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Zhang N, Zhang H, Liang X, Xu Y, Wang G, Bai Y, Zhou Z, Pu Y, Zhou Y, Xue M, Liang H. Neuroprotective effect of folic acid by maintaining DNA stability and mitochondrial homeostasis through the ATM/CHK2/P53/PGC-1α pathway in alcohol-exposed mice. Food Funct 2025. [PMID: 40421718 DOI: 10.1039/d5fo00260e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2025]
Abstract
Excessive drinking leads to alcoholic brain injury, which is characterized by neuroinflammation, cognitive decline and motor dysfunction. These pathological features are closely related to chromosomal DNA damage and mitochondrial dysfunction. In this study, we aimed to uncover the neuroprotective effects of folic acid (FA) in mice with alcoholic brain injury. C57BL/6J mice were used to establish the murine model of alcoholic brain injury after 12 weeks of alcohol exposure. FA treatment significantly increased the levels of ATP and mitochondrial DNA (mtDNA) copy number in brain tissues of alcohol-exposed mice, and regulated the imbalance of mitochondrial homeostasis in cortical nerve cells. Furthermore, it could reduce the leakage of mtDNA into the cytoplasm, thereby inhibiting the cGAS/STING/NLRP3 inflammatory pathway and alleviating neuroinflammation. In addition, FA treatment reduced DNA damage in peripheral blood lymphocytes and decreased the expression of 53BP1 and γ-H2AX proteins in brain tissues of alcohol-exposed mice. At the molecular level, FA reduced DNA damage by downregulating the ATM/CHK2/P53 pathway and induced the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), which further inversely enhanced mitochondrial function through positive feedback. Collectively, this study provides experimental evidence that FA protects DNA stability and mitochondrial homeostasis in alcohol-exposed mice by downregulating the ATM/CHK2/P53/PGC-1α signaling pathway.
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Affiliation(s)
- Nan Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
| | - Huaqi Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
| | - Xi Liang
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
| | - Yan Xu
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
| | - Guifa Wang
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
| | - Yixian Bai
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
| | - Zijian Zhou
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
| | - Yexin Pu
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
| | - Yifan Zhou
- School of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, 750004, PR China
| | - Meilan Xue
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
| | - Hui Liang
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
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Zhang Y, Pan K, Xu A, Sun S, Huang Q, Wang Y, Wang H, Han Q, Li D, Ding Q, Li J. n-3 polyunsaturated fatty acids-enriched fish oil attenuates chronic alcohol-induced liver injury via a mechanism involving the upregulation of Retsat. J Nutr Biochem 2025:109971. [PMID: 40409513 DOI: 10.1016/j.jnutbio.2025.109971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 05/04/2025] [Accepted: 05/19/2025] [Indexed: 05/25/2025]
Abstract
This study aimed to delineate the protective role of fish oil against alcoholic liver disease (ALD), identify the principal active component between eicosapentaenoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3), and elucidate the molecular mechanisms. C57BL/6J mice were randomly assigned to receive either an alcohol-fed (AF) or pair-fed control (PF) diet, enriched with fish oil (FO) or corn oil (CO) for four weeks. Additionally, a series of in vitro experiments were performed using AML-12 cells to further investigate potential mechanisms. The results showed that plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly lower in the AF-FO group compared to the AF-CO group, indicating that fish oil alleviated alcohol-induced liver damage. Hepatic antioxidant markers, including glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were also higher in the AF-FO group than in the AF-CO group. Transcriptomic analysis revealed FO supplementation significantly affected genes involved in oxidoreductase activity and lipid metabolism pathways, with Retsat being the most up-regulated gene. The in vitro experiments indicated that DHA, but not EPA, markedly increased Retsat expression, cell viability, and the expression of genes related to oxidoreductase activity and lipid metabolism, compared to linoleic acid (LA, C18:2 n-6). Notably, knocking down Retsat abolished the protective effects of DHA. In conclusion, dietary fish oil mitigated chronic alcohol-induced liver injury primarily through DHA by upregulating Retsat and downstream genes associated with oxidoreductase function and lipid metabolism.
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Affiliation(s)
- Yuxuan Zhang
- School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310051, China
| | - Kaixin Pan
- School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310051, China
| | - Angcheng Xu
- School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310051, China
| | - Shuzhen Sun
- School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310051, China
| | - Qingling Huang
- School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310051, China
| | - Yicheng Wang
- School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310051, China
| | - Hao Wang
- School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310051, China
| | - Qiang Han
- School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310051, China
| | - Duo Li
- Institute of Nutrition and Health, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China
| | - Qinchao Ding
- School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310051, China
| | - Jiaomei Li
- School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310051, China.
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Joshi AA, Hegde MV, Zanwar AA. Potential of flaxseed oil blends to modulate tissue fatty acid composition and determination of safety parameters in Wistar rats. Lipids 2025; 60:125-141. [PMID: 39797657 DOI: 10.1002/lipd.12431] [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: 04/02/2024] [Revised: 11/26/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025]
Abstract
Non-communicable diseases (NCD) are associated with inflammation and oxidative stress which is further associated with omega-6 (ω6) and omega-3 (ω3) fatty acid (FA) imbalance favoring ω6 FA. By improving ω3 FA consumption, this imbalance can be altered to control NCD. Previously we have reported blends of flaxseed oil (FSO, ω3 FA) with palm olein (PO) or coconut oil (CO) were thermo-oxidatively stable with good storage stability and could improve ω6:ω3 ratio in cell lines. In the present study safety of these blends along with their efficacy to improve tissue FA composition particularly ω6:ω3 ratio was evaluated in Wistar rats. Institutional ethics committee approval was obtained initially. Wistar rats were supplemented with individual oils or blends (FSO with PO or CO, 20:80 by volume, 1.0 mL/day/200 gm body weight) for 3 months. Throughout the study period, there were no adverse effect of blends on feed intake and body weight gain. After 3 months, blood and serum were subjected for hematological, biochemical assessment. Vital organs were harvested for histopathological and FA composition investigations. Hematological, biochemical, and tissue histopathological parameters were comparable with Control (group receiving only normal diet). Interestingly serum lipid profile was improved by the blend supplementation. Except brain, FA composition was altered in liver, heart, adipose tissue, and RBC with lowering of ω6:ω3 ratio but there was no favorable effect on inflammatory markers and adipokines in the blend supplemented groups. Thus, to conclude, FSO blends with PO or CO were able to lower tissue ω6:ω3 ratio without adverse effects.
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Affiliation(s)
- Asavari Anirudha Joshi
- Centre for Innovation in Nutrition Health Disease, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Mahabaleshwar Vishnu Hegde
- Centre for Innovation in Nutrition Health Disease, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Anand Arvind Zanwar
- Centre for Innovation in Nutrition Health Disease, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, India
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Eslami Z, Joshaghani H, Eghbal Moghanlou A, Norouzi A, Mirghani SJ. Atorvastatin and flaxseed dietary treatments improve dyslipidemia and liver injuries in a diet-induced rat model of non-alcoholic fatty liver disease. AVICENNA JOURNAL OF PHYTOMEDICINE 2025; 15:1102-1112. [PMID: 40365191 PMCID: PMC12068500 DOI: 10.22038/ajp.2024.25220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 09/17/2024] [Indexed: 05/15/2025]
Abstract
Objective Non-alcoholic fatty liver disease (NAFLD) as the most common chronic liver disease is associated with metabolic disorders including dysregulated lipid and glucose metabolism. There is no approved drug treatment for NAFLD; thus, new therapies are needed. We studied the antidyslipidemic effects of atorvastatin and/or possibly hepatoprotective effects of flaxseed/ flaxseed oil in a rat model of NAFLD. Materials and Methods Fifty-six male Wistar rats were divided randomly into seven groups: 1) control, 2) high-fructose diet (HFD), 3) HFD +atorvastatin (20 mg/kg), 4) HFD+ flaxseed (40 g/kg), 5) HFD+ flaxseed oil (40 mg/kg), 6) HFD+flaxseed (40 g/kg) + atorvastatin (20 mg/kg) and 7) HFD+flaxseed oil (40 g/kg) +atorvastatin (20 mg/kg). The interventions were done for 23 weeks, after which anthropometric indices, lipid profile, liver enzymes, fasting blood glucose, and kidney indices were analyzed. Scoring of hematoxylin-eosin-stained liver sections was used to assess the severity of NAFLD. Results All the treatments reduced mesenteric fat mass, and the amount of fat around the liver, except in HFD+ flaxseed +atorvastatin group. The interventions improved NAFLD activity score, which considers steatosis, lobular inflammation, and hepatocyte ballooning. However, atorvastatin was most efficient in reducing inflammation and hepatocyte ballooning. While atorvastatin reduced only Gamma-glutamyltransferase (GGT) levels, flaxseed or flaxseed oil mono- and combination therapies reduced serum levels of all liver enzymes. The interventions improved the serum lipid profile and all, except atorvastatin decreased fasting blood glucose. Conclusion Flaxseed therapies improved NAFLD-associated liver injuries and dyslipidemia, while atorvastatin mostly reduced hepatocyte ballooning and lobular inflammation.
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Affiliation(s)
- Zahra Eslami
- Department of Clinical Biochemistry, Hamadan University of medical science, Hamadan, Iran
| | - Hamidreza Joshaghani
- Laboratory sciences research center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Abdorreza Eghbal Moghanlou
- Istanbul esenyurt University, Physical Education and Sports High School, Coaching Education Department, Istanbul, Turkey
| | - Alireza Norouzi
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
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Gopalsamy RG, Antony PJ, Athesh K, Hillary VE, Montalvão MM, Hariharan G, Santana LADM, Borges LP, Gurgel RQ. Dietary essential oil components: A systematic review of preclinical studies on the management of gastrointestinal diseases. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 140:156630. [PMID: 40085990 DOI: 10.1016/j.phymed.2025.156630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 02/24/2025] [Accepted: 03/06/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND The gut is responsible for the digestion and absorption of nutrients, immune regulation, and barrier function. However, factors like poor diet, stress, and infection, can disrupt the balance of the gut microbiota and lead to intestinal inflammation and dysfunction. PURPOSE This systematic review aims to evaluate the effects of dietary plants-derived essential oil components on gut health and intestinal functions in animal models. METHODS The literature was gathered from the Scopus, Web of Science, PubMed, and Embase databases by using related search terms, such as "dietary plants", "dietary sources", "essential oils", "gut health", "intestine", "anti-inflammatory", "antioxidant", and "gut microbiota". RESULTS The results indicate that plant-derived dietary essential oil components, such as butyrolactone-I, carvacrol, cinnamaldehyde, citral, D-limonene, eugenol, farnesol, geraniol, indole, nerolidol, oleic acid, thymol, trans-anethole, vanillin, α-bisabolol, α-linolenic acid, α-pinene, α-terpineol, β-carotene, β-caryophyllene, and β-myrcene have been found to regulate gut health by influencing vital signalling pathways associated with inflammation. Dietary essential oil components modulate the expression of tumor necrosis factor alpha, interleukin 1 beta (IL-1β), interleukin (IL)-6, IL-10, inducible nitric oxide synthase, cyclooxygenase-2, toll-like receptor-4, matrix metalloproteinase, and interferon gamma in mitigating gut inflammation. The primary signalling molecules controlled by these molecules were AMP-activated protein kinase (AMPK), protein kinase B, extracellular signal-regulated kinase, c-Jun N-terminal kinase, mitogen-activated protein kinase, myeloid differentiation primary response 88, nuclear factor erythroid-2-related factor-2, and phosphoinositide 3-kinase (PI3K). Moreover, these phytochemicals have been shown to improve glucose homeostasis by regulating glucose transporter 4, glucagon-like peptide-1, peroxisome proliferator-activated receptor gamma, nuclear factor kappa B, AMPK, PI3K, and uncoupling protein-1. They can also reduce thiobarbituric acid reactive substance, malondialdehyde, and oxidative stress and enhance superoxide dismutase, catalase, and glutathione peroxidase levels. CONCLUSION In conclusion, dietary plants-derived essential oil components have the potential to mitigate inflammation and oxidative stress in the gut. However, additional clinical investigations are necessary to confirm their complete potential in improving human gut health functions.
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Affiliation(s)
- Rajiv Gandhi Gopalsamy
- Division of Phytochemistry and Drug-Design, Department of Biosciences, Rajagiri College of Social Sciences (Autonomous), Kochi, Kerala, India; Postgraduate Program of Health Sciences (PPGCS), Federal University of Sergipe, Campus Prof. João Cardoso Nascimento, Aracaju, Sergipe, Brazil
| | - Poovathumkal James Antony
- Department of Microbiology, North Bengal University, St. Joseph's College, Darjeeling, West Bengal, India
| | - Kumaraswamy Athesh
- School of Sciences, Bharata Mata College (Autonomous), Kochi, Kerala, India
| | - Varghese Edwin Hillary
- Division of Phytochemistry and Drug-Design, Department of Biosciences, Rajagiri College of Social Sciences (Autonomous), Kochi, Kerala, India
| | | | | | | | - Lysandro Pinto Borges
- Department of Pharmacy, Federal University of Sergipe, São Cristovão, Sergipe, Brazil
| | - Ricardo Queiroz Gurgel
- Postgraduate Program of Health Sciences (PPGCS), Federal University of Sergipe, Campus Prof. João Cardoso Nascimento, Aracaju, Sergipe, Brazil.
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Xue C, Wang T, Chen Y, Zhang H, Wang H, Li Q. Evaluation of gut microbiota alterations following orlistat administration in obese mice. Front Endocrinol (Lausanne) 2025; 15:1337245. [PMID: 40078888 PMCID: PMC11896870 DOI: 10.3389/fendo.2024.1337245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 12/16/2024] [Indexed: 03/14/2025] Open
Abstract
Background The gut microbiota plays a pivotal role in various metabolic disorders. Orlistat has shown beneficial effects on weight loss and metabolism, but its direct impact on the gut microbiota has not been extensively reported. Thus, this study aimed to explore the effects of orlistat on the gut microbiota in mice with high-fat diet-induced obesity. Methods Thirty male C57BL/6J mice were randomly divided into a normal control group (fed a standard diet, N), and a model group (fed a 60% fat diet). A body weight exceeding the basal body weight by 130% defined a successfully established obesity model. The model group was further divided into a positive control group (fed a 60% fat diet, F), and an orlistat group (fed a 60% fat diet and treated with orlistat at 30 mg/kg, bid, A), with 10 mice in each group. The parameters assessed included weight loss, fasting plasma glucose (FPG) levels, and intestinal hormones. Gut microbiota diversity was analyzed using high-throughput sequencing. Results Orlistat treatment significantly reduced body weight and FPG levels, and increased glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels in obese mice. High-fat diet-fed mice exhibited increased microbial diversity and richness, which were significantly diminished by orlistat administration. Additionally, orlistat treatment led to a significant decrease in the proportion of Bacteroidetes and an increase in the proportion of Helicobacter and Allobaculum. Notable shifts in the abundances of Bacteroidetes were observed, correlating with changes in several functional metabolic pathways, including "cell motility" and "neurodegenerative diseases." Co-occurrence network analysis suggested a more complex bacterial network in orlistat-treated mice, alongside a reduction in the density of bacterial correlation networks. Conclusions Our study demonstrates that orlistat's beneficial effects on body weight, FPG, GLP-1, and GIP are likely mediated through modifications in the gut microbiota composition.
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Affiliation(s)
- Chang Xue
- Department of Endocrinology & Metabolism, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Tianying Wang
- Clinical Research Center, Qingdao Municipal Hospital, Qingdao, China
| | - Yang Chen
- Department of Microbiology, Harbin Medical University, Harbin, China
| | - He Zhang
- Department of Endocrinology & Metabolism, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hongjie Wang
- Department of Endocrinology & Metabolism, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Qiang Li
- Department of Endocrinology & Metabolism, Shenzhen University General Hospital, Shenzhen, China
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Li M, Jiang N, Guo G, Lu S, Li Z, Mu Y, Xia X, Xu Z, Hu Y, Xiang X. Perilla Seed Oil: A Review of Health Effects, Encapsulation Strategies and Applications in Food. Foods 2024; 13:3615. [PMID: 39594031 PMCID: PMC11593517 DOI: 10.3390/foods13223615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 11/01/2024] [Accepted: 11/12/2024] [Indexed: 11/28/2024] Open
Abstract
Perilla (Perilla frutescens L.) is an annual herbaceous plant whose seed oil is rich in unsaturated fatty acids such as alpha-linolenic acid (ALA). This oil exhibits various health benefits, including antioxidant, anti-inflammatory, lipid-lowering, hypoglycemic, neuroprotective and immunomodulatory activities. In addition, incorporating perilla oil into a diet can effectively increase the abundance of beneficial bacteria in the gut microbiota. However, perilla oil is prone to oxidation, which reduces its nutritional value and lowers its bioavailability. To address these issues, encapsulation technologies such as emulsions, oleogels, liposomes and microcapsules have been employed, showing promising results. Nonetheless, further research is needed to fully elucidate the underlying mechanisms of perilla seed oil's health effects, validate its benefits through large-scale human clinical trials and optimize encapsulation techniques. Future investigations should also explore the synergistic effects of combining perilla seed oil with other functional components and its role in modulating gut microbiota to achieve comprehensive health benefits.
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Affiliation(s)
- Min Li
- Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Key Laboratory of Industrial Microbiology, National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Research Center of Food Fermentation Engineering and Technology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei University of Technology, Wuhan 430068, China;
- Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Key Laboratory of Oilseeds Processing, Ministry of Agriculture and Rural Affairs, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Wuhan 430062, China; (N.J.); (G.G.); (S.L.); (Z.L.); (Y.M.); (X.X.); (Z.X.)
| | - Nanjie Jiang
- Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Key Laboratory of Oilseeds Processing, Ministry of Agriculture and Rural Affairs, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Wuhan 430062, China; (N.J.); (G.G.); (S.L.); (Z.L.); (Y.M.); (X.X.); (Z.X.)
| | - Guangqi Guo
- Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Key Laboratory of Oilseeds Processing, Ministry of Agriculture and Rural Affairs, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Wuhan 430062, China; (N.J.); (G.G.); (S.L.); (Z.L.); (Y.M.); (X.X.); (Z.X.)
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China
| | - Shuaijun Lu
- Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Key Laboratory of Oilseeds Processing, Ministry of Agriculture and Rural Affairs, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Wuhan 430062, China; (N.J.); (G.G.); (S.L.); (Z.L.); (Y.M.); (X.X.); (Z.X.)
- School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China
| | - Ziliang Li
- Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Key Laboratory of Oilseeds Processing, Ministry of Agriculture and Rural Affairs, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Wuhan 430062, China; (N.J.); (G.G.); (S.L.); (Z.L.); (Y.M.); (X.X.); (Z.X.)
- School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China
| | - Yujie Mu
- Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Key Laboratory of Oilseeds Processing, Ministry of Agriculture and Rural Affairs, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Wuhan 430062, China; (N.J.); (G.G.); (S.L.); (Z.L.); (Y.M.); (X.X.); (Z.X.)
| | - Xiaoyang Xia
- Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Key Laboratory of Oilseeds Processing, Ministry of Agriculture and Rural Affairs, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Wuhan 430062, China; (N.J.); (G.G.); (S.L.); (Z.L.); (Y.M.); (X.X.); (Z.X.)
| | - Zhenxia Xu
- Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Key Laboratory of Oilseeds Processing, Ministry of Agriculture and Rural Affairs, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Wuhan 430062, China; (N.J.); (G.G.); (S.L.); (Z.L.); (Y.M.); (X.X.); (Z.X.)
| | - Yong Hu
- Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Key Laboratory of Industrial Microbiology, National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Research Center of Food Fermentation Engineering and Technology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei University of Technology, Wuhan 430068, China;
| | - Xia Xiang
- Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Key Laboratory of Oilseeds Processing, Ministry of Agriculture and Rural Affairs, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Wuhan 430062, China; (N.J.); (G.G.); (S.L.); (Z.L.); (Y.M.); (X.X.); (Z.X.)
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Xue X, Zhou H, Gao J, Li X, Wang J, Bai W, Bai Y, Fan L, Chang H, Shi S. The impact of traditional Chinese medicine and dietary compounds on modulating gut microbiota in hepatic fibrosis: A review. Heliyon 2024; 10:e38339. [PMID: 39391468 PMCID: PMC11466535 DOI: 10.1016/j.heliyon.2024.e38339] [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: 09/02/2024] [Revised: 09/21/2024] [Accepted: 09/23/2024] [Indexed: 10/12/2024] Open
Abstract
Traditional Chinese medicine (TCM) and dietary compounds have a profound influence on the regulation of gut microbiota (GM) in hepatic fibrosis (HF). Certain substances found in both food and herbs that are edible and medicinal, such as dietary fiber, polyphenols, and polysaccharides, can generate beneficial metabolites like short-chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (Trp). These compounds contribute to regulate the GM, reduce levels of endotoxins in the liver, and alleviate fibrosis and inflammation in the liver. Furthermore, they enhance the composition and functionality of GM, promoting the growth of beneficial bacteria while inhibiting the proliferation of harmful bacteria. These mechanisms mitigate the inflammatory response in the intestines and maintain the integrity of the intestinal barrier. The purpose of this review is to analyze how the GM regulates the pathogenesis of HF, evaluate the regulatory effect of TCM and dietary compounds on the intestinal microflora, with a particular emphasis on modulating flora structure, enhancing gut barrier function, and addressing associated pathogenic factors, thereby provide new insights for the treatment of HF.
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Affiliation(s)
- Xingting Xue
- Department of Pharmacy, Baotou Medical College, Baotou, 014040, China
| | - Hongbing Zhou
- Department of Pharmacy, Baotou Medical College, Baotou, 014040, China
| | - Jiaxing Gao
- Department of Pharmacy, Baotou Medical College, Baotou, 014040, China
| | - Xinghua Li
- Changzhi People's Hospital, The Affiliated Hospital of Changzhi Medical College, Changzhi, Shanxi Province, China
| | - Jia Wang
- Department of Pharmacy, Baotou Medical College, Baotou, 014040, China
| | - Wanfu Bai
- Department of Pharmacy, Baotou Medical College, Baotou, 014040, China
| | - Yingchun Bai
- Department of Pharmacy, Baotou Medical College, Baotou, 014040, China
| | - Liya Fan
- Department of Pharmacy, Baotou Medical College, Baotou, 014040, China
| | - Hong Chang
- Department of Pharmacy, Baotou Medical College, Baotou, 014040, China
| | - Songli Shi
- Department of Pharmacy, Baotou Medical College, Baotou, 014040, China
- Institute of Bioactive Substance and Function of Mongolian Medicine and Chinese Materia Medica, Baotou Medical College, Baotou, China
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Guo J, Chen X, Zhou M, Yu X, Zhu H, Xiao K, Chen G, Liu Y. Flaxseed Oil Attenuates Intestinal Damage by Regulating Ferroptosis Signaling Pathway Following LPS Challenge in Piglets. Mol Nutr Food Res 2024; 68:e2400199. [PMID: 39148171 DOI: 10.1002/mnfr.202400199] [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: 03/14/2024] [Revised: 07/07/2024] [Indexed: 08/17/2024]
Abstract
SCOPE Ferroptosis has been demonstrated to play an important role in various tissue injuries and diseases. Flaxseed oil (FO) has been proven to have benefits for intestinal health. This study aims to explore whether FO relieved lipopolysaccharide (LPS)-induced intestinal injury through modulating ferroptosis signaling pathway. METHODS AND RESULTS A total of 120 weaned piglets are fed diets with 3% soybean oil (SO) or 3% FO for 4 weeks. At the end of the trial, 24 piglets selected from two dietary treatment groups are used in a 2 × 2 factorial design with oil treatment (3% SO versus 3% FO) and LPS challenge (saline versus LPS). At 4 h postinjection with LPS, 24 piglets are slaughtered and intestinal samples are collected. FO improves growth performance of pigs. After LPS treatment, FO mitigates intestinal morphological damage and functional damage. Notably, FO reverses the typical ultra-morphology and biochemical indexes of ferroptosis involving glutathione, malondialdehyde, and 4-hydroxynonenal contents. Mechanistically, FO ameliorates the changes on mRNA or protein abundance of key ferroptosis signals including transferrin receptor protein 1 (TFR1), recombinant iron responsive element binding protein 2 (IREB2), FTL, HSPB1, ferritin heavy chain 1 (FTH1), ferroportin 1 (FPN1), SLC7A11, solute carrier family 3 member 2 (SLC3A2), glutathione peroxidase 4 (GPX4), and arachidonate-15-lipoxygenase (ALOX15). CONCLUSIONS FO improves growth performance and mitigates intestinal structural and functional damage, which is involved in regulating ferroptosis signaling pathway.
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Affiliation(s)
- Junjie Guo
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, People's Republic of China
| | - Xiaoqian Chen
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China
| | - Mohan Zhou
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China
| | - Xintian Yu
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China
| | - Huiling Zhu
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China
| | - Kan Xiao
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China
| | - Guoshun Chen
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, People's Republic of China
| | - Yulan Liu
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China
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10
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Wang X, Pan L, Gu J, Gu L, Lou M, Liu Y. Associations Between Gut Microbiota and Alcohol Abuse: A Mendelian Randomisation and Bioinformatics Study. J Mol Neurosci 2024; 74:80. [PMID: 39186136 DOI: 10.1007/s12031-024-02259-7] [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: 03/11/2024] [Accepted: 08/19/2024] [Indexed: 08/27/2024]
Abstract
Alcohol abuse, also known as Alcohol Use Disorder (AUD), is a substance dependency psychiatric disorder. We aimed to establish a causal relationship between specific gut microbiota and alcohol abuse using Mendelian Randomisation (MR) and bioinformatics methods. We acquired summary data of genome-wide association studies (GWAS) for gut microbiota and alcohol abuse from the Mibiogen and Finngen databases, respectively. We conducted MR analyses using various methodologies and mapped the single nucleotide polymorphisms (SNPs) to genes via the FUMA GWAS platform. We further performed multiple enrichment analyses and a Multi-variable Mendelian Randomisation (MVMR) approach to examine whether gut microbiota influences alcohol abuse by modulating neurotransmitter-related amino acids. The MR analysis revealed an inverse relationship between the genus Eubacterium ventriosum group and the Porphyromonadaceae family with alcohol abuse. Gene enrichment analysis showed that these genes are expressed in brain tissue and are involved in addictive disorders, psychiatric conditions, immunological processes, neurotransmitter synthesis and synaptic regulation. MVMR analysis suggested that the Porphyromonadaceae family as well as genus Eubacterium ventriosum group may suppress alcohol abuse through the metabolism of neurotransmitter-related amino acids, especially Tryptophan. The MR analysis and bioinformatics investigations indicate that the genus Eubacterium ventriosum group and Porphyromonadaceae family confer a protective effect against alcohol abuse, potentially through the modulation of synaptic function.
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Affiliation(s)
- Xu Wang
- Department of Neurosurgery, Nanjing Medical University, Shanghai General Hospital, Shanghai, China
- Department of Neurosurgery, Shanghai Jiao Tong University School of Medicine, Shanghai General Hospital, Shanghai, China
- Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lei Pan
- Department of Neurosurgery, Nanjing Medical University, Shanghai General Hospital, Shanghai, China
- Department of Neurosurgery, Nanjing Medical University, Shanghai Songjiang District Central Hospital, Shanghai, China
| | - Jingyan Gu
- Department of Neurosurgery, Shanghai Jiao Tong University School of Medicine, Shanghai General Hospital, Shanghai, China
- Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lianping Gu
- Department of Neurosurgery, Nanjing Medical University, Shanghai General Hospital, Shanghai, China
- Department of Neurosurgery, Shanghai Jiao Tong University School of Medicine, Shanghai General Hospital, Shanghai, China
- Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Meiqing Lou
- Department of Neurosurgery, Nanjing Medical University, Shanghai General Hospital, Shanghai, China.
- Department of Neurosurgery, Shanghai Jiao Tong University School of Medicine, Shanghai General Hospital, Shanghai, China.
- Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Yaohua Liu
- Department of Neurosurgery, Nanjing Medical University, Shanghai General Hospital, Shanghai, China.
- Department of Neurosurgery, Shanghai Jiao Tong University School of Medicine, Shanghai General Hospital, Shanghai, China.
- Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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11
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Wei F, Hughes M, Omer M, Ngo C, Pugazhendhi AS, Kolanthai E, Aceto M, Ghattas Y, Razavi M, Kean TJ, Seal S, Coathup M. A Multifunctional Therapeutic Strategy Using P7C3 as A Countermeasure Against Bone Loss and Fragility in An Ovariectomized Rat Model of Postmenopausal Osteoporosis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2308698. [PMID: 38477537 PMCID: PMC11151083 DOI: 10.1002/advs.202308698] [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] [Indexed: 03/14/2024]
Abstract
By 2060, an estimated one in four Americans will be elderly. Consequently, the prevalence of osteoporosis and fragility fractures will also increase. Presently, no available intervention definitively prevents or manages osteoporosis. This study explores whether Pool 7 Compound 3 (P7C3) reduces progressive bone loss and fragility following the onset of ovariectomy (OVX)-induced osteoporosis. Results confirm OVX-induced weakened, osteoporotic bone together with a significant gain in adipogenic body weight. Treatment with P7C3 significantly reduced osteoclastic activity, bone marrow adiposity, whole-body weight gain, and preserved bone area, architecture, and mechanical strength. Analyses reveal significantly upregulated platelet derived growth factor-BB and leukemia inhibitory factor, with downregulation of interleukin-1 R6, and receptor activator of nuclear factor kappa-B (RANK). Together, proteomic data suggest the targeting of several key regulators of inflammation, bone, and adipose turnover, via transforming growth factor-beta/SMAD, and Wingless-related integration site/be-catenin signaling pathways. To the best of the knowledge, this is first evidence of an intervention that drives against bone loss via RANK. Metatranscriptomic analyses of the gut microbiota show P7C3 increased Porphyromonadaceae bacterium, Candidatus Melainabacteria, and Ruminococcaceae bacterium abundance, potentially contributing to the favorable inflammatory, and adipo-osteogenic metabolic regulation observed. The results reveal an undiscovered, and multifunctional therapeutic strategy to prevent the pathological progression of OVX-induced bone loss.
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Affiliation(s)
- Fei Wei
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
| | - Megan Hughes
- School of BiosciencesCardiff UniversityWalesCF10 3ATUK
| | - Mahmoud Omer
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
| | - Christopher Ngo
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
| | | | - Elayaraja Kolanthai
- Advanced Materials Processing and Analysis Centre, Nanoscience Technology Center (NSTC)University of Central FloridaOrlandoFL32826USA
| | - Matthew Aceto
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
| | - Yasmine Ghattas
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
| | - Mehdi Razavi
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
| | - Thomas J Kean
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
| | - Sudipta Seal
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
- Advanced Materials Processing and Analysis Centre, Nanoscience Technology Center (NSTC)University of Central FloridaOrlandoFL32826USA
| | - Melanie Coathup
- Biionix ClusterUniversity of Central FloridaOrlandoFL82816USA
- College of MedicineUniversity of Central FloridaOrlandoFL32827USA
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12
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Lontro Alves L, Gomes Pereira P, Torres Ciambarella B, Porto Campos M, Rabelo K, Rosa Nascimento AL, Leal de Carvalho dos Santos Cunha R, Borba Vieira Andrade C, Cesar Nunes Moraes A, Bernardi A, Verdini Guimarães F, Fuentes Ribeiro da Silva J, José de Carvalho J. Beneficial Effects of Capybara Oil Supplementation on Steatosis and Liver Apoptosis in Obese Mice. J Obes 2024; 2024:7204607. [PMID: 38831961 PMCID: PMC11147678 DOI: 10.1155/2024/7204607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 04/30/2024] [Accepted: 05/09/2024] [Indexed: 06/05/2024] Open
Abstract
Obesity is a complex chronic disease characterized by excess body fat (adipose) that is harmful to health and has been a major global health problem. It may be associated with several diseases, such as nonalcoholic fatty liver disease (NAFLD). Polyunsaturated fatty acids (PUFA) are lipid mediators that have anti-inflammatory characteristics and can be found in animals and plants, with capybara oil (CO) being a promising source. So, we intend to evaluate the hepatic pathophysiological alterations in C57Bl/6 mice with NAFLD, caused by obesity, and the possible beneficial effects of OC in the treatment of this disease. Eighteen 3-month-old male C57Bl/6 mice received a control or high-fat diet for 18 weeks. From the 15th to the 18th week, the animals received treatment-through orogastric gavage-with placebo or free capybara oil (5 g/kg). Parameters inherent to body mass, glucose tolerance, evaluation of liver enzymes, percentage of hepatic steatosis, oxidative stress, the process of cell death with the apoptotic biomarkers (Bax, Bcl2, and Cytochrome C), and the ultrastructure of hepatocytes were analyzed. Even though the treatment with CO was not able to disassemble the effects on the physiological parameters, it proved to be beneficial in reversing the morphological and ultrastructural damage present in the hepatocytes. Thus, demonstrating that CO has beneficial effects in reducing steatosis and the apoptotic pathway, it is a promising treatment for NAFLD.
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Affiliation(s)
- Luciana Lontro Alves
- Ultrastructure and Tissue Biology Laboratory, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Priscila Gomes Pereira
- Ultrastructure and Tissue Biology Laboratory, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Bianca Torres Ciambarella
- Ultrastructure and Tissue Biology Laboratory, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Miguel Porto Campos
- Ultrastructure and Tissue Biology Laboratory, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Kíssila Rabelo
- Ultrastructure and Tissue Biology Laboratory, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil
- Interdisciplinary Laboratory of Medical Research, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Ana Lúcia Rosa Nascimento
- Ultrastructure and Tissue Biology Laboratory, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | | | - Cherley Borba Vieira Andrade
- Ultrastructure and Tissue Biology Laboratory, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil
| | - Alan Cesar Nunes Moraes
- Ultrastructure and Tissue Biology Laboratory, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil
- Electron Microscopy Laboratory of Biology Institute, Federal Fluminense University, Rio de Janeiro, Brazil
| | - Andressa Bernardi
- Inflammation Laboratory, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | | | | | - Jorge José de Carvalho
- Ultrastructure and Tissue Biology Laboratory, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil
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13
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Geng Q, Xu Y, Huang W, Hu Y, Jin H, Hua H, Kong D. The Potential Mechanism of the Anti-Liver Fibrotic Effect of Curcumin in the Gut-Liver Axis. J Med Food 2024; 27:404-418. [PMID: 38669311 DOI: 10.1089/jmf.2023.k.0273] [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] [Indexed: 04/28/2024] Open
Abstract
This study aimed to explore the curative effect of curcumin on liver fibrosis and its correlation with the gut-liver axis in animal models. Histological staining was utilized to conduct histological analysis of the liver and intestine. An automatic biochemical analyzer or enzyme-linked immunosorbent assay system was utilized for analyzing the biochemical indexes in mice. Western blotting was employed to examine the level of relevant proteins. Furthermore, 16S rRNA high-throughput sequencing was performed to explore the impact of curcumin on intestinal microorganisms in rats with liver fibrosis. Ultrahigh-performance liquid chromatography with quadrupole-orbitrap mass spectrometry was utilized to analyze the effect of curcumin on rat feces metabolites. Our results showed that curcumin reduced the formation of collagen fibers caused by carbon tetrachloride in a dose-dependent manner. In addition, curcumin was able to restore intestinal permeability in rats with liver fibrosis. By adopting α diversity analysis (Chao 1 index, Shannon index, and Simpson index), we observed that both the diversity and the abundance of intestinal flora in rats with liver fibrosis were increased. The principal component analysis diagram demonstrated that curcumin could enhance the abundance and diversity of intestinal flora, and also restore the composition of model rat flora, which was similar to that in normal rats, thereby correcting the imbalance of flora in rats with liver fibrosis. In addition, curcumin regulated feces metabolites and their signaling pathways, including glycerophospholipid metabolism, pantothenate and CoA biosynthesis. Our findings suggest that curcumin exhibits antiliver fibrosis effects, and its antiliver fibrosis effects might correlate with gut-liver axis.
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Affiliation(s)
- Qiao Geng
- Chinese Medicine Modernization and Big Data Research Center, Nanjing Hospital of Chinese Medicine Affiliated with Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Yanyan Xu
- Department of colorectal surgery, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Weifang Huang
- Chinese Medicine Modernization and Big Data Research Center, Nanjing Hospital of Chinese Medicine Affiliated with Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Yang Hu
- Chinese Medicine Modernization and Big Data Research Center, Nanjing Hospital of Chinese Medicine Affiliated with Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Heiying Jin
- Department of colorectal surgery, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Haibing Hua
- Department of Gastroenterology, Jiangyin Hospital of Chinese Medicine Affiliated with Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Jiangyin, Jiangsu Province, China
| | - Desong Kong
- Chinese Medicine Modernization and Big Data Research Center, Nanjing Hospital of Chinese Medicine Affiliated with Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
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14
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Acosta JE, Burns JL, Hillyer LM, Van K, Brendel EBK, Law C, Ma DWL, Monk JM. Effect of Lifelong Exposure to Dietary Plant and Marine Sources of n-3 Polyunsaturated Fatty Acids on Morphologic and Gene Expression Biomarkers of Intestinal Health in Early Life. Nutrients 2024; 16:719. [PMID: 38474847 DOI: 10.3390/nu16050719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 02/26/2024] [Accepted: 02/27/2024] [Indexed: 03/14/2024] Open
Abstract
Altered intestinal health is also associated with the incidence and severity of many chronic inflammatory conditions, which could be attenuated via dietary n-3 PUFA interventions. However, little is known about the effect of lifelong exposure to n-3 PUFA from plant and marine sources (beginning in utero via the maternal diet) on early life biomarkers of intestinal health. Harems of C57Bl/6 mice were randomly assigned to one of three isocaloric AIN-93G modified diets differing in their fat sources consisting of the following: (i) 10% safflower oil (SO, enriched in n-6 PUFA), (ii) 3% flaxseed oil + 7% safflower oil (FX, plant-based n-3 PUFA-enriched diet), or (iii) 3% menhaden fish oil + 7% safflower oil (MO, marine-based n-3 PUFA-enriched diet). Mothers remained on these diets throughout pregnancy and offspring (n = 14/diet) continued on the same parental diet until termination at 3 weeks of age. In ileum, villi:crypt length ratios were increased in both the FX and MO dietary groups compared to SO (p < 0.05). Ileum mRNA expression of critical intestinal health biomarkers was increased by both n-3 PUFA-enriched diets including Relmβ and REG3γ compared to SO (p < 0.05), whereas only the FX diet increased mRNA expression of TFF3 and Muc2 (p < 0.05) and only the MO diet increased mRNA expression of ZO-1 (p < 0.05). In the proximal colon, both the FX and MO diets increased crypt lengths compared to SO (p < 0.05), whereas only the MO diet increased goblet cell numbers compared to SO (p < 0.05). Further, the MO diet increased proximal colon mRNA expression of Relmβ and REG3γ (p < 0.05) and both MO and FX increased mRNA expression of Muc2 compared to SO (p < 0.05). Collectively, these results demonstrate that lifelong exposure to dietary n-3 PUFA, beginning in utero, from both plant and marine sources, can support intestinal health development in early life. The differential effects between plant and marine sources warrants further investigation for optimizing health.
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Affiliation(s)
- Julianna E Acosta
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada
| | - Jessie L Burns
- Department of Health Sciences, Carleton University, Ottawa, ON K1S 5B6, Canada
| | - Lyn M Hillyer
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada
| | - Kelsey Van
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada
| | - Elaina B K Brendel
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada
| | - Camille Law
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada
| | - David W L Ma
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada
| | - Jennifer M Monk
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada
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15
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Qiu J, Dong F, Zhuge H, Han Q, Li J, Guo R, Dou X, Li J, Li S. Preventive effect of low-carbohydrate high-fat dietary pattern on liver disease caused by alcohol consumption via a 6pgd-involved mechanism in mice. Food Funct 2024; 15:732-746. [PMID: 38117162 DOI: 10.1039/d3fo04335e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2023]
Abstract
A low-carbohydrate high-fat (LCHF) dietary pattern has been reported to improve chronic metabolic diseases. However, whether and how the LCHF diet affects the pathological progression in patients with alcohol-related liver diseases (ALD) is largely unknown. This study was conducted to evaluate the effect of the LCHF diet on ALD and clarify its potential mechanism(s). The ALD model was established by feeding C57BL/6N mice with a Lieber-DeCarli liquid alcohol diet with a modified carbohydrate/fat ratio under an isoenergetic pattern. After an eight-week intervention, we observed that the LCHF diet significantly reduced alcohol-induced hepatic steatosis and liver injury, along with improved lipid metabolic-related gene disorders and redox imbalance. The alcohol-stimulated increase in pro-inflammatory cytokine cytokines expression, including TNF-α, IL-1β, and IL-6, was markedly reversed by the LCHF diet. Liver transcriptome sequencing and qPCR validation showed that twenty-four alcohol-disturbed genes were significantly reversed by LCHF-diet intervention. The top differentially expressed genes were selected for further investigation. Among them, 6-phosphogluconate dehydrogenase (6PGD) was significantly up-regulated by alcohol treatment in both the liver and cultured hepatocytes. Spearman correlation analysis revealed that 6PGD was positively associated with hepatic steatosis, liver injury, and oxidative stress indexes. In vitro, the 6PGD knockdown ameliorated alcohol-induced hepatotoxicity and intracellular lipid accumulation, as well as lipid metabolic-related gene disorders, implying the involvement of 6PGD in LCHF-protected ALD. In conclusion, LCHF diet intervention alleviated chronic alcohol consumption-induced liver dysfunction in mice. 6PGD is a potential novel target for ALD prevention that contributes to LCHF-improved ALD. A LCHF diet might be a promising choice for ALD management.
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Affiliation(s)
- Jiannan Qiu
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR. China.
- School of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR. China
| | - Fan Dong
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR. China.
| | - Hui Zhuge
- School of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR. China
| | - Qiang Han
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR. China.
| | - Jiaomei Li
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR. China.
| | - Rui Guo
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR. China.
| | - Xiaobing Dou
- School of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR. China
| | - Jiayu Li
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR. China.
| | - Songtao Li
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR. China.
- Department of Clinical Nutrition, Affiliated Zhejiang Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR. China
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16
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Li M, Gou D, Gong P, Di W, Wang L, Ding J, Chang Y, Zuo R. An Investigation on the Effects of Dietary Vitamin E on Juvenile Sea Urchin ( Strongylocentrotus intermedius): Growth, Intestinal Microbiota, Immune Response, and Related Gene Expression. BIOLOGY 2023; 12:1523. [PMID: 38132349 PMCID: PMC10740812 DOI: 10.3390/biology12121523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/07/2023] [Accepted: 12/12/2023] [Indexed: 12/23/2023]
Abstract
A 90 d feeding experiment was conducted to investigate the effects of vitamin E (VE) on growth, intestinal microbiota, immune response, and related gene expression of juvenile sea urchin (Strongylocentrotus intermedius). Six dry feeds were made to contain graded levels of VE (78, 105, 152, 235, 302, and 390 mg/kg); these were named E78, E105, E152, E235, E302, and E390, respectively. Dry feed E50 and fresh kelp (HD) were used as the control diets. There were six replicates of cages in each dietary group, and each cage held 20 sea urchins with an initial body weight of approximately 1.50 g. Results exhibited that weight gain rate and gonadosomatic index (GSI) of the sea urchins were not significantly affected by dietary VE ranging from 78 to 390 mg/kg. Sea urchins in the dry feed groups showed poorer growth performance, but significantly higher GSI than those in the fresh kelp groups. The pepsin and lipase activities were not significantly promoted by low or moderate VE, but were inhibited by a high level of VE (302-390 mg/kg), while amylase and cellulase activities were significantly increased by low or moderate VE, with the highest values observed in the E105 and E235 groups, respectively. VE addition at a low dosage (105-152 mg/kg) showed inhibitory effects on immune and antioxidant enzyme activities and expression of inflammation-related genes, but showed no beneficial effects at moderate or high dosage (235-390 mg/kg), while a moderate or relatively higher level of VE (235-302 mg/kg) significantly increased the expression of several immune-related genes. The relative abundance of Proteobacteria, Actinobacteria, Ruegeria, and Maliponia in the intestine of the sea urchins increased with the increase in VE in the dry feeds. On the contrary, the relative abundance of the Firmicutes, Bacteroidetes, Escherichia-Shigella, Bacteroides, and Clostridium sensu stricto 1 gradually decreased as VE content increased. These results indicated that a moderate level of VE (172.5-262.4) can achieve ideal digestive enzyme activities and growth performance, but a relatively higher level of VE (235-302 mg/kg) was beneficial for maintaining the immune and antioxidant capacity of juvenile S. intermedius by regulating the expression of inflammation- and immune-related genes and abundance of some bacteria to a healthy state.
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Affiliation(s)
- Min Li
- Key Laboratory of Mariculture and Stock Enhancement in North China’s Sea (Ministry of Agriculture and Rural Affairs), Dalian Ocean University, Dalian 116023, China; (M.L.); (Y.C.)
- Department of Marine Biology, Weihai Ocean Vocational College, Weihai 264300, China
| | - Dan Gou
- Key Laboratory of Mariculture and Stock Enhancement in North China’s Sea (Ministry of Agriculture and Rural Affairs), Dalian Ocean University, Dalian 116023, China; (M.L.); (Y.C.)
| | - Panke Gong
- Key Laboratory of Mariculture and Stock Enhancement in North China’s Sea (Ministry of Agriculture and Rural Affairs), Dalian Ocean University, Dalian 116023, China; (M.L.); (Y.C.)
| | - Weixiao Di
- Key Laboratory of Mariculture and Stock Enhancement in North China’s Sea (Ministry of Agriculture and Rural Affairs), Dalian Ocean University, Dalian 116023, China; (M.L.); (Y.C.)
| | - Lina Wang
- Key Laboratory of Mariculture and Stock Enhancement in North China’s Sea (Ministry of Agriculture and Rural Affairs), Dalian Ocean University, Dalian 116023, China; (M.L.); (Y.C.)
| | - Jun Ding
- Key Laboratory of Mariculture and Stock Enhancement in North China’s Sea (Ministry of Agriculture and Rural Affairs), Dalian Ocean University, Dalian 116023, China; (M.L.); (Y.C.)
| | - Yaqing Chang
- Key Laboratory of Mariculture and Stock Enhancement in North China’s Sea (Ministry of Agriculture and Rural Affairs), Dalian Ocean University, Dalian 116023, China; (M.L.); (Y.C.)
| | - Rantao Zuo
- Key Laboratory of Mariculture and Stock Enhancement in North China’s Sea (Ministry of Agriculture and Rural Affairs), Dalian Ocean University, Dalian 116023, China; (M.L.); (Y.C.)
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17
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Das A, Tang YLM, Althumiri NA, Garcia-Larsen V, Schattenberg JM, Alqahtani SA. Fatty acid composition but not quantity is an important indicator of non-alcoholic fatty liver disease: a systematic review. Eur J Clin Nutr 2023; 77:1113-1129. [PMID: 37661229 DOI: 10.1038/s41430-023-01335-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 08/14/2023] [Accepted: 08/17/2023] [Indexed: 09/05/2023]
Abstract
BACKGROUND There is still paucity on the effects of dietary and supplemental fatty acid on non-alcoholic fatty liver disease (NAFLD). The aim of this review is to systematically review and summarise the effect of fatty acids intake on liver-related outcomes in adult patients with NAFLD. METHODS The review was conducted using Cochrane CENTRAL Library, Scopus, Embase, MEDLINE, PubMed, and Web of Science. A total of 2786 records were identified, and of these, 36 studies (31 were randomised control trials (RCTs), and 5 were case-control studies) were included. Quality assessment was conducted using the Revised Cochrane Risk of Bias tool and Joanna Briggs Institute checklists. RESULTS Of 36 articles, 79% of RCTs and 66% of case-control studies had a low risk of bias. Potential heterogeneity has been observed in assessment of liver-related outcomes. According to the RCTs, there was moderate evidence (3/6 studies) that a diet characterised by a high MUFA, PUFA and low SFA showed reduced liver fat and stiffness. The using of culinary fats that are high in MUFA (4/6 studies) reduces liver steatosis. n-3 PUFA supplementation in combination with a hypocaloric or heart healthy diet with a low SFA improved liver enzyme level (5/14 studies) and steatosis score (3/14 studies). CONCLUSIONS Effects on NAFLD parameters, including liver fat content (assessed via magnetic resonance imaging/spectroscopy), stiffness and steatosis score (assessed by ultrasonography), were primarily related to fatty acid composition independent of energy intake. Further investigation is needed to determine the mechanism of specific fatty acid on the accumulation of liver fat.
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Affiliation(s)
- Arpita Das
- Department of Nutrition and Dietetics, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
| | - Yu Lung Malcolm Tang
- Department of Nutrition and Dietetics, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
| | | | - Vanessa Garcia-Larsen
- Program in Human Nutrition, Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Jörn M Schattenberg
- Metabolic Liver Research Program, I. Department of Medicine, University Medical Centre, Mainz, Germany
| | - Saleh A Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
- Liver Transplantation Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
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Chu Z, Hu Z, Luo Y, Zhou Y, Yang F, Luo F. Targeting gut-liver axis by dietary lignans ameliorate obesity: evidences and mechanisms. Crit Rev Food Sci Nutr 2023; 65:243-264. [PMID: 37870876 DOI: 10.1080/10408398.2023.2272269] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2023]
Abstract
An imbalance between energy consumption and energy expenditure causes obesity. It is characterized by increased adipose accumulation and accompanied by chronic low-grade inflammation. Many studies have suggested that the gut microbiota of the host mediates the relationship between high-fat diet consumption and the development of obesity. Diet and nutrition of the body are heavily influenced by gut microbiota. The alterations in the microbiota in the gut may have effects on the homeostasis of the host's energy levels, systemic inflammation, lipid metabolism, and insulin sensitivity. The liver is an important organ for fat metabolism and gut-liver axis play important role in the fat metabolism. Gut-liver axis is a bidirectional relationship between the gut and its microbiota and the liver. As essential plant components, lignans have been shown to have different biological functions. Accumulating evidences have suggested that lignans may have lipid-lowering properties. Lignans can regulate the level of the gut microbiota and their metabolites in the host, thereby affecting signaling pathways related to fat synthesis and metabolism. These signaling pathways can make a difference in inhibiting fat accumulation, accelerating energy metabolism, affecting appetite, and inhibiting chronic inflammation. It will provide the groundwork for future studies on the lipid-lowering impact of lignans and the creation of functional meals based on those findings.
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Affiliation(s)
- Zhongxing Chu
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan, P.R. China
| | - Zuomin Hu
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan, P.R. China
| | - Yi Luo
- Department of Clinic Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, P.R. China
| | - Yaping Zhou
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan, P.R. China
| | - Feiyan Yang
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan, P.R. China
| | - Feijun Luo
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan, P.R. China
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19
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Godoy G, Bernardo C, Casagrande L, Sérgio M, Zanoni J, Perles J, Curi R, Bazotte R. Linseed oil attenuates fatty liver disease in mice fed a high-carbohydrate diet. Braz J Med Biol Res 2023; 56:e12927. [PMID: 37703111 PMCID: PMC10496762 DOI: 10.1590/1414-431x2023e12927] [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: 06/07/2023] [Accepted: 07/27/2023] [Indexed: 09/15/2023] Open
Abstract
The impact of linseed oil as a lipid source on liver disease induced by a high-carbohydrate diet (HCD) was evaluated. Adult male Swiss mice received an HCD containing carbohydrates (72.1%), proteins (14.2%), and lipids (4.0%). The Control HCD group (HCD-C) received an HCD containing lard (3.6%) and soybean oil (0.4%) as lipid sources. The L10 and L100 groups received an HCD with 10 and 100% linseed oil as lipid sources, respectively. A group of mice were euthanized before receiving the diets (day 0) and the remaining groups after 56 days of receiving the diets (HCD-C, L10, and L-100 groups). Morphological and histopathological analyses, as well as collagen deposition were evaluated. Perivenous hepatocytes (PVH) of the HCD-C group were larger (P<0.05) than periportal hepatocytes (PPH) in the median lobe (ML) and left lobe (LL). There was a greater (P<0.05) deposition of type I collagen in PPH (vs PVH) and in the ML (vs LL). The ML exhibited a higher proportion of apoptotic bodies, inflammatory infiltrate, and hepatocellular ballooning. All these alterations (hepatocyte size, deposition of type I collagen, apoptotic bodies, inflammatory infiltrate, and hepatocellular ballooning) induced by HCD were prevented or attenuated in L10 and L100 groups. Another indicator of the beneficial effects of linseed oil was the lower (P<0.05) number of binucleated hepatocytes (HCD-C vs L10 or L100 group). In general, the L100 group had greater effects than the L10 group. In conclusion, linseed oil impedes or reduces the liver injury progression induced by an HCD.
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Affiliation(s)
- G. Godoy
- Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brasil
| | - C.C.O. Bernardo
- Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brasil
| | - L. Casagrande
- Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brasil
| | - M.L.M. Sérgio
- Departamento de Ciências Morfológicas, Universidade Estadual de Maringá, Maringá, PR, Brasil
| | - J.N. Zanoni
- Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brasil
- Departamento de Ciências Morfológicas, Universidade Estadual de Maringá, Maringá, PR, Brasil
| | - J.V.C.M. Perles
- Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brasil
- Departamento de Ciências Morfológicas, Universidade Estadual de Maringá, Maringá, PR, Brasil
| | - R. Curi
- Programa de Pós-graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil
- Seção de Produção de Imunobiológicos, Centro Bioindustrial, Instituto Butantan, São Paulo, SP, Brasil
| | - R.B. Bazotte
- Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Maringá, PR, Brasil
- Departamento de Farmacologia e Terapêutica, Universidade Estadual de Maringá, Maringá, PR, Brasil
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20
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Wei H, Yu C, Zhang C, Ren Y, Guo L, Wang T, Chen F, Li Y, Zhang X, Wang H, Liu J. Butyrate ameliorates chronic alcoholic central nervous damage by suppressing microglia-mediated neuroinflammation and modulating the microbiome-gut-brain axis. Biomed Pharmacother 2023; 160:114308. [PMID: 36709599 DOI: 10.1016/j.biopha.2023.114308] [Citation(s) in RCA: 79] [Impact Index Per Article: 39.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 01/17/2023] [Accepted: 01/25/2023] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Alcohol abuse triggers neuroinflammation, leading to neuronal damage and further memory and cognitive impairment. Few satisfactory advances have been made in the management of alcoholic central nervous impairment. Therefore, novel and more practical treatment options are urgently needed. Butyrate, a crucial metabolite of short-chain fatty acids (SCFAs), has been increasingly demonstrated to protect against numerous metabolic diseases. However, the impact of butyrate on chronic alcohol consumption-induced central nervous system (CNS) lesions remains unknown. METHODS In this study, we assessed the possible effects and underlying mechanisms of butyrate on the attenuation of alcohol-induced CNS injury in mice. Firstly, sixty female C57BL/6 J mice were randomly divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with sodium butyrate (NaB) group (PF/NaB) and AF with NaB group (AF/NaB). Each group was fed a modified Lieber-DeCarli liquid diet with or without alcohol. After six weeks of feeding, the mice were euthanized and the associated indicators were investigated. RESULTS As indicated by the behavioral tests and brain morphology, dietary NaB administration significantly ameliorated aberrant behaviors, including locomotor hypoactivity, anxiety disorder, depressive behavior, impaired learning, spatial recognition memory, and effectively reduced chronic alcoholic central nervous system damage. To further understand the underlying mechanisms, microglia-mediated inflammation and the associated M1/M2 polarization were measured separately. Firstly, pro-inflammatory TNF-α, IL-1β, and IL-6 in brain and peripheral blood circulation were decreased, but IL-10 were increased in the AF/NaB group compared with the AF/CON group. Consistently, the abnormal proportions of activated and resting microglial cells in the hippocampus and cortex regions after excessive alcohol consumption were significantly reduced with NaB treatment. Moreover, the rectification of microglia polarization (M1/M2) imbalance was found after NaB administration via binding GPR109A, up-regulating the expression of PPAR-γ and down-regulating TLR4/NF-κB activation. In addition to the direct suppression of neuroinflammation, intriguingly, dietary NaB intervention remarkably increased the levels of intestinal tight junction protein occludin and gut morphological barrier, attenuated the levels of serum lipopolysaccharide (LPS) and dysbiosis of gut microbiota, suggesting that NaB supplementation effectively improved the integrity and permeability of gut microecology. Finally, the neurotransmitters including differential Tryptophan (Trp) and Kynurenine (Kyn) were found with dietary NaB administration, which showed significantly altered and closely correlated with the gut microbiota composition, demonstrating the complex interactions in the microbiome-gut-brain axis involved in the efficacy of dietary NaB therapy for alcoholic CNS lesions. CONCLUSION Dietary microbial metabolite butyrate supplementation ameliorates chronic alcoholic central nervous damage and improves related memory and cognitive functions through suppressing microglia-mediated neuroinflammation by GPR109A/PPAR-γ/TLR4-NF-κB signaling pathway and modulating microbiota-gut-brain axis.
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Affiliation(s)
- Huiling Wei
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Chunyang Yu
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Chun Zhang
- Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Yi Ren
- Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Li Guo
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Ting Wang
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Feifei Chen
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Yiwei Li
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Xiaoxia Zhang
- College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Hao Wang
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
| | - Juan Liu
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
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21
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Anti-Melanogenesis Effects of a Cyclic Peptide Derived from Flaxseed via Inhibition of CREB Pathway. Int J Mol Sci 2022; 24:ijms24010536. [PMID: 36613979 PMCID: PMC9820828 DOI: 10.3390/ijms24010536] [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: 11/18/2022] [Revised: 12/09/2022] [Accepted: 12/12/2022] [Indexed: 12/30/2022] Open
Abstract
Linosorbs (Los) are cyclic peptides from flaxseed oil composed of the LO mixture (LOMIX). The activity of LO has been reported as being anti-cancer and anti-inflammatory. However, the study of skin protection has still not proceeded. In particular, there are poorly understood mechanisms of melanogenesis to LO. Therefore, we investigated the anti-melanogenesis effects of LOMIX and LO, and its activity was examined in mouse melanoma cell lines. The treatment of LOMIX (50 and 100 μg/mL) and LO (6.25-50 μM) suppressed melanin secretion and synthesis, which were 3-fold increased, in a dose-dependent manner, up to 95%. In particular, [1-9-NαC]-linusorb B3 (LO1) and [1-9-NαC]-linusorb B2 (LO2) treatment (12.5 and 25 μM) highly suppressed the synthesis of melanin in B16F10 cell lines up to 90%, without toxicity. LOMIX and LOs decreased the 2- or 3-fold increased mRNA levels, including the microphthalmia-associated transcription factor (MITF), Tyrosinase, tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2) at the highest concentration (25 μM). Moreover, the treatment of 25 μM LO1 and LO2 inhibited the expression of MITF and phosphorylation of upper regulatory proteins such as CREB and PKA. Taken together, these results suggested that LOMIX and its individual LO could inhibit melanin synthesis via downregulating the CREB-dependent signaling pathways, and it could be used for novel therapeutic materials in hyperpigmentation.
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22
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Butyrate ameliorates inflammation of alcoholic liver disease by suppressing the LPS-TLR4-NF-κB/NLRP3 axis via binding GPR43-β-arrestin2. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
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23
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α-Linolenic acid regulates macrophages via GPR120-NLRP3 inflammasome pathway to ameliorate diabetic rats. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Mueed A, Shibli S, Korma SA, Madjirebaye P, Esatbeyoglu T, Deng Z. Flaxseed Bioactive Compounds: Chemical Composition, Functional Properties, Food Applications and Health Benefits-Related Gut Microbes. Foods 2022; 11:3307. [PMCID: PMC9602266 DOI: 10.3390/foods11203307] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Flaxseed (Linum usitatissimum L.) has gained worldwide recognition as a health food because of its abundance in diverse nutrients and bioactive compounds such as oil, fatty acids, proteins, peptides, fiber, lignans, carbohydrates, mucilage, and micronutrients. These constituents attribute a multitude of beneficial properties to flaxseed that makes its use possible in various applications, such as nutraceuticals, food products, cosmetics, and biomaterials. The importance of these flaxseed components has also increased in modern times because of the newer trend among consumers of greater reliance on a plant-based diet for fulfilling their nutritional requirements, which is perceived to be hypoallergenic, more environmentally friendly, sustainable, and humane. The role of flaxseed substances in the maintenance of a healthy composition of the gut microbiome, prevention, and management of multiple diseases has recently been elucidated in various studies, which have highlighted its importance further as a powerful nutritional remedy. Many articles previously reported the nutritive and health benefits of flaxseed, but no review paper has been published reporting the use of individual flaxseed components in a manner to improve the techno-functional properties of foods. This review summarizes almost all possible applications of flaxseed ingredients in food products from an extensive online literature survey; moreover, it also outlines the way forward to make this utilization even better.
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Affiliation(s)
- Abdul Mueed
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Sahar Shibli
- National Agriculture Research Center, Food Science Research Institute, Islamabad 44000, Pakistan
| | - Sameh A. Korma
- Department of Food Science, Faculty of Agriculture, Zagazig University, Zagazig 44519, Egypt
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China
| | - Philippe Madjirebaye
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Tuba Esatbeyoglu
- Department of Food Development and Food Quality, Institute of Food Science and Human Nutrition, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, 30167 Hannover, Germany
- Correspondence: (T.E.); (Z.D.); Tel.: +49-5117625589 (T.E.); +86-791-88304402 (Z.D.)
| | - Zeyuan Deng
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
- Correspondence: (T.E.); (Z.D.); Tel.: +49-5117625589 (T.E.); +86-791-88304402 (Z.D.)
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25
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Zhang H, Zuo Y, Zhao H, Zhao H, Wang Y, Zhang X, Zhang J, Wang P, Sun L, Zhang H, Liang H. Folic acid ameliorates alcohol-induced liver injury via gut–liver axis homeostasis. Front Nutr 2022; 9:989311. [PMID: 36337656 PMCID: PMC9632181 DOI: 10.3389/fnut.2022.989311] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 09/28/2022] [Indexed: 11/23/2022] Open
Abstract
The gut–liver axis (GLA) plays an important role in the development of alcohol-induced liver injury. Alcohol consumption is typically associated with folic acid deficiency. However, no clear evidence has confirmed the effect of folic acid supplementation on alcohol-induced liver injury via GLA homeostasis. In this study, male C57BL/6J mice were given 56% (v/v) ethanol and 5.0 mg/kg folic acid daily by gavage for 10 weeks to investigate potential protective mechanisms of folic acid in alcohol-induced liver injury via GLA homeostasis. Histopathological and biochemical analyses showed that folic acid improved lipid deposition and inflammation in the liver caused by alcohol consumption and decreased the level of ALT, AST, TG, and LPS in serum. Folic acid inhibited the expression of the TLR4 signaling pathway and its downstream inflammatory mediators in the liver and upregulated the expression of ZO-1, claudin 1, and occludin in the intestine. But compared with the CON group, folic acid did not completely eliminate alcohol-induced intestine and liver injury. Furthermore, folic acid regulated alcohol-induced alterations in gut microbiota. In alcohol-exposed mice, the relative abundance of Bacteroidota was significantly increased, and the relative abundance of unclassified_Lachnospiraceae was significantly decreased. Folic acid supplementation significantly increased the relative abundance of Verrucomicrobia, Lachnospiraceae_NK4A136_group and Akkermansia, and decreased the relative abundance of Proteobacteria. The results of Spearman’s correlation analysis showed that serum parameters and hepatic inflammatory cytokines were significantly correlated with several bacteria, mainly including Bacteroidota, Firmicutes, and unclassified_Lachnospiraceae. In conclusion, folic acid could ameliorate alcohol-induced liver injury in mice via GLA homeostasis to some extent, providing a new idea and method for prevention of alcohol-induced liver injury.
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Affiliation(s)
- Huaqi Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
| | - Yuwei Zuo
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
| | - Huichao Zhao
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
| | - Hui Zhao
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
| | - Yutong Wang
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
| | - Xinyu Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
| | - Jiacheng Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
| | - Peng Wang
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
| | - Lirui Sun
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
| | - Huizhen Zhang
- Qingdao Institute for Food and Drug Control, Qingdao, China
| | - Hui Liang
- Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, Qingdao, China
- *Correspondence: Hui Liang,
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Tang H, Xu Z, Lin J, Sun W, Xie Y. Effect of dietary flaxseed oil on the prognosis of acute anterior cruciate ligament rupture: a randomized placebo-controlled trial. Am J Transl Res 2022; 14:7252-7259. [PMID: 36398219 PMCID: PMC9641443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 08/30/2022] [Indexed: 06/16/2023]
Abstract
OBJECTIVE This study aimed to explore whether dietary flaxseed oil has effects on acute anterior cruciate ligament (ACL) rupture prognosis after surgical reconstruction. METHODS Patients with primary acute ACL rupture diagnosed by magnetic resonance imaging and clinical examination were recruited at Quanzhou First Hospital Affiliated to Fujian Medical University and randomized to either the placebo group or the flaxseed oil group by computer-generated random numbers. Patients in the placebo group took six corn oil capsules daily, while patients in the flaxseed oil group took six flaxseed oil capsules daily. The outcomes were evaluated by specific scales. RESULTS Compared to the placebo group, the flaxseed oil group showed significantly higher International Knee Documentation Committee (IKDC) score (P = 0.007) and total Knee Injury and Osteoarthritis Outcome Score (KOOS) (P = 0.0003) after two-year administration. Patients treated with flaxseed oil exhibited a significantly higher rate of return to sporting level before injury (P = 0.04) and a lower rate of occurrence of giving way (P = 0.04) than those in the placebo group. Patients with flaxseed oil showed significantly less severe adverse events on index knee (P = 0.047). CONCLUSION The administration of dietary flaxseed oil enhanced the prognosis of acute ACL rupture.
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Affiliation(s)
- Haifeng Tang
- Department of Orthopedics, Quanzhou First Hospital Affiliated to Fujian Medical University Anji Road, Quanzhou 362000, Fujian, China
| | - Zhitong Xu
- Department of Orthopedics, Quanzhou First Hospital Affiliated to Fujian Medical University Anji Road, Quanzhou 362000, Fujian, China
| | - Jinding Lin
- Department of Orthopedics, Quanzhou First Hospital Affiliated to Fujian Medical University Anji Road, Quanzhou 362000, Fujian, China
| | - Weijun Sun
- Department of Orthopedics, Quanzhou First Hospital Affiliated to Fujian Medical University Anji Road, Quanzhou 362000, Fujian, China
| | - Yongsong Xie
- Department of Orthopedics, Quanzhou First Hospital Affiliated to Fujian Medical University Anji Road, Quanzhou 362000, Fujian, China
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Beneficial Effects of Flaxseed and/or Mulberry Extracts Supplementation in Ovariectomized Wistar Rats. Nutrients 2022; 14:nu14153238. [PMID: 35956414 PMCID: PMC9370575 DOI: 10.3390/nu14153238] [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: 06/04/2022] [Revised: 07/14/2022] [Accepted: 07/14/2022] [Indexed: 11/29/2022] Open
Abstract
Low endogenous estrogen action causes several injuries. Medicinal plants, such as flaxseed and mulberry, contain substances that have been shown to be effective to the organism. The aim was to verify the effects of flaxseed and/or mulberry extracts on ovariectomized Wistar rats. The animals received supplements of extracts and estrogen or saline by gavage for 60 days and were weighed weekly. Vaginal wash, blood, pituitary, uterus, liver, and kidneys were collected. Phenolic compounds and the antioxidant activity of the extracts, lipid profile, uric acid, liver enzymes, and pituitary weight were measured. Histomorphometric for uterine wall and histopathological analyses for liver and kidney were performed. Flaxseed and mulberry extracts showed great antioxidant activity and large amounts of phenolic compounds. The treatment with extracts had less weight gain, increased pituitary weight, the predominance of vaginal epithelial cells, and reduced TC, LDL-c and lipase activity, similar to estrogen animals. Estrogen or flaxseed + mulberry animals reduced VLDL-c and TAG. HDL-c, uric acid, and liver enzymes did not differ. Estrogen or extracts demonstrated trophic action on the endometrial thickness and have not shown hepatotoxicity or nephrotoxicity. We suggested the beneficial effects of flaxseed and mulberry extract as an alternative to reduce and/or prevent the negative effects caused by low estrogenic action.
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Zhao F, Chen J, Guo R, Zhu J, Gu W, Li S, Li J. Absolute quantitative lipidomics reveals lipids profiling in liver of mice with early-stage alcoholic liver disease. Nutr Metab (Lond) 2022; 19:42. [PMID: 35790996 PMCID: PMC9254412 DOI: 10.1186/s12986-022-00679-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 06/28/2022] [Indexed: 11/10/2022] Open
Abstract
Background Alcoholic liver disease (ALD) is one of the most prevalent chronic liver disease worldwide. Alcohol-induced alterations in hepatic lipids play an important role in ALD develpoment and progression. The present study aimed to thoroughly describe the changes of lipid profiling in liver of mice with early-stage alcoholic liver disease. Methods C57BL/6J male mice aged 7-week were randomized into alcohol-fed (AF) group and pair-fed control group (PF) (n = 10 per group). The early stage of ALD was induced with Lieber-DeCarli liquid diet. The lipids profiling was analyzed by absolute quantitative lipidomics with UHPLC-QTRAP-MS/MS. Results Alcohol intake significantly increased the levels of alanine aminotransferase (ALT) in plasma, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and triacylglycerols (TAG) levels in liver. Lipidomis analyses showed that 41 TAGs were up-regulated and 8 TAGs were down-regulated in response to alcohol intake. The 8 decreased TAGs were with more double bond, longer carbon chain length and mostly contained docosahexaenoic acid (C22:6n-3) and eicosapentaenoic acid (C20:5n-3), compared with the up-regulated TAGs. Furthermore, the down-regulated TAG(56:9)_FA20:5 was inversely associated with ALT and IL-6 levels. In addition, several altered lysophosphatidylcholines (LPC), lysophosphatidylethanolamines (LPE) and hexosylceramides (HCER) were all significantly decreased in response to alcohol consumption, especially HCer(18:1/22:0), with the top reduction among all the down-regulated lipids. Conclusions These findings suggest that not only the up-regulated lipids, alcohol-induced reduction in some specific lipids might also contribute to the ALD development, especially TAG(56:9)_FA20:5 and HCer(18:1/22:0). Their physiological functions and effects on ALD development warrants further investigation. Supplementary Information The online version contains supplementary material available at 10.1186/s12986-022-00679-z.
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Leng J, Tian HJ, Fang Y, Hu YY, Peng JH. Amelioration of Non-Alcoholic Steatohepatitis by Atractylodes macrocephala Polysaccharide, Chlorogenic Acid, and Geniposide Combination Is Associated With Reducing Endotoxin Gut Leakage. Front Cell Infect Microbiol 2022; 12:827516. [PMID: 35865826 PMCID: PMC9294165 DOI: 10.3389/fcimb.2022.827516] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 06/03/2022] [Indexed: 01/01/2023] Open
Abstract
Gut-derived lipopolysaccharide (LPS) leaking through the dysfunctional intestinal barrier contributes to the onset of non-alcoholic steatohepatitis (NASH) by triggering inflammation in the liver. In the present study, a combination consisting of Atractylodes macrocephala polysaccharide (A), chlorogenic acid (C), and geniposide (G) (together, ACG), was shown to ameliorate NASH in mice and reduce hepatic LPS signaling and endotoxemia without decreasing the abundance of identified Gram-negative bacteria through restoring the intestinal tight junctions. Our data indicated that inhibition of LPS gut leakage by the ACG combination contributed to its amelioration of NASH.
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Affiliation(s)
- Jing Leng
- Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hua-jie Tian
- Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
| | - Yi Fang
- Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
| | - Yi-yang Hu
- Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
- Institute of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Jing-hua Peng, ; Yi-yang Hu,
| | - Jing-hua Peng
- Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
- *Correspondence: Jing-hua Peng, ; Yi-yang Hu,
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Zafari N, Velayati M, Fahim M, Maftouh M, Pourali G, Khazaei M, Nassiri M, Hassanian SM, Ghayour-Mobarhan M, Ferns GA, Kiani MA, Avan A. Role of gut bacterial and non-bacterial microbiota in alcohol-associated liver disease: Molecular mechanisms, biomarkers, and therapeutic prospective. Life Sci 2022; 305:120760. [PMID: 35787997 DOI: 10.1016/j.lfs.2022.120760] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/20/2022] [Accepted: 06/28/2022] [Indexed: 12/17/2022]
Abstract
Alcohol-associated liver disease (ALD) comprises a spectrum of liver diseases that include: steatosis to alcohol-associated hepatitis, cirrhosis, and ultimately hepatocellular carcinoma. The pathophysiology and potential underlying mechanisms for alcohol-associated liver disease are unclear. Moreover, the treatment of ALD remains a challenge. Intestinal microbiota include bacteria, fungi, and viruses, that are now known to be important in the development of ALD. Alcohol consumption can change the gut microbiota and function leading to liver disease. Given the importance of interactions between intestinal microbiota, alcohol, and liver injury, the gut microbiota has emerged as a potential biomarker and therapeutic target. This review focuses on the potential mechanisms by which the gut microbiota may be involved in the pathogenesis of ALD and explains how this can be translated into clinical management. We discuss the potential of utilizing the gut microbiota signature as a biomarker in ALD patients. Additionally, we present an overview of the prospect of modulating the intestinal microbiota for the management of ALD.
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Affiliation(s)
- Nima Zafari
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahla Velayati
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mostafa Fahim
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mina Maftouh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ghazaleh Pourali
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammadreza Nassiri
- Recombinant Proteins Research Group, The Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Mohammad Ali Kiani
- Department of Pediatrics, Akbar Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pediatric Gastroenterology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Zhao L, Wang S, Zhang N, Zhou J, Mehmood A, Raka RN, Zhou F, Zhao L. The Beneficial Effects of Natural Extracts and Bioactive Compounds on the Gut-Liver Axis: A Promising Intervention for Alcoholic Liver Disease. Antioxidants (Basel) 2022; 11:antiox11061211. [PMID: 35740108 PMCID: PMC9219895 DOI: 10.3390/antiox11061211] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 06/15/2022] [Accepted: 06/19/2022] [Indexed: 12/10/2022] Open
Abstract
Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. It can cause fatty liver (steatosis), steatohepatitis, fibrosis, cirrhosis, and liver cancer. Alcohol consumption can also disturb the composition of gut microbiota, increasing the composition of harmful microbes and decreasing beneficial ones. Restoring eubiosis or preventing dysbiosis after alcohol consumption is an important strategy in treating ALD. Plant natural products and polyphenolic compounds exert beneficial effects on several metabolic disorders associated with ALD. Natural products and related phytochemicals act through multiple pathways, such as modulating gut microbiota, improving redox stress, and anti-inflammation. In the present review article, we gather information on natural extract and bioactive compounds on the gut-liver axis for the possible treatment of ALD. Supplementation with natural extracts and bioactive compounds promoted the intestinal tight junction, protected against the alcohol-induced gut leakiness and inflammation, and reduced endotoxemia in alcohol-exposed animals. Taken together, natural extracts and bioactive compounds have strong potential against ALD; however, further clinical studies are still needed.
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Affiliation(s)
- Liang Zhao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (S.W.); (A.M.); (R.N.R.)
| | - Shaoxuan Wang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (S.W.); (A.M.); (R.N.R.)
| | - Nanhai Zhang
- Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (N.Z.); (J.Z.)
| | - Jingxuan Zhou
- Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (N.Z.); (J.Z.)
| | - Arshad Mehmood
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (S.W.); (A.M.); (R.N.R.)
- Department of Food Science and Technology, University of Haripur, Haripur 22620, Pakistan
| | - Rifat Nowshin Raka
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (S.W.); (A.M.); (R.N.R.)
| | - Feng Zhou
- Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (N.Z.); (J.Z.)
- Correspondence: (F.Z.); (L.Z.)
| | - Lei Zhao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (L.Z.); (S.W.); (A.M.); (R.N.R.)
- Correspondence: (F.Z.); (L.Z.)
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Fu A, Li J, Ding Q, Guo R, Pi A, Yang W, Chen Y, Dou X, Song Z, Li S. Upregulation of 4-Hydroxynonenal Contributes to the Negative Effect of n-6 Polyunsaturated Fatty Acid on Alcohol-Induced Liver Injury and Hepatic Steatosis. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:6418-6428. [PMID: 35588299 DOI: 10.1021/acs.jafc.2c00852] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
The present study aimed to investigate the effects of saturated fatty acids (SFA) and n-6 polyunsaturated fatty acids (PUFA) on alcoholic liver disease (ALD) and the underlying mechanisms. C57BL/6J male mice were randomly fed a corn oil or palm oil diet (rich in n-6 PUFA and SFA, respectively) with or without ethanol for four weeks (n = 10/group). A series of experiments in vitro with AML-12 hepatocyte were conducted to better elucidate the potential mechanisms underlying the phenomenon observed in animals. Compared with palm oil, corn oil aggravated alcohol-induced liver injury and hepatic steatosis, indicated by a histological analysis and significant elevations of plasma alanine aminotransferase and hepatic triacylglycerol (TG) level. Apoptosis-associated proteins in the ASK1-JNK pathway were significantly enhanced in the liver of mice from the corn oil + ethanol group than in the palm oil + ethanol group. The corn oil + ethanol diet also inhibited the activation of both AMPK and downstream protein acetyl-CoA carboxylase (ACC) and promoted the SREBP-1c expression, subsequently accelerating lipid synthesis. In addition, 4-hydroxynonenal (4-HNE) levels in plasma and liver were significantly upregulated in response to corn oil + ethanol feeding. Interestingly, the in vitro study showed that 4-HNE significantly attenuated cell viability, elevated the expression of cleaved-caspase 3 protein and TG level, and regulated key molecules in ASK1-JNK and AMPK pathways in a dose-dependent manner. In conclusion, the n-6 PUFA diet showed a negative effect on alcohol-induced liver injury and steatosis. It might be related to the upregulation of 4-HNE and subsequent changes of proteins, namely, ASK1, JNK, AMPK, ACC, and SREBP-1c.
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Affiliation(s)
- Ai Fu
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310013, China
- School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310013, China
| | - Jiaomei Li
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310013, China
- Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou 310013, China
| | - Qinchao Ding
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310013, China
- Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou 310013, China
| | - Rui Guo
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310013, China
- Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou 310013, China
| | - Aiwen Pi
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310013, China
- School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310013, China
| | - Wenwen Yang
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310013, China
- School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310013, China
| | - Yanli Chen
- School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310013, China
| | - Xiaobing Dou
- School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310013, China
| | - Zhenyuan Song
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago 60612, Illinois, United States
| | - Songtao Li
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310013, China
- Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou 310013, China
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Henneke L, Schlicht K, Andreani NA, Hollstein T, Demetrowitsch T, Knappe C, Hartmann K, Jensen-Kroll J, Rohmann N, Pohlschneider D, Geisler C, Schulte DM, Settgast U, Türk K, Zimmermann J, Kaleta C, Baines JF, Shearer J, Shah S, Shen-Tu G, Schwarz K, Franke A, Schreiber S, Laudes M. A dietary carbohydrate - gut Parasutterella - human fatty acid biosynthesis metabolic axis in obesity and type 2 diabetes. Gut Microbes 2022; 14:2057778. [PMID: 35435797 PMCID: PMC9037427 DOI: 10.1080/19490976.2022.2057778] [Citation(s) in RCA: 86] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Recent rodent microbiome experiments suggest that besides Akkermansia, Parasutterella sp. are important in type 2 diabetes and obesity development. In the present translational human study, we aimed to characterize Parasutterella in our European cross-sectional FoCus cohort (n = 1,544) followed by validation of the major results in an independent Canadian cohort (n = 438). In addition, we examined Parasutterella abundance in response to a weight loss intervention (n = 55). Parasutterella was positively associated with BMI and type 2 diabetes independently of the reduced microbiome α/β diversity and low-grade inflammation commonly found in obesity. Nutritional analysis revealed a positive association with the dietary intake of carbohydrates but not with fat or protein consumption. Out of 126 serum metabolites differentially detectable by untargeted HPLC-based MS-metabolomics, L-cysteine showed the strongest reduction in subjects with high Parasutterella abundance. This is of interest, since Parasutterella is a known high L-cysteine consumer and L-cysteine is known to improve blood glucose levels in rodents. Furthermore, metabolic network enrichment analysis identified an association of high Parasutterella abundance with the activation of the human fatty acid biosynthesis pathway suggesting a mechanism for body weight gain. This is supported by a significant reduction of the Parasutterella abundance during our weight loss intervention. Together, these data indicate a role for Parasutterella in human type 2 diabetes and obesity, whereby the link to L-cysteine might be relevant in type 2 diabetes development and the link to the fatty acid biosynthesis pathway for body weight gain in response to a carbohydrate-rich diet in obesity development.
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Affiliation(s)
- Lea Henneke
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Kristina Schlicht
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Nadia A. Andreani
- Section of Evolutionary Medicine, Institute for Experimental Medicine University of Kiel, Kiel, Germany,Guest group for evolutionary medicine Max-Planck-Institute of Evolutionary Biology, Plön, Germany
| | - Tim Hollstein
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Tobias Demetrowitsch
- Division of Food Technology, Department of Human Nutrition, University of Kiel, Kiel, Germany
| | - Carina Knappe
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Katharina Hartmann
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Julia Jensen-Kroll
- Division of Food Technology, Department of Human Nutrition, University of Kiel, Kiel, Germany
| | - Nathalie Rohmann
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Daniela Pohlschneider
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Corinna Geisler
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Dominik M. Schulte
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Ute Settgast
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Kathrin Türk
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany
| | - Johannes Zimmermann
- Research Group Medical System Biology, Institute of Experimental Medicine, University of Kiel, Kiel, Germany
| | - Christoph Kaleta
- Research Group Medical System Biology, Institute of Experimental Medicine, University of Kiel, Kiel, Germany
| | - John F. Baines
- Section of Evolutionary Medicine, Institute for Experimental Medicine University of Kiel, Kiel, Germany,Guest group for evolutionary medicine Max-Planck-Institute of Evolutionary Biology, Plön, Germany
| | - Jane Shearer
- Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Faculty Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - Shrushti Shah
- Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Faculty Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - Grace Shen-Tu
- Alberta’s Tomorrow Project, Cancer Control Alberta, Alberta Health Services, Edmonton, AB, Canada
| | - Karin Schwarz
- Division of Food Technology, Department of Human Nutrition, University of Kiel, Kiel, Germany
| | - Andre Franke
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Stefan Schreiber
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Matthias Laudes
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Kiel, Germany,Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, University Medical Centre Schleswig-Holstein, Kiel University, Kiel, Germany,CONTACT Matthias Laudes Institute of Diabetes and Clinical Metabolic Research, University of Kiel, Düsternbrooker Weg 17, 24105Kiel, Germany
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Liu J, Yang D, Wang X, Asare PT, Zhang Q, Na L, Shao L. Gut Microbiota Targeted Approach in the Management of Chronic Liver Diseases. Front Cell Infect Microbiol 2022; 12:774335. [PMID: 35444959 PMCID: PMC9014089 DOI: 10.3389/fcimb.2022.774335] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 02/21/2022] [Indexed: 12/12/2022] Open
Abstract
The liver is directly connected to the intestines through the portal vein, which enables the gut microbiota and gut-derived products to influence liver health. There is accumulating evidence of decreased gut flora diversity and alcohol sensitivity in patients with various chronic liver diseases, including non-alcoholic/alcoholic liver disease, chronic hepatitis virus infection, primary sclerosing cholangitis and liver cirrhosis. Increased intestinal mucosal permeability and decline in barrier function were also found in these patients. Followed by bacteria translocation and endotoxin uptake, these will lead to systemic inflammation. Specific microbiota and microbiota-derived metabolites are altered in various chronic liver diseases studies, but the complex interaction between the gut microbiota and liver is missing. This review article discussed the bidirectional relationship between the gut and the liver, and explained the mechanisms of how the gut microbiota ecosystem alteration affects the pathogenesis of chronic liver diseases. We presented gut-microbiota targeted interventions that could be the new promising method to manage chronic liver diseases.
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Affiliation(s)
- Jing Liu
- Department of Research, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital; The College of Medical Technology, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Dakai Yang
- Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Xiaojing Wang
- School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Paul Tetteh Asare
- Human and Animal Health Unit, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
| | - Qingwen Zhang
- Department of Research, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital; The College of Medical Technology, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Lixin Na
- Department of Research, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital; The College of Medical Technology, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Lei Shao
- School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai, China
- *Correspondence: Lei Shao,
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Chen L, Zhu Y, Hou X, Yang L, Chu H. The Role of Gut Bacteria and Fungi in Alcohol-Associated Liver Disease. Front Med (Lausanne) 2022; 9:840752. [PMID: 35308525 PMCID: PMC8927088 DOI: 10.3389/fmed.2022.840752] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 01/31/2022] [Indexed: 12/12/2022] Open
Abstract
Cirrhosis and liver cancer caused by alcohol-associated liver disease (ALD) are serious threats to people's health. In addition to hepatic cell apoptosis and liver inflammation caused by oxidative stress during alcohol metabolism, intestinal microbiota disorders are also involved in the onset and development of ALD. Ethanol and its' oxidative and non-oxidative metabolites, together with dysbiosis-caused-inflammation, destroys the intestinal barrier. Changes of several microbial metabolites, such as bile acids, short-chain fatty acids, and amino acid, are closely associated with gut dysbiosis in ALD. The alcohol-caused dysbiosis can further influence intestinal barrier-related proteins, such as mucin2, bile acid-related receptors, and aryl hydrocarbon receptor (AhR), and these abnormal changes also participate in the injury of the intestinal barrier and hepatic steatosis. Gut-derived bacteria, fungi, and their toxins, such as lipopolysaccharide (LPS) and β-glucan translocate into the liver through the damaged intestinal barrier and promote the progression of inflammation and fibrosis of ALD. Thus, the prevention of alcohol-induced disruption of intestinal permeability has a beneficial effect on ALD. Currently, multiple therapeutic treatments have been applied to restore the gut microbiota of patients with ALD. Fecal microbial transplantation, probiotics, antibiotics, and many other elements has already shown their ability of restoring the gut microbiota. Targeted approaches, such as using bacteriophages to remove cytolytic Enterococcus faecalis, and supplement with Lactobacillus, Bifidobacterium, or boulardii are also powerful therapeutic options for ALD.
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Affiliation(s)
- Liuying Chen
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yixin Zhu
- Department of Medicine, University of California, San Diego, San Diego, CA, United States
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ling Yang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huikuan Chu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Li Y, Yu Z, Liu Y, Wang T, Liu Y, Bai Z, Ren Y, Ma H, Bao T, Lu H, Wang R, Yang L, Yan N, Yan R, Jia S, Zhang X, Wang H. Dietary α-Linolenic Acid-Rich Flaxseed Oil Ameliorates High-Fat Diet-Induced Atherosclerosis via Gut Microbiota-Inflammation-Artery Axis in ApoE−/− Mice. Front Cardiovasc Med 2022; 9:830781. [PMID: 35295260 PMCID: PMC8918482 DOI: 10.3389/fcvm.2022.830781] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 01/24/2022] [Indexed: 12/12/2022] Open
Abstract
Atherosclerosis (AS) is closely associated with abnormally chronic low-grade inflammation and gut dysbiosis. Flaxseed oil (FO) rich in omega-3 polyunsaturated fatty acids (PUFAs), which are mainly composed of alpha-linolenic acid (ALA, 18:3 omega-3), has been demonstrated to exhibit pleiotropic benefits in chronic metabolic diseases. However, the impact of dietary ALA-rich FO on AS and its associated underlying mechanisms remain poorly understood. Thus, the present study was designed as two phases to investigate the effects in atherosclerotic Apolipoprotein E (ApoE)−/− mice. In the initial portion, the ApoE−/− mice were randomly allocated to three groups: control group (CON), model group (MOD), and FO-fed model group (MOD/FO) and were treated for 12 weeks. The second phase used antibiotic (AB)-treated ApoE−/− mice were divided into two groups: AB-treated model group (AB/MOD) and FO-fed AB-treated model group (AB/FO). In the results, the dietary ALA-rich FO administration ameliorated atherosclerotic lesion, as well as the parameters of AS (body weights (BWs) and the total bile acids (TBA). Chronic systemic/vascular inflammatory cytokines and in situ macrophages (Mψs) were reduced with FO intervention. In addition, the FO improved the gut integrity and permeability by decreasing the plasma lipopolysaccharide (LPS). Moreover, gut dysbiosis and metabolites [short-chain fatty acids (SCFAs) and bile acids (BAs)] in AS were modulated after FO treatment. Intriguingly, during an AB-treated condition, a significantly weakened amelioration of FO-treated on AS proposed that the intestinal microbiota contributed to the FO effects. A correlation analysis showed close relationships among gut bacteria, metabolites, and inflammation. Collectively, these results suggested that the dietary ALA-rich FO ameliorated the AS in ApoE−/− mice via the gut microbiota-inflammation-artery axis.
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Affiliation(s)
- Yiwei Li
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China
| | - Zhi Yu
- Department of Anesthesiology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
| | - Yuanyuan Liu
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China
| | - Ting Wang
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China
| | - Yajuan Liu
- Clinical Medical College, Ningxia Medical University, Yinchuan, China
- Department of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, China
| | - Zhixia Bai
- Clinical Medical College, Ningxia Medical University, Yinchuan, China
- Department of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, China
| | - Yi Ren
- Clinical Medical College, Ningxia Medical University, Yinchuan, China
| | - Huiyan Ma
- Clinical Medical College, Ningxia Medical University, Yinchuan, China
- Department of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, China
| | - Ting Bao
- Clinical Medical College, Ningxia Medical University, Yinchuan, China
| | - Haixia Lu
- Department of Anesthesiology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
| | - Rui Wang
- Clinical Medical College, Ningxia Medical University, Yinchuan, China
| | - Libo Yang
- Department of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, China
| | - Ning Yan
- Department of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, China
| | - Ru Yan
- Department of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, China
| | - Shaobin Jia
- Department of Cardiovascular Diseases, Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, China
- Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, China
| | - Xiaoxia Zhang
- College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, China
- *Correspondence: Xiaoxia Zhang
| | - Hao Wang
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China
- Hao Wang
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Li D, Luo F, Guo T, Han S, Wang H, Lin Q. Targeting NF-κB pathway by dietary lignans in inflammation: expanding roles of gut microbiota and metabolites. Crit Rev Food Sci Nutr 2022; 63:5967-5983. [PMID: 35068283 DOI: 10.1080/10408398.2022.2026871] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Inflammation is a major factor affecting human health. Nuclear factor-kappa B (NF-κB) plays a vital role in the development of inflammation, and the promoters of most inflammatory cytokine genes have NF-κB-binding sites. Targeting NF-κB could be an exciting route for the prevention and treatment of inflammatory diseases. As important constituents of natural plants, lignans are proved to have numerous biological functions. There are growing pieces of evidence demonstrate that lignans have the potential anti-inflammatory activities. In this work, the type, structure and source of lignans and the influence on mitigating the inflammation are systematically summarized. This review focuses on the targeting NF-κB signaling pathway in the inflammatory response by different lignans and their molecular mechanisms. Lignans also regulate gut microflora and change gut microbial metabolites, which exert novel pathway to prevent NF-κB activation. Taken together, lignans target NF-κB with various mechanisms to inhibit inflammatory cytokine expressions in the inflammatory response. It will provide a scientific theoretical basis for further research on the anti-inflammatory effects of lignans and the development of functional foods.
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Affiliation(s)
- Dan Li
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha, China
| | - Feijun Luo
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha, China
| | - Tianyi Guo
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha, China
| | - Shuai Han
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha, China
| | - Hanqing Wang
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha, China
| | - Qinlu Lin
- Hunan Key Laboratory of Grain-oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha, China
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Xia H, Shi X, Zhou B, Sui J, Yang C, Liu H, Yang L, Wang S, Sun G. Milled flaxseed-added diets ameliorated hepatic inflammation by reducing gene expression of TLR4/NF-κB pathway and altered gut microbiota in STZ-induced type 1 diabetic mice. FOOD SCIENCE AND HUMAN WELLNESS 2022. [DOI: 10.1016/j.fshw.2021.07.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Yawale P, Upadhyay N, Ganguly S, Kumar S. A comprehensive review on recent novel food and industrial applications of flaxseed: 2014 onwards. FOOD AND FEED RESEARCH 2022. [DOI: 10.5937/ffr0-35420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Flaxseed or linseed is an oilseed obtained from a plant, known as the flax (Linum usitatissimum). It is a valuable source of various bioactive components such as omega-3 polyunsaturated fatty acids, proteins, lignans, dietary fibres and phytochemicals. The in-vivo, in-vitro studies and research on human subjects and in animal models, conducted throughout the globe, on health benefits associated with the consumption of various forms of flaxseed are discussed in this review. It provides an insight into recent developments and potential applications of flaxseeds in the form of whole seeds, meals, flour or oil in an array of food and feed products and non-food industrial applications. The details about novel health benefits associated with flaxseeds and information related to commercially available flaxseed-based i.e. enriched products are also the salient feature of the review. Here, we have provided the state of the art of most recent comprehensive information post the first detailed review on flaxseed as a modern food released in 2014.
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Yawale P, Upadhyay N, Ganguly S, Kumar S. A comprehensive review on recent novel food and industrial applications of flaxseed: 2014 onwards. FOOD AND FEED RESEARCH 2022. [DOI: 10.5937/ffr49-35420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Flaxseed or linseed is an oilseed obtained from a plant, known as the flax (Linum usitatissimum). It is a valuable source of various bioactive components such as omega-3 polyunsaturated fatty acids, proteins, lignans, dietary fibres and phytochemicals. The in-vivo, in-vitro studies and research on human subjects and in animal models, conducted throughout the globe, on health benefits associated with the consumption of various forms of flaxseed are discussed in this review. It provides an insight into recent developments and potential applications of flaxseeds in the form of whole seeds, meals, flour or oil in an array of food and feed products and non-food industrial applications. The details about novel health benefits associated with flaxseeds and information related to commercially available flaxseed-based i.e. enriched products are also the salient feature of the review. Here, we have provided the state of the art of most recent comprehensive information post the first detailed review on flaxseed as a modern food released in 2014.
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Magalhães P, Domingues RM, Alves E. Hemp Seeds, Flaxseed, and Açaí Berries: Health Benefits and Nutritional
Importance with Emphasis on the Lipid Content. CURRENT NUTRITION & FOOD SCIENCE 2022. [DOI: 10.2174/1573401317666210624142643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Abstract:
Some plant seeds and berries have gained increased recognition due to their wide
variety of bioactive compounds. Many of these foods are rich in lipids with high nutritional
value, of which n-3 and n-6 essential fatty acids stand out. However, knowledge of the chemical
composition and biological activity of these compounds and their value as a source of
healthy lipids is far from being fully explored.
The benefits of the intake of hemp seeds, flaxseed, and açaí berries, considered functional
foods, have been compiled in this review. Likewise, their general chemical composition will be
described to evaluate their relevance in a healthy diet, highlighting their lipid components and
health lipid indices.
The fibres and essential fatty acids of hemp seeds and flaxseed and the antioxidant properties
of açaí berries provide them protective roles against several chronic non-communicable diseases
and represent significant beneficial effects that add value to these healthy natural products.
More research is needed to deepen the knowledge on their lipids’ molecular composition and
bioactivity.
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Affiliation(s)
- Pedro Magalhães
- Department of Chemistry, Mass Spectrometry Centre, LAQV-REQUIMTE, University of Aveiro, Aveiro, Portugal
| | - Rosário M. Domingues
- Department of Chemistry, Mass Spectrometry Centre, LAQV-REQUIMTE, University of Aveiro, Aveiro, Portugal
- Department of Chemistry, Centre for Environmental and Marine Studies, CESAM, University of Aveiro, Aveiro,
Portugal
| | - Eliana Alves
- Department of Chemistry, Mass Spectrometry Centre, LAQV-REQUIMTE, University of Aveiro, Aveiro, Portugal
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Li BY, Li HY, Zhou DD, Huang SY, Luo M, Gan RY, Mao QQ, Saimaiti A, Shang A, Li HB. Effects of Different Green Tea Extracts on Chronic Alcohol Induced-Fatty Liver Disease by Ameliorating Oxidative Stress and Inflammation in Mice. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:5188205. [PMID: 35003517 PMCID: PMC8731271 DOI: 10.1155/2021/5188205] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 10/06/2021] [Accepted: 12/05/2021] [Indexed: 12/20/2022]
Abstract
Alcoholic fatty liver disease (AFLD) is a common chronic liver disease and has become a critical global public health problem. Green tea is a popular drink worldwide and contains several bioactive compounds. Different green teas could contain diverse compounds and possess distinct bioactivities. In the present study, the effects of 10 green teas on chronic alcohol induced-fatty liver disease in mice were explored and compared. The results showed that several green teas significantly reduced triacylglycerol levels in serum and liver as well as the aminotransferase activities in mice at a dose of 200 mg/kg, suggesting that they possess hepatoprotective effects. Moreover, several green teas remarkably decreased the expression of cytochrome P450 2E1, the levels of malondialdehyde and 4-hydroxynonenoic acid, and the contents of proinflammatory cytokines, indicating that they could alleviate oxidation damage and inflammation induced by chronic alcohol exposure. In addition, Seven Star Matcha Tea and Selenium-Enriched Matcha Tea could increase glutathione level. Furthermore, the main phytochemical components in green teas were determined and quantified by high-performance liquid chromatography, and the correlation analysis showed that gallic acid, gallocatechin, catechin, chlorogenic acid, and epigallocatechin gallate might at least partially contribute to protective effects on AFLD. In conclusion, Selenium-Enriched Chaoqing Green Tea, Xihu Longjing Tea, Taiping Houkui Tea, and Selenium-Enriched Matcha Tea showed the strongest preventive effects on AFLD. This research also provides the public with new insights about the effects of different green teas on AFLD.
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Affiliation(s)
- Bang-Yan Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
| | - Hang-Yu Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
| | - Dan-Dan Zhou
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
| | - Si-Yu Huang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
| | - Min Luo
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
| | - Ren-You Gan
- Research Center for Plants and Human Health, Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610213, China
| | - Qian-Qian Mao
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
| | - Adila Saimaiti
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
| | - Ao Shang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
| | - Hua-Bin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
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Sun Y, Kang K, Li YL, Sang LX, Chang B. Tea polyphenols protect mice from acute ethanol-Induced liver injury by modulating the gut microbiota and short-chain fatty acids. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104865] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Wang L, Wang Y, Zhang P, Song C, Pan F, Li G, Peng L, Yang Y, Wei Z, Huang F. Gut microbiota changes in patients with spondyloarthritis: A systematic review. Semin Arthritis Rheum 2021; 52:151925. [PMID: 34844732 DOI: 10.1016/j.semarthrit.2021.11.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 10/30/2021] [Accepted: 11/04/2021] [Indexed: 12/22/2022]
Abstract
OBJECTIVE Gut microbiota has been proposed as a pivotal role in the progression of Spondyloarthritis (SpA), however diverse results remain to be synthesized. We performed a systematic review to collect evidence on the characteristic of the gut microbiota in patients with SpA, as compared to controls. METHODS We systematically searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases, through June 1, 2021 for studies that compared gut microbiota of cases with SpA versus healthy controls. RESULTS Of 3756 records identified, 28 studies from 23 articles were included in the analysis. Results of β-diversity showed SpA patients hold a significantly different microbial composition compared with controls. Several taxa-level differences of gut microbiota between SpA (and its subtypes) cases and controls were identified. Fourteen studies including only patients with ankylosing spondylitis (AS) reported increased amounts of Actinobacteria, Dialister, Streptococcus, and Clostridium bolteae, and decreased amounts of Bacteroidales and Parasutterella in AS cases versus controls in ≥ 3 studies. Dialister invisus was increased in axial-SpA cases versus controls in 3 studies. Bacteroides fragilis was increased in enthesitis-related arthritis (ERA) cases versus controls in 2 studies. For all SpA studies, Proteobacteria, Enterobacteriaceae, and Bacteroidaceae were increased, whereas Bacteroidetes, Bacteroidales, and Akkermansia were decreased in cases versus controls in ≥ 3 studies. Over 40% of the studies showed comparable data of both sex and age between cases and controls. CONCLUSION The microbial characteristics of SpA summarized in the systematic review laid the groundwork for evidence-based microbial treatment. The microbial variance among subtypes of SpA remains to be explored. Further studies are needed to elucidate how the altered microbiota participate in the pathogenesis of SpA.
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Affiliation(s)
- Lei Wang
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China
| | - Yiwen Wang
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Pei Zhang
- School of Medicine, Nankai University, Tianjin, China
| | - Chuan Song
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China
| | - Fei Pan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Gang Li
- Health Service Department of the Guard Bureau of the Joint Staff Department, Beijing, China
| | - Lihua Peng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yunsheng Yang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Zhimin Wei
- Health Service Department of the Guard Bureau of the Joint Staff Department, Beijing, China.
| | - Feng Huang
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
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Gao B, Zhu Y, Gao N, Shen W, Stärkel P, Schnabl B. Integrative Analysis of Metabolome and Microbiome in Patients with Progressive Alcohol-Associated Liver Disease. Metabolites 2021; 11:metabo11110766. [PMID: 34822424 PMCID: PMC8621614 DOI: 10.3390/metabo11110766] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 11/05/2021] [Accepted: 11/07/2021] [Indexed: 12/12/2022] Open
Abstract
Alcohol-associated liver disease is one of the most prevalent diseases around the world, with 10–20% of patients developing progressive liver disease. To identify the complex and correlated nature of metabolic and microbial data types in progressive liver disease, we performed an integrated analysis of the fecal and serum metabolomes with the gut microbiome in a cohort of 38 subjects, including 15 patients with progressive liver disease, 16 patients with non-progressive liver disease, and 7 control subjects. We found that although patients were generally clustered in three groups according to disease status, metabolites showed better separation than microbial species. Furthermore, eight serum metabolites were correlated with two microbial species, among which seven metabolites were decreased in patients with progressive liver disease. Five fecal metabolites were correlated with three microbial species, among which four metabolites were decreased in patients with progressive liver disease. When predicting progressive liver disease from non-progressive liver disease using correlated metabolic and microbial signatures with the random forest model, correlated serum metabolites and microbial species showed great predictive power, with the area under the receiver operating characteristic curve achieving 0.91. The multi-omics signatures identified in this study are helpful for the early identification of patients with progressive alcohol-associated liver disease, which is a key step for therapeutic intervention.
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Affiliation(s)
- Bei Gao
- School of Marine Sciences, Nanjing University of Information Science and Technology, Nanjing 210044, China;
- Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA;
| | - Yixin Zhu
- Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA;
| | - Nan Gao
- School of Biological and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, China;
| | - Weishou Shen
- School of Environmental Science and Engineering, Nanjing University of Information Science and Technology, Nanjing 210044, China;
- Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, Collaborative Inovation Center of Atmospheric Environment and Equipment Technology, Nanjing 210044, China
| | - Peter Stärkel
- Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, 1200 Brussels, Belgium
- Department of Hepato-Gastroenterology, St. Luc University Hospital, Université Catholique de Louvain, 1200 Brussels, Belgium
- Correspondence: (P.S.); (B.S.)
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA;
- Department of Medicine, VA San Diego Healthcare System, San Diego, CA 92161, USA
- Correspondence: (P.S.); (B.S.)
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Kuracha MR, Thomas P, Tobi M, McVicker BL. Role of cell-free network communication in alcohol-associated disorders and liver metastasis. World J Gastroenterol 2021; 27:7080-7099. [PMID: 34887629 PMCID: PMC8613644 DOI: 10.3748/wjg.v27.i41.7080] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 07/02/2021] [Accepted: 09/30/2021] [Indexed: 02/06/2023] Open
Abstract
The aberrant use of alcohol is a major factor in cancer progression and metastasis. Contributing mechanisms include the systemic effects of alcohol and the exchange of bioactive molecules between cancerous and non-cancerous cells along the brain-gut-liver axis. Such interplay leads to changes in molecular, cellular, and biological functions resulting in cancer progression. Recent investigations have examined the role of extracellular vesicles (EVs) in cancer mechanisms in addition to their contribution as diagnostic biomarkers. Also, EVs are emerging as novel cell-free mediators in pathophysiological scenarios including alcohol-mediated gut microbiome dysbiosis and the release of nanosized EVs into the circulatory system. Interestingly, EVs in cancer patients are enriched with oncogenes, miRNA, lipids, and glycoproteins whose delivery into the hepatic microenvironment may be enhanced by the detrimental effects of alcohol. Proof-of-concept studies indicate that alcohol-associated liver disease is impacted by the effects of exosomes, including altered immune responses, reprogramming of stromal cells, and remodeling of the extracellular matrix. Moreover, the culmination of alcohol-related changes in the liver likely contributes to enhanced hepatic metastases and poor outcomes for cancer patients. This review summarizes the numerous aspects of exosome communications between organs with emphasis on the relationship of EVs in alcohol-associated diseases and cancer metastasis. The potential impact of EV cargo and release along a multi-organ axis is highly relevant to the promotion of tumorigenic mechanisms and metastatic disease. It is hypothesized that EVs target recipient tissues to initiate the formation of prometastatic niches and cancer progression. The study of alcohol-associated mechanisms in metastatic cancers is expected to reveal a better understanding of factors involved in the growth of secondary malignancies as well as novel approaches for therapeutic interventions.
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Affiliation(s)
- Murali R Kuracha
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Peter Thomas
- Department of Surgery, Creighton University School of Medicine, Omaha, NE 68178, United States
| | - Martin Tobi
- Research and Development Service, Detroit VAMC, Detroit, MI 48201, United States
- Department of Medicine, Central Michigan University College of Medicine, Detroit, MI 48201, United States
| | - Benita L McVicker
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
- Research Service, Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
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Li Y, Li J, Xu F, Liu G, Pang B, Liao N, Li H, Shi J. Gut microbiota as a potential target for developing anti-fatigue foods. Crit Rev Food Sci Nutr 2021:1-16. [PMID: 34592876 DOI: 10.1080/10408398.2021.1983768] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Fatigue has many negative effects on human health. As such, it is desirable to develop anti-fatigue foods and understand the mechanisms of their action. Based on a comprehensive review of the literature, this article discusses the important roles of gut microbiota in fatigue and anti-fatigue. Studies have shown that an increase in pathogenic bacteria and a decrease in beneficial bacteria co-exist when fatigue is present in both rodents and humans, whereas changes in gut microbiota were reported after intervention with anti-fatigue foods. The roles of gut microbiota in the activities of anti-fatigue foods can also be explained in the causes and the effects of fatigue. Among the causes of fatigue, the accumulation of lactic acid, decrease of energy, and reduction of central nervous system function were related to gut microbiota metabolism. Among the harmful effects of fatigue, oxidative stress, inflammation, and intestinal barrier dysfunction were related to gut microbiota dysbiosis. Furthermore, gut microbiota, together with anti-fatigue foods, can inhibit pathogen growth, convert foods into highly anti-oxidative or anti-inflammatory products, produce short-chain fatty acids, maintain intestinal barrier integrity, inhibit intestinal inflammation, and stimulate the production of neurotransmitters that regulate the central nervous system. Therefore, it is believed that gut microbiota play important roles in the activities of anti-fatigue foods and may provide new insights on the development of anti-fatigue foods.
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Affiliation(s)
- Yinghui Li
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China
| | - Junjun Li
- College of Enology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China
| | - Fengqin Xu
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China
| | - Guanwen Liu
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China
| | - Bing Pang
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China
| | - Ning Liao
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China
| | - Huixin Li
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China
| | - Junling Shi
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China
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Abdelhamid AM, Elsheakh AR, Suddek GM, Abdelaziz RR. Telmisartan alleviates alcohol-induced liver injury by activation of PPAR-γ/ Nrf-2 crosstalk in mice. Int Immunopharmacol 2021; 99:107963. [PMID: 34273638 DOI: 10.1016/j.intimp.2021.107963] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 07/01/2021] [Accepted: 07/04/2021] [Indexed: 02/07/2023]
Abstract
Excessive consumption of alcohol may induce severe liver damage, in part via oxidative stress and inflammatory responses, which implicates these processes as potential therapeutic approaches. Prior literature has shown that Telmisartan (TEL) may provide protective effects, presumably mediated by its anti-oxidant and anti-inflammatory activities. The purpose of this study was to determine TEL's hepatoprotective effects and to identify its possible curative mechanisms in alcoholic liver disease. A mouse chronic alcohol plus binge feedings model was used in the current study for induction of alcoholic liver disease (ALD). Our results showed that TEL (10 mg/kg/day) has the ability to reduce serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). TEL also increased the activity of superoxide dismutase (SOD) and glutathione (GSH) with concomitant reduction of nitric oxide (NO) malonaldehyde (MDA) in the liver homogenate. Moreover, TEL downregulated nuclear factor kappa B (NF-κB) expression and decreased liver content of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). These anti-inflammatory and anti-oxidant activities were associated with a significant increase in the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), peroxisome proliferator-activated receptors -γ (PPAR-γ), and heme oxygenase-1 (Hmox-1). In conclusion, TEL's hepatoprotective effects against ALD may be attributable to its anti-inflammatory and anti-oxidant activities which may be in part via the modulation of PPAR-γ/ Nrf-2/ NF-κB crosstalk.
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Affiliation(s)
- Amir Mohamed Abdelhamid
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Egypt; Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Egypt
| | - Ahmed Ramadan Elsheakh
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Egypt
| | - Ghada Mohamed Suddek
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Egypt
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Zhang H, Gao X, Li K, Liu Y, Hettiarachichi DS, Sunderland B, Li D. Sandalwood seed oil ameliorates hepatic insulin resistance by regulating the JNK/NF-κB inflammatory and PI3K/AKT insulin signaling pathways. Food Funct 2021; 12:2312-2322. [PMID: 33617622 DOI: 10.1039/d0fo03051a] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Sandalwood (santalum spicatum) seed oil (SSO) is rich in ximenynic acid. The aim of the present study was to investigate the effect of SSO on high-fat/high-sucrose diet (HFHSD) induced insulin resistance (IR) in comparison with fish oil (FO), sunflower oil (SO) and linseed oil (LO). Fifty male Sprague-Dawley rats were randomly divided into five dietary groups: standard chow diet (controls), HFHSD plus 7% SSO, HFHSD plus 7% FO, HFHSD plus 7% SO and HFHSD plus 7% LO. After 12 weeks of feeding, the rats were sacrificed, and the serum parameters, hepatic lipids and underlying molecular mechanisms were studied. SSO, FO or LO significantly prevented glucose intolerance, hyperglycaemia, obesity, and hepatic lipid accumulation, and decreased the homeostasis model assessment of IR (HOMA-IR) and the serum levels of pro-inflammatory factors (IL-6, IL-1β and TNF-α) compared with SO. In addition, SSO activated the PI3K/AKT insulin signaling pathway and down-regulated the JNK/NF-κB inflammatory signaling pathway in the liver. In summary, our results proved that SSO exerted an ameliorative effect on IR by regulating the hepatic inflammation related blockage of the insulin signaling pathway in the rats.
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Affiliation(s)
- Huijun Zhang
- Institute of Nutrition & Health, College of Public Health, Qingdao University, Qingdao, China.
| | - Xiang Gao
- Institute of Nutrition & Health, College of Public Health, Qingdao University, Qingdao, China. and College of Life Sciences, Qingdao University, Qingdao, China
| | - Kelei Li
- Institute of Nutrition & Health, College of Public Health, Qingdao University, Qingdao, China.
| | - Yandi Liu
- School of Pharmacy, Curtin University, Perth, Australia
| | | | | | - Duo Li
- Institute of Nutrition & Health, College of Public Health, Qingdao University, Qingdao, China. and Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China
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50
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Li B, Mao Q, Zhou D, Luo M, Gan R, Li H, Huang S, Saimaiti A, Shang A, Li H. Effects of Tea against Alcoholic Fatty Liver Disease by Modulating Gut Microbiota in Chronic Alcohol-Exposed Mice. Foods 2021; 10:1232. [PMID: 34071491 PMCID: PMC8228948 DOI: 10.3390/foods10061232] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 05/24/2021] [Accepted: 05/26/2021] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota dysbiosis has been a crucial contributor to the pathogenesis of alcoholic fatty liver disease (AFLD). Tea is a popular beverage worldwide and exerts antioxidant and anti-inflammatory activities, as well as hepatoprotective effects. However, the potential role of gut microbiota regulated by tea in the prevention and management of AFLD remains unclear. Here, the protective effects of oolong tea, black tea, and dark tea on AFLD and its regulation of gut microbiota in chronic alcohol-exposed mice were explored and investigated. The results revealed that tea supplementation significantly prevented liver steatosis, decreased oxidative stress and inflammation, and modulated gut microbiota in chronic alcohol-exposed mice, especially oolong tea and dark tea. However, black tea showed less effectiveness against liver injury caused by alcohol. Moreover, the diversity, structure and composition of chronic alcohol-disrupted gut microbiota were restored by the supplementation of oolong tea and dark tea based on the analysis of gut microbiota. Furthermore, the relationship between liver injury biochemical indicators and gut microbiota indicated that some specific bacteria, such as Bacteroides, Alloprevotella, and Parabacteroides were closely associated with AFLD. In addition, the phytochemical components in tea extracts were measured by high-performance liquid chromatography, which could contribute to preventive effects on AFLD. In summary, oolong tea and dark tea could prevent chronic alcohol exposure-induced AFLD by modulating gut microbiota.
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Affiliation(s)
- Bangyan Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Qianqian Mao
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Dandan Zhou
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Min Luo
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Renyou Gan
- Research Center for Plants and Human Health, Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610213, China;
- Key Laboratory of Coarse Cereal Processing (Ministry of Agriculture and Rural Affairs), Sichuan Engineering & Technology Research Center of Coarse Cereal Industralization, Chengdu University, Chengdu 610106, China
| | - Hangyu Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Siyu Huang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Adila Saimaiti
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Ao Shang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Huabin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
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