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Wang C, Li M, Zhang J, Li H, Li Y, Huang S, Zhu H, Liu Z. Associations of the Intake of Individual and Multiple Flavonoids with Metabolic Dysfunction Associated Steatotic Liver Disease in the United States. Nutrients 2025; 17:205. [PMID: 39861335 PMCID: PMC11768006 DOI: 10.3390/nu17020205] [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: 12/09/2024] [Revised: 12/29/2024] [Accepted: 01/05/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Evidence regarding the individual and combined impact of dietary flavonoids on the risk of metabolic dysfunction associated with steatotic liver disease (MASLD) remains scarce. Our objective is to evaluate the association between individual and multiple dietary flavonoids with MASLD in adults. METHODS Data sets were obtained from the National Health and Nutrition Examination Survey (NHANES), 2017-2018. In total, 2581 participants aged over 18 years, with complete information on dietary flavonoid intake, MASLD, and covariates, were included. Flavonoid intake was energy-adjusted using the residual method. Logistic regression analysis was employed to examine the impact of total flavonoid intake on MASLD. Weighted quantile sum (WQS) analyses were used to evaluate the combined and individual effects of flavonoids on MASLD and to identify the predominant types with the most significant contribution to MASLD prevention. RESULTS The highest tertile of total flavonoid intake was associated with a 29% reduction in the risk of MASLD compared to the lowest tertile after multivariable adjustments (OR: 0.71, 95% CI: 0.51-0.97). The WQS analysis revealed that anthocyanidins, flavones, and flavanones were the most critical contributors among six subclasses (weights = 0.317, 0.279, and 0.227, respectively) and naringenin, apigenin, and delphinidin were the most critical contributors among 29 monomers. (weights = 0.240, 0.231, and 0.114, respectively). Also, a higher intake of anthocyanidins, flavones, naringenin, apigenin, and delphinidin was linked to a reduced risk of MASLD (p < 0.05). CONCLUSIONS Our findings suggested that a higher flavonoid intake is associated with a lower risk of MASLD, with anthocyanidins, flavones, flavanones, naringenin, apigenin, delphinidin, and myricetin contributing most to the protective effects of flavonoids.
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Affiliation(s)
- Chen Wang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, 74 Zhong Shan Road 2, Guangzhou 510080, China; (C.W.); (M.L.); (J.Z.); (S.H.); (H.Z.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Mengchu Li
- Department of Nutrition, School of Public Health, Sun Yat-sen University, 74 Zhong Shan Road 2, Guangzhou 510080, China; (C.W.); (M.L.); (J.Z.); (S.H.); (H.Z.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Jiali Zhang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, 74 Zhong Shan Road 2, Guangzhou 510080, China; (C.W.); (M.L.); (J.Z.); (S.H.); (H.Z.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Hongguang Li
- Department of Clinical Nutrition, Zhongshan City People’s Hospital, Zhongshan 528400, China; (H.L.); (Y.L.)
| | - Yue Li
- Department of Clinical Nutrition, Zhongshan City People’s Hospital, Zhongshan 528400, China; (H.L.); (Y.L.)
| | - Siyu Huang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, 74 Zhong Shan Road 2, Guangzhou 510080, China; (C.W.); (M.L.); (J.Z.); (S.H.); (H.Z.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Huilian Zhu
- Department of Nutrition, School of Public Health, Sun Yat-sen University, 74 Zhong Shan Road 2, Guangzhou 510080, China; (C.W.); (M.L.); (J.Z.); (S.H.); (H.Z.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Zhaoyan Liu
- Department of Nutrition, School of Public Health, Sun Yat-sen University, 74 Zhong Shan Road 2, Guangzhou 510080, China; (C.W.); (M.L.); (J.Z.); (S.H.); (H.Z.)
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
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Sethi N, Khokhar M, Mathur M, Batra Y, Mohandas A, Tomo S, Rao M, Banerjee M. Therapeutic Potential of Nutraceuticals against Drug-Induced Liver Injury. Semin Liver Dis 2024; 44:430-456. [PMID: 39393795 DOI: 10.1055/s-0044-1791559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/13/2024]
Abstract
Drug-induced liver injury (DILI) continues to be a major concern in clinical practice, thus necessitating a need for novel therapeutic approaches to alleviate its impact on hepatic function. This review investigates the therapeutic potential of nutraceuticals against DILI, focusing on examining the underlying molecular mechanisms and cellular pathways. In preclinical and clinical studies, nutraceuticals, such as silymarin, curcumin, and N-acetylcysteine, have demonstrated remarkable efficacy in attenuating liver injury induced by diverse pharmaceutical agents. The molecular mechanisms underlying these hepatoprotective effects involve modulation of oxidative stress, inflammation, and apoptotic pathways. Furthermore, this review examines cellular routes affected by these nutritional components focusing on their influence on hepatocytes, Kupffer cells, and stellate cells. Key evidence highlights that autophagy modulation as well as unfolded protein response are essential cellular processes through which nutraceuticals exert their cytoprotective functions. In conclusion, nutraceuticals are emerging as promising therapeutic agents for mitigating DILI, by targeting different molecular pathways along with cell processes involved in it concurrently.
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Affiliation(s)
- Namya Sethi
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Manoj Khokhar
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Mitali Mathur
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Yashi Batra
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Amal Mohandas
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Sojit Tomo
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Mahadev Rao
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Karnataka, India
| | - Mithu Banerjee
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
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He S, Chen H, Yi Y, Hou D, Fu X, Xie J, Zhang J, Liu C, Ru X, Wang J. A novel bioinformatics strategy to uncover the active ingredients and molecular mechanisms of Bai Shao in the treatment of non-alcoholic fatty liver disease. Front Pharmacol 2024; 15:1406188. [PMID: 39005933 PMCID: PMC11239447 DOI: 10.3389/fphar.2024.1406188] [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: 03/24/2024] [Accepted: 06/10/2024] [Indexed: 07/16/2024] Open
Abstract
Introduction: As a new discipline, network pharmacology has been widely used to disclose the material basis and mechanism of Traditional Chinese Medicine in recent years. However, numerous researches indicated that the material basis of TCMs identified based on network pharmacology was the mixtures of beneficial and harmful substances rather than the real material basis. In this work, taking the anti-NAFLD (non-alcoholic fatty liver disease) effect of Bai Shao (BS) as a case, we attempted to propose a novel bioinformatics strategy to uncover the material basis and mechanism of TCMs in a precise manner. Methods: In our previous studies, we have done a lot work to explore TCM-induced hepatoprotection. Here, by integrating our previous studies, we developed a novel computational pharmacology method to identify hepatoprotective ingredients from TCMs. Then the developed method was used to discover the material basis and mechanism of Bai Shao against Non-alcoholic fatty liver disease by combining with the techniques of molecular network, microarray data analysis, molecular docking, and molecular dynamics simulation. Finally, literature verification method was utilized to validate the findings. Results: A total of 12 ingredients were found to be associated with the anti-NAFLD effect of BS, including monoterpene glucosides, flavonoids, triterpenes, and phenolic acids. Further analysis found that IL1-β, IL6, and JUN would be the key targets. Interestingly, molecular docking and molecular dynamics simulation analysis showed that there indeed existed strong and stable binding affinity between the active ingredients and the key targets. In addition, a total of 23 NAFLD-related KEGG pathways were enriched. The major biological processes involved by these pathways including inflammation, apoptosis, lipid metabolism, and glucose metabolism. Of note, there was a great deal of evidence available in the literature to support the findings mentioned above, indicating that our method was reliable. Discussion: In summary, the contributions of this work can be summarized as two aspects as follows. Firstly, we systematically elucidated the material basis and mechanism of BS against NAFLD from multiple perspectives. These findings further enhanced the theoretical foundation of BS on NAFLD. Secondly, a novel computational pharmacology research strategy was proposed, which would assist network pharmacology to uncover the scientific connotation TCMs in a more precise manner.
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Affiliation(s)
- Shuaibing He
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Hantao Chen
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Yanfeng Yi
- Department of Life Sciences and Health, School of Science and Engineering, Huzhou College, Huzhou, China
| | - Diandong Hou
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Xuyan Fu
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Jinlu Xie
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Juan Zhang
- XinJiang Institute of Chinese Materia Medica and Ethnodrug, Urumqi, China
| | - Chongbin Liu
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Xiaochen Ru
- Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China
- Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China
| | - Juan Wang
- School of Traditional Chinese Medicine, Zhejiang Pharmaceutical University, Ningbo, China
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Tang X, Zhou Y, Liu F, Wang B, Mao B, Zhang Q, Zhao J, Chen W, Cui S. A Pueraria lobata root extract alleviates high-fat diet-induced non-alcoholic fatty liver disease by modulating the gut microbiota and associated metabolites. FOOD BIOSCI 2024; 59:103746. [DOI: 10.1016/j.fbio.2024.103746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Wei S, Jiang Y, Li M, Zhao L, Wang T, Wei M, Zhao Q, Zeng J, Zhao Y, Shen J, Du F, Chen Y, Deng S, Xiao Z, Li Z, Wu X. Chemical profiling and quality evaluation of Liuweizhiji Gegen-Sangshen oral liquid by UPLC-Q-TOF-MS and HPLC-diode array detector fingerprinting. PHYTOCHEMICAL ANALYSIS : PCA 2024; 35:860-872. [PMID: 38361458 DOI: 10.1002/pca.3333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/17/2024] [Accepted: 01/18/2024] [Indexed: 02/17/2024]
Abstract
INTRODUCTION Liuweizhiji Gegen-Sangshen (LGS) oral liquid is a Chinese patent medicine that is widely used for the prevention and treatment of alcoholic liver disease in clinical practice. However, the chemical complexity of LGS has not yet been investigated. OBJECTIVE The aim of this study was to rapidly identify chemical constituents of LGS and establish a quality control method based on fingerprint and quantitative analysis. METHODOLOGY A comprehensive strategy was used by combining qualitative analysis by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and fingerprint analysis by high-performance liquid chromatography with diode array detection (HPLC-DAD). RESULTS A total of 162 chemical components in LGS, including 91 flavonoids, 31 organic acids, and 20 phenolic compounds, were identified or preliminarily characterized in both positive and negative ion modes based on the UPLC-Q-TOF-MS results. Of these, 37 were confirmed with the reference standards. In fingerprint analysis, 23 peaks were chosen as common peaks and used to evaluate the similarity of different batches of LGS. Subsequently, a rapid quantification method was optimized and validated for the simultaneous determination of multiple chemical markers in LGS. The validated quantitative method was successfully used to analyze different batches of LGS samples. CONCLUSION The proposed comprehensive strategy combining HPLC-DAD fingerprinting and multi-component quantification demonstrated satisfactory results with high efficiency, accuracy, and reliability. This can be used as a reference for the overall quality consistency evaluation of Chinese patent medicines.
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Affiliation(s)
- Shulin Wei
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Yu Jiang
- Department of Gerontology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Mingxing Li
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Long Zhao
- Department of Spleen and Stomach Diseases, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Tiangang Wang
- Department of Spleen and Stomach Diseases, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Mei Wei
- Department of Spleen and Stomach Diseases, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Qianyun Zhao
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Jiuping Zeng
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Yueshui Zhao
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Jing Shen
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Fukuan Du
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Yu Chen
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Shuai Deng
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Zhangang Xiao
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Zhi Li
- Department of Spleen and Stomach Diseases, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
- The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou city, The Affiliated Traditional Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Xu Wu
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
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Shalapy NM, Liu M, Kang W. Protective effects of hepatic diseases by bioactive phytochemicals in Fusarium oxysporum - A review. Heliyon 2024; 10:e26562. [PMID: 38455549 PMCID: PMC10918022 DOI: 10.1016/j.heliyon.2024.e26562] [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: 09/23/2023] [Revised: 01/29/2024] [Accepted: 02/15/2024] [Indexed: 03/09/2024] Open
Abstract
Lately, liver diseases were categorized as one of the most prevalent health problems globally as it causes a severe threat to mankind all over the world due to the wide range of occurrence. There are multiple factors causing hepatic disorders, such as alcohol, virus, poisons, adverse effects of drugs, poor diet, inherited conditions and obesity. Liver diseases have various types including alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune hepatitis, liver cancer, hepatocellular carcinoma, liver fibrosis and hepatic inflammation. Therefore, it is imperative to find effective and efficacious agents in managing liver diseases. Fusarium oxysporum, an endophytic fungus and containing many bioactive compounds, could be served as a forked medication for enormous number and types of maladies. It was characterized by producing biochemical compounds which had rare pharmacological properties as it may be found in a limit number of other medicinal plants. The majority of the past researches related to Fusarium oxysporum recited the fungal negative field either on the pathogenic effects of the fungus on economical crops or on the fungal chemical components to know how to resist it. The present review will highlight on the bright side of Fusarium oxysporum and introduce the functional activities of its chemical compounds for treating its target diseases. The key point of illustrated studies in this article is displaying wide range of detected bioactive compounds isolated from Fusarium oxysporum and in other illustrated studies it was elucidated the therapeutical and pharmacological potency of these biologically active compounds (isolated from medicinal plants sources) against different types of liver diseases including non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and others. It was demonstrated that F. oxysporum contains unique types of isoflavones, flavonoids, phenols and another active chemical compounds, and these compounds showed recently a fabulous clinical contribution in the therapy of liver injury diseases, which opens new and unprecedented way for evaluating the maintaining efficacy of Fusarium oxysporum bioactive compounds in dealing with hepatic complications and its remedy impacting on liver diseases and injured hepatocytes through recommending implement a practical study.
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Affiliation(s)
- Nashwa M. Shalapy
- National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng, 475004, China
- Microbial Chemistry Department, Biotechnology Research Institute, National Research Center, Cairo, Egypt
| | - Ming Liu
- National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng, 475004, China
| | - Wenyi Kang
- National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng, 475004, China
- Joint International Research Laboratory of Food & Medicine Resource Function, Henan Province, Kaifeng, 475004, China
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Senaldi L, Hassan N, Cullen S, Balaji U, Trigg N, Gu J, Finkelstein H, Phillips K, Conine C, Smith-Raska M. Khdc3 Regulates Metabolism Across Generations in a DNA-Independent Manner. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.02.27.582278. [PMID: 38464133 PMCID: PMC10925209 DOI: 10.1101/2024.02.27.582278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/12/2024]
Abstract
Genetic variants can alter the profile of heritable molecules such as small RNAs in sperm and oocytes, and in this manner ancestral genetic variants can have a significant effect on offspring phenotypes even if they are not themselves inherited. Here we show that wild type female mice descended from ancestors with a mutation in the mammalian germ cell gene Khdc3 have hepatic metabolic defects that persist over multiple generations. We find that genetically wild type females descended from Khdc3 mutants have transcriptional dysregulation of critical hepatic metabolic genes, which persist over multiple generations and pass through both female and male lineages. This was associated with dysregulation of hepatically-metabolized molecules in the blood of these wild type mice with mutational ancestry. The oocytes of Khdc3-null females, as well as their wild type descendants, had dysregulation of multiple small RNAs, suggesting that these epigenetic changes in the gametes transmit the phenotype between generations. Our results demonstrate that ancestral mutation in Khdc3 can produce transgenerational inherited phenotypes, potentially indefinitely.
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Affiliation(s)
- Liana Senaldi
- Division of Neonatology, Department of Pediatrics, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA
- Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY, USA
| | - Nora Hassan
- Division of Neonatology, Department of Pediatrics, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA
| | - Sean Cullen
- Division of Neonatology, Department of Pediatrics, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA
- Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY, USA
| | - Uthra Balaji
- Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY, USA
| | - Natalie Trigg
- Departments of Genetics and Paediatrics, University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Jinghua Gu
- Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY, USA
| | - Hailey Finkelstein
- Division of Neonatology, Department of Pediatrics, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA
| | - Kathryn Phillips
- Division of Neonatology, Department of Pediatrics, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA
| | - Colin Conine
- Departments of Genetics and Paediatrics, University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Matthew Smith-Raska
- Division of Neonatology, Department of Pediatrics, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA
- Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY, USA
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Wang R, Mao Y, Yu C, Rong Z, Wang R, Wang Y, Lv L, Gao Y, Wang Z, Zhang H. Research Progress of Natural Products with the Activity of Anti-nonalcoholic Steatohepatitis. Mini Rev Med Chem 2024; 24:1894-1929. [PMID: 38752645 DOI: 10.2174/0113895575306598240503054317] [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: 01/26/2024] [Revised: 03/19/2024] [Accepted: 03/29/2024] [Indexed: 10/16/2024]
Abstract
Nonalcoholic steatohepatitis (NASH), a multi-target disease, is becoming a global epidemic. Although several anti-NASH drug candidates are being evaluated in late-stage clinical trials, none have been approved by the FDA to date. Given the global prevalence of the disease, the lack of effective drugs, and the very limited therapeutic efficacy of most of the existing synthetic drugs focusing on a single target, there is an urgent need to continue to develop new therapeutic agents. In contrast, many natural products, including pure compounds and crude extracts, possess hepatoprotective activities. Usually, these natural components are characterized by multi-targeting and low side effects. Therefore, natural products are important resources for the development of new anti- NASH drugs. In this paper, we focus on reviewing the anti-NASH potential, structure, and some of the side effects of natural products based on structural classification. We hope this mini-review will help researchers design and develop new anti-NASH drugs, especially based on the structure of natural products.
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Affiliation(s)
- Rui Wang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Yuheng Mao
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Chunping Yu
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Zhenji Rong
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Ruyue Wang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Yixin Wang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Linjin Lv
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Yang Gao
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Zhigang Wang
- Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin 150040, China
| | - Hailong Zhang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
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Li YM, He HW, Zhang N. Targeting Protein Phosphatases for the Treatment of Chronic Liver Disease. Curr Drug Targets 2024; 25:171-189. [PMID: 38213163 DOI: 10.2174/0113894501278886231221092522] [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: 10/12/2023] [Revised: 11/27/2023] [Accepted: 11/29/2023] [Indexed: 01/13/2024]
Abstract
There exists a huge number of patients suffering from chronic liver disease worldwide. As a disease with high incidence and mortality worldwide, strengthening the research on the pathogenesis of chronic liver disease and the development of novel drugs is an important issue related to the health of all human beings. Phosphorylation modification of proteins plays a crucial role in cellular signal transduction, and phosphatases are involved in the development of liver diseases. Therefore, this article summarized the important role of protein phosphatases in chronic liver disease with the aim of facilitating the development of drugs targeting protein phosphatases for the treatment of chronic liver disease.
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Affiliation(s)
- Yi-Ming Li
- NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Hong-Wei He
- NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Na Zhang
- NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
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Zakaria Z, Othman ZA, Nna VU, Mohamed M. The promising roles of medicinal plants and bioactive compounds on hepatic lipid metabolism in the treatment of non-alcoholic fatty liver disease in animal models: molecular targets. Arch Physiol Biochem 2023; 129:1262-1278. [PMID: 34153200 DOI: 10.1080/13813455.2021.1939387] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 06/01/2021] [Indexed: 12/13/2022]
Abstract
Imbalance in hepatic lipid metabolism can lead to an abnormal triglycerides deposition in the hepatocytes which can cause non-alcoholic fatty liver disease (NAFLD). Four main mechanisms responsible for regulating hepatic lipid metabolism are fatty acid uptake, de novo lipogenesis, lipolysis and fatty acid oxidation. Controlling the expression of transcription factors at molecular level plays a crucial role in NAFLD management. This paper reviews various medicinal plants and their bioactive compounds emphasising mechanisms involved in hepatic lipid metabolism, other important NAFLD pathological features, and their promising roles in managing NAFLD through regulating key transcription factors. Although there are many medicinal plants popularly investigated for NAFLD treatment, there is still little information and scientific evidence available and there has been no research on clinical trials scrutinised on this matter. This review also aims to provide molecular information of medicinal plants in NALFD treatment that might have potentials for future scientifically controlled studies.
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Affiliation(s)
- Zaida Zakaria
- Department of Physiology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Zaidatul Akmal Othman
- Department of Physiology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia
- Unit of Physiology, Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu, Malaysia
| | - Victor Udo Nna
- Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, Calabar, Nigeria
| | - Mahaneem Mohamed
- Department of Physiology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia
- Unit of Integrative Medicine, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia
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11
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Zeng Y, Wu R, Wang F, Li S, Li L, Li Y, Qin P, Wei M, Yang J, Wu J, Chen A, Ke G, Yan Z, Yang H, Chen Z, Wang Z, Xiao W, Jiang Y, Chen X, Zeng Z, Zhao X, Chen P, Gong S. Liberation of daidzein by gut microbial β-galactosidase suppresses acetaminophen-induced hepatotoxicity in mice. Cell Host Microbe 2023; 31:766-780.e7. [PMID: 37100057 DOI: 10.1016/j.chom.2023.04.002] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 02/11/2023] [Accepted: 04/03/2023] [Indexed: 04/28/2023]
Abstract
Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI). The impact of the gut microbiota and associated metabolites on APAP and liver function remains unclear. We show that APAP disturbance is associated with a distinct gut microbial community, with notable decreases in Lactobacillus vaginalis. Mice receiving L. vaginalis showed resistance to APAP hepatotoxicity due to the liberation of the isoflavone daidzein from the diet by bacterial β-galactosidase. The hepatoprotective effects of L. vaginalis in APAP-exposed germ-free mice were abolished with a β-galactosidase inhibitor. Similarly, β-galactosidase-deficient L. vaginalis produced poorer outcomes in APAP-treated mice than the wild-type strain, but these differences were overcome with daidzein administration. Mechanistically, daidzein prevented ferroptotic death, which was linked to decreased expression of farnesyl diphosphate synthase (Fdps) that activated a key ferroptosis pathway involving AKT-GSK3β-Nrf2. Thus, liberation of daidzein by L. vaginalis β-galactosidase inhibits Fdps-mediated hepatocyte ferroptosis, providing promising therapeutic approaches for DILI.
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Affiliation(s)
- Yunong Zeng
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China
| | - Rong Wu
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China
| | - Fangzhao Wang
- Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Shan Li
- Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Lei Li
- Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Yanru Li
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China
| | - Ping Qin
- Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Mingyuan Wei
- Institute of Ecological Science, School of Life Science, South China Normal University, Guangzhou 510631, China
| | - Junhao Yang
- Institute of Ecological Science, School of Life Science, South China Normal University, Guangzhou 510631, China
| | - Jie Wu
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Ali Chen
- Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Guibao Ke
- Department of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China
| | - Zhengzheng Yan
- Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Hong Yang
- Department of Critical Care Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510665, China
| | - Zhongqing Chen
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Zhang Wang
- Institute of Ecological Science, School of Life Science, South China Normal University, Guangzhou 510631, China
| | - Wei Xiao
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Yong Jiang
- Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Xia Chen
- Department of Obstetrics and Gynecology, First People's Hospital of Foshan, Foshan 528000, China
| | - Zhenhua Zeng
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Xiaoshan Zhao
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
| | - Peng Chen
- Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
| | - Shenhai Gong
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
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12
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Yang Z, Gong D, He X, Huang F, Sun Y, Hu Q. Association between daidzein intake and metabolic associated fatty liver disease: A cross-sectional study from NHANES 2017-2018. Front Nutr 2023; 10:1113789. [PMID: 36860686 PMCID: PMC9968739 DOI: 10.3389/fnut.2023.1113789] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 01/26/2023] [Indexed: 02/15/2023] Open
Abstract
Background Metabolic associated fatty liver disease (MAFLD) has become the most common liver disease globally, yet no new drugs have been approved for clinical treatment. Therefore, we investigated the relationship between dietary intake of soy-derived daidzein and MAFLD, to find potentially effective treatments. Methods We conducted a cross-sectional study using data from 1,476 participants in National Health and Nutrition Examination Survey (NHANES) from 2017 to 2018 and their associated daidzein intake from the flavonoid database in the USDA Food and Nutrient Database for Dietary Studies (FNDDS). We investigated the relationship between MAFLD status, controlled attenuation parameter (CAP), AST/Platelet Ratio Index (APRI), Fibrosis-4 Index (FIB-4), liver stiffness measurement (LSM), nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), hepatic steatosis index (HSI), fatty liver index (FLI), and daidzein intake by adjusting for confounding variables using binary logistic regression models and linear regression models. Results In the multivariable-adjusted model II, there was a negative association between daidzein intake and the incidence of MAFLD (OR for Q4 versus Q1 was 0.65, 95% confidence interval [CI] = 0.46-0.91, p = 0.0114, p for trend was 0.0190). CAP was also negatively associated with daidzein intake, β = -0.37, 95% CI: -0.63 to -0.12, p = 0.0046 in model II after adjusting for age, sex, race, marital status, education level, family income-to-poverty ratio (PIR), smoking, and alcohol consumption. Stratified by quartiles of daidzein intake, trend analysis of the relationship between daidzein intake and CAP remained significant (p for trend = 0.0054). In addition, we also found that HSI, FLI, and NFS were negatively correlated with daidzein intake. LSM was negatively related to daidzein intake but had no statistical significance. The correlation between APRI, FIB-4, and daidzein intake was not strong (although p < 0.05, β values were all 0). Conclusion We found that MAFLD prevalence, CAP, HSI, and FLI, all decreased with increased daidzein intake, suggesting that daidzein intake may improve hepatic steatosis. Therefore, dietary patterns of soy food or supplement consumption may be a valuable strategy to reduce the disease burden and the prevalence of MAFLD.
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Affiliation(s)
- Zheng Yang
- Department of Infectious Disease, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
| | - Daoqing Gong
- Teaching Office, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
| | - Xinxiang He
- Department of Infectious Disease, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
| | - Fei Huang
- Department of Infectious Disease, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
| | - Yi Sun
- Department of Dermatology, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China,*Correspondence: Yi Sun, ✉
| | - Qinming Hu
- Department of Infectious Disease, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China,Qinming Hu, ✉
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Singh S, Grewal S, Sharma N, Behl T, Gupta S, Anwer MK, Vargas-De-La-Cruz C, Mohan S, Bungau SG, Bumbu A. Unveiling the Pharmacological and Nanotechnological Facets of Daidzein: Present State-of-the-Art and Future Perspectives. Molecules 2023; 28:1765. [PMID: 36838751 PMCID: PMC9958968 DOI: 10.3390/molecules28041765] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/02/2023] [Accepted: 02/10/2023] [Indexed: 02/17/2023] Open
Abstract
Herbal drugs have been attracting much scientific interest in the last few decades and nowadays, phytoconstituents-based research is in progress to disclose their unidentified medicinal potential. Daidzein (DAI) is the natural phytoestrogen isoflavone derived primarily from leguminous plants, such as the soybean and mung bean, and its IUPAC name is 4',7-dihydroxyisoflavone. This compound has received great attention as a fascinating pharmacophore with remarkable potential for the therapeutic management of several diseases. Certain pharmacokinetic properties of DAI such as less aqueous solubility, low permeability, and poor bioavailability are major obstacles restricting the therapeutic applications. In this review, distinctive physicochemical characteristics and pharmacokinetics of DAI has been elucidated. The pharmacological applications in treatment of several disorders like oxidative stress, cancer, obesity, cardiovascular, neuroprotective, diabetes, ovariectomy, anxiety, and inflammation with their mechanism of action are explained. Furthermore, this review article comprehensively focuses to provide up-to-date information about nanotechnology-based formulations which have been investigated for DAI in preceding years which includes polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, polymer-lipid nanoparticles, nanocomplexes, polymeric micelles, nanoemulsion, nanosuspension, liposomes, and self-microemulsifying drug delivery systems.
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Affiliation(s)
- Sukhbir Singh
- Department of Pharmaceutics, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to Be University), Ambala 133207, India
| | - Sonam Grewal
- Department of Pharmaceutics, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to Be University), Ambala 133207, India
| | - Neelam Sharma
- Department of Pharmaceutics, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to Be University), Ambala 133207, India
| | - Tapan Behl
- School of Health Sciences & Technology, University of Petroleum and Energy Studies, Bidholi, Dehradun 248007, India
| | - Sumeet Gupta
- Department of Pharmacology, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to Be University), Ambala 133207, India
| | - Md. Khalid Anwer
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia
| | - Celia Vargas-De-La-Cruz
- Department of Pharmacology, Bromatology and Toxicology, Faculty of Pharmacy and Biochemistry, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru
- E-Health Research Center, Universidad de Ciencias y Humanidades, Lima 15081, Peru
| | - Syam Mohan
- School of Health Sciences & Technology, University of Petroleum and Energy Studies, Bidholi, Dehradun 248007, India
- Substance Abuse and Toxicology Research Centre, Jazan University, Jazan 45142, Saudi Arabia
- Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Science, Saveetha University, Chennai 602117, India
| | - Simona Gabriela Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
- Doctoral School of Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
| | - Adrian Bumbu
- Department of Surgery, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
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14
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Mechanistic insights into dietary (poly)phenols and vascular dysfunction-related diseases using multi-omics and integrative approaches: Machine learning as a next challenge in nutrition research. Mol Aspects Med 2023; 89:101101. [PMID: 35728999 DOI: 10.1016/j.mam.2022.101101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 06/09/2022] [Accepted: 06/11/2022] [Indexed: 02/04/2023]
Abstract
Dietary (poly)phenols have been extensively studied for their vasculoprotective effects and consequently their role in preventing or delaying onsets of cardiovascular and metabolic diseases. Even though early studies have ascribed the vasculoprotective properties of (poly)phenols primarily on their putative free radical scavenging properties, recent data indicate that in biological systems, (poly)phenols act primarily through genomic and epigenomic mechanisms. The molecular mechanisms underlying their health properties are still not well identified, mainly due to the use of physiologically non-relevant conditions (native molecules or extracts at high concentrations, rather than circulating metabolites), but also due to the use of targeted genomic approaches aiming to evaluate the effect only on few specific genes, thus preventing to decipher detailed molecular mechanisms involved. The use of state-of-the-art untargeted analytical methods represents a significant breakthrough in nutrigenomics, as these methods enable detailed insights into the effects at each specific omics level. Moreover, the implementation of multi-omics approaches allows integration of different levels of regulation of cellular functions, to obtain a comprehensive picture of the molecular mechanisms of action of (poly)phenols. In combination with bioinformatics and the methods of machine learning, multi-omics has potential to make a huge contribution to the nutrition science. The aim of this review is to provide an overview of the use of the omics, multi-omics, and integrative approaches in studying the vasculoprotective properties of dietary (poly)phenols and address the potentials for use of the machine learning in nutrigenomics.
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15
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Saeed F, Afzaal M, Shah YA, Khan MH, Hussain M, Ikram A, Ateeq H, Noman M, Saewan SA, Khashroum AO. Miso: A traditional nutritious & health-endorsing fermented product. Food Sci Nutr 2022; 10:4103-4111. [PMID: 36514754 PMCID: PMC9731531 DOI: 10.1002/fsn3.3029] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 07/26/2022] [Accepted: 07/28/2022] [Indexed: 12/16/2022] Open
Abstract
Consumer demand for fermented foods with a well-balanced nutrient profile has been increasing owing to their ability to prevent chronic diseases as well as their functional, nutritional, and nutraceutical benefits. Among those functional foods, miso is a well-known traditional fermented food with a distinctive savory flavor and aroma that is most commonly used as a seasoning in miso soup. Among different fermented products, miso is derived from soybeans and grains as a result of the activities of Koji enzymes and beneficial microbes. Additionally, the microbial community of miso is thought to be crucial in enhancing its distinct flavor and texture as well as its nutritional properties. Despite the importance of microorganisms in the production of miso, there has been relatively little research done to characterize and describe the nutritional and medicinal potential of miso. In this review, the potential therapeutic properties, i.e., anticancer, antimicrobial, and antiobesity, of miso have been discussed comprehensively. This review envisions the production technology, its history, microbial population, nutritional properties, and the potential health benefits of miso associated with its consumption.
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Affiliation(s)
- Farhan Saeed
- Department of Food SciencesGovernment College UniversityFaisalabadPakistan
| | - Muhammad Afzaal
- Department of Food SciencesGovernment College UniversityFaisalabadPakistan
| | - Yasir Abbas Shah
- Department of Food SciencesGovernment College UniversityFaisalabadPakistan
| | | | - Muzzamal Hussain
- Department of Food SciencesGovernment College UniversityFaisalabadPakistan
| | - Ali Ikram
- University Institute of Food Science and Technology, The University of LahoreLahorePakistan
| | - Huda Ateeq
- Department of Food SciencesGovernment College UniversityFaisalabadPakistan
| | - Muhammad Noman
- Department of Food SciencesGovernment College UniversityFaisalabadPakistan
| | - Shamaail A. Saewan
- Department of Food SciencesCollege of Agriculture, University of BasrahBasrahIraq
| | - Ashraf O. Khashroum
- Department of Plant Production and Protection, Faculty of AgricultureJerash UniversityJerashJordan
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16
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Lim DW, Wang JH. Gut Microbiome: The Interplay of an "Invisible Organ" with Herbal Medicine and Its Derived Compounds in Chronic Metabolic Disorders. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:13076. [PMID: 36293657 PMCID: PMC9603471 DOI: 10.3390/ijerph192013076] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/29/2022] [Accepted: 10/09/2022] [Indexed: 06/16/2023]
Abstract
Resembling a concealed "organ" in a holobiont, trillions of gut microbes play complex roles in the maintenance of homeostasis, including participating in drug metabolism. The conventional opinion is that most of any drug is metabolized by the host and that individual differences are principally due to host genetic factors. However, current evidence indicates that only about 60% of the individual differences in drug metabolism are attributable to host genetics. Although most common chemical drugs regulate the gut microbiota, the gut microbiota is also known to be involved in drug metabolism, like the host. Interestingly, many traditional herbal medicines and derived compounds are biotransformed by gut microbiota, manipulating the compounds' effects. Accordingly, the gut microbiota and its specified metabolic pathways can be deemed a promising target for promoting drug efficacy and safety. However, the evidence regarding causality and the corresponding mechanisms concerning gut microbiota and drug metabolism remains insufficient, especially regarding drugs used to treat metabolic disorders. Therefore, the present review aims to comprehensively summarize the bidirectional roles of gut microbiota in the effects of herbal medicine in metabolic diseases to provide vital clues for guiding the clinical application of precision medicine and personalized drug development.
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Affiliation(s)
- Dong-Woo Lim
- Department of Diagnostics, College of Korean Medicine, Dongguk University, Dongguk-Ro 32, Goyang 10326, Korea
| | - Jing-Hua Wang
- Institute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon 35235, Korea
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17
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Tan P, Jin L, Qin X, He B. Natural flavonoids: Potential therapeutic strategies for non-alcoholic fatty liver disease. Front Pharmacol 2022; 13:1005312. [PMID: 36188561 PMCID: PMC9524541 DOI: 10.3389/fphar.2022.1005312] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 08/26/2022] [Indexed: 01/30/2023] Open
Abstract
The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly worldwide; however, there are currently limited treatments for NAFLD. The disease spectrum includes simple fatty liver, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and progression to hepatocellular carcinoma (NASH-HCC). The therapeutic effects of NAFLD remain controversial. Although researchers have conducted studies on the pathogenesis of NAFLD, its pathogenesis and anti-NAFLD mechanisms have not been fully elucidated. Previous studies have found that flavonoids, as natural substances with extensive pharmacological activity and good therapeutic effects, have excellent antioxidant, anti-inflammatory, metabolic disease improvement, anti-tumor, and other properties and can significantly alleviate NAFLD. Flavonoids could be further developed as therapeutic drugs for NAFLD. In this paper, the pathogenesis of NAFLD and the mechanisms of flavonoids against NAFLD are summarized to provide a theoretical basis for screening flavonoids against non-alcoholic liver injury.
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Affiliation(s)
- Panli Tan
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Li Jin
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiang Qin
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Beihui He
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
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18
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Xiao CW, Hendry A. Hypolipidemic Effects of Soy Protein and Isoflavones in the Prevention of Non-Alcoholic Fatty Liver Disease- A Review. PLANT FOODS FOR HUMAN NUTRITION (DORDRECHT, NETHERLANDS) 2022; 77:319-328. [PMID: 35678936 PMCID: PMC9463339 DOI: 10.1007/s11130-022-00984-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 05/30/2022] [Indexed: 06/15/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and affects about 25% of the population globally. Obesity and diabetes are the main causes of the disease characterized by excessive accumulation of lipids in the liver. There is currently no direct pharmacological treatments for NAFLD. Dietary intervention and lifestyle modification are the key strategies in the prevention and treatment of the disease. Soy consumption is associated with many health benefits such as decreased incidence of coronary heart disease, type-2 diabetes, atherosclerosis and obesity. The hypolipidemic functions of soy components have been shown in both animal studies and human clinical trials. Dietary soy proteins and associated isoflavones suppressed the formation and accumulation of lipid droplets in the liver and improved NAFLD-associated metabolic syndrome. The molecular mechanism(s) underlying the effects of soy components are mainly through modulation of transcription factors, sterol regulatory element-binding protein-1 and peroxisome proliferator-activated receptor-γ2, and expressions of their target genes involved in lipogenesis and lipolysis as well as lipid droplet-promoting protein, fat-specific protein-27. Inclusion of appropriate amounts of soy protein and isoflavones in the diets might be a useful approach to decrease the prevalence of NAFLD and mitigate disease burden.
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Affiliation(s)
- Chao-Wu Xiao
- Nutrition Research Division, Bureau of Nutritional Sciences, Food Directorate, Health Products and Food Branch, Health Canada, 2203C Banting Research Centre, Ottawa, ON, K1A 0L2, Canada.
- Food and Nutrition Science Program, Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada.
| | - Amy Hendry
- Nutrition Research Division, Bureau of Nutritional Sciences, Food Directorate, Health Products and Food Branch, Health Canada, 2203C Banting Research Centre, Ottawa, ON, K1A 0L2, Canada
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19
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Hakkak R, Spray B, Børsheim E, Korourian S. Diet Containing Soy Protein Concentrate With Low and High Isoflavones for 9 Weeks Protects Against Non-alcoholic Fatty Liver Steatosis Using Obese Zucker Rats. Front Nutr 2022; 9:913571. [PMID: 35811988 PMCID: PMC9258741 DOI: 10.3389/fnut.2022.913571] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 05/25/2022] [Indexed: 12/05/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), is one of the main liver diseases in the US and the world which often is related to obesity. Previously, we reported short- and long-term consumption of soy protein isolate diet with high isoflavones can reduce liver steatosis in the male and female obese Zucker rat model. However, the effects of high vs. low soy isoflavones on NAFLD is less known. The objectives of the present study were to examine the role of isoflavones levels in soy protein concentrate diets on protection against NAFLD in an obese rat model. Forty-two 6-week old lean (L, n = 21) and obese (O, n = 21) Zucker rats were randomly assigned to 1 of 3 dietary groups: casein diet (C = control), soy protein concentrate with low isoflavones (LIF), or soy protein concentrate with high isoflavones (HIF) for 9 weeks. Rats were weighed twice weekly. After 9 weeks, rats were sacrificed and samples of livers were taken for histopathological analysis. Serums were collected to measure ALT and AST levels. Results indicate that obese rats gained significantly more weight than lean rats for all three diet groups (P < 0.001). No significant difference in body weight between LC, LLIF and LHIF was noted. However, the OLIF and OHIF rats gained significantly more weight than OC rats (P < 0.001). Liver steatosis scores were significantly greater in obese rats compared to lean rats (P < 0.001). The OLIF and OHIF-fed rats had significantly reduced steatosis scores than OC rats (P = 0.013 and P < 0.001, respectively). The serum ALT levels were significantly greater in OC, OLIF and OHIF compared to LC, LLIF and LHIF, respectively (P < 0.001, P < 0.001, and P = 0.011). AST serum levels were greater in OC and OLIF compared to LC and LLIF, respectively (P = 0.001 and P = 0.022). In summary, we found that soy protein concentrate with isoflavones protects against liver steatosis and the protection is greater with a higher concentration of isoflavones.
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Affiliation(s)
- Reza Hakkak
- Department of Dietetics and Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR, United States
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
- Arkansas Children's Research Institute, Little Rock, AR, United States
- *Correspondence: Reza Hakkak
| | - Beverly Spray
- Arkansas Children's Research Institute, Little Rock, AR, United States
| | - Elisabet Børsheim
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
- Arkansas Children's Research Institute, Little Rock, AR, United States
- Arkansas Children's Nutrition Center, Little Rock, AR, United States
| | - Soheila Korourian
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United States
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Associations of Urinary Phytoestrogen Concentrations with Nonalcoholic Fatty Liver Disease among Adults. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:4912961. [PMID: 35399831 PMCID: PMC8989597 DOI: 10.1155/2022/4912961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/15/2022] [Accepted: 03/18/2022] [Indexed: 11/17/2022]
Abstract
Phytoestrogens can alleviate some pathological processes related to nonalcoholic fatty liver disease (NAFLD). However, there are limited and contradictory studies on the relationships between phytoestrogens (especially single phytoestrogen) and NAFLD. The purpose of this study was to explore the relationships between urinary phytoestrogen concentrations and NAFLD in American adults. This cross-sectional study used the data of the National Health and Nutrition Examination Survey from 1999 to 2010, and 2294 adults were finally enrolled in this study. The concentrations of phytoestrogens were measured in urine samples, and urinary phytoestrogens were divided into tertiles according to the concentration distributions. The diagnosis of NAFLD was determined by the United States fatty liver index. The main analysis used a multivariate logistic regression model. The fully adjusted models included gender, age, race, education, marriage, poverty, body mass index, waist circumference, smoking, diabetes, hypertension, total cholesterol, high-density lipoprotein cholesterol, triglycerides, and other five phytoestrogens. In the fully adjusted model, the urinary enterolactone (ENL) concentration was negatively correlated with NAFLD (OR of Tertile 3 : 0.48, 95% CI 0.25–0.94). When stratified by age and gender, the urinary ENL concentration was negatively correlated with NAFLD in males aged 40–59 years (OR of Tertile 3 : 0.08, 95% CI 0.01–0.82), while the urinary equol concentration was positively correlated with NAFLD in such population (OR of Tertile 3 : 4.27, 95% CI 1.02–17.85). In addition, a negative correlation between enterodiol (END) concentration and NAFLD was observed in males aged 60 years or over (OR of Tertile 2 : 0.18, 95% CI 0.05–0.69). Collectively, in middle-aged males, urinary ENL may be associated with a lower risk of NAFLD, while urinary equol may be related to a higher risk. In addition, urinary END has a possible relationship with a reduced risk of NAFLD in elder males. Definitely, clinical randomized controlled trials are needed to further verify the conclusions.
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He H, Peng S, Song X, Jia R, Zou Y, Li L, Yin Z. Protective effect of isoflavones and triterpenoid saponins from pueraria lobata on liver diseases: A review. Food Sci Nutr 2022; 10:272-285. [PMID: 35035928 PMCID: PMC8751448 DOI: 10.1002/fsn3.2668] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 11/03/2021] [Accepted: 11/04/2021] [Indexed: 01/30/2023] Open
Abstract
In recent years, with the improvement of people's living standard and the change of diet structure, liver disease and its related complications have become a significant public health problem globally. Pueraria lobata (Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep) belongs to the genus Pueraria, which is widely planted and used as medicine and food in Asia with a long history. A variety of natural active products, including puerarin, daidzein, formononetin, genistein, and soyasaponin, have been isolated and identified from pueraria lobata. A large number of studies have shown that various natural active products of pueraria lobata can play a protective role in different types of liver diseases by regulating oxidative stress, inflammatory response, lipid metabolism, etc. In this review, we focused on the protective effects of isoflavones and triterpenoid saponins from pueraria lobata on the liver through different targeted therapeutic mechanisms. What's more, we summarized their therapeutic potential for different types of liver diseases to provide evidence for their clinical application.
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Affiliation(s)
- Heng He
- Natural Medicine Research CenterCollege of Veterinary MedicineSichuan Agricultural UniversityChengduChina
| | - Shuwei Peng
- Natural Medicine Research CenterCollege of Veterinary MedicineSichuan Agricultural UniversityChengduChina
| | - Xu Song
- Natural Medicine Research CenterCollege of Veterinary MedicineSichuan Agricultural UniversityChengduChina
| | - Renyong Jia
- Key Laboratory of Animal Disease and Human Health of Sichuan ProvinceSichuan Agricultural UniversityChengduChina
| | - Yuanfeng Zou
- Natural Medicine Research CenterCollege of Veterinary MedicineSichuan Agricultural UniversityChengduChina
| | - Lixia Li
- Natural Medicine Research CenterCollege of Veterinary MedicineSichuan Agricultural UniversityChengduChina
| | - Zhongqiong Yin
- Natural Medicine Research CenterCollege of Veterinary MedicineSichuan Agricultural UniversityChengduChina
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Morán-Costoya A, Proenza AM, Gianotti M, Lladó I, Valle A. Sex Differences in Nonalcoholic Fatty Liver Disease: Estrogen Influence on the Liver-Adipose Tissue Crosstalk. Antioxid Redox Signal 2021; 35:753-774. [PMID: 33736456 DOI: 10.1089/ars.2021.0044] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Significance: Nonalcoholic fatty liver disease (NAFLD) is a hepatic and systemic disorder with a complex multifactorial pathogenesis. Owing to the rising incidence of obesity and diabetes mellitus, the prevalence of NAFLD and its impact on global health care are expected to increase in the future. Differences in NAFLD exist between males and females, and among females depending on their reproductive status. Clinical and preclinical data show that females in the fertile age are more protected against NAFLD, and studies in postmenopausal women and ovariectomized animal models support a protective role for estrogens. Recent Advances: An efficient crosstalk between the liver and adipose tissue is necessary to regulate lipid and glucose metabolism, protecting the liver from steatosis and insulin resistance contributing to NALFD. New advances in the knowledge of sexual dimorphism in liver and adipose tissue are providing interesting clues about the sex differences in NAFLD pathogenesis that could inspire new therapeutic strategies. Critical Issues: Sex hormones influence key master regulators of lipid metabolism and oxidative stress in liver and adipose tissue. All these sex-biased metabolic adjustments shape the crosstalk between liver and adipose tissue, contributing to the higher protection of females to NAFLD. Future Directions: The development of novel drugs based on the protective action of estrogens, but without its feminizing or undesired side effects, might provide new therapeutic strategies for the management of NAFLD. Antioxid. Redox Signal. 35, 753-774.
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Affiliation(s)
- Andrea Morán-Costoya
- Energy Metabolism and Nutrition Group, Department of Fundamental Biology and Health Sciences, Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, Palma, Spain.,Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain
| | - Ana M Proenza
- Energy Metabolism and Nutrition Group, Department of Fundamental Biology and Health Sciences, Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, Palma, Spain.,Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.,Center for Biomedical Research in the Pathophysiology of Obesity and Nutrition Network, Carlos III Health Institute, Madrid, Spain
| | - Magdalena Gianotti
- Energy Metabolism and Nutrition Group, Department of Fundamental Biology and Health Sciences, Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, Palma, Spain.,Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.,Center for Biomedical Research in the Pathophysiology of Obesity and Nutrition Network, Carlos III Health Institute, Madrid, Spain
| | - Isabel Lladó
- Energy Metabolism and Nutrition Group, Department of Fundamental Biology and Health Sciences, Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, Palma, Spain.,Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.,Center for Biomedical Research in the Pathophysiology of Obesity and Nutrition Network, Carlos III Health Institute, Madrid, Spain
| | - Adamo Valle
- Energy Metabolism and Nutrition Group, Department of Fundamental Biology and Health Sciences, Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, Palma, Spain.,Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.,Center for Biomedical Research in the Pathophysiology of Obesity and Nutrition Network, Carlos III Health Institute, Madrid, Spain
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Xiong P, Zhu YF. Soy diet for nonalcoholic fatty liver disease: A meta-analysis of randomized controlled trials. Medicine (Baltimore) 2021; 100:e25817. [PMID: 34087824 PMCID: PMC8183754 DOI: 10.1097/md.0000000000025817] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 04/13/2021] [Indexed: 01/04/2023] Open
Abstract
INTRODUCTION The efficacy of soy diet for nonalcoholic fatty liver disease remains controversial. We conduct a systematic review and meta-analysis to explore the influence of soy diet vs placebo on the treatment of non-alcoholic fatty liver disease. METHODS We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through October 2020 for randomized controlled trials assessing the efficacy of soy diet vs placebo for nonalcoholic fatty liver disease. This meta-analysis is performed using the random-effect model. RESULTS Five randomized controlled trials are included in the meta-analysis. Overall, compared with control group for nonalcoholic fatty liver disease, soy diet is associated with significantly reduced HOMA-IR (standard mean difference [SMD] = -0.42; 95% confidence interval [CI] = -0.76 to -0.08; P = .01), increased insulin (SMD = -0.64; 95% CI = -0.98 to -0.30; P = .0002) and decreased malondialdehyde (SMD = -0.43; 95% CI = -0.74 to -0.13; P = .005), but demonstrated no substantial impact on body mass index (SMD = 0.17; 95% CI = -0.20 to 0.53; P = .37), alanine aminotransferase (SMD = -0.01; 95% CI = -0.61 to 0.60; P = .98), aspartate-aminotransferase (SMD = 0.01; 95% CI = -0.47 to 0.49; P = .97), total cholesterol (SMD = 0.05; 95% CI = -0.25 to 0.35; P = .73) or low density lipoprotein (SMD = 0; 95% CI = -0.30 to 0.30; P = .99). CONCLUSIONS Soy diet may benefit to alleviate insulin resistance for nonalcoholic fatty liver disease.
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Affiliation(s)
- Pian Xiong
- Department of Infectious Disease, The Fourth Affiliated Hospital Zhejiang University, School of Medicine, Yiwu
| | - Yong-Fen Zhu
- Department of Hepatology and infection, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, China
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The Role of Isoflavones in Type 2 Diabetes Prevention and Treatment-A Narrative Review. Int J Mol Sci 2020; 22:ijms22010218. [PMID: 33379327 PMCID: PMC7795922 DOI: 10.3390/ijms22010218] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 12/21/2020] [Accepted: 12/25/2020] [Indexed: 02/07/2023] Open
Abstract
Given the growing number of type 2 diabetic individuals and the substantial social and financial costs associated with diabetes management, every effort should be made to improve its prevention and treatment methods. There is an ongoing search for natural dietary compounds that could be used for this purpose. This narrative review focuses on the therapeutic potential of isoflavones in diabetes prevention and treatment. This review summarizes (i) the molecular mechanisms of isoflavones action that are critical to their anti-diabetic properties; (ii) preclinical (in vitro and in vivo) studies evaluating the influence of isoflavones on the function of key organs involved in the pathogenesis of diabetes; and (iii) epidemiological studies and clinical trials that assessed the effectiveness of isoflavones in the prevention and treatment of type 2 diabetes in humans. Apart from discussing the effects of isoflavones on the function of organs “classically” associated with the pathogenesis of diabetes (pancreas, liver, muscles, and adipose tissue), the impact of these compounds on other organs that contribute to the glucose homeostasis (gastrointestinal tract, kidneys, and brain) is also reviewed.
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Tung YC, Chou RF, Nagabhushanam K, Ho CT, Pan MH. 3'-Hydroxydaidzein Improves Obesity Through the Induced Browning of Beige Adipose and Modulation of Gut Microbiota in Mice with Obesity Induced by a High-Fat Diet. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:14513-14522. [PMID: 33231468 DOI: 10.1021/acs.jafc.0c06138] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Obesity is an important health issue nowadays. 3'-Hydroxydaidzein (OHD) is a metabolite of daidzein (DAI) that can be found in fermented soybean products, such as miso. DAI has been known to affect lipid accumulation, but the effect of OHD on lipid accumulation still needs to be investigated. In this study, we investigated the effects of OHD on mice with obesity induced by a high-fat diet (HFD). The results showed that mice treated with 0.1% OHD (HOHD) significantly reduced their body weight and inguinal fat without altering their food intake compared with the HFD group. The HOHD and DAI groups' hyperlipidemia were alleviated through decreased serum triacylglycerols and total cholesterol levels. The adipocyte sizes in inguinal fat were significantly smaller in the HOHD and DAI groups compared with the HFD group. Both the HOHD and DAI groups had increased PRDM16, C/EBP β, p-p38, SIRT1, PGC1 α, and UCP1 protein expression in their inguinal adipose tissue compared with the HFD group. Moreover, the OHD and DAI groups had significantly lower amounts of Lachnospira and GCA_900066225 compared with the HFD group. Collectively, OHD can ameliorate HFD-induced obesity in mice by stimulating the browning of the white adipose tissue and modulating gut microbiota.
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Affiliation(s)
- Yen-Chen Tung
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan
- Department of Nutrition, China Medical University, Taichung 40402, Taiwan
| | - Rou-Fong Chou
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan
| | | | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901, United States
| | - Min-Hsiung Pan
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
- Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan
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Nutraceutical Properties of Polyphenols against Liver Diseases. Nutrients 2020; 12:nu12113517. [PMID: 33203174 PMCID: PMC7697723 DOI: 10.3390/nu12113517] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 11/08/2020] [Accepted: 11/12/2020] [Indexed: 02/07/2023] Open
Abstract
Current food tendencies, suboptimal dietary habits and a sedentary lifestyle are spreading metabolic disorders worldwide. Consequently, the prevalence of liver pathologies is increasing, as it is the main metabolic organ in the body. Chronic liver diseases, with non-alcoholic fatty liver disease (NAFLD) as the main cause, have an alarming prevalence of around 25% worldwide. Otherwise, the consumption of certain drugs leads to an acute liver failure (ALF), with drug-induced liver injury (DILI) as its main cause, or alcoholic liver disease (ALD). Although programs carried out by authorities are focused on improving dietary habits and lifestyle, the long-term compliance of the patient makes them difficult to follow. Thus, the supplementation with certain substances may represent a more easy-to-follow approach for patients. In this context, the consumption of polyphenol-rich food represents an attractive alternative as these compounds have been characterized to be effective in ameliorating liver pathologies. Despite of their structural diversity, certain similar characteristics allow to classify polyphenols in 5 groups: stilbenes, flavonoids, phenolic acids, lignans and curcuminoids. Herein, we have identified the most relevant compounds in each group and characterized their main sources. By this, authorities should encourage the consumption of polyphenol-rich products, as most of them are available in quotidian life, which might reduce the socioeconomical burden of liver diseases.
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Venetsanaki V, Polyzos SA. Menopause and Non-Alcoholic Fatty Liver Disease: A Review Focusing on Therapeutic Perspectives. Curr Vasc Pharmacol 2020; 17:546-555. [PMID: 29992886 DOI: 10.2174/1570161116666180711121949] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Revised: 06/05/2018] [Accepted: 06/14/2018] [Indexed: 02/06/2023]
Abstract
There is increasing evidence that menopause is associated with the progression and severity of non-alcoholic fatty liver disease (NAFLD). Estrogen deficiency worsens non-alcoholic steatohepatitis (NASH) in mice models with fatty liver. The prevalence of NAFLD seems to be higher in postmenopausal compared with premenopausal women. Although more data are needed, lower serum estradiol levels are associated with NASH in postmenopausal women. Apart from estrogen deficiency, relative androgen excess and decrease in sex hormone-binding protein are observed in postmenopausal women. These hormonal changes seem to interplay with an increase in abdominal adipose mass, also observed in postmenopausal women, and aging, which are both closely related to the severity and progressive forms of NAFLD. NAFLD adds extra morbidity to postmenopausal women, possibly increasing the risk of type 2 diabetes mellitus and cardiovascular disease. Improving parameters of the metabolic syndrome via modifications in diet and physical exercise may reduce the risk of NAFLD and its related morbidity. Limited studies have shown a beneficial effect of hormone replacement therapy (HRT) on NAFLD, although adverse hepatic effects have been attributed to progesterone in one study. Phytoestrogens may be alternatives to HRT, but their long-term efficacy and safety remain to be shown. The aim of this review was to summarize evidence linking menopause with NAFLD with a special focus on potential therapeutic perspectives.
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Affiliation(s)
- Vasiliki Venetsanaki
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stergios A Polyzos
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Li H, Jia E, Hong Y, Chen Y, Jiao J. Phytoestrogens and NAFLD: Possible Mechanisms of Action. Mini Rev Med Chem 2020; 20:578-583. [PMID: 31902357 DOI: 10.2174/1389557520666200103114123] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 12/18/2018] [Accepted: 02/22/2019] [Indexed: 01/08/2023]
Abstract
Nonalcoholic Fatty Liver Disease (NAFLD) includes a variety of changes including nonalcoholic
fatty liver, cirrhosis and Hepatocellular Carcinoma (HCC), which are associated with metabolic
disorders and cardiovascular diseases. The pathogenesis of NAFLD is complex and multifactorial.
Many studies have shown that estrogen has a protective effect on premenopausal women with metabolic
disorders and non-alcoholic fatty liver disease. Estrogen supplements may, at least in theory,
prevent the development and progression of NAFLD. Phytoestrogen is extracted from plants, especially
legumes, whose molecular structure and biological activity are similar to those of mammals estrogen,
therefore it could replace the role of estrogen and prevent the occurrence of adverse reactions to
estrogen. In this article, we review the published literature related to phytoestrogens and NAFLD as
well as suggest the possible mechanisms that may underlie the association between phytoestrogens and
NAFLD.
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Affiliation(s)
- Hui Li
- Department of Dentistry, China-Japan Union Hospital, Jilin University, Changchun, China
| | - Erna Jia
- Department of Gastroenterolgy and Hepatology, China-Japan Union Hospital, Jilin University, Changchun, China
| | - Yu Hong
- Department of Gastroenterolgy and Hepatology, China-Japan Union Hospital, Jilin University, Changchun, China
| | - Yanzhen Chen
- Department of Gastroenterolgy and Hepatology, China-Japan Union Hospital, Jilin University, Changchun, China
| | - Jian Jiao
- Department of Gastroenterolgy and Hepatology, China-Japan Union Hospital, Jilin University, Changchun, China
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Maleki Z, Jazayeri S, Eslami O, Shidfar F, Hosseini AF, Agah S, Norouzi H. Effect of soy milk consumption on glycemic status, blood pressure, fibrinogen and malondialdehyde in patients with non-alcoholic fatty liver disease: a randomized controlled trial. Complement Ther Med 2019; 44:44-50. [DOI: 10.1016/j.ctim.2019.02.020] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Revised: 02/26/2019] [Accepted: 02/27/2019] [Indexed: 12/30/2022] Open
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Cardoso AL, Fernandes A, Aguilar-Pimentel JA, de Angelis MH, Guedes JR, Brito MA, Ortolano S, Pani G, Athanasopoulou S, Gonos ES, Schosserer M, Grillari J, Peterson P, Tuna BG, Dogan S, Meyer A, van Os R, Trendelenburg AU. Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases. Ageing Res Rev 2018; 47:214-277. [PMID: 30071357 DOI: 10.1016/j.arr.2018.07.004] [Citation(s) in RCA: 303] [Impact Index Per Article: 43.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Revised: 07/08/2018] [Accepted: 07/10/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Use of the frailty index to measure an accumulation of deficits has been proven a valuable method for identifying elderly people at risk for increased vulnerability, disease, injury, and mortality. However, complementary molecular frailty biomarkers or ideally biomarker panels have not yet been identified. We conducted a systematic search to identify biomarker candidates for a frailty biomarker panel. METHODS Gene expression databases were searched (http://genomics.senescence.info/genes including GenAge, AnAge, LongevityMap, CellAge, DrugAge, Digital Aging Atlas) to identify genes regulated in aging, longevity, and age-related diseases with a focus on secreted factors or molecules detectable in body fluids as potential frailty biomarkers. Factors broadly expressed, related to several "hallmark of aging" pathways as well as used or predicted as biomarkers in other disease settings, particularly age-related pathologies, were identified. This set of biomarkers was further expanded according to the expertise and experience of the authors. In the next step, biomarkers were assigned to six "hallmark of aging" pathways, namely (1) inflammation, (2) mitochondria and apoptosis, (3) calcium homeostasis, (4) fibrosis, (5) NMJ (neuromuscular junction) and neurons, (6) cytoskeleton and hormones, or (7) other principles and an extensive literature search was performed for each candidate to explore their potential and priority as frailty biomarkers. RESULTS A total of 44 markers were evaluated in the seven categories listed above, and 19 were awarded a high priority score, 22 identified as medium priority and three were low priority. In each category high and medium priority markers were identified. CONCLUSION Biomarker panels for frailty would be of high value and better than single markers. Based on our search we would propose a core panel of frailty biomarkers consisting of (1) CXCL10 (C-X-C motif chemokine ligand 10), IL-6 (interleukin 6), CX3CL1 (C-X3-C motif chemokine ligand 1), (2) GDF15 (growth differentiation factor 15), FNDC5 (fibronectin type III domain containing 5), vimentin (VIM), (3) regucalcin (RGN/SMP30), calreticulin, (4) PLAU (plasminogen activator, urokinase), AGT (angiotensinogen), (5) BDNF (brain derived neurotrophic factor), progranulin (PGRN), (6) α-klotho (KL), FGF23 (fibroblast growth factor 23), FGF21, leptin (LEP), (7) miRNA (micro Ribonucleic acid) panel (to be further defined), AHCY (adenosylhomocysteinase) and KRT18 (keratin 18). An expanded panel would also include (1) pentraxin (PTX3), sVCAM/ICAM (soluble vascular cell adhesion molecule 1/Intercellular adhesion molecule 1), defensin α, (2) APP (amyloid beta precursor protein), LDH (lactate dehydrogenase), (3) S100B (S100 calcium binding protein B), (4) TGFβ (transforming growth factor beta), PAI-1 (plasminogen activator inhibitor 1), TGM2 (transglutaminase 2), (5) sRAGE (soluble receptor for advanced glycosylation end products), HMGB1 (high mobility group box 1), C3/C1Q (complement factor 3/1Q), ST2 (Interleukin 1 receptor like 1), agrin (AGRN), (6) IGF-1 (insulin-like growth factor 1), resistin (RETN), adiponectin (ADIPOQ), ghrelin (GHRL), growth hormone (GH), (7) microparticle panel (to be further defined), GpnmB (glycoprotein nonmetastatic melanoma protein B) and lactoferrin (LTF). We believe that these predicted panels need to be experimentally explored in animal models and frail cohorts in order to ascertain their diagnostic, prognostic and therapeutic potential.
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Duru K, Kovaleva E, Danilova I, van der Bijl P, Belousova A. The potential beneficial role of isoflavones in type 2 diabetes mellitus. Nutr Res 2018; 59:1-15. [DOI: 10.1016/j.nutres.2018.06.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Revised: 06/22/2018] [Accepted: 06/24/2018] [Indexed: 01/07/2023]
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Huang YC, Wu BH, Chu YL, Chang WC, Wu MC. Effects of Tempeh Fermentation with Lactobacillus plantarum and Rhizopus oligosporus on Streptozotocin-Induced Type II Diabetes Mellitus in Rats. Nutrients 2018; 10:E1143. [PMID: 30135362 PMCID: PMC6163431 DOI: 10.3390/nu10091143] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Revised: 08/13/2018] [Accepted: 08/17/2018] [Indexed: 12/13/2022] Open
Abstract
The increased consumption of high fat-containing foods has been linked to the prevalence of obesity and abnormal metabolic syndromes. Rhizopus oligosporus, a fungus in the family Mucoraceae, is widely used as a starter for homemade tempeh. Although R. oligosporus can prevent the growth of other microorganisms, it grows well with lactic acid bacteria (LAB). Lactobacillus plantarum can produce β-glucosidase, which catalyzes the hydrolysis of glucoside isoflavones into aglycones (with greater bioavailability). Therefore, the development of a soybean-based functional food by the co-inoculation of R. oligosporus and L. plantarum is a promising approach to increase the bioactivity of tempeh. In this study, the ameliorative effect of L. plantarum in soy tempeh on abnormal carbohydrate metabolism in high-fat diet (HFD)-induced hyperglycemic rats was evaluated. The co-incubation of L. plantarum with R. oligosporus during soy tempeh fermentation reduced the homeostatic model assessment of insulin resistance, HbA1c, serum glucose, total cholesterol, triglyceride, free fatty acid, insulin, and low-density lipoprotein contents, and significantly increased the high-density lipoprotein content in HFD rats. It also increased the LAB counts, as well as the bile acid, cholesterol, triglyceride, and short-chain fatty acid contents in the feces of HFD rats. Our results suggested that the modulation of serum glucose and lipid levels by LAB occurs via alterations in the internal microbiota, leading to the inhibition of cholesterol synthesis and promotion of lipolysis. Tempeh, which was produced with both L. plantarum and R. oligosporus, might be a beneficial dietary supplement for individuals with abnormal carbohydrate metabolism.
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Affiliation(s)
- Ying-Che Huang
- Graduate Institute of Bioresources, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.
| | - Bo-Hua Wu
- Department of Food Science, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.
| | - Yung-Lin Chu
- International Master's Degree Program in Food Science, International College, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.
| | - Wen-Chang Chang
- Department of Food Science, National Chiayi University, Chiayi 60004, Taiwan.
| | - Ming-Chang Wu
- Graduate Institute of Bioresources, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.
- Department of Food Science, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.
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Eslami O, Shidfar F, Maleki Z, Jazayeri S, Hosseini AF, Agah S, Ardiyani F. Effect of Soy Milk on Metabolic Status of Patients with Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial. J Am Coll Nutr 2018; 38:51-58. [DOI: 10.1080/07315724.2018.1479990] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Omid Eslami
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Farzad Shidfar
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Maleki
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Shima Jazayeri
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Agha Fatemeh Hosseini
- Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Farnaz Ardiyani
- Department of Radiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Kim MS, Kim B, Park H, Ji Y, Holzapfel W, Kim DY, Hyun CK. Long-term fermented soybean paste improves metabolic parameters associated with non-alcoholic fatty liver disease and insulin resistance in high-fat diet-induced obese mice. Biochem Biophys Res Commun 2018; 495:1744-1751. [PMID: 29222051 DOI: 10.1016/j.bbrc.2017.12.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Accepted: 12/01/2017] [Indexed: 12/22/2022]
Abstract
Recently, Korean traditional fermented soybean paste, called Doenjang, has attracted attention for its protective effect against diet-related chronic diseases such as obesity and type 2 diabetes. Long-term fermented soybean pastes (LFSPs) are made by fermentation with naturally-occurring microorganisms for several months, whereas short-term fermented soybean pastes (SFSPs) are produced by shorter-time fermentation inoculated with a starter culture. Here, we demonstrate that administration of LFSP, but not SFSP, protects high-fat diet (HFD)-fed obese mice against non-alcohol fatty liver disease (NAFLD) and insulin resistance. LFSP suppressed body weight gain in parallel with reduction in fat accumulation in mesenteric adipose tissue (MAT) and the liver via modulation of MAT lipolysis and hepatic lipid uptake. LFSP-treated mice also had improved glucose tolerance and increased adiponectin levels concomitantly with enhanced AMPK activation in skeletal muscle and suppressed expression of pro-inflammatory cytokines in skeletal muscle and the liver. LFSP also attenuated HFD-induced gut permeability and lowered serum lipopolysaccharide level, providing an evidence for its probiotic effects, which was supported by the observation that treatment of a probiotic mixture of LFSP-originated Bacillus strains protected mice against HFD-induced adiposity and glucose intolerance. Our findings suggest that the intake of LFSP, but not SFSP, offers protection against NAFLD and insulin resistance, which is an effect of long-term fermentation resulting in elevated contents of active ingredients (especially flavonoids) and higher diversity and richness of Bacillus probiotic strains compared to SFSP.
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Affiliation(s)
- Min-Seok Kim
- School of Life Science, Handong Global University, Pohang, Gyungbuk, Republic of Korea
| | - Bobae Kim
- School of Life Science, Handong Global University, Pohang, Gyungbuk, Republic of Korea; Department of Advanced Green Energy and Environment, Handong Global University, Pohang, Gyungbuk, Republic of Korea
| | - Haryung Park
- Department of Advanced Green Energy and Environment, Handong Global University, Pohang, Gyungbuk, Republic of Korea
| | - Yosep Ji
- Department of Advanced Green Energy and Environment, Handong Global University, Pohang, Gyungbuk, Republic of Korea; Holzapfel Effective Microbes (HEM), Pohang, Gyungbuk, Republic of Korea
| | - Wilhelm Holzapfel
- Department of Advanced Green Energy and Environment, Handong Global University, Pohang, Gyungbuk, Republic of Korea; Holzapfel Effective Microbes (HEM), Pohang, Gyungbuk, Republic of Korea
| | - Do-Young Kim
- Research & Development Team, Advanced Bio Convergence Center, Pohang Technopark Foundation, Pohang, Gyungbuk, Republic of Korea
| | - Chang-Kee Hyun
- School of Life Science, Handong Global University, Pohang, Gyungbuk, Republic of Korea; Department of Advanced Green Energy and Environment, Handong Global University, Pohang, Gyungbuk, Republic of Korea.
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35
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Go H, Ryuk JA, Hwang JT, Ko BS. Effects of three different formulae of Gamisoyosan on lipid accumulation induced by oleic acid in HepG2 cells. Integr Med Res 2017; 6:395-403. [PMID: 29296566 PMCID: PMC5741383 DOI: 10.1016/j.imr.2017.08.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 08/21/2017] [Accepted: 08/24/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Gamisoyosan (GSS) is an herbal formula which has been used to treat women's diseases for several hundred years in Korea. GSS is one of the three most common prescriptions among women and is used to treat menopausal symptoms. Fatty liver disease is also common in postmenopausal women and can precede more severe diseases, such as steatohepatitis. The present study compared the effects of GSS on fatty liver using three different formulae, Dongui-Bogam (KIOM A), Korean Pharmacopeia (KIOM B) and Korean National Health Insurance (KIOM C). METHODS In oleic acid-induced HepG2 fatty liver cells, cellular lipid accumulation, triglycerides and total cholesterol were measured after treatment with three GSS formulae and simvastatin as a positive control. To investigate the phytoestrogen activity of GSS, MCF-7 cells were treated with GSS, and hormone levels were quantified. Also, qualitative analysis was performed with UPLC. RESULTS All types of GSS decreased cellular lipid accumulation. KIOM A was slightly less effective than the other two GSS formulae. KIOM B and KIOM C decreased cellular triglycerides more effective than simvastatin, but KIOM A did not affect cellular triglycerides. Cellular total cholesterol was decreased by all GSS and simvastatin. GSS showed phytoestrogen activity in MCF-7 cells. From the UPLC analysis data, geniposide, paeoniflorin and glycyrrhizin were detected form three GSS formulae. CONCLUSION These results suggest that all GSS formulae have a beneficial effect on fatty liver disease during menopause and that differences of formula have no effect on the efficacy of the prescription.
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Affiliation(s)
| | | | | | - Byoung Seob Ko
- Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea
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36
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Wang S, Wang Y, Pan MH, Ho CT. Anti-obesity molecular mechanism of soy isoflavones: weaving the way to new therapeutic routes. Food Funct 2017; 8:3831-3846. [PMID: 29043346 DOI: 10.1039/c7fo01094j] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Obesity is ringing alarm bells globally. Advances in food science and nutrition research have been devoted to identifying food components that exert anti-obesity effects, as well as investigating the molecular mechanisms by which they modulate the progression of obesity. Soy foods have attracted much interest as high-protein components of the human diet and as unique sources of isoflavones. As they have similar chemical structures to endogenous estrogens, isoflavones are believed to interact with intracellular estrogen receptors, which results in reductions in the accumulation of lipids and the distribution of adipose tissue. Both in vitro and in vivo studies have revealed other signaling pathways in which isoflavones are involved in the inhibition of adipogenesis and lipogenesis by interacting with various transcription factors and upstream signaling molecules. Although the biological mechanisms that cause the biphasic effects of isoflavones and various controversial results remain unknown, it is noteworthy that isoflavones exhibit pleiotropic effects in the human body to regulate metabolism and balance, which may potentially prevent and treat obesity.
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Affiliation(s)
- Siyu Wang
- Department of Food Science, Rutgers University, New Brunswick, NJ 08901, USA.
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Cross TWL, Zidon TM, Welly RJ, Park YM, Britton SL, Koch LG, Rottinghaus GE, de Godoy MRC, Padilla J, Swanson KS, Vieira-Potter VJ. Soy Improves Cardiometabolic Health and Cecal Microbiota in Female Low-Fit Rats. Sci Rep 2017; 7:9261. [PMID: 28835674 PMCID: PMC5569109 DOI: 10.1038/s41598-017-08965-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 07/20/2017] [Indexed: 12/13/2022] Open
Abstract
Phytoestrogen-rich soy is known to ameliorate menopause-associated obesity and metabolic dysfunction for reasons that are unclear. The gut microbiota have been linked with the development of obesity and metabolic dysfunction. We aimed to determine the impact of soy on cardiometabolic health, adipose tissue inflammation, and the cecal microbiota in ovariectomized (OVX) rats bred for low-running capacity (LCR), a model that has been previously shown to mimic human menopause compared to sham-operated (SHM) intact control LCR rats. In this study, soy consumption, without affecting energy intake or physical activity, significantly improved insulin sensitivity and body composition of OVX rats bred for low-running capacity. Furthermore, soy significantly improved blood lipid profile, adipose tissue inflammation, and aortic stiffness of LCR rats. Compared to a soy-free control diet, soy significantly shifted the cecal microbial community of LCR rats, resulting in a lower Firmicutes:Bacteroidetes ratio. Correlations among metabolic parameters and cecal bacterial taxa identified in this study suggest that taxa Prevotella, Dorea, and Phascolarctobacterium may be taxa of interest. Our results suggest that dietary soy ameliorates adiposity, insulin sensitivity, adipose tissue inflammation, and arterial stiffness and exerts a beneficial shift in gut microbial communities in a rat model that mimics human menopause.
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Affiliation(s)
- Tzu-Wen L Cross
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
- Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
| | - Terese M Zidon
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, 65211, USA
| | - Rebecca J Welly
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, 65211, USA
| | - Young-Min Park
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, 65211, USA
| | - Steven L Britton
- Department of Anesthesiology, University of Michigan, Ann Arbor, MI, 48109, USA
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Lauren G Koch
- Department of Anesthesiology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - George E Rottinghaus
- Department of Biomedical Sciences, University of Missouri, Columbia, MO, 65211, USA
| | - Maria R Cattai de Godoy
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
- Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
| | - Jaume Padilla
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, 65211, USA
- Department of Child Health, University of Missouri, Columbia, MO, 65211, USA
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, 65211, USA
| | - Kelly S Swanson
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
- Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
| | - Victoria J Vieira-Potter
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, 65211, USA.
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Soy compared with milk protein in a Western diet changes fecal microbiota and decreases hepatic steatosis in obese OLETF rats. J Nutr Biochem 2017; 46:125-136. [PMID: 28605664 DOI: 10.1016/j.jnutbio.2017.05.004] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 04/10/2017] [Accepted: 05/16/2017] [Indexed: 12/17/2022]
Abstract
Soy protein is effective at preventing hepatic steatosis; however, the mechanisms are poorly understood. We tested the hypothesis that soy vs. dairy protein-based diet would alter microbiota and attenuate hepatic steatosis in hyperphagic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Male OLETF rats were randomized to "Western" diets containing milk protein isolate (MPI), soy protein isolate (SPI) or 50:50 MPI/SPI (MS) (n=9-10/group; 21% kcal protein) for 16 weeks. SPI attenuated (P<.05) fat mass and percent fat by ~10% compared with MS, but not compared with MPI. Serum thiobarbituric acid reactive substance and total and low-density lipoprotein cholesterol concentrations were lower (P<.05) with dietary SPI vs. MPI and MS. Histological hepatic steatosis was lower (P<.05) in SPI compared with MPI or MS. Lipidomic analyses revealed reductions (P<.05) in hepatic diacylglycerols but not triacylglycerols in SPI compared with MPI, which was associated with lower hepatic de novo lipogenesis (ACC, FAS and SCD-1 protein content, and hepatic 16:1 n-7 and 18:1 n-7 PUFA concentrations) (P<.05) compared with MPI and MS; however, MPI displayed elevated hepatic mitochondrial function compared with SPI and MS. Fecal bacterial 16S rRNA analysis revealed SPI-intake elicited increases (P<.05) in Lactobacillus and decreases (P<.05) in Blautia and Lachnospiraceae suggesting decreases in fecal secondary bile acids in SPI rats. SPI and MS exhibited greater (P<.05) hepatic Fxr, Fgfr4, Hnf4a, HmgCoA reductase and synthase mRNA expression compared with MPI. Overall, dietary SPI compared with MPI decreased hepatic steatosis and diacylglycerols, changed microbiota populations and altered bile acid signaling and cholesterol homeostasis in a rodent model of obesity.
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39
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Bell A, Korourian S, Zeng H, Phelps J, Hakkak R. A diet containing a high- versus low-daidzein level does not protect against liver steatosis in the obese Zucker rat model. Food Funct 2017; 8:1293-1298. [PMID: 28244519 DOI: 10.1039/c6fo01772j] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The prevalence of obesity is increasing worldwide. Obesity increases the risk for non-alcoholic fatty liver disease through adipokine dysregulation and inflammation. Previously, we have reported that a high-isoflavone soy protein isolate (HISPI) diet is associated with significantly heavier body weights and reduced liver steatosis in obese Zucker rats (OZR) compared to a casein diet. The objective of this study was to investigate whether daidzein, a soy isoflavone in HISPI, is responsible for increased body weight gain or reduced liver steatosis. We hypothesized that a casein diet containing high daidzein (HD) compared to low daidzein (LD) would mitigate hepatic steatosis in female OZR. We used 19 five-week-old female OZR (fa/fa). Rats were randomly assigned to a modified AIN-93G diet containing HD (0.121 g kg-1 feed) or LD (0.01 g kg-1 feed). Rats were weighed twice weekly. Feed intake was measured once weekly, and kcal per kg of body weight was calculated. After 8 weeks, rats were sacrificed. Serum and livers were collected. Sections of the liver lobe were fixed in 10% buffered formalin and stained with hematoxylin and eosin. Steatosis was semiquantitated as a score of 1 to 4 based upon the relative degree of steatosis within hepatocytes: (1) <25%, (2) 25%-50%, (3) 50%-75%, and (4) >75%. Serum leptin and adiponectin were measured by ELISA. Our results did not show significant differences in mean liver steatosis scores, body weights, energy intake, and serum leptin and adiponectin levels between diet groups. In conclusion, daidzein may not be the main component of HISPI responsible for increasing body weight or reducing liver steatosis in OZR.
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Affiliation(s)
- Andrea Bell
- Arkansas Children's Research Institute, Little Rock, Arkansas, USA. and Department of Dietetics and Nutrition, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Soheila Korourian
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Huawei Zeng
- United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA
| | - Joshua Phelps
- Department of Dietetics and Nutrition, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Reza Hakkak
- Arkansas Children's Research Institute, Little Rock, Arkansas, USA. and Department of Dietetics and Nutrition, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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40
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Akhlaghi M. Non-alcoholic Fatty Liver Disease: Beneficial Effects of Flavonoids. Phytother Res 2016; 30:1559-1571. [DOI: 10.1002/ptr.5667] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Revised: 05/23/2016] [Accepted: 05/24/2016] [Indexed: 12/31/2022]
Affiliation(s)
- Masoumeh Akhlaghi
- Nutrition Research Center, School of Nutrition and Food Sciences; Shiraz University of Medical Sciences; Shiraz Iran
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41
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Salomone F, Godos J, Zelber-Sagi S. Natural antioxidants for non-alcoholic fatty liver disease: molecular targets and clinical perspectives. Liver Int 2016; 36:5-20. [PMID: 26436447 DOI: 10.1111/liv.12975] [Citation(s) in RCA: 181] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Accepted: 09/18/2015] [Indexed: 12/11/2022]
Abstract
Non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), is emerging as a main health problem in industrialized countries. Lifestyle modifications are effective in the treatment of NAFLD; however, the long-term compliance is low. Therefore, several pharmacological treatments have been proposed but none has shown significant efficacy or long-term safety. Natural polyphenols are a heterogeneous class of polyphenolic compounds contained in vegetables, which are being proposed for the treatment of different metabolic disorders. Although the beneficial effect of these compounds has traditionally related to their antioxidant properties, they also exert several beneficial effects on hepatic and extra-hepatic glucose and lipid homeostasis. Furthermore, natural polyphenols exert antifibrogenic and antitumoural effects in animal models, which appear relevant from a clinical point of view because of the association of NASH with cirrhosis and hepatocellular carcinoma. Several polyphenols, such anthocyanins, curcumin and resveratrol and those present in coffee, tea, soy are available in the diet and their consumption can be proposed as part of a healthy diet for the treatment of NAFLD. Other phenolic compounds, such as silymarin, are commonly consumed worldwide as nutraceuticals or food supplements. Natural antioxidants are reported to have beneficial effects in preclinical models of NAFLD and in pilot clinical trials, and thus need clinical evaluation. In this review, we summarize the existing evidence regarding the potential role of natural antioxidants in the treatment of NAFLD and examine possible future clinical applications.
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Affiliation(s)
- Federico Salomone
- Division of Gastroenterology, Ospedale di Acireale, Azienda Sanitaria Provinciale di Catania, Catania, Italy
| | - Justyna Godos
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Shira Zelber-Sagi
- The Liver Unit, Gastroenterology Department, Tel-Aviv Medical Center, Tel Aviv, Israel.,School of Public Health, University of Haifa, Haifa, Israel
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42
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Van De Wier B, Koek GH, Bast A, Haenen GRMM. The potential of flavonoids in the treatment of non-alcoholic fatty liver disease. Crit Rev Food Sci Nutr 2015; 57:834-855. [DOI: 10.1080/10408398.2014.952399] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Qiu LX, Chen T. Novel insights into the mechanisms whereby isoflavones protect against fatty liver disease. World J Gastroenterol 2015; 21:1099-1107. [PMID: 25632182 PMCID: PMC4306153 DOI: 10.3748/wjg.v21.i4.1099] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2014] [Revised: 07/11/2014] [Accepted: 09/05/2014] [Indexed: 02/06/2023] Open
Abstract
Fatty liver disease (FLD) is a growing public health problem worldwide. There is an urgent requirement for alternative and natural medicine to treat this disease. As phytochemicals, isoflavones have attracted considerable attention for the prevention of FLD. Numerous studies have revealed that isoflavones protect against FLD through various pathways which modulate fatty acid β-oxidation, lipid synthesis, and oxidative stress. Recently, the aldose reductase (AR)/polyol pathway has been reported to be involved in the development of FLD by modulating hepatic fructose production, peroxisome proliferator-activated receptor (PPAR)α activity, cytochrome P450 (CYP)2E1 expression, and gut bacterial endotoxin-induced cytokine release. It has been reported that some isoflavones are potent AR inhibitors. Here, we review the anti-FLD actions of isoflavones and the proposed mechanism whereby isoflavones protect against FLD, with regard to the AR/polyol pathway. We propose that isoflavones block the AR/polyol pathway and in turn reduce fructose production and subsequent fat accumulation in the liver in diabetic or high-glucose-diet mice. In addition, in rodents with alcoholic liver disease or nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, inhibition of AR by isoflavones may improve PPARα-mediated fatty acid oxidation, reduce hepatic steatosis, and attenuate CYP2E1-mediated oxidative stress or AR/gut bacterial endotoxin-mediated cytokine overproduction, to alleviate progression of FLD.
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Chen T, Zhong FJ, Hong YM, Su WJ, Zhuang LL, Qiu LX. Effect of Trifolium pratense extract on methionine-choline-deficient diet-induced steatohepatitis in C57BL/6 mice. Chin J Nat Med 2014; 12:194-8. [PMID: 24702805 DOI: 10.1016/s1875-5364(14)60032-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2012] [Indexed: 02/09/2023]
Abstract
AIM The potential of Trifolium pratense (red clover) extract in the prevention of lipid disorder has attracted increasing attention in recent years. In this study, the aim was to determine whether and how red clover extract affected the development of murine diet-induced non-alcoholic steatohepatitis. METHODS Non-alcoholic steatohepatitis was induced in C57BL/6 mice by feeding mice with a methionine-choline-deficient (MCD) diet. Hematoxylin and eosin staining was used for histological analyses. Real-time PCR was used to analyze the mRNA expression levels. RESULTS Hepatic steatosis and necroinflammation was observed in MCD diet-fed mice, and this diet-induced steatosis was significantly attenuated, whereas liver inflammation was not significantly attenuated, by red clover extract treatment. Consistent with the results of H&E staining, the MCD diet-induced increase of liver triglycerides and cholesterol levels were significantly reduced by red clover extract treatment. However, with the improvement in hepatic steatosis, mRNA levels of acetyl CoA oxidase, carnitine palmitoyl transferase-1, and liver fatty acid-binding protein, three genes regulated by peroxisome proliferator-activated receptor (PPAR) α, were unaffected. CONCLUSION Red clover extract alleviated MCD diet-induced hepatic steatosis, but did not ameliorate liver inflammation in C57BL/6 mice, and the improvement in hepatic steatosis was not through activating PPARα.
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Affiliation(s)
- Tong Chen
- School of Life Sciences, Longyan University, Longyan 364000, China; Fujian Key Laboratory of Preventive Veterinary Medicine and Biotechnology, Longyan 364000, China
| | - Fo-Jin Zhong
- School of Life Sciences, Longyan University, Longyan 364000, China
| | - Ya-Min Hong
- School of Life Sciences, Longyan University, Longyan 364000, China
| | - Wei-Jiao Su
- School of Life Sciences, Longyan University, Longyan 364000, China
| | - Li-Li Zhuang
- School of Life Sciences, Longyan University, Longyan 364000, China
| | - Long-Xin Qiu
- School of Life Sciences, Longyan University, Longyan 364000, China; Fujian Key Laboratory of Preventive Veterinary Medicine and Biotechnology, Longyan 364000, China.
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45
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Consumption ofPuerariaFlower Extract Reduces Body Mass Indexviaa Decrease in the Visceral Fat Area in Obese Humans. Biosci Biotechnol Biochem 2014; 76:1511-7. [DOI: 10.1271/bbb.120235] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
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46
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Liu J, Zhang H, Ji B, Cai S, Wang R, Zhou F, Yang J, Liu H. A diet formula of Puerariae radix, Lycium barbarum, Crataegus pinnatifida, and Polygonati rhizoma alleviates insulin resistance and hepatic steatosis in CD-1 mice and HepG2 cells. Food Funct 2014; 5:1038-49. [DOI: 10.1039/c3fo60524h] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
According to the principles of traditional Chinese medicine, medicinal and edible herbs exhibit holistic effects through their actions on multiple target organs.
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Affiliation(s)
- Jia Liu
- Beijing Key Laboratory of Functional Food from Plant Resources
- College of Food Science & Nutritional Engineering
- China Agricultural University
- Beijing 100083, People's Republic of China
| | - HongJuan Zhang
- Beijing Ribio Biotech Co., Ltd
- Beijing 100094, People's Republic of China
| | - BaoPing Ji
- Beijing Key Laboratory of Functional Food from Plant Resources
- College of Food Science & Nutritional Engineering
- China Agricultural University
- Beijing 100083, People's Republic of China
| | - ShengBao Cai
- Research Center of Food Engineering
- Faculty of chemical engineering
- Kunming University of Science and Technology
- Kunming, People's Republic of China
| | - RuoJun Wang
- Beijing Key Laboratory of Functional Food from Plant Resources
- College of Food Science & Nutritional Engineering
- China Agricultural University
- Beijing 100083, People's Republic of China
| | - Feng Zhou
- Beijing Key Laboratory of Functional Food from Plant Resources
- College of Food Science & Nutritional Engineering
- China Agricultural University
- Beijing 100083, People's Republic of China
| | - JunSi Yang
- Beijing Key Laboratory of Functional Food from Plant Resources
- College of Food Science & Nutritional Engineering
- China Agricultural University
- Beijing 100083, People's Republic of China
| | - HuiJun Liu
- Beijing Key Laboratory of Functional Food from Plant Resources
- College of Food Science & Nutritional Engineering
- China Agricultural University
- Beijing 100083, People's Republic of China
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Sakamoto Y, Naka A, Ohara N, Kondo K, Iida K. Daidzein regulates proinflammatory adipokines thereby improving obesity-related inflammation through PPARγ. Mol Nutr Food Res 2013; 58:718-26. [PMID: 24343975 DOI: 10.1002/mnfr.201300482] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Revised: 09/23/2013] [Accepted: 09/27/2013] [Indexed: 01/08/2023]
Abstract
SCOPE Daidzein was recently reported to act like an activator of peroxisome proliferator-activated receptor γ (PPARγ) thereby enhancing differentiation of adipocytes. Although PPARγ plays a role in adipokine expression, it has not been well researched whether daidzein affects expression of adipokines. This study aimed to clarify the effects of daidzein on proinflammatory adipokines and adipose inflammation causing insulin resistance in obesity. METHODS AND RESULTS 3T3-L1 adipocytes were treated with daidzein or genistein. Diet-induced obese C57BL/6J mice were fed high-fat high-sucrose diets with daidzein (1.0 g/kg chow) for 12 wk. The results showed that both isoflavones, especially daidzein, stimulated adipogenic differentiation in 3T3-L1 adipocytes with the activation of PPARγ. Daidzein also increased adiponectin expression and decreased MCP-1 expression with the consistent regulation of their secretion. In obese mice, daidzein inhibited hypertrophy in fat cell size and improved insulin sensitivity, concomitant with upregulation of PPARγ in fat tissue. Decreased expression of MCP-1 and TNF-α, and increased expression of adiponectin were also observed in adipose tissue of daidzein-fed mice. Additionally, daidzein administration significantly inhibited macrophage accumulation in adipose tissue. CONCLUSION Daidzein regulates adipokine expression through the PPARγ, thereby improving the adverse effects of adipose inflammation, such as insulin resistance, in obesity.
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Affiliation(s)
- Yuri Sakamoto
- Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan
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Pan MH, Lai CS, Tsai ML, Ho CT. Chemoprevention of nonalcoholic fatty liver disease by dietary natural compounds. Mol Nutr Food Res 2013; 58:147-71. [PMID: 24302567 DOI: 10.1002/mnfr.201300522] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Revised: 09/25/2013] [Accepted: 10/09/2013] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver disease that is not from excess alcohol consumption, but is often associated with obesity, type 2 diabetes, and metabolic syndrome. NAFLD pathogenesis is complicated and involves oxidative stress, lipotoxicity, mitochondrial damage, insulin resistance, inflammation, and excessive dietary fat intake, which increase hepatic lipid influx and de novo lipogenesis and impair insulin signaling, thus promoting hepatic triglyceride accumulation and ultimately NAFLD. Overproduction of proinflammatory adipokines from adipose tissue also affects hepatic metabolic function. Current NAFLD therapies are limited; thus, much attention has been focused on identification of potential dietary substances from fruits, vegetables, and edible plants to provide a new strategy for NAFLD treatment. Dietary natural compounds, such as carotenoids, omega-3-PUFAs, flavonoids, isothiocyanates, terpenoids, curcumin, and resveratrol, act through a variety of mechanisms to prevent and improve NAFLD. Here, we summarize and briefly discuss the currently known targets and signaling pathways as well as the role of dietary natural compounds that interfere with NAFLD pathogenesis.
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Affiliation(s)
- Min-Hsiung Pan
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
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Xiao CW, Wood CM, Weber D, Aziz SA, Mehta R, Griffin P, Cockell KA. Dietary supplementation with soy isoflavones or replacement with soy proteins prevents hepatic lipid droplet accumulation and alters expression of genes involved in lipid metabolism in rats. GENES AND NUTRITION 2013; 9:373. [PMID: 24292949 DOI: 10.1007/s12263-013-0373-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2013] [Accepted: 11/19/2013] [Indexed: 12/22/2022]
Abstract
Accumulation of hepatic lipid droplet (HLD) is the hallmark pathology of non-alcoholic fatty liver disease (NAFLD). This study examined the effects of soy isoflavones (ISF) and different amounts of soy proteins on the accumulation of HLD, lipid metabolism and related gene expression in rats. Weanling Sprague-Dawley rats were fed diets containing either 20 % casein protein without (D1) or with (D2) supplemental ISF (50 mg/kg diet) or substitution of casein with increasing amounts of alcohol-washed soy protein isolate (SPI, 5, 10, and 20 %; D3, D4, D5) for 90 days. Dietary casein (20 %) induced accumulation of HLD in female, but not in male rats. Both soy proteins and ISF remarkably prevented the formation of HLD. Soy proteins lowered hepatic total cholesterol and triglyceride in a dose-dependent manner. Interestingly, soy proteins but not ISF significantly increased free fatty acids in the liver of the female rats compared to D1. Proteomic analysis showed that at least 3 enzymes involved in lipogenesis were down-regulated and 7 proteins related to fatty acid β-oxidation or lipolysis were up-regulated by soy protein over D1. Additionally, 9 differentially expressed proteins identified were related to amino acid metabolism, 5 to glycolysis and 2 to cholesterol metabolism. Dietary ISF and SPI markedly reduced hepatic-peroxisome-proliferator-activated receptor γ2 (PPARγ2) and fat-specific protein 27 (FSP27) in female rats. Overall, this study has shown that partial or full replacement of dietary casein by soy protein or supplementation with soy ISF can effectively prevent the accumulation of HLD. The potential molecular mechanism(s) involved might be due to suppression of lipogenesis and stimulation of lipolysis and down-regulation of PPARγ2 and FSP27. This suggests that consumption of soy foods or supplements might be a useful strategy for the prevention or treatment of fatty liver diseases.
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Affiliation(s)
- Chao Wu Xiao
- Nutrition Research Division, Bureau of Nutritional Sciences, Health Products and Food Branch, Health Canada, Ottawa, ON, K1A 0K9, Canada,
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Jung JH, Kim HS. The inhibitory effect of black soybean on hepatic cholesterol accumulation in high cholesterol and high fat diet-induced non-alcoholic fatty liver disease. Food Chem Toxicol 2013; 60:404-12. [PMID: 23900008 DOI: 10.1016/j.fct.2013.07.048] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Revised: 07/16/2013] [Accepted: 07/18/2013] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is defined as excess of fat in the liver. We investigated the effects of black soybean on the cholesterol metabolism and insulin resistance of mice fed high cholesterol/fat diets. Mice were randomly allocated into four groups that were fed different diets: the normal cholesterol/fat diet; high cholesterol/fat diets (HCD); and HCD with 1%, and 4% black soybean powder (1B-HCD, and 4B-HCD). Liver total cholesterol and triglyceride concentrations were significantly lower in the black soybean-supplemented groups than that in the HCD group. PCR revealed significantly lower hepatic SREBP2 and HMG-CoA reductase mRNA levels of black soybean-supplemented mice. Real-time PCR revealed significantly higher hepatic ABCA1 mRNA level of black soybean-supplemented mice, which may increase cholesterol efflux. Liver bile acids concentration was significantly high in the 4B-HCD group. Black soybean stimulated secretion of adiponectin, activation of pAMPK, and eliminated free fatty acids in the liver. Black soybean supplementation decreased MDA and nitrate level. The activities of SOD, catalase, and GPx were restored by black soybean supplementation. Our data strongly indicate that black soybean influences the balance between oxidative and antioxidative stress. We suggest that black soybean improves cholesterol metabolism, insulin resistance, and alleviates oxidative damage in NAFLD.
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Affiliation(s)
- Ji-Hye Jung
- Division of Biological Science, College of Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea
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