11, and NUSAP1. Conclusion CM, screened by bioinformatics and network pharmacology, can inhibit H226 cells by downregulating CCNB2, KIF11, and NUSAP1.
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Affiliation(s)
- Qingqing Shan
- West China Hospital of Sichuan University, Chengdu, China
| | - Yifan Zhang
- Chengdu First People’s Hospital, Chengdu, China
| | - Xu Zhang
- Chengdu First People’s Hospital, Chengdu, China
| | - Wei Wang
- Chengdu First People’s Hospital, Chengdu, China
| | - Zongan Liang
- West China Hospital of Sichuan University, Chengdu, China
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Alami F, Alizadeh M, Shateri K. The effect of a fruit-rich diet on liver biomarkers, insulin resistance, and lipid profile in patients with non-alcoholic fatty liver disease: a randomized clinical trial. Scand J Gastroenterol 2022; 57:1238-1249. [PMID: 35710164 DOI: 10.1080/00365521.2022.2071109] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Despite confirmed dietary approaches to improve the Non-Alcoholic Fatty Liver Disease (NAFLD), the effect of fruits on NAFLD is not clear. The present study aimed to investigate the effect of a fruit rich diet (FRD) on liver steatosis, liver enzymes, Insulin resistance, and lipid profile in patients with NAFLD. METHODS Eighty adults with NAFLD participated in this randomized controlled trial. The participants were randomly assigned to the FRD group with consumption of at least 4 servings of fruits daily or the control group with fruits consumption of less than 2 servings/day. The grade of steatosis, serum levels of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), glucose, and homeostatic model assessment for insulin resistance (HOMA-IR) were measured at the baseline and at the end of the study. RESULTS After 6 months of intervention, the FRD group had significantly higher BMI (31.40 ± 2.61 vs. 25.68 ± 2.54, p < .001), WC (113.5 ± 10.7 vs. 100.5 ± 7.5, p < .001), the grade of steatosis, ALT (89.1 ± 92.9 vs. 32.0 ± 19.2, p < .001), AST (74.5 ± 107.8 vs. 24.0 ± 8.5, p < .001), ALP (273.4 ± 128.5 vs. 155.0 ± 43.9, p < .001), GGT (92.7 ± 16.2 vs. 21.2 ± 7.7, p < .001), TC (206.1 ± 40.5 vs. 172.7 ± 42.4, p < .01), LDL (126.9 ± 32.3 vs. 99.8 ± 29.8, p < .001), glucose (115.5 ± 30.0 vs. 97.7 ± 19.0, p < .01), and insulin resistance (7.36 ± 4.37 vs. 2.66 ± 1.27, p < .001), and lower HDL (41.4 ± 8.9 vs. 53.8 ± 15.1, p < .001) compared to the control group. Adjusting for BMI and calorie intake did not change the results. CONCLUSION The results of the present study indicated that consumption of fruits more than 4 servings/day exacerbates steatosis, dyslipidemia, and glycemic control in NAFLD patients. Further studies are needed to identify the underlying mechanisms of the effects of fruits on NAFLD. CLINICAL TRIAL REGISTRATION This trial was registered at Iranian randomized clinical trial website with IRCT registration no. IRCT20201010048982N1on October 15, 2020.
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Affiliation(s)
- Farkhondeh Alami
- Student Research Committee, Department of Nutrition, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Mohammad Alizadeh
- Food and Beverages Safety Research Center, Department of Nutrition, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Kamran Shateri
- Department of Gastroenterology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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Choi SE, Hwang Y, Lee SJ, Jung H, Shin TH, Son Y, Park S, Han SJ, Kim HJ, Lee KW, Lee G, Kemper JK, Song HK, Kang Y. Mitochondrial protease ClpP supplementation ameliorates diet-induced NASH in mice. J Hepatol 2022; 77:735-747. [PMID: 35421426 DOI: 10.1016/j.jhep.2022.03.034] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 02/18/2022] [Accepted: 03/21/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND & AIMS Mitochondrial dysfunction is considered a pathogenic linker in the development of non-alcoholic steatohepatitis (NASH). Inappropriate mitochondrial protein-quality control, possibly induced by insufficiency of the mitochondrial matrix caseinolytic protease P (ClpP), can potentially cause mitochondrial dysfunction. Herein, we aimed to investigate hepatic ClpP levels in a diet-induced model of NASH and determine whether supplementation of ClpP can ameliorate diet-induced NASH. METHODS NASH was induced by a high-fat/high-fructose (HF/HFr) diet in C57BL/6J mice. Stress/inflammatory signals were induced in mouse primary hepatocytes (MPHs) by treatment with palmitate/oleate (PA/OA). ClpP levels in hepatocytes were reduced using the RNAi-mediated gene knockdown technique but increased through the viral transduction of ClpP. ClpP activation was induced by administering a chemical activator of ClpP. RESULTS Hepatic ClpP protein levels in C57BL/6J mice fed a HF/HFr diet were lower than the levels in those fed a normal chow diet. PA/OA treatment also decreased the ClpP protein levels in MPHs. Overexpression or activation of ClpP reversed PA/OA-induced mitochondrial dysfunction and stress/inflammatory signal activation in MPHs, whereas ClpP knockdown induced mitochondrial dysfunction and stress/inflammatory signals in these cells. On the other hand, ClpP overexpression or activation improved HF/HFr-induced NASH characteristics such as hepatic steatosis, inflammation, fibrosis, and injury in the C57BL/6J mice, whereas ClpP knockdown further augmented steatohepatitis in mice fed a HF/HFr diet. CONCLUSIONS Reduced ClpP expression and subsequent mitochondrial dysfunction are key to the development of diet-induced NASH. ClpP supplementation through viral transduction or chemical activation represents a potential therapeutic strategy to prevent diet-induced NASH. LAY SUMMARY Western diets, containing high fat and high fructose, often induce non-alcoholic steatohepatitis (NASH). Mitochondrial dysfunction is considered pathogenically linked to diet-induced NASH. We observed that the mitochondrial protease ClpP decreased in the livers of mice fed a western diet and supplementation of ClpP ameliorated western diet-induced NASH.
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Affiliation(s)
- Sung-E Choi
- Department of Physiology, Ajou University School of Medicine, Suwon, Gyunggi-do, Republic of Korea 443-749
| | - Yoonjung Hwang
- Department of Physiology, Ajou University School of Medicine, Suwon, Gyunggi-do, Republic of Korea 443-749
| | - Soo-Jin Lee
- Department of Physiology, Ajou University School of Medicine, Suwon, Gyunggi-do, Republic of Korea 443-749
| | - Hyunkyung Jung
- Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA 61801
| | - Tae Hwan Shin
- Department of Physiology, Ajou University School of Medicine, Suwon, Gyunggi-do, Republic of Korea 443-749
| | - Youngho Son
- Department of Physiology, Ajou University School of Medicine, Suwon, Gyunggi-do, Republic of Korea 443-749; Department of Biomedical Science, The Graduate School, Ajou University, Suwon, Gyunggi-do, Republic of Korea 443-749
| | - Seokho Park
- Department of Physiology, Ajou University School of Medicine, Suwon, Gyunggi-do, Republic of Korea 443-749; Department of Biomedical Science, The Graduate School, Ajou University, Suwon, Gyunggi-do, Republic of Korea 443-749
| | - Seung Jin Han
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Gyunggi-do, Republic of Korea 443-749
| | - Hae Jin Kim
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Gyunggi-do, Republic of Korea 443-749
| | - Kwan Woo Lee
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Gyunggi-do, Republic of Korea 443-749
| | - Gwang Lee
- Department of Physiology, Ajou University School of Medicine, Suwon, Gyunggi-do, Republic of Korea 443-749
| | - Jongsook Kim Kemper
- Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA 61801
| | - Hyun Kyu Song
- School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea 136-701
| | - Yup Kang
- Department of Physiology, Ajou University School of Medicine, Suwon, Gyunggi-do, Republic of Korea 443-749.
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The effects of seaweed supplementation consumption for improvement of liver injury in patients with non-alcoholic fatty liver disease: a systematic review. Clin Exp Hepatol 2022; 8:171-177. [PMID: 36685265 PMCID: PMC9850310 DOI: 10.5114/ceh.2022.118275] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 05/19/2022] [Indexed: 01/25/2023] Open
Abstract
Seaweed is a food that is widely consumed by Asian people and has many health benefits, including lipid and glycemic reduction, but the effect of seaweed on non-alcoholic fatty liver disease (NAFLD) has not been widely discussed. This study aims to compare the effect of seaweed consumption on improving liver injury in NAFLD patients. The primary outcome is the change of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and g-glutamyl transferase [GGT]), while the secondary outcome includes body weight, waist circumstance, body mass index (BMI), lipid profile, insulin level, and insulin sensitivity and any related metabolic indicators. There was significant liver improvement in the intervention group, but some parameters from secondary outcomes showed no significant effect. Further studies with larger and heterogeneous populations are still needed to confirm the effectiveness of seaweed supplementation in NAFLD patients.
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Okulicz M, Hertig I, Król E, Szkudelski T. Effects of Allyl Isothiocyanate on Oxidative and Inflammatory Stress in Type 2 Diabetic Rats. Molecules 2022; 27:molecules27175568. [PMID: 36080332 PMCID: PMC9457932 DOI: 10.3390/molecules27175568] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/18/2022] [Accepted: 08/24/2022] [Indexed: 12/02/2022] Open
Abstract
Oxidative stress and inflammation play a crucial role in the pathogenesis and progression of diabetes. Currently, there is a growing need to exploit plant-derived bioactive compounds to support conventional therapies. The purpose of this study was to explore allyl isothiocyanate (AITC) potency in reducing oxidative and inflammatory stress along with its profitable modulation trace element status in pathological conditions such as diabetes. Two weeks of oral AITC treatments (2.5, 5, and 25 mg/kg body weight per day) were evaluated in Wistar rats with diabetes induced by a high-fat diet and streptozotocin. The study included AITC influence on antioxidant factors (SOD, CAT, GST, Nrf2), stress and inflammatory markers (cortisol, CRP, IL-1β, IL-6, TNFα, NF-κB), lipid peroxidation indices (TBARS, -SH groups), and trace element status (Fe, Zn, and Cu) in the detoxification and lymphoid organs. Independently of dose, AITC increased cortisol levels in rat blood serum and decreased total thiol groups (T-SH) and protein-bound thiol groups (PB-SH) collaterally with raised thiobarbituric acid reactive substances (TBARS) in diabetic rat liver. The inflammation and oxidative effects were enhanced by an AITC dose increase. The highest dose of AITC, 25 mg/kg b.w., strongly affected the inflammation process by increasing IL-6, IL-1β, and TNFα in the blood serum, and it upregulated Nrf2 transcription factor with increased SOD, GPx, and GST activities in the liver. AITC showed an equivocal effect on profitable modulation of disturbances in mineral homeostasis in the liver, kidney, and spleen. Our findings revealed that two-week AITC treatment exacerbated oxidative and inflammation status in diabetic rats.
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Affiliation(s)
- Monika Okulicz
- Department of Animal Physiology, Biochemistry and Biostructure, Faculty of Veterinary Medicine and Animal Sciences, Poznań University of Life Sciences, Wołyńska 35, 60-637 Poznań, Poland
- Correspondence: ; Tel.: +48-61-8487196
| | - Iwona Hertig
- Department of Animal Physiology, Biochemistry and Biostructure, Faculty of Veterinary Medicine and Animal Sciences, Poznań University of Life Sciences, Wołyńska 35, 60-637 Poznań, Poland
| | - Ewelina Król
- Department of Human Nutrition and Dietetics, Poznań University of Life Sciences, Wojska Polskiego 31, 60-624 Poznań, Poland
| | - Tomasz Szkudelski
- Department of Animal Physiology, Biochemistry and Biostructure, Faculty of Veterinary Medicine and Animal Sciences, Poznań University of Life Sciences, Wołyńska 35, 60-637 Poznań, Poland
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Moradi F, Heidari Z, Teimori A, Ghazvini M, Imani ZF, Naeini AA. The Association Between the Dietary Inflammatory Index (DII) and Some Serum Oxidative Stress Markers in Non-Alcoholic Fatty Liver Disease: Case- Control. Int J Prev Med 2022; 13:93. [PMID: 35958363 PMCID: PMC9362752 DOI: 10.4103/ijpvm.ijpvm_411_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Accepted: 11/20/2020] [Indexed: 12/04/2022] Open
Abstract
PURPOSE Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder. The purpose of this study was to determine the relationship between the dietary inflammatory index (DII) and the serum oxidative stress markers in patients with NAFLD. METHODS In this case-control study, 121 patients with NAFLD and 119 healthy subjects were frequency-matched on gender. DII scores were calculated by using a 168-item food frequency questionnaire (FFQ). Blood samples were collected to measure serum oxidative markers. Linear regression and odds ratio (OR) were also used in this study. RESULTS The mean ± standard deviation of age for case and control group was 38.04 ± 6.7 and 35.6 ± 10.2, respectively. The gender ratio (female to male) for the case and control group was 1:1.42 and 1:1.38, respectively. The mean of the DII in the patient group was significantly higher than the healthy group, (P-values < 0.01). There was a significant negative relationship between TAC and DII (B = -2.63 (95%CI: -4.59, -0.68) and there was also a positive relationship between Malondialdehyde (MDA) and DII (B = 0.15 (95%CI: 0.02, 0.28) in the healthy group, but they were not significant in the case group. After multivariate adjustment, subjects in the most pro-inflammatory DII group had 73 times higher odds of NAFLD compared to subjects in tertile 1 (OR = 72.9; 95%CI (14.3-371.9)). CONCLUSIONS Our findings suggest a direct association between the pro inflammatory properties of diet in patient and healthy group, but no relationship between TAC, MDA, and DII in the case group.
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Affiliation(s)
- Fateme Moradi
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zahra Heidari
- Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Azam Teimori
- Department of Internal Medicine, School of Medicine Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammadreza Ghazvini
- Isfahan Center of Health Research, National Institute of Health Research, Isfahan, Iran
| | - Zahra Faghih Imani
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amirmansour Alavi Naeini
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran,Address for correspondence: Dr. Amirmansour Alavi Naeini, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran. E-mail:
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Moradi F, Moosavian SP, Djafari F, Teimori A, Imani ZF, Naeini AA. The association between major dietary patterns with the risk of non-alcoholic fatty liver disease, oxidative stress and metabolic parameters: A case-control study. J Diabetes Metab Disord 2022; 21:657-667. [PMID: 35673496 PMCID: PMC9167161 DOI: 10.1007/s40200-022-01028-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 03/06/2022] [Indexed: 11/11/2022]
Abstract
Purpose Non-alcoholic fatty liver disease (NAFLD) is caused by the increase of fat in the liver. The present study aimed to study the association between different dietary patterns and NAFLD in adults. Methods This study included 121 adult patients with NAFLD and 119 non-NAFLD. Dietary intake was calculated by a 168-item food frequency questionnaire. Biochemical markers were measured. Dietary patterns were determined by factor analysis. The association between dietary patterns and NAFLD was evaluated using multiple logistic regression analysis. Results Two dietary patterns (healthy, western) were recognized in participants. Western dietary pattern was related with 72 percent increase in the odds of NAFLD (OR: 1.72; 95% CI: 1.32,2.14), after adjustment for covariates. Healthy dietary pattern was associated with 38 percent lower odds of NAFLD (OR: 0.38; 95% CI: 0.11, 0.65). Adherence to the western diet was related to 0.486 greater amounts of ALT, 3.248 mg/dl higher levels of FBS, and 3.989 mg/dl greater amounts of TG and 2.354 mg/dl greater amounts of MDA after adjusting for confounding factors (p > 0.001, p = 0.042, p > 0.001, p = 0.036 respectively). The healthy dietary pattern score was negatively associated with FBS and Cholesterol and TG levels (p = 0.035, p = 0.048, and p = 0.025), respectively. Moreover, it was associated with 3.211 mg/dl higher levels of TAC (p = 0.049). Conclusions There is a significant relationship between dietary patterns and non-alcoholic fatty liver disease. Adherence to a western dietary pattern is related to an increase in non-alcoholic fatty liver disease.
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Affiliation(s)
- Fateme Moradi
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Seyedeh Parisa Moosavian
- Department of Community Nutrition, Vice-Chancellery for Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farhang Djafari
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Azam Teimori
- Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zahra Faghih Imani
- Department of Clinical Nutrition, School of Nutrition & Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amirmansour Alavi Naeini
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
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Nonalcoholic Fatty Liver Disease in Patients with Inherited and Sporadic Motor Neuron Degeneration. Genes (Basel) 2022; 13:genes13060936. [PMID: 35741698 PMCID: PMC9222520 DOI: 10.3390/genes13060936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 05/20/2022] [Accepted: 05/22/2022] [Indexed: 02/04/2023] Open
Abstract
We describe evidence of fatty liver disease in patients with forms of motor neuron degeneration with both genetic and sporadic etiology compared to controls. A group of 13 patients with motor neuron disease underwent liver imaging and laboratory analysis. The cohort included five patients with hereditary spastic paraplegia, four with sporadic amyotrophic lateral sclerosis (ALS), three with familial ALS, and one with primary lateral sclerosis. A genetic mutation was reported in nine of the thirteen motor neuron disease (MND) patients. Fatty liver disease was detected in 10 of 13 (77%) MND patients via magnetic resonance spectroscopy, with an average dome intrahepatic triacylglycerol content of 17% (range 2–63%, reference ≤5.5%). Liver ultrasound demonstrated evidence of fatty liver disease in 6 of the 13 (46%) patients, and serum liver function testing revealed significantly elevated alanine aminotransferase levels in MND patients compared to age-matched controls. Fatty liver disease may represent a non-neuronal clinical component of various forms of MND.
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Bove M, Lama A, Schiavone S, Pirozzi C, Tucci P, Sikora V, Trinchese G, Corso G, Morgese MG, Trabace L. Social isolation triggers oxidative status and impairs systemic and hepatic insulin sensitivity in normoglycemic rats. Biomed Pharmacother 2022; 149:112820. [PMID: 35290886 DOI: 10.1016/j.biopha.2022.112820] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 02/28/2022] [Accepted: 03/09/2022] [Indexed: 11/11/2022] Open
Abstract
Drug-naïve psychotic patients show metabolic and hepatic dysfunctions. The rat social isolation model of psychosis allows to investigate mechanisms leading to these disturbances to which oxidative stress crucially contributes. Here, we investigated isolation-induced central and peripheral dysfunctions in glucose homeostasis and insulin sensitivity, along with redox dysregulation. Social isolation did not affect basal glycemic levels and the response to glucose and insulin loads in the glucose and insulin tolerance tests. However, HOMA-Index value were increased in isolated (ISO) rats. A hypothalamic reduction of AKT phosphorylation and a trend toward an increase in AMPK phosphorylation were observed following social isolation, accompanied by reduced GLUT-4 levels. Social isolation also induced a reduction of phosphorylation of the insulin receptor, of AKT and GLUT-2, and a decreased phosphorylation of AMPK in the liver. Furthermore, a significant reduction in hepatic CPT1 and PPAR-α levels was detected. ISO rats also showed significant elevations in hepatic ROS amount, lipid peroxidation and NOX4 expression, whereas no differences were detected in NOX2 and NOX1 levels. Expression of SOD2 in the mitochondrial fraction and SOD1 in the cytosolic fraction was not altered following social isolation, whereas SOD activity was increased. Furthermore, a decrease of hepatic CAT and GSH amount was observed in ISO rats compared to GRP animals. Our data suggest that the increased oxidant status and antioxidant capacity modifications may trigger hepatic and systemic insulin resistance, by altering signal hormone pathway and sustaining subsequent alteration of glucose homeostasis and metabolic impairment observed in the social isolation model of psychosis.
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Affiliation(s)
- Maria Bove
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20, Foggia 71122, Italy.
| | - Adriano Lama
- Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano, 49, Naples 80131, Italy.
| | - Stefania Schiavone
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20, Foggia 71122, Italy.
| | - Claudio Pirozzi
- Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano, 49, Naples 80131, Italy.
| | - Paolo Tucci
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20, Foggia 71122, Italy.
| | - Vladyslav Sikora
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20, Foggia 71122, Italy; Department of Pathology, Sumy State University, 2, Rymskogo-Korsakova st., Sumy 40007, Ukraine.
| | - Giovanna Trinchese
- Department of Biology, University of Naples Federico II, "Complesso Universitario di Monte Sant'Angelo", Cupa Nuova Cinthia 21 - Building 7, Naples 80126, Italy.
| | - Gaetano Corso
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20, Foggia 71122, Italy.
| | - Maria Grazia Morgese
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20, Foggia 71122, Italy.
| | - Luigia Trabace
- Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20, Foggia 71122, Italy.
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Alzahrani NS, Alshammari GM, El-Ansary A, Yagoub AEA, Amina M, Saleh A, Yahya MA. Anti-Hyperlipidemia, Hypoglycemic, and Hepatoprotective Impacts of Pearl Millet ( Pennisetum glaucum L.) Grains and Their Ethanol Extract on Rats Fed a High-Fat Diet. Nutrients 2022; 14:nu14091791. [PMID: 35565759 PMCID: PMC9105973 DOI: 10.3390/nu14091791] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/18/2022] [Accepted: 04/22/2022] [Indexed: 12/17/2022] Open
Abstract
This study tested the anti-hyperlipidemic, hypoglycemic, hepatoprotective, and anti-inflammatory effects of whole pearl millet grain powder (MPG) and its ethanol extract (MPGethaolE) in obese rats fed a high-fat diet. The rats were divided into eight groups based on the treatments they received: control, high fat diet (HFD), HFD + MGE (25 mg/Kg), HFD + MPGethaolE (50 mg/Kg), HFD + MPGethaolE (100 mg/Kg), HFD + MPG (10%), HFD + MPG (20%), and HFD + MPG (30%). The final body weight, visceral, epididymal fat pads, and the liver weight were significantly decreased, in a dose-dependent manner, in HFD fed rats that were co-administered either the MPG powder or MPGethaolE. In the same line, serum levels of triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein-cholesterol (LDL-c), as well as fasting glucose, insulin, HOMA-IR, and serum levels of lipopolysaccharides (LPS), interleukine-6 (IL-6), interleukine-10 (IL-10), C-reactive protein (CRP), tumor necrosis factor (TNF-α), and adiponectin were progressively decreased while serum levels of high-density lipoproteins (HDL-c) were significantly increased when increasing the doses of both treatments. In conclusion, both the raw powder and ethanolic extract of MP have a comparative dose-dependent anti-obesity, hypoglycemic, hypolipidemic, anti-inflammatory, and anti-steatotic in HFD-fed rats.
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Affiliation(s)
- Nadiah S. Alzahrani
- Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Saudi Arabia; (N.S.A.); (A.E.A.Y.); (A.S.); (M.A.Y.)
| | - Ghedeir M. Alshammari
- Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Saudi Arabia; (N.S.A.); (A.E.A.Y.); (A.S.); (M.A.Y.)
- Correspondence:
| | - Afaf El-Ansary
- Central Research Laboratory, Female Campus, King Saud University, Riyadh 11472, Saudi Arabia;
| | - Abu ElGasim A. Yagoub
- Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Saudi Arabia; (N.S.A.); (A.E.A.Y.); (A.S.); (M.A.Y.)
| | - Musarat Amina
- Department of Pharmacognosy, Pharmacy College, King Saud University, Riyadh 11451, Saudi Arabia;
| | - Ali Saleh
- Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Saudi Arabia; (N.S.A.); (A.E.A.Y.); (A.S.); (M.A.Y.)
| | - Mohammed Abdo Yahya
- Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Saudi Arabia; (N.S.A.); (A.E.A.Y.); (A.S.); (M.A.Y.)
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Jiang JJ, Zhang GF, Zheng JY, Sun JH, Ding SB. Targeting Mitochondrial ROS-Mediated Ferroptosis by Quercetin Alleviates High-Fat Diet-Induced Hepatic Lipotoxicity. Front Pharmacol 2022; 13:876550. [PMID: 35496312 PMCID: PMC9039018 DOI: 10.3389/fphar.2022.876550] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 03/24/2022] [Indexed: 12/31/2022] Open
Abstract
Background: The protective effect of quercetin on nonalcoholic fatty liver disease (NAFLD) has been reported, but its mechanism remains poorly understood. Recently, quercetin was reported to be capable of inhibiting ferroptosis, which is a recognized type of regulated cell death. Moreover, hepatic ferroptosis plays an important role in the progression of NAFLD, but experimental evidence is limited. Hence, our study aimed to investigate the effect of quercetin on hepatic ferroptosis in high-fat diet (HFD)-induced NAFLD and further elucidate the underlying molecular mechanism. Methods: C57BL/6J mice were fed either a normal diet (ND), an HFD, or an HFD supplemented with quercetin for 12 weeks. Hepatic lipid peroxidation, steatosis, ferroptosis and iron overload were examined. In vitro, steatotic L-02 cells was used to study the potential mechanism. Results: We found that the HFD caused lipid peroxidation, lipid accumulation and ferroptosis in the liver, which were rescued by quercetin supplementation. Consistent with the in vivo results, quercetin alleviated lipid droplet accumulation and reduced the levels of lipid reactive oxygen species (ROS) and ferroptosis in steatotic L-02 cells. Using a mitochondrial ROS (MtROS) scavenger (Mito-TEMPO) and ferroptosis specific inhibitor (Fer-1), we found that quercetin remarkably alleviated lipid droplet accumulation and lipid peroxidation by reducing MtROS-mediated ferroptosis in steatotic L-02 cells. Conclusion: Our data showed that HFD consumption induced lipid accumulation and triggered ferroptosis in liver, ultimately leading to hepatic lipotoxicity, which can be alleviated by quercetin. Findings from this study provide new insight into the mechanism by which quercetin can be used for the prevention and treatment of NAFLD.
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Affiliation(s)
- Jin-Jin Jiang
- Jiangsu Vocational College of Medicine, Yancheng, China
| | - Guo-Fu Zhang
- Department of Public Health, Xinxiang Medical University, Xinxiang, China
| | - Jia-Yi Zheng
- Jiangsu Vocational College of Medicine, Yancheng, China
| | - Ji-Hu Sun
- Jiangsu Vocational College of Medicine, Yancheng, China
- *Correspondence: Shi-Bin Ding, ; Ji-Hu Sun,
| | - Shi-Bin Ding
- Jiangsu Vocational College of Medicine, Yancheng, China
- *Correspondence: Shi-Bin Ding, ; Ji-Hu Sun,
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Fucoxanthin Attenuates Free Fatty Acid-Induced Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism/Oxidative Stress/Inflammation via the AMPK/Nrf2/TLR4 Signaling Pathway. Mar Drugs 2022; 20:md20040225. [PMID: 35447899 PMCID: PMC9027317 DOI: 10.3390/md20040225] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 03/23/2022] [Accepted: 03/23/2022] [Indexed: 02/06/2023] Open
Abstract
Fucoxanthin, a xanthophyll carotenoid abundant in brown algae, is reported to have several biological functions, such as antioxidant, anti-inflammatory, and anti-tumor activities, in mice. We investigated the effects and mechanisms of fucoxanthin in the mixture oleate/palmitate = 2/1(FFA)-induced nonalcoholic fatty liver disease (NAFLD) cell model in this study. The results showed that the content of superoxide dismutase in the FFA group was 9.8 ± 1.0 U/mgprot, while that in the fucoxanthin high-dose (H-Fx) group (2 μg/mL) increased to 22.9 ± 0.6 U/mgprot. The content of interleukin-1β in the FFA group was 89.3 ± 3.6 ng/mL, while that in the H-Fx group was reduced to 53.8 ± 2.8 ng/mL. The above results indicate that fucoxanthin could alleviate the FFA-induced oxidative stress and inflammatory levels in the liver cells. Oil red-O staining revealed visible protrusions and a significant decrease in the number of lipid droplets in the cytoplasm of cells in the fucoxanthin group. These findings on the mechanisms of action suggest that fucoxanthin can repair FFA-induced NAFLD via the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and nuclear factor erythroid-2-related factor 2-mediated (Nrf2) signaling pathway, as well as by downregulating the expression of the Toll-like receptor 4-mediated (TLR4) signaling pathway. Fucoxanthin exhibited alleviating effects in the FFA-induced NAFLD model and could be explored as a potential anti-NAFLD substance.
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Mahmoudi A, Butler AE, Majeed M, Banach M, Sahebkar A. Investigation of the Effect of Curcumin on Protein Targets in NAFLD Using Bioinformatic Analysis. Nutrients 2022; 14:nu14071331. [PMID: 35405942 PMCID: PMC9002953 DOI: 10.3390/nu14071331] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 03/15/2022] [Accepted: 03/21/2022] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder. Defects in function/expression of genes/proteins are critical in initiation/progression of NAFLD. Natural products may modulate these genes/proteins. Curcumin improves steatosis, inflammation, and fibrosis progression. Here, bioinformatic tools, gene−drug and gene-disease databases were utilized to explore targets, interactions, and pathways through which curcumin could impact NAFLD. METHODS: Significant curcumin−protein interaction was identified (high-confidence:0.7) in the STITCH database. Identified proteins were investigated to determine association with NAFLD. gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for significantly involved targets (p < 0.01). Specificity of obtained targets with NAFLD was estimated and investigated in Tissue/Cells−gene associations (PanglaoDB Augmented 2021, Mouse Gene Atlas) and Disease−gene association-based EnrichR algorithms (Jensen DISEASES, DisGeNET). RESULTS: Two collections were constructed: 227 protein−curcumin interactions and 95 NAFLD-associated genes. By Venn diagram, 14 significant targets were identified, and their biological pathways evaluated. Based on gene ontology, most targets involved stress and lipid metabolism. KEGG revealed chemical carcinogenesis, the AGE-RAGE signaling pathway in diabetic complications and NAFLD as the most common significant pathways. Specificity to diseases database (EnrichR algorithm) revealed specificity for steatosis/steatohepatitis. CONCLUSION: Curcumin may improve, or inhibit, progression of NAFLD through activation/inhibition of NAFLD-related genes.
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Affiliation(s)
- Ali Mahmoudi
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 9177899191, Iran;
| | - Alexandra E. Butler
- Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya 15503, Bahrain;
| | | | - Maciej Banach
- Nephrology and Hypertension, Department of Preventive Cardiology and Lipidology, Medical University of Lodz, 93-338 Lodz, Poland
- Cardiovascular Research Centre, University of Zielona Gora, 65-417 Zielona Gora, Poland
- Correspondence: (M.B.); (A.S.)
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177899191, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad 9177899191, Iran
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 9177899191, Iran
- Correspondence: (M.B.); (A.S.)
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Xu Z, Lin S, Tong Z, Chen S, Cao Y, Li Q, Jiang Y, Cai W, Tong Y, Zahra BS, Wang P. Crocetin ameliorates non-alcoholic fatty liver disease by modulating mitochondrial dysfunction in L02 cells and zebrafish model. JOURNAL OF ETHNOPHARMACOLOGY 2022; 285:114873. [PMID: 34848360 DOI: 10.1016/j.jep.2021.114873] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Traditional Chinese medicine considers that the etiology and pathogenesis of non-alcoholic fatty liver disease (NAFLD) are related to liver depression and qi stagnation. Saffron and its active ingredient, crocetin (CCT), are used for the treatment of metabolic diseases owing to their "Liver deobstruent" and "Liver tonic" effects. However, the effect of CCT on NAFLD has not been fully elucidated. In the present study, the effect and potential molecular mechanism of CCT were explored in both in vivo and in vitro models of NAFLD. MATERIALS AND METHODS CCT was isolated from saffron and purity and structure characterization were performed using HPLC, MS, 1H-NMR, and 13C-NMR. The effect of CCT on the viability of L02 cells and its maximum tolerable concentration (MTC) in zebrafish were investigated. Free fatty acids (FFA) and thioacetamide (TAA) were used to induce lipid accumulation in L02 cells and steatosis in zebrafish, respectively. The effects of CCT on indexes related to lipid metabolism, oxidative stress, and mitochondrial function in NAFLD models were explored using biochemical assay kits, Western blot analysis, Reverse Transcription-Polymerase Chain Reaction (RT-PCR), histopathology analysis, and determination of mitochondrial membrane potential (ΔΨm). Morphological analysis of mitochondria was performed using transmission electron microscopy (TEM). RESULTS The levels of triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), and alanine/aspartate aminotransferases (ALT/AST) activities in FFA treated L02 cells were significantly reduced after CCT treatment. CCT treatment significantly increased ATP concentration, ΔΨm, and activities of superoxide dismutase (SOD), catalase (CAT), and cytochrome c oxidase (COX IV) in FFA treated L02 cells. TEM images showed restoration of mitochondrial morphology. CCT decreased ATP concentration and upregulated expression of B-cell lymphoma-2 (Bcl-2) and COX IV, whereas, CCT downregulated expression of BCL2-Associated X (Bax) and cleaved caspase-3 in TAA treated zebrafish. These findings indicated that mitochondrial dysfunction was alleviated after CCT treatment. Oil Red O staining of L02 cells and zebrafish showed that CCT treatment reversed the accumulation of lipid droplets. CONCLUSION In summary, CCT treatment effectively alleviated the symptoms of NAFLD and restored mitochondrial function in L02 cells and zebrafish NAFLD model.
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Affiliation(s)
- Zijin Xu
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Susu Lin
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Zheren Tong
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Suhong Chen
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, People's Republic of China
| | - Yifeng Cao
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Qiaoqiao Li
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Yuli Jiang
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Weijie Cai
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, People's Republic of China
| | - Yingpeng Tong
- School of Life Sciences, Taizhou University, Taizhou, 318000, People's Republic of China
| | - Bathaie S Zahra
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box. 14115-133, Tehran, Islamic Republic of Iran
| | - Ping Wang
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China.
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Diet and Male Fertility: The Impact of Nutrients and Antioxidants on Sperm Energetic Metabolism. Int J Mol Sci 2022; 23:ijms23052542. [PMID: 35269682 PMCID: PMC8910394 DOI: 10.3390/ijms23052542] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/21/2022] [Accepted: 02/24/2022] [Indexed: 12/12/2022] Open
Abstract
Diet might affect male reproductive potential, but the biochemical mechanisms involved in the modulation of sperm quality remain poorly understood. While a Western diet is considered a risk factor for male infertility, the Mediterranean diet seems to protect against male infertility; moreover, the role of a vegetarian habitus in the preservation of sperm quality is controversial. The aim of this review is to analyze the molecular effects of single nutrients on sperm quality, focusing on their involvement in biochemical mechanisms related to sperm bioenergetics. It appears that diets rich in saturated fatty acids (SFA) and low in polyunsaturated fatty acids (PUFA) negatively affect sperm quality, whereas unsaturated fatty acids supplementation ameliorates sperm quality. In fact, the administration of PUFA, especially omega-3 PUFA, determined an increase in mitochondrial energetic metabolism and a reduction in oxidative damage. Carbohydrates and proteins are also nutritional modulators of oxidative stress and testosterone levels, which are strictly linked to sperm mitochondrial function, a key element for sperm quality. Moreover, many dietary natural polyphenols differentially affect (positively or negatively) the mitochondrial function, depending on their concentration. We believe that an understanding of the biochemical mechanisms responsible for sperm quality will lead to more targeted and effective therapeutics for male infertility.
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de Brito WA, Ferreira MRA, de Sousa Dantas D, Soares LAL. Biological activities of Eugenia uniflora L. (pitangueira) extracts in oxidative stress-induced pathologies: A systematic review and meta‐analysis of animal studies. PHARMANUTRITION 2022. [DOI: 10.1016/j.phanu.2022.100290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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Prikhodko VA, Bezborodkina NN, Okovityi SV. Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates. Biomedicines 2022; 10:274. [PMID: 35203484 PMCID: PMC8869100 DOI: 10.3390/biomedicines10020274] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/22/2022] [Accepted: 01/24/2022] [Indexed: 02/08/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), or metabolic (dysfunction)-associated fatty liver disease (MAFLD), is characterized by high global incidence and prevalence, a tight association with common metabolic comorbidities, and a substantial risk of progression and associated mortality. Despite the increasingly high medical and socioeconomic burden of NAFLD, the lack of approved pharmacotherapy regimens remains an unsolved issue. In this paper, we aimed to provide an update on the rapidly changing therapeutic landscape and highlight the major novel approaches to the treatment of this disease. In addition to describing the biomolecules and pathways identified as upcoming pharmacological targets for NAFLD, we reviewed the current status of drug discovery and development pipeline with a special focus on recent evidence from clinical trials.
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Affiliation(s)
- Veronika A. Prikhodko
- Department of Pharmacology and Clinical Pharmacology, Saint Petersburg State Chemical and Pharmaceutical University, 14A Prof. Popov Str., 197022 St. Petersburg, Russia;
| | - Natalia N. Bezborodkina
- Zoological Institute, Russian Academy of Sciences, 1 Universitetskaya emb., 199034 St. Petersburg, Russia;
| | - Sergey V. Okovityi
- Department of Pharmacology and Clinical Pharmacology, Saint Petersburg State Chemical and Pharmaceutical University, 14A Prof. Popov Str., 197022 St. Petersburg, Russia;
- Scientific, Clinical and Educational Center of Gastroenterology and Hepatology, Saint Petersburg State University, 7/9 Universitetskaya emb., 199034 St. Petersburg, Russia
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Gao W, Xu B, Zhang Y, Liu S, Duan Z, Chen Y, Zhang X. Baicalin Attenuates Oxidative Stress in a Tissue-Engineered Liver Model of NAFLD by Scavenging Reactive Oxygen Species. Nutrients 2022; 14:541. [PMID: 35276900 PMCID: PMC8840060 DOI: 10.3390/nu14030541] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 01/18/2022] [Accepted: 01/19/2022] [Indexed: 12/14/2022] Open
Abstract
Oxidative stress plays an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Baicalin has been shown to exert protective effects in various liver diseases. The mechanism of baicalin's antioxidative effect in NAFLD is currently unclear. The aim of this study was to investigate the effects and mechanisms of baicalin on oxidative stress in a new tissue-engineered liver model of NAFLD. The 3D model of NAFLD was induced by a fat-supplemented medium (fatty acids, FFA group) for 8 days and baicalin was administered on the 5th day. CCK-8 assay showed that baicalin at concentrations below 100 μM had no obvious cytotoxicity. Baicalin inhibited apoptosis and lactate dehydrogenase release in the FFA group. Baicalin reduced the levels of reactive oxygen species and malondialdehyde induced by FFA, and increased superoxide dismutase and glutathione amounts. However, it did not upregulate nuclear erythroid 2-related factor 2 compared with the FFA group. Mitochondrial morphology was partially restored after baicalin treatment, and ATP5A expression and mitochondrial membrane potential were increased. The superoxide anion scavenging ability of baicalin was enhanced in a dose-dependent manner. In summary, baicalin reduces oxidative stress and protects the mitochondria to inhibit apoptosis in the 3D NAFLD model via its own antioxidant activity.
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Affiliation(s)
- Wen Gao
- Department II of Liver Diseases, Beijing Youan Hospital Affiliated to Capital Medical University, Beijing 100069, China; (W.G.); (B.X.)
| | - Bin Xu
- Department II of Liver Diseases, Beijing Youan Hospital Affiliated to Capital Medical University, Beijing 100069, China; (W.G.); (B.X.)
| | - Yizhi Zhang
- Beijing Key Laboratory of Liver Failure and Artificial Liver Treatment, Department IV of Liver Diseases, Beijing Youan Hospital Affiliated to Capital Medical University, Beijing 100069, China; (Y.Z.); (S.L.); (Z.D.)
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China
| | - Shuang Liu
- Beijing Key Laboratory of Liver Failure and Artificial Liver Treatment, Department IV of Liver Diseases, Beijing Youan Hospital Affiliated to Capital Medical University, Beijing 100069, China; (Y.Z.); (S.L.); (Z.D.)
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China
| | - Zhongping Duan
- Beijing Key Laboratory of Liver Failure and Artificial Liver Treatment, Department IV of Liver Diseases, Beijing Youan Hospital Affiliated to Capital Medical University, Beijing 100069, China; (Y.Z.); (S.L.); (Z.D.)
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China
| | - Yu Chen
- Beijing Key Laboratory of Liver Failure and Artificial Liver Treatment, Department IV of Liver Diseases, Beijing Youan Hospital Affiliated to Capital Medical University, Beijing 100069, China; (Y.Z.); (S.L.); (Z.D.)
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China
| | - Xiaohui Zhang
- Beijing Key Laboratory of Liver Failure and Artificial Liver Treatment, Department IV of Liver Diseases, Beijing Youan Hospital Affiliated to Capital Medical University, Beijing 100069, China; (Y.Z.); (S.L.); (Z.D.)
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Capital Medical University, Beijing 100069, China
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