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Chen X, Memory Kunda LS, Li X, Wang N, Huang Y, Hao Y, He Q, Liao W, Chen J. A Comprehensive Review of Beneficial Effects of Phytosterols on Glycolipid Metabolism and Related Mechanisms. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:3826-3841. [PMID: 39927454 DOI: 10.1021/acs.jafc.4c10375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/11/2025]
Abstract
Phytosterols are widely distributed in various plant foods, such as nuts, grains, vegetables, and so on. Phytosterols have been broadly applied in functional foods, supplements, and pharmaceutical products due to their excellent cholesterol-lowering effect. Besides the cholesterol-lowering effect, recently, phytosterols have been found to exert a beneficial effect on glycolipid metabolism, which contributes to multiple metabolic diseases, such as diabetes, cardiovascular disease, and fatty liver. Constant development of new drugs with a single target fails to effectively curb the occurrence of metabolic diseases and complications, such as multiple organ damage, and phytosterols attract special attention due to varieties of biological activities, especially the regulation of glycolipid metabolism through multiple targets. Present review gives a comprehensive review of the effects of phytosterols on glycolipid metabolism and related mechanism. We also review the promising update of phytosterol in the treatment of two major metabolic diseases, including diabetes and nonalcohol fatty liver disease. This review can help to extend the understanding of the potential of phytosterols for mixed dyslipidemia and related metabolic diseases.
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Affiliation(s)
- Xiao Chen
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Lwara Sophie Memory Kunda
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Xinyang Li
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Nan Wang
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Yangjia Huang
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Yuting Hao
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Qi He
- School of Public Health, Southern Medical University, Guangzhou, Guangdong 510640, China
| | - Wenzhen Liao
- Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Jinyuan Chen
- Institute of Scientific Research, Southern Medical University, Guangzhou 510515, China
- TCM-Integrated Hospital, Southern Medical University, Guangzhou 510515, China
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Gillet R, Cerda-Drago TG, Brañes MC, Valenzuela R. Submicron Dispersions of Phytosterols Reverse Liver Steatosis with Higher Efficacy than Phytosterol Esters in a Diet Induced-Fatty Liver Murine Model. Int J Mol Sci 2025; 26:564. [PMID: 39859279 PMCID: PMC11766071 DOI: 10.3390/ijms26020564] [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: 12/06/2024] [Revised: 01/06/2025] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Consumption of phytosterols is a nutritional strategy employed to reduce cholesterol absorption, but recent research shows that their biological activity might go beyond cholesterol reduction for the treatment of metabolic dysfunction-associated fatty liver disease (MAFLD), and novel phytosterol formulations, such as submicron dispersions, could improve these effects. We explored the therapeutic activity of phytosterols, either formulated as submicron dispersions of phytosterols (SDPs) or conventional phytosterol esters (PEs), in a mouse model of MAFLD. MAFLD was induced in mice by atherogenic diet (AD) feeding. The reversion of distorted serum and liver parameter values after a period of AD feeding was investigated after supplementation of the AD with SDPs, PEs, or a placebo (PT). Additionally, the metabolic parameters of fatty acid synthesis, fatty acid oxidation, and inflammation were studied to understand the mechanism of action of phytosterols. AD supplementation with SDPs was shown to reduce liver fat, along with showing a significant improvement in liver triglycerides (TGs), free fatty acids (FFAs), and liver cholesterol levels. These results were reinforced by the analyses of the liver steatosis scores, and liver histologies, where SDP intervention showed a consistent improvement. Treatment with PEs showed slighter effects in the same analyses, and no effects were observed with the PT treatment. Additionally, SDP intervention reversed, with a higher efficacy than PEs, the effect of AD on the serum levels of TGs, total- and LDL-cholesterol levels, and glucose levels. And, exceptionally, while SDP improved HDL-cholesterol serum levels, PEs did not show any effect on this parameter. We provide evidence for the therapeutical activity of phytosterols in MAFLD beyond the regulation of cholesterol levels, which is increased when the phytosterols are formulated as submicron dispersions compared to ester formulations.
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Affiliation(s)
- Raimundo Gillet
- Naturalis Research Consortium, Santiago 8700548, Chile; (R.G.); (T.G.C.-D.); (M.C.B.)
| | - Tomás G. Cerda-Drago
- Naturalis Research Consortium, Santiago 8700548, Chile; (R.G.); (T.G.C.-D.); (M.C.B.)
| | - María C. Brañes
- Naturalis Research Consortium, Santiago 8700548, Chile; (R.G.); (T.G.C.-D.); (M.C.B.)
| | - Rodrigo Valenzuela
- Department of Nutrition, Faculty of Medicine, University of Chile, Santiago 8380000, Chile
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Sun J, Jin X, Li Y. OTUD7B inhibited hepatic injury from NAFLD by inhibiting K48-linked ubiquitination and degradation of β-catenin. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167555. [PMID: 39520879 DOI: 10.1016/j.bbadis.2024.167555] [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: 06/07/2024] [Revised: 09/27/2024] [Accepted: 10/26/2024] [Indexed: 11/16/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the prevalent liver disease. Ovarian tumor domain-containing 7B (OTUD7B) is a deubiquitinating enzyme and its role in NAFLD remains unclear. In high-fat diet (HFD)-induced NAFLD mouse model and palmitic acid (PA)-treated HepG2 cells, OTUD7B expression was decreased. Adenoviral overexpression of OTUD7B in mice resulted in reduced body weight and liver injury, with decreased serum aminotransferase (ALT) and aspartate aminotransferase (AST) levels. OTUD7B overexpression attenuated hepatic lipid deposition (serum TG, TC, LDL-C, HDLC, and FFA levels), which might be through the suppression of lipogenesis and β-oxidation-related genes. The contents of hepatic inflammatory factors (TNF-α, IL-6, and IL-1β) were decreased following OTUD7B overexpression in NAFLD mice. A mechanism study indicated that the protective effect of OTUD7B overexpression might be associated with β-catenin signal activation. OTUD7B overexpression promoted PA-induced β-catenin activity in TopFlash assay, and increased total β-catenin and c-myc levels in cells. The increase in β-catenin levels was contributed to the stabilization via inhibiting K48-linked ubiquitination and proteasomal degradation by OTUD7B. NR4A2 role in NASH has been proved. NR4A2 ChIP-seq and RNA-seq data excluded transcriptional regulation of NR4A2 to OTUD7B, and it was experimentally evidenced that NR4A2 bound to OTUD7B promoter region and positively transcriptionally regulate OTUD7B expression. In summary, OTUD7B overexpression ameliorated hepatic inflammation and steatosis in NAFLD. The possible mechanism of OTUD7B might be through the inhibition of β-catenin degradation by removing K48-linked ubiquitination, which might be regulated by NR4A2.
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Affiliation(s)
- Jing Sun
- Department of Gastroenterology, the First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xiuli Jin
- Department of Gastroenterology, the First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yiling Li
- Department of Gastroenterology, the First Hospital of China Medical University, Shenyang, Liaoning, China.
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Svobodová G, Horní M, Velecká E, Boušová I. Metabolic dysfunction-associated steatotic liver disease-induced changes in the antioxidant system: a review. Arch Toxicol 2025; 99:1-22. [PMID: 39443317 PMCID: PMC11748479 DOI: 10.1007/s00204-024-03889-x] [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: 07/11/2024] [Accepted: 10/09/2024] [Indexed: 10/25/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition characterized by liver steatosis, inflammation, consequent fibrosis, and cirrhosis. Chronic impairment of lipid metabolism is closely related to oxidative stress, leading to cellular lipotoxicity, mitochondrial dysfunction, and endoplasmic reticulum stress. The detrimental effect of oxidative stress is usually accompanied by changes in antioxidant defense mechanisms, with the alterations in antioxidant enzymes expression/activities during MASLD development and progression reported in many clinical and experimental studies. This review will provide a comprehensive overview of the present research on MASLD-induced changes in the catalytic activity and expression of the main antioxidant enzymes (superoxide dismutases, catalase, glutathione peroxidases, glutathione S-transferases, glutathione reductase, NAD(P)H:quinone oxidoreductase) and in the level of non-enzymatic antioxidant glutathione. Furthermore, an overview of the therapeutic effects of vitamin E on antioxidant enzymes during the progression of MASLD will be presented. Generally, at the beginning of MASLD development, the expression/activity of antioxidant enzymes usually increases to protect organisms against the increased production of reactive oxygen species. However, in advanced stage of MASLD, the expression/activity of several antioxidants generally decreases due to damage to hepatic and extrahepatic cells, which further exacerbates the damage. Although the results obtained in patients, in various experimental animal or cell models have been inconsistent, taken together the importance of antioxidant enzymes in MASLD development and progression has been clearly shown.
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Affiliation(s)
- Gabriela Svobodová
- Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05, Hradec Králové, Czech Republic
| | - Martin Horní
- Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05, Hradec Králové, Czech Republic
| | - Eva Velecká
- Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05, Hradec Králové, Czech Republic
| | - Iva Boušová
- Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05, Hradec Králové, Czech Republic.
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Hao L, Li S, Chen G, Hu X. Regulation of UCP2 in nonalcoholic fatty liver disease: From mechanisms to natural product. Chem Biol Drug Des 2024; 103. [DOI: 10.1111/cbdd.14461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 01/09/2024] [Indexed: 01/04/2025]
Abstract
AbstractNonalcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with lipid deposition in liver cells and/or subsequent inflammation, excluding other known causes. NAFLD is a subset of metabolic syndrome that ranges from simple steatohepatitis (NASH), fibrosis to cirrhosis and hepatocellular carcinoma (HCC). At present, the pathogenesis of NAFLD remains unclear. Among the many factors that shape these transitions, uncoupling protein 2 (UCP2) may be involved in every stage of the disease. UCP2 is a carrier protein that responds to fatty acids (FAs) in mitochondrial intima and has a wide tissue distribution. However, the biological function of UCP2 has not been fully elucidated, and most of our current knowledge comes from cell and animal experiments. These data suggest that UCP2 plays a role in lipid metabolism, oxidative stress, apoptosis, and even cancer. In this review, we summarize the structure, distribution, and biological function of UCP2 and its role in the progression of NAFLD, as well as natural products targeting UCP2 to improve NAFLD.
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Affiliation(s)
- Liyuan Hao
- Hospital of Chengdu University of Traditional Chinese Medicine Chengdu China
- Chengdu University of Traditional Chinese Medicine Chengdu China
| | - Shenghao Li
- Hospital of Chengdu University of Traditional Chinese Medicine Chengdu China
- Chengdu University of Traditional Chinese Medicine Chengdu China
| | - Guo Chen
- Hospital of Chengdu University of Traditional Chinese Medicine Chengdu China
| | - Xiaoyu Hu
- Hospital of Chengdu University of Traditional Chinese Medicine Chengdu China
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Munawar M, Khan MS, Saeed M, Younas U, Farag MR, Di Cerbo A, El-Shall N, Loschi AR, Dhama K, Alagawany M. Phytosterol: nutritional significance, health benefits, and its uses in poultry and livestock nutrition. Anim Biotechnol 2023; 34:3206-3215. [PMID: 35839248 DOI: 10.1080/10495398.2022.2099882] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
Medicinal plants with active ingredients have shown great potential as natural and sustainable additives in livestock and poultry diets as growth promoters, performance, feed conversion ratio, digestibility of nutrient enhancers, and antioxidants and immune system modulators. Among active ingredients, phytosterols, which are plant-based bio-factors that may be found in seeds, fruits, grains, vegetables and legumes, are thought to be involved in the aforementioned activities but are also widely known in human medicine due to their efficacy in treating diabetes, coronary heart disease, and tumors. Nevertheless, phytosterols can also promote carcinogens production, angiogenesis inhibition, metastasis, infiltration, and cancer cells proliferation. This review focuses on the deepening of the biological role and health benefits of phytosterols and their new potential application in poultry and livestock nutrition.
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Affiliation(s)
- Mahzaib Munawar
- Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan
| | | | - Muhammad Saeed
- Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan
| | - Umair Younas
- Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan
| | - Mayada R Farag
- Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
| | - Alessandro Di Cerbo
- School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Nahed El-Shall
- Poultry and Fish Diseases Department, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt
| | - Anna Rita Loschi
- School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Italy
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Mahmoud Alagawany
- Poultry Department, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
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Tamilmani P, Sathibabu Uddandrao VV, Chandrasekaran P, Saravanan G, Brahma Naidu P, Sengottuvelu S, Vadivukkarasi S. Linalool attenuates lipid accumulation and oxidative stress in metabolic dysfunction-associated steatotic liver disease via Sirt1/Akt/PPRA-α/AMPK and Nrf-2/HO-1 signaling pathways. Clin Res Hepatol Gastroenterol 2023; 47:102231. [PMID: 37865226 DOI: 10.1016/j.clinre.2023.102231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 10/13/2023] [Accepted: 10/18/2023] [Indexed: 10/23/2023]
Abstract
INTRODUCTION Linalool is a monoterpene that occurs naturally in various aromatic plants and is identified in our previous study as a potential candidate for protection against high-fat diet (HFD)-induced metabolic dysfunction-associated steatotic liver disease (MASLD). However, little is known about its direct effects on hepatic lipid metabolism and oxidative stress. Therefore, this study aims to investigate the therapeutic effect of linalool against MASLD and the underlying mechanism. METHODS To establish a rat model of MASLD, male Wistar rats were fed HFD for 16 weeks and orally administered linalool (100 mg/kg body weight) for 45 days starting from week 14. RESULTS Linalool significantly reduced HFD-induced liver lipid accumulation and restored altered adipokine levels. Mechanistically, linalool downregulated the mRNA expression of sterol regulatory element binding protein 1 and its lipogenesis target genes fatty acid synthase and acetyl-CoA carboxylase, and upregulated the mRNA expression of genes involved in fatty acid oxidation (peroxisome proliferator-activated receptor (PPAR)-alpha [PPAR-α], lipoprotein lipase and protein kinase B [Akt]) as well as the upstream mediators sirtuin 1 (Sirt1) and AMP-activated protein kinase (AMPK) in the liver of MASLD rats. In addition, linalool also curbed oxidative stress by increasing antioxidant enzymes and activating nuclear erythroid-2-related factor 2 (Nrf-2) and its downstream target genes involved in antioxidant properties. CONCLUSION Therefore, this study concludes that linalool attenuates lipid accumulation in the liver by inhibiting de novo lipogenesis, promoting fatty acid oxidation, and attenuating oxidative stress by regulating Sirt1/Akt/PPRA-α/AMPK and Nrf-2/ HO-1 signaling pathways.
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Affiliation(s)
- P Tamilmani
- Department of Biochemistry, K.S. Rangasamy College of Arts and Science (Autonomous), Namakkal District, Tiruchengode, Tamil Nadu 637215, India; Department of Biochemistry, PGP College of Arts and Science, Namakkal, Tamil Nadu 637207, India; Department of Biochemistry, Muthayammal College of Arts and Science, Rasipuram, Tamil Nadu 637408, India
| | - V V Sathibabu Uddandrao
- Department of Biochemistry, K.S. Rangasamy College of Arts and Science (Autonomous), Namakkal District, Tiruchengode, Tamil Nadu 637215, India
| | - P Chandrasekaran
- Department of Biochemistry, K.S. Rangasamy College of Arts and Science (Autonomous), Namakkal District, Tiruchengode, Tamil Nadu 637215, India
| | - G Saravanan
- Department of Biochemistry, K.S. Rangasamy College of Arts and Science (Autonomous), Namakkal District, Tiruchengode, Tamil Nadu 637215, India
| | - Parim Brahma Naidu
- Animal Physiology and Biochemistry Laboratory, ICMR-National Animal Resource Facility for Biomedical Research (ICMR-NARFBR), Hyderabad 500078, India
| | - S Sengottuvelu
- Department of Pharmacology, Nandha College of Pharmacy, Erode, Tamil Nadu 638052, India
| | - S Vadivukkarasi
- Department of Biochemistry, K.S. Rangasamy College of Arts and Science (Autonomous), Namakkal District, Tiruchengode, Tamil Nadu 637215, India.
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An M, Heo H, Park J, Jeong HS, Kim Y, Lee J. Unsaponifiable Matter from Wheat Bran Cultivated in Korea Inhibits Hepatic Lipogenesis by Activating AMPK Pathway. Foods 2023; 12:4016. [PMID: 37959135 PMCID: PMC10650137 DOI: 10.3390/foods12214016] [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: 10/10/2023] [Revised: 10/26/2023] [Accepted: 10/31/2023] [Indexed: 11/15/2023] Open
Abstract
Unsaponifiable matter (USM) from wheat bran, a by-product obtained from wheat milling, is abundant in health-promoting compounds such as phytosterols, tocopherols, policosanols, and alkylresorcinols. This study aimed to examine the effects of USM from the wheat bran of normal and waxy type wheat, Saekeumkang (SKK) and Shinmichal (SMC), on hepatic lipid accumulation in free fatty acid (FFA)-induced hepatocytes and to investigate the cellular mechanism. The total phytochemical contents were 46.562 g/100 g USM and 38.130 g/100 g USM from SKK and SMC, respectively. FFA treatment increased intracellular lipid accumulation by approximately 260% compared to the control group; however, treatment with USM from SKK and SMC significantly attenuated lipid accumulation in the hepatocytes in a dose-dependent manner. Moreover, USM downregulated the expression of lipogenic factors such as fatty acid synthase and sterol regulatory-element-binding protein 1c by approximately 40% compared to the FFA treatment group. Treatment with USM promoted lipolysis and positively regulated the expression of the proteins involved in β-oxidation, including peroxisome proliferator-activated receptor α and its downstream protein, carnitine palmitoyltransferase 1A. Moreover, the blockade of AMPK activation significantly abolished the inhibitory effects of USM on hepatic lipid accumulation. These results indicated that the USM from both SKK and SMC can alleviate lipid accumulation in hepatocytes in an AMPK-dependent manner. Therefore, USM from wheat bran may be useful as a therapeutic intervention for treating metabolic-dysfunction-associated fatty liver disease.
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Affiliation(s)
- Minju An
- Department of Food Science and Biotechnology, Chungbuk National University, Cheongju 28644, Republic of Korea; (M.A.); (H.H.); (H.-S.J.)
| | - Huijin Heo
- Department of Food Science and Biotechnology, Chungbuk National University, Cheongju 28644, Republic of Korea; (M.A.); (H.H.); (H.-S.J.)
| | - Jinhee Park
- Wheat Research Team, National Institute of Crop Science, Rural Development Administration, Wanju 55365, Republic of Korea;
| | - Heon-Sang Jeong
- Department of Food Science and Biotechnology, Chungbuk National University, Cheongju 28644, Republic of Korea; (M.A.); (H.H.); (H.-S.J.)
| | - Younghwa Kim
- Department of Food Science and Biotechnology, Kyungsung University, Busan 48434, Republic of Korea
| | - Junsoo Lee
- Department of Food Science and Biotechnology, Chungbuk National University, Cheongju 28644, Republic of Korea; (M.A.); (H.H.); (H.-S.J.)
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Abo-Zaid OA, Moawed FS, Ismail ES, Farrag MA. β-sitosterol attenuates high- fat diet-induced hepatic steatosis in rats by modulating lipid metabolism, inflammation and ER stress pathway. BMC Pharmacol Toxicol 2023; 24:31. [PMID: 37173727 PMCID: PMC10182633 DOI: 10.1186/s40360-023-00671-0] [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: 12/18/2022] [Accepted: 04/24/2023] [Indexed: 05/15/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disorder. The naturally occurring phytosterol; β-sitosterol has antiobesogenic and anti-diabetic properties. The purpose of this study was to explore the role of β-sitosterol in preventing hepatic steatosis induced by a high-fat diet (HFD) in rats. In the current study, to induce NAFLD in the female Wister rats, an HFD was administered to them for 8 weeks. The pathogenic severity of steatosis in rats receiving an HFD diet was dramatically decreased by oral administration of β-sitosterol. After administering β-sitosterol to HFD-induced steatosis for three weeks, several oxidative stress-related markers were then assessed. We showed that β-sitosterol reduced steatosis and the serum levels of triglycerides, transaminases (ALT and AST) and inflammatory markers (IL-1β and iNOS) compared to HFD-fed rats. Additionally, β-sitosterol reduced endoplasmic reticulum stress by preventing the overexpression of inositol-requiring enzyme-1 (IRE-1α), X-box binding protein 1(sXBP1) and C/EBP homologous protein (CHOP) genes which, showing a function in the homeostatic regulation of protein folding. Also, it was found that the expression of the lipogenic factors; peroxisome proliferator-activated receptor (PPAR-α), sterol regulatory element binding protein (SREBP-1c) and carnitine palmitoyltransferase-1(CPT-1), which are involved in the regulation of the fatty acid oxidation process, may be regulated by β-sitosterol. It can be concluded that β-sitosterol may prevent NAFLD by reducing oxidative stress, endoplasmic reticulum stress and inflammatory responses, which supports the possibility of using β-sitosterol as an alternative therapy for NAFLD. Together, β-sitosterol may be an option for NAFLD prevention.
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Affiliation(s)
- Omayma Ar Abo-Zaid
- Molecular Biology Department, Faculty of Vet. Med, Benha University, Banha, Egypt
| | - Fatma Sm Moawed
- Health Radiation Research, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
| | - Effet Soliman Ismail
- Molecular Biology Department, Faculty of Vet. Med, Benha University, Banha, Egypt
| | - Mostafa A Farrag
- Radiation Biology, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt
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Buț MG, Jîtcă G, Imre S, Vari CE, Ősz BE, Jîtcă CM, Tero-Vescan A. The Lack of Standardization and Pharmacological Effect Limits the Potential Clinical Usefulness of Phytosterols in Benign Prostatic Hyperplasia. PLANTS (BASEL, SWITZERLAND) 2023; 12:1722. [PMID: 37111945 PMCID: PMC10142909 DOI: 10.3390/plants12081722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 04/14/2023] [Accepted: 04/18/2023] [Indexed: 06/19/2023]
Abstract
The prevalence of benign prostatic hyperplasia (BPH) markedly increases with age. Phytotherapeutic approaches have been developed over time owing to the adverse side effects of conventional medications such as 5-reductase inhibitors and α1-adrenergic receptor antagonists. Therefore, dietary supplements (DS) containing active compounds that benefit BPH are widely available. Phytosterols (PSs) are well recognized for their role in maintaining blood cholesterol levels; however, their potential in BPH treatment remains unexplored. This review aims to provide a general overview of the available data regarding the clinical evidence and a good understanding of the detailed pharmacological roles of PSs-induced activities at a molecular level in BPH. Furthermore, we will explore the authenticity of PSs content in DS used by patients with BPH compared to the current legislation and appropriate analytical methods for tracking DS containing PSs. The results showed that PSs might be a useful pharmacological treatment option for men with mild to moderate BPH, but the lack of standardized extracts linked with the regulation of DS containing PSs and experimental evidence to elucidate the mechanisms of action limit the use of PSs in BPH. Moreover, the results suggest multiple research directions in this field.
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Affiliation(s)
- Mădălina-Georgiana Buț
- Doctoral School of Medicine and Pharmacy, I.O.S.U.D, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mures, 540139 Târgu Mures, Romania; (M.-G.B.); (C.-M.J.)
- Department of Biochemistry, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mures, 540139 Târgu Mures, Romania;
| | - George Jîtcă
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mures, 540139 Târgu Mures, Romania; (C.E.V.); (B.E.Ő.)
| | - Silvia Imre
- Department of Analytical Chemistry and Drug Analysis, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mures, 540139 Târgu Mures, Romania;
| | - Camil Eugen Vari
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mures, 540139 Târgu Mures, Romania; (C.E.V.); (B.E.Ő.)
| | - Bianca Eugenia Ősz
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mures, 540139 Târgu Mures, Romania; (C.E.V.); (B.E.Ő.)
| | - Carmen-Maria Jîtcă
- Doctoral School of Medicine and Pharmacy, I.O.S.U.D, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mures, 540139 Târgu Mures, Romania; (M.-G.B.); (C.-M.J.)
| | - Amelia Tero-Vescan
- Department of Biochemistry, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mures, 540139 Târgu Mures, Romania;
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Efficacy of Submicron Dispersible Free Phytosterols on Non-Alcoholic Fatty Liver Disease: A Pilot Study. J Clin Med 2023; 12:jcm12030979. [PMID: 36769628 PMCID: PMC9918217 DOI: 10.3390/jcm12030979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND No pharmacological treatment is yet approved for non-alcoholic fatty liver disease (NAFLD). Plant sterols have shown healthy properties beyond lowering LDL-cholesterol, including lowering triglycerides and lipoprotein plasma levels. Despite pre-clinical data suggesting their involvement in liver fat control, no clinical study has yet been successful. AIMS Testing a sub-micron, free, phytosterol dispersion efficacy on NAFLD. METHODS A prospective, uncontrolled pilot study was carried out on 26 patients with ≥17.4% liver steatosis quantified by magnetic resonance imaging. Subjects consumed daily a sub-micron dispersion providing 2 g of phytosterols. Liver fat, plasma lipids, lipoproteins, liver enzymes, glycemia, insulinemia, phytosterols, liposoluble vitamins and C-reactive protein were assessed at baseline and after one year of treatment. RESULTS Liver steatosis relative change was -19%, and 27% of patients reduced liver fat by more than 30%. Statistically and clinically significant improvements in plasma triglycerides, HDL-C, VLDL and HDL particle number and C-reactive protein were obtained, despite the rise of aspartate aminotransferase, glycemia and insulinemia. Though phytosterol plasma levels were raised by >30%, no adverse effects were presented, and even vitamin D increased by 23%. CONCLUSIONS Our results are the first evidence in humans of the efficacy of submicron dispersible phytosterols for the treatment of liver steatosis, dyslipidemia and inflammatory status in NAFLD.
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12
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Saudi Traditional Fermented Goat Milk Protects against Experimental Non-Alcoholic Fatty Liver Disease by Hypoglycaemic and Antioxidant Potentials. FERMENTATION 2022. [DOI: 10.3390/fermentation8120735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
This study examined the effect of fermented goat milk (oggtt) against non-alcoholic fatty liver disease (NAFLD) in rats induced by chronic high-fat diet (HFD) treatments. Both control-fed and HFD-fed adult male rats received the same vehicle or treatment with two doses of freshly collected oggtt (2 mL or 5 mL) for 12 weeks (n = 8/group). The treatment of the control and HFD-fed rats with oggtt in both doses significantly reduced weight gain, but fasting serum glucose and insulin levels as well as HOMA-IR levels were lowered only in the HFD-fed rats. Treatment improved HFD-induced glucose and insulin homeostasis impairment as measured by the oral glucose tolerance test. Both doses of oggtt reduced serum levels of liver function markers and C-reactive protein (CRP) as well as hepatic levels of malondialdehyde (MDA), tumour necrosis factor-α (TNF-α), and in-terlukin-6 (IL-6) in HFD-fed rats. In addition, the oggtt doses reduced serum and hepatic levels of triglycerides (TGs) and cholesterol (CHOL) as well as serum levels of low-density lipoproteins (LDL) in these rats. These biochemical endpoints were reflected by the improvement in liver histology and reduction in the number of fatty vacuolated and pyknotic cells. In both the control and HFD-fed rats, oggtt at both doses stimulated levels of superoxide dismutase (SOD) and glutathione (GSH). All these effects were more profound with the highest dose of oggtt. In conclusion, the finding of this study strongly supports the use of oggtt as a functional food to treat NAFLD, as it has shown hypoglycaemic and antioxidant properties.
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13
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ELKATTAWY HA, MAHMOUD ABDELMONEM ELSHERBINI D, ALI EBRAHIM H, ABDULLAH DM, AL-ZAHABY SA, NOSERY Y, EL-SAYED HASSAN A. Rho-kinase inhibition ameliorates non-alcoholic fatty liver disease in type 2 diabetic rats. Physiol Res 2022; 71:615-630. [PMID: 36047723 PMCID: PMC9841803 DOI: 10.33549/physiolres.934869] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is linked to type 2 diabetes mellitus (T2DM), obesity, and insulin resistance. The Rho/ROCK pathway had been involved in the pathophysiology of diabetic complications. This study was designed to assess the possible protective impacts of the Rho/Rho-associated coiled-coil containing protein kinase (Rho/ROCK) inhibitor fasudil against NAFLD in T2DM rats trying to elucidate the underlying mechanisms. Animals were assigned into control rats, non-treated diabetic rats with NAFLD, and diabetic rats with NAFLD that received fasudil treatment (10 mg/kg per day) for 6 weeks. The anthropometric measures and biochemical analyses were performed to assess metabolic and liver function changes. The inflammatory and oxidative stress markers and the histopathology of rat liver tissues were also investigated. Groups with T2DM showed increased body weight, serum glucose, and insulin resistance. They exhibited disturbed lipid profile, enhancement of inflammatory cytokines, and deterioration of liver function. Fasudil administration reduced body weight, insulin resistance, and raised liver enzymes. It improved the disturbed lipid profile and attenuated liver inflammation. Moreover, it slowed down the progression of high fat diet (HFD)-induced liver injury and reduced the caspase-3 expression. The present study demonstrated beneficial amelioration effect of fasudil on NAFLD in T2DM. The mechanisms underlying these impacts are improving dyslipidemia, attenuating oxidative stress, downregulated inflammation, improving mitochondrial architecture, and inhibiting apoptosis.
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Affiliation(s)
- Hany A. ELKATTAWY
- Department of Basic Medical Sciences, College of Medicine, Almaarefa University, Riyadh, Kingdom of Saudi Arabia,Medical Physiology Department, College of Medicine, Zagazig University, Egypt
| | - Dalia MAHMOUD ABDELMONEM ELSHERBINI
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Kingdom of Saudi Arabia,Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Hasnaa ALI EBRAHIM
- Department of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Kingdom of Saudi Arabia
| | - Doaa M. ABDULLAH
- Clinical Pharmacology Department, College of Medicine, Zagazig University, Egypt
| | | | - Yousef NOSERY
- Pathology Department, College of Medicine, Zagazig University, Egypt
| | - Ahmed EL-SAYED HASSAN
- Medical Physiology Department, College of Medicine, Zagazig University, Egypt,Department of Basic Medical Sciences, College of Medicine, Sulaiman AlRajhi University, Kingdom of Saudi Arabia
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14
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Cao L, Wu Y, Li W, Zhang Z, Niu Y, Li C, Gu S. Cornus officinalis vinegar reduces body weight and attenuates hepatic steatosis in mouse model of nonalcoholic fatty liver disease. J Food Sci 2022; 87:3248-3259. [PMID: 35673882 DOI: 10.1111/1750-3841.16178] [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: 10/14/2019] [Revised: 01/07/2022] [Accepted: 04/13/2022] [Indexed: 11/27/2022]
Abstract
This study aimed to determine the main bioactive components of Cornus officinalis vinegar (COV) and assess the effects of COV on the body weight (BW) and hepatic steatosis in a nonalcoholic fatty liver disease (NAFLD) mouse model. Seven-week-old KM female mice were divided into five treatment groups: (1) Normal control (NC) group, (2) high fat diet (HFD) group, (3) low concentration treatment group (3.5% COV), (4) medium concentration treatment group (5.0% COV), and (5) high concentration treatment group (6.5% COV). Mice in the NC group were fed with a normal chow diet, and those in the other four groups were fed with a HFD known for causing obesity for 10 weeks. Then, mice in the three COV treatment groups were orally administered with COV once a day for 6 weeks. Results showed that the contents of loganin and morroniside in COV reached 16.82 and 51.17 µg/ml, respectively, and COV also contained multiple organic acids. COV significantly reduced BW, abdominal fat weight, liver weight, and the levels of glucose, triglyceride, and low-density lipoprotein cholesterol of serum and increased the levels of high-density lipoprotein cholesterol of serum (p < 0.05). COV also improved the liver function and anti-oxidant activity of liver (p < 0.05). COV treatments increased the interleukin-10 expression and reduced the tumor necrosis factor-α expression in the liver tissue of NAFLD mice (p < 0.05). Histopathological observation revealed that COV suppressed hepatic lipid accumulation and steatosis. The results suggest that COV may contribute to the alleviation of NAFLD and obesity.
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Affiliation(s)
- Li Cao
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, Henan, P.R. China
| | - Ying Wu
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, Henan, P.R. China
| | - Wenwen Li
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, Henan, P.R. China
| | - Zengmiao Zhang
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, Henan, P.R. China
| | - Yaping Niu
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, Henan, P.R. China
| | - Chenchen Li
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, Henan, P.R. China
| | - Shaobin Gu
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, Henan, P.R. China
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15
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The Role of Phytosterols in Nonalcoholic Fatty Liver Disease. Nutrients 2022; 14:nu14112187. [PMID: 35683987 PMCID: PMC9182996 DOI: 10.3390/nu14112187] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 05/20/2022] [Accepted: 05/21/2022] [Indexed: 02/01/2023] Open
Abstract
Nonalcoholic fatty liver disease is now recognized as the most common cause of chronic liver disease with an increasing prevalence in both adults and children. Although the symptoms are absent or poorly expressed in most cases, some patients may progress to end-stage liver disease. The pathogenesis of NAFLD is known to be multifactorial. Current therapeutic recommendations focus on lifestyle changes in order to reduce the incidence of risk factors and drugs targeting major molecular pathways potentially involved in the development of this disease. Given that a pharmacological treatment, completely safe and effective, is not currently known in recent years more research has been done on the effects that some bio-active natural compounds, derived from plants, have in preventing the onset and progression of NAFLD. Numerous studies, in animals and humans, have shown that phytosterols (PSs) play an important role in this pathology. Phytosterols are natural products that are found naturally in plant. More than 250 phytosterols have been identified, but the most common in the diet are stigmasterol, β-sitosterol, and campesterol. Consumption of dietary PSs can reduce serum cholesterol levels. Due to these properties, most studies have focused on their action on lipid metabolism and the evolution of NAFLD. PSs may reduce steatosis, cytotoxicity oxidative stress, inflammation, and apoptosis. The purpose of this review is to provide an overview of the importance of dietary phytosterols, which are a window of opportunity in the therapeutic management of NAFLD.
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16
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Ding X, Xu Y, Nie P, Zhong L, Feng L, Guan Q, Song L. Changes in the serum metabolomic profiles of subjects with NAFLD in response to n-3 PUFAs and phytosterol ester: a double-blind randomized controlled trial. Food Funct 2022; 13:5189-5201. [PMID: 35438091 DOI: 10.1039/d1fo03921k] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease and threatens human health worldwide. As shown in our previous study, co-supplementation with phytosterol ester (PSE) (3.3 g day-1) and n-3 polyunsaturated fatty acids (PUFAs) (450 mg eicosapentaenoic acid (EPA) + 1500 mg docosahexaenoic acid (DHA) per day) was more effective at ameliorating hepatic steatosis than treatment with PSE or n-3 PUFAs alone. In the present study, we further investigated the changes in the serum metabolic profiles of subjects with NAFLD in response to n-3 PUFAs and PSE. Thirty-one differentially altered serum metabolites were annotated using the nontargeted ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MSE) analysis technique. Multivariable statistical and clustering analyses showed that co-supplementation of n-3 PUFAs and PSE was more effective at improving metabolic disorders in patients with NAFLD than treatment with n-3 PUFAs or PSE alone. The regulated metabolic pathways included metabolism of retinol, linoleic acid, arachidonic acid, glycerophospholipid, sphingolipid, and steroid hormone biosynthesis. Overall, the co-supplementation of n-3 PUFAs and PSE significantly increased the serum levels of PUFA-containing phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC), perillyl alcohol and retinyl ester in patients with NAFLD after 12 weeks of intervention, and the levels of PC (14:0/20:5, 15:0/20:5), LysoPC (20:5, 22:6) and retinyl ester correlated negatively with the degree of hepatic steatosis. The regulatory effect of co-supplementation of n-3 PUFAs and PSE on metabolomic profiles may explain their potential role in alleviating hepatic steatosis in patients with NAFLD.
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Affiliation(s)
- Xinwen Ding
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Yinfei Xu
- The First People's Hospital of Ningyang County, Tai'an City 270018, Shandong Province, People's Republic of China
| | - Pan Nie
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Lingyue Zhong
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Lei Feng
- Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China
| | - Qi Guan
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Lihua Song
- School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
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17
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Fang J, Lin Y, Xie H, Farag MA, Feng S, Li J, Shao P. Dendrobium officinale leaf polysaccharides ameliorated hyperglycemia and promoted gut bacterial associated SCFAs to alleviate type 2 diabetes in adult mice. Food Chem X 2022; 13:100207. [PMID: 35498995 PMCID: PMC9039915 DOI: 10.1016/j.fochx.2022.100207] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Revised: 11/17/2021] [Accepted: 01/05/2022] [Indexed: 02/07/2023] Open
Abstract
Fractions of LDOP show the hypoglycemic effect and can restore histological function of T2D mice. There is a difference in the anti-T2D effect between LDOP-A and LDOP-B. LDOP-A modulated the gut microbiota composition of T2D mice. LDOP-A promotes the formation of SCFAs in T2D mice, especially butyric acid. Compared with LDOP-B, LDOP-A shows greater potential to ameliorate T2D. The present study aimed to explore the possible mechanisms underlying Dendrobium officinale leaf polysaccharides of different molecular weight to alleviate glycolipid metabolic abnormalities, organ dysfunction and gut microbiota dysbiosis of T2D mice. An ultrafiltration membrane was employed to separate two fractions from Dendrobium officinale leaf polysaccharide named LDOP-A and LDOP-B. Here, we present data supporting that oral administration of LDOP-A and LDOP-B ameliorated hyperglycemia, inhibited insulin resistance, reduced lipid concentration, improved β-cell function. LDOP-A with lower molecular weight exhibited improved effect on diabetes than LDOP-B, concurrent with increased levels of colonic short-chain fatty acids (SCFAs) i.e., butyrate, decreased ratio of Firmicutes to Bacteroidetes phyla, and increased abundance of the gut beneficial bacteria i.e., Lactobacillus, Bifidobacterium and Akkermansia. These results suggest that LDOP-A possesses a stronger effect in ameliorating T2D than LDOP-B which may be related to the distinct improved SCFAs levels produced by the change of intestinal flora microstructure.
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Key Words
- AUC, The area under the concentration–time curve
- Dendrobium officinale
- FBG, fasting blood glucose
- FT-IR, Fourier-transform infrared
- GLP-1, glucagon-like peptide-1
- GLUT4, glucose transporter type 4
- H&E, hematoxylin and eosin
- HDL-c, high-density lipoprotein cholesterol
- HFD, high-fat diet
- HOMA-IR, homeostasis model assessment-insulin resistance
- HOMA-β, β-cell sensitivity
- IC, ion Chromatography
- IL-6, interleukin-6
- Intestinal microflora
- LDL-c, low-density lipoprotein cholesterol
- LDOP, Dendrobium officinale leaf polysaccharide
- Mw, molecular weight
- OGTT, oral glucose tolerance test
- OTUs, operational taxonomic units
- PAS, periodic acid-Schiff
- PYY, peptide YY
- Polysaccharide
- SCFAs, short chain fatty acids
- STZ, streptozotocin
- Short-chain fatty acids
- T2D, Type 2 Diabetic
- TG, triglycerides
- TNF-α, tumor necrosis factor-alpha
- Type 2 Diabetes
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Affiliation(s)
- Jingyu Fang
- Department of Food Science and Technology, Zhejiang University of Technology, Zhejiang, Hangzhou 310014, China
| | - Yang Lin
- Department of Food Science and Technology, Zhejiang University of Technology, Zhejiang, Hangzhou 310014, China
| | - Hualing Xie
- Department of Food Science and Technology, Zhejiang University of Technology, Zhejiang, Hangzhou 310014, China
| | - Mohamed A Farag
- Pharmacognosy Department, College of Pharmacy, Cairo University, Kasr El Aini St., Cairo, 11562, Egypt.,Department of Chemistry, School of Science & Engineering, The American University in Cairo, New Cairo 11835, Egypt
| | - Simin Feng
- Department of Food Science and Technology, Zhejiang University of Technology, Zhejiang, Hangzhou 310014, China
| | - Jinjun Li
- Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Ping Shao
- Department of Food Science and Technology, Zhejiang University of Technology, Zhejiang, Hangzhou 310014, China.,Key Laboratory of Food Macromolecular Resources Processing Technology Research, China National Light Industry, Hangzhou 310021, China
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18
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Du S, Zhu X, Zhou N, Zheng W, Zhou W, Li X. Curcumin alleviates hepatic steatosis by improving mitochondrial function in postnatal overfed rats and fatty L02 cells through the SIRT3 pathway. Food Funct 2022; 13:2155-2171. [PMID: 35113098 DOI: 10.1039/d1fo03752h] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Postnatal overfeeding could increase the risk of non-alcoholic fatty liver disease (NAFLD) in adulthood. This study investigated the effects of curcumin (CUR) on hepatic steatosis in postnatal overfed rats and elucidated potential mechanisms in mitochondrial functions. Male rats were adjusted to ten (normal litter, NL) or three (small litter, SL) at postnatal day 3. After weaning, NL rats were fed with normal diet (NL) or a high-fat diet (NH) for 10 weeks. SL rats were fed with normal diet (SL), a high-fat diet (SH), a normal diet supplemented with 2% CUR (SL-CUR) or a high-fat diet supplemented with 2% CUR (SH-CUR). At week 13, compared with NL rats, SL and NH rats showed increased body weight, glucose intolerance, dyslipidemia and hepatic lipid accumulation, and these changes were more obvious in SH rats. The opposite trends were observed in SL-CUR and SH-CUR rats. Moreover, CUR could preserve mitochondrial biogenesis and antioxidant response in postnatal overfed rats, and upregulated the mRNA and protein levels of SIRT3. In vitro, L02 cells were exposed to free fatty acids and/or CUR. CUR decreased the levels of cellular lipids and mitochondrial reactive oxygen species, and increased the mitochondrial DNA copy number and superoxide dismutase activity in fatty L02 cells. However, these effects were blocked after SIRT3 silencing. It was concluded that postnatal overfeeding damaged mitochondrial biogenesis and antioxidant response, and increased hepatic lipids and the severity of high-fat-induced NAFLD, while CUR alleviated hepatic steatosis, at least partially, by enhancing mitochondrial function through SIRT3.
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Affiliation(s)
- Susu Du
- Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, 210008, Jiangsu Province, China.
| | - Xiaolei Zhu
- Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, 210008, Jiangsu Province, China.
| | - Nan Zhou
- Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, 210008, Jiangsu Province, China.
| | - Wen Zheng
- Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, 210008, Jiangsu Province, China.
| | - Wei Zhou
- Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, 210008, Jiangsu Province, China.
| | - Xiaonan Li
- Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, 210008, Jiangsu Province, China. .,Institute of Pediatric Research, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China
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19
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Smirne C, Croce E, Di Benedetto D, Cantaluppi V, Comi C, Sainaghi PP, Minisini R, Grossini E, Pirisi M. Oxidative Stress in Non-Alcoholic Fatty Liver Disease. LIVERS 2022; 2:30-76. [DOI: 10.3390/livers2010003] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it still remains an orphan of adequate therapies. This review highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive oxygen species generators, including those produced in the gastrointestinal tract, contribute to the lipotoxic hepatic (and extrahepatic) damage by fatty acids and a great variety of their biologically active metabolites in a “multiple parallel-hit model”. This leads to inflammation and fibrogenesis and contributes to NAFLD progression. The alterations of the oxidant/antioxidant balance affect also metabolism-related organelles, leading to lipid peroxidation, mitochondrial dysfunction, and endoplasmic reticulum stress. This OS-induced damage is at least partially counteracted by the physiological antioxidant response. Therefore, modulation of this defense system emerges as an interesting target to prevent NAFLD development and progression. For instance, probiotics, prebiotics, diet, and fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. The OS and its counter-regulation are under the influence of individual genetic and epigenetic factors as well. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors, coupled with new OS biomarkers, will likely assist in noninvasive diagnosis and monitoring of NAFLD progression and in further personalizing treatments.
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Affiliation(s)
- Carlo Smirne
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Eleonora Croce
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Davide Di Benedetto
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Vincenzo Cantaluppi
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Cristoforo Comi
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Pier Paolo Sainaghi
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Rosalba Minisini
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Elena Grossini
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy
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20
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Hoebinger C, Rajcic D, Hendrikx T. Oxidized Lipids: Common Immunogenic Drivers of Non-Alcoholic Fatty Liver Disease and Atherosclerosis. Front Cardiovasc Med 2022; 8:824481. [PMID: 35083304 PMCID: PMC8784685 DOI: 10.3389/fcvm.2021.824481] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 12/15/2021] [Indexed: 12/17/2022] Open
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD), ranging from simple steatosis to inflammatory steatohepatitis (NASH) and cirrhosis, continues to rise, making it one of the major chronic liver diseases and indications for liver transplantation worldwide. The pathological processes underlying NAFLD not only affect the liver but are also likely to have systemic effects. In fact, growing evidence indicates that patients with NAFLD are at increased risk for developing atherosclerosis. Indeed, cardiovascular complications are the leading cause of mortality in NAFLD patients. Here, we aim to address common pathophysiological molecular pathways involved in chronic fatty liver disease and atherosclerosis. In particular, we focus on the role of oxidized lipids and the formation of oxidation-specific epitopes, which are important targets of host immunity. Acting as metabolic danger signals, they drive pro-inflammatory processes and thus contribute to disease progression. Finally, we summarize encouraging studies indicating that oxidized lipids are promising immunological targets to improve intervention strategies for NAFLD and potentially limit the risk of developing atherosclerosis.
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Affiliation(s)
- Constanze Hoebinger
- Department of Laboratory Medicine, Klinisches Institut für Labormedizin (KILM), Medical University Vienna, Vienna, Austria
| | - Dragana Rajcic
- Department of Laboratory Medicine, Klinisches Institut für Labormedizin (KILM), Medical University Vienna, Vienna, Austria
| | - Tim Hendrikx
- Department of Laboratory Medicine, Klinisches Institut für Labormedizin (KILM), Medical University Vienna, Vienna, Austria.,Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, Netherlands
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21
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Banerjee A, Mukherjee S, Maji BK. Coccinia grandis
alleviates flavor‐enhancing high‐lipid diet induced hepatocellular inflammation and apoptosis. J Food Biochem 2022; 46:e14092. [DOI: 10.1111/jfbc.14092] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/19/2021] [Accepted: 01/06/2022] [Indexed: 12/17/2022]
Affiliation(s)
- Arnab Banerjee
- Department of Physiology (UG & PG) Serampore College Serampore India
| | - Sandip Mukherjee
- Department of Physiology (UG & PG) Serampore College Serampore India
| | - Bithin Kumar Maji
- Department of Physiology (UG & PG) Serampore College Serampore India
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22
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Wu Z, Wang J, Feng J, Ying L. MicroRNA-122-5p prevents proliferation and promotes apoptosis of hepatic stellate cells by suppressing the cellular-Abelsongene/histone deacetylases 2 pathway. Hum Exp Toxicol 2022; 41:9603271221084672. [PMID: 35303413 DOI: 10.1177/09603271221084672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Liver fibrosis is a wound-healing response and the activation of the hepatic stellate cell (HSC) is the core of hepatic fibrosis. MicroRNAs (miRNAs) participate in the development of fibrosis. It is reported that histone deacetylases (HDAC2) tyrosine phosphorylation by cellular-Abelsongene (c-Abl) induces malignant growth of cells. Here, we investigated the effect of miR-122-5p on the proliferation and apoptosis of HSCs. Normal human HSC line LX-2 and LX-2 cells stimulated by transforming growth factor (TGF)-β1 for 24 h were cultured and assigned into the blank group and the TGF-β1 group. The miR-122-5p inhibitor and its negative control were transfected into LX-2 cells and miR-122-5p mimic and its negative control were transfected into LX-2 cells stimulated by TGF-β1. The result showed that miR-122-5p expression was decreased in TGF-β1-stimulated LX-2 cells. miR-122-5p overexpression reduced the mRNA and protein levels of collagen I and α-smooth muscle actin, inhibited cell proliferation, and accelerated cell apoptosis. miR-122-5p targeted c-Abl. Meanwhile, miR-122-5p overexpression inhibited HSC activation by suppressing the c-Abl/HDAC2 pathway. In summary, miR-122-5p overexpression exerted anti-fibrosis effect and inhibited HSC activation by suppressing the c-Abl/HDAC2 pathway.
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Affiliation(s)
- ZongYang Wu
- Department of Hepatobiliary and Pancreatic Surgery, 11797The Affiliated People's Hospital of Ningbo University, Ningbo, China
| | - JinBo Wang
- Department of Hepatobiliary and Pancreatic Surgery, 11797The Affiliated People's Hospital of Ningbo University, Ningbo, China
| | - JiYe Feng
- Department of Hepatobiliary and Pancreatic Surgery, 11797The Affiliated People's Hospital of Ningbo University, Ningbo, China
| | - LiPing Ying
- Department of Hepatobiliary and Pancreatic Surgery, 11797The Affiliated People's Hospital of Ningbo University, Ningbo, China
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23
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Yang JW, Ji HF. Phytosterols as bioactive food components against nonalcoholic fatty liver disease. Crit Rev Food Sci Nutr 2021:1-12. [PMID: 34871105 DOI: 10.1080/10408398.2021.2006137] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Phytosterols are bioactive food components widely present in cell membranes of plants, especially in nuts and oilseeds. In recent years, many studies have shown that phytosterols possess therapeutic potentials for nonalcoholic fatty liver disease (NAFLD). This review summarizes the effects of phytosterols from in vitro and in vivo studies to lower the levels of total cholesterol (TC) and triglycerides (TG), and the evidence supporting the potential of phytosterols against NAFLD. The potential mechanisms by which phytosterols improve NAFLD may include (i) competition with cholesterol; (ii) regulation of key factors involved in cholesterol and TG metabolism; and (iii) inhibition of liver inflammation and (iv) regulation of liver fatty acid composition. In summary, phytosterols are potential natural ingredients with good safety profile against NAFLD, which deserve more future studies.
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Affiliation(s)
- Jing-Wen Yang
- Institute of Biomedical Research, Shandong University of Technology, Zibo, Shandong, People's Republic of China.,Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Zibo Key Laboratory of New Drug Development of Neurodegenerative diseases, School of Life Sciences, Shandong University of Technology, Zibo, Shandong, People's Republic of China
| | - Hong-Fang Ji
- Institute of Biomedical Research, Shandong University of Technology, Zibo, Shandong, People's Republic of China.,Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Zibo Key Laboratory of New Drug Development of Neurodegenerative diseases, School of Life Sciences, Shandong University of Technology, Zibo, Shandong, People's Republic of China
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24
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Yuan C, Ding X, Jiang L, Ye W, Xu J, Qian L. Effects of dietary phytosterols supplementation on serum parameters, nutrient digestibility and digestive enzyme of white feather broilers. ITALIAN JOURNAL OF ANIMAL SCIENCE 2021. [DOI: 10.1080/1828051x.2021.2000895] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Chunchun Yuan
- Key Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Xiaoqing Ding
- Key Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Lai Jiang
- Key Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Wenxin Ye
- Key Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Jinghong Xu
- Key Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Lichun Qian
- Key Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China
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25
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Nattagh-Eshtivani E, Barghchi H, Pahlavani N, Barati M, Amiri Y, Fadel A, Khosravi M, Talebi S, Arzhang P, Ziaei R, Ghavami A. Biological and pharmacological effects and nutritional impact of phytosterols: A comprehensive review. Phytother Res 2021; 36:299-322. [PMID: 34729825 DOI: 10.1002/ptr.7312] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 09/01/2021] [Accepted: 09/30/2021] [Indexed: 12/20/2022]
Abstract
Phytosterols (PSs), classified into plant sterols and stanols, are bioactive compounds found in foods of plant origin. PSs have been proposed to exert a wide number of pharmacological properties, including the potential to reduce total and low-density lipoprotein (LDL) cholesterol levels and thereby decreasing the risk of cardiovascular diseases. Other health-promoting effects of PSs include anti-obesity, anti-diabetic, anti-microbial, anti-inflammatory, and immunomodulatory effects. Also, anticancer effects have been strongly suggested, as phytosterol-rich diets may reduce the risk of cancer by 20%. The aim of this review is to provide a general overview of the available evidence regarding the beneficial physiological and pharmacological activities of PSs, with special emphasis on their therapeutic potential for human health and safety. Also, we will explore the factors that influence the physiologic response to PSs.
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Affiliation(s)
- Elyas Nattagh-Eshtivani
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hanieh Barghchi
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Naseh Pahlavani
- Nutrition and Biochemistry Department, School of Medicine, Social Development and Health Promotion Research Center, Gonabad University of Medical Sciences, Gonabad, Iran.,Department of Clinical Biochemistry and Nutrition, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Mehdi Barati
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Yasaman Amiri
- Medical School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Abdulmannan Fadel
- School of Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK
| | - Maryam Khosravi
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Saeedeh Talebi
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Pishva Arzhang
- Department of Biochemistry and Diet Therapy, Faculty of Nutritional Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Rahele Ziaei
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Abed Ghavami
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
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26
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Banerjee A, Mukherjee S, Maji BK. Monosodium glutamate causes hepato-cardiac derangement in male rats. Hum Exp Toxicol 2021; 40:S359-S369. [PMID: 34560825 DOI: 10.1177/09603271211049550] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
People in the fast-food era rely on pre-packaged foods and engage in limited physical activity, which leads to a shift in eating patterns. Monosodium glutamate (MSG), a dietary ingredient used in this sort of cuisine, has been found to be hazardous to both experimental animals and humans. The objective of this study was to explore at the unnecessary changes caused by consuming MSG in secret and exceeding the recommended dosage. Hence, we decided to evaluate the impact of MSG by using three different doses (200, 400, and 600 mg/kg body weight orally) for 28 days in rats. We uncovered that all three MSG dosages result in a rise in body weight, dyslipidemia, inflammatory response, and hepato-cardiac marker enzymes, all of which imply hepatic and cardiac toxicity. Furthermore, changes in redox status suggest oxidative stress, which was higher in all three MSG dosages although not as much as in the MSG-600 group when compared to control. Such effects eventually manifested themselves in tissue architecture of the liver and heart, resulting in severe hepato-cardiac derangement, but the degree of tissue damage was greater in the MSG-600 group. As a result, it is possible that MSG has a negative influence on the liver and heart. However, the MSG-600 group showed a substantial effect, indicating that MSG should not be used in food preparation. Therefore, the findings of the study may aid in the formulation of health-care strategies and serve as a warning to the general public regarding the use of MSG in daily diet.
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Affiliation(s)
- Arnab Banerjee
- Department of Physiology (UG & PG), Serampore College, West Bengal, India
| | - Sandip Mukherjee
- Department of Physiology (UG & PG), Serampore College, West Bengal, India
| | - Bithin Kumar Maji
- Department of Physiology (UG & PG), Serampore College, West Bengal, India
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27
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Abstract
More than 50% of the UK coastline is situated in Scotland under legislative jurisdiction; therefore, there is a great opportunity for regionally focused economic development by the rational use of sustainable marine bio-sources. We review the importance of seaweeds in general, and more specifically, wrack brown seaweeds which are washed from the sea and accumulated in the wrack zone and their economic impact. Rules and regulations governing the harvesting of seaweed, potential sites for harvesting, along with the status of industrial application are discussed. We describe extraction and separation methods of natural products from these seaweeds along with their phytochemical profiles. Many potential applications for these derivatives exist in agriculture, energy, nutrition, biomaterials, waste treatment (composting), pharmaceuticals, cosmetics and other applications. The chemical diversity of the natural compounds present in these seaweeds is an opportunity to further investigate a range of chemical scaffolds, evaluate their biological activities, and develop them for better pharmaceutical or biotechnological applications. The key message is the significant opportunity for the development of high value products from a seaweed processing industry in Scotland, based on a sustainable resource, and locally regulated.
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28
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Maheshwari G, Wen G, Gessner DK, Ringseis R, Lochnit G, Eder K, Zorn H, Timm T. Tandem mass tag-based proteomics for studying the effects of a biotechnologically produced oyster mushroom against hepatic steatosis in obese Zucker rats. J Proteomics 2021; 242:104255. [PMID: 33957313 DOI: 10.1016/j.jprot.2021.104255] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/22/2021] [Accepted: 04/28/2021] [Indexed: 12/12/2022]
Abstract
Hepatic steatosis is a very common response to liver injury and often attributed to metabolic disorders. Prior studies have demonstrated the efficacy of a biotechnologically produced oyster mushroom (Pleurotus sajor-caju, PSC) in alleviating hepatic steatosis in obese Zucker rats. This study aims to elucidate molecular events underlying the anti-steatotic effects of PSC. Tandem mass tag (TMT) peptide labeling coupled with LC-MS/MS/MS was used to quantify and compare proteins in the livers of lean Zucker rats fed a control diet (LC), obese Zucker rats fed the same control diet (OC) and obese Zucker rats fed the control diet supplemented with 5% PSC (OPSC) for 4 weeks. Using this technique 3128 proteins could be quantified, out of which 108 were differentially abundant between the OPSC and OC group. Functional enrichment analysis of the up-regulated proteins showed that these proteins were mainly involved in metabolic processes, while the down-regulated proteins were involved in inflammatory processes. Results from proteomic analysis were successfully validated for two up-regulated (carbonic anhydrase 3, regucalcin) and two down-regulated (cadherin-17, ceruloplasmin) proteins by means of immunoblotting. SIGNIFICANCE: Valorization of low-grade agricultural waste by edible fungi, such as the mushroom Pleurotus sajor-caju (PSC), represents a promising strategy for the production of protein rich biomass since they boast of a unique enzyme system that has the ability to recover nutrients and energy from biodegradable waste. Herein, we describe the metabolic effects of PSC feeding using a combined quantitative proteomics and bioinformatics approach. In total, 108 proteins were identified to be regulated by PSC feeding in the liver of the obese rats. Complementary usage of a bioinformatics approach allowed us to decipher the mechanisms underlying the recently observed lipid-lowering and anti-inflammatory activity of PSC feeding in obese Zucker rats, namely a reduction of fatty acid synthesis, an improvement of hepatoprotective mechanisms and an enhancement of anti-inflammatory effects.
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Affiliation(s)
- Garima Maheshwari
- Institute of Food Chemistry and Food Biotechnology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany; Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany
| | - Gaiping Wen
- Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany
| | - Denise K Gessner
- Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany
| | - Robert Ringseis
- Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany
| | - Günter Lochnit
- Protein Analytics, Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University Giessen, Friedrichstrasse 24, 35392 Giessen, Germany
| | - Klaus Eder
- Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany
| | - Holger Zorn
- Institute of Food Chemistry and Food Biotechnology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany; Fraunhofer Institute for Molecular Biology and Applied Ecology, Ohlebergsweg 12, 35392 Giessen, Germany.
| | - Thomas Timm
- Protein Analytics, Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University Giessen, Friedrichstrasse 24, 35392 Giessen, Germany
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29
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Banerjee A, Mukherjee S, Maji BK. Worldwide flavor enhancer monosodium glutamate combined with high lipid diet provokes metabolic alterations and systemic anomalies: An overview. Toxicol Rep 2021; 8:938-961. [PMID: 34026558 PMCID: PMC8120859 DOI: 10.1016/j.toxrep.2021.04.009] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 04/20/2021] [Accepted: 04/25/2021] [Indexed: 12/13/2022] Open
Abstract
Flavor enhancing high lipid diet acts as silent killer. Monosodium glutamate mixed with high lipid diet alters redox-status. Monosodium glutamate mixed with high lipid diet induces systemic anomalies. In this fast-food era, people depend on ready-made foods and engage in minimal physical activities that ultimately change their food habits. Majorities of such foods have harmful effects on human health due to higher percentages of saturated fatty acids, trans-fatty acids, and hydrogenated fats in the form of high lipid diet (HLD). Moreover, food manufacturers add monosodium glutamate (MSG) to enhance the taste and palatability of the HLD. Both MSG and HLD induce the generation of reactive oxygen species (ROS) and thereby alter the redox-homeostasis to cause systemic damage. However, MSG mixed HLD (MH) consumption leads to dyslipidemia, silently develops non-alcoholic fatty liver disease followed by metabolic alterations and systemic anomalies, even malignancies, via modulating different signaling pathways. This comprehensive review formulates health care strategies to create global awareness about the harmful impact of MH on the human body and recommends the daily consumption of more natural foods rich in antioxidants instead of toxic ingredients to counterbalance the MH-induced systemic anomalies.
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30
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Subramanian G, Shanmugamprema D, Subramani R, Muthuswamy K, Ponnusamy V, Tankay K, Velusamy T, Krishnan V, Subramaniam S. Anti-Obesity Effect of T. Chebula Fruit Extract on High Fat Diet Induced Obese Mice: A Possible Alternative Therapy. Mol Nutr Food Res 2021; 65:e2001224. [PMID: 33754444 DOI: 10.1002/mnfr.202001224] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 02/18/2021] [Indexed: 12/23/2022]
Abstract
Occurrence of obesity and its associated metabolic disorders continues to escalate. The present study evaluates the anti-obesity effects of ethanolic fruit extract of Terminalia chebula (EETC) on high fat diet induced obese mice. The bioactive compounds present in the EETC is evaluated by Fourier-transform infrared (FT-IR), Gas chromatography-mass spectrometry (GC-MS), and Liquid chromatography-mass spectrometry (LC-MS) analysis. The effects of EETC on energy intake, glucose tolerance, and various biochemical parameters were analyzed using laboratory mice. Relative gene expression of Fatty acid synthase (FAS), Peroxisome proliferator-activated receptors α (PPARα), Carnitine palmitoyltransferase-1 (CPT-1), Tumor necrosis factor alpha (TNF-α) as well as Interleukin 6 (IL-6) were analyzed in liver and adipose tissues. The findings reveal the hypolipidemic and anti-obesity potential of EETC on high fat fed obese mice. EETC exerts its anti-obesity effects by suppressing lipogenesis through reduction in lipogenic enzyme (FAS) expression, increased fatty acid oxidation via PPARα and CPT-1 and by triggering the anti-inflammatory responses. To our knowledge, this is the first report of the effect of EETC on PPARα and CPT-1 in in vivo.
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Affiliation(s)
- Gowtham Subramanian
- Molecular Physiology Laboratory, Department of Biochemistry, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India
| | - Deepankumar Shanmugamprema
- Molecular Physiology Laboratory, Department of Biochemistry, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India
| | - Ramya Subramani
- Molecular Physiology Laboratory, Department of Biochemistry, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India
| | - Karthi Muthuswamy
- Molecular Physiology Laboratory, Department of Biochemistry, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India
| | - Vinithra Ponnusamy
- Molecular Physiology Laboratory, Department of Biochemistry, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India
| | - Kalpana Tankay
- Molecular Physiology Laboratory, Department of Biochemistry, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India
| | - Thirunavukkarasu Velusamy
- Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India
| | - Vasanth Krishnan
- Molecular Biology Laboratory, Department of Botany, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India
| | - Selvakumar Subramaniam
- Molecular Physiology Laboratory, Department of Biochemistry, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India
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31
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Tokoro M, Gotoh K, Kudo Y, Hirashita Y, Iwao M, Arakawa M, Endo M, Oribe J, Masaki T, Honda K, Kakuma T, Seike M, Murakami K, Shibata H. α-Tocopherol suppresses hepatic steatosis by increasing CPT-1 expression in a mouse model of diet-induced nonalcoholic fatty liver disease. Obes Sci Pract 2021; 7:91-99. [PMID: 33680496 PMCID: PMC7909598 DOI: 10.1002/osp4.460] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 09/29/2020] [Accepted: 09/30/2020] [Indexed: 12/12/2022] Open
Abstract
Aim Antioxidant therapy for with vitamin E appears to be effective for the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanism of action and optimal therapeutic dosage is unclear. The present study was undertaken to examine whether the effects of α‐tocopherol (α‐Toc) on NAFLD are dose‐dependent in a diet‐induced obese model. Methods Male mice were fed standard chow, high‐fat (HF) diet, HF diet with low‐dose, or with high dose of α‐Toc supplementation. Histological findings, triglyceride content, and the levels of protein expression related to fatty acid synthesis/oxidation such as carnitine palmitoyltransferase I (CPT‐1) of liver were evaluated. In addition, 2‐tetradecylglycidic acid (TDGA), a CPT‐1 inhibitor, was administered to mice fed HF diet with low‐dose of α‐Toc. Finally, HepG2 cells in fat‐loaded environment were treated with 0–50 μM α‐Toc. Results Treatment of low‐dose of α‐Toc decreased HF‐induced hepatic fat accumulation, but this finding was not observed in treatment of high dose of α‐Toc. HF‐induced reduction of CPT‐1 was attenuated with low‐dose of α‐Toc but not with high dose of α‐Toc. TDGA suppressed the improvement of histological findings in liver induced by low‐dose of α‐Toc treatment. CPT‐1 expression in HepG2 cells increased in response to low‐dose of α‐Toc, but not in high dose. Conclusions Dual action of α‐Toc on CPT‐1 protein levels was observed. The effect of vitamin E on NAFLD may be not be dose‐dependent.
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Affiliation(s)
- Masanori Tokoro
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan.,Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Koro Gotoh
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan
| | - Yoko Kudo
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Yuka Hirashita
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Masao Iwao
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Mie Arakawa
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Mizuki Endo
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Junya Oribe
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Takayuki Masaki
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan
| | - Koichi Honda
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Tetsuya Kakuma
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan
| | - Masataka Seike
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Kazunari Murakami
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Hirotaka Shibata
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan
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Cocci P, Moruzzi M, Martinelli I, Maggi F, Micioni Di Bonaventura MV, Cifani C, Mosconi G, Tayebati SK, Damiano S, Lupidi G, Amantini C, Tomassoni D, Palermo FA. Tart cherry (Prunus cerasus L.) dietary supplement modulates visceral adipose tissue CB1 mRNA levels along with other adipogenesis-related genes in rat models of diet-induced obesity. Eur J Nutr 2021; 60:2695-2707. [PMID: 33386893 DOI: 10.1007/s00394-020-02459-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 12/07/2020] [Indexed: 12/19/2022]
Abstract
PURPOSE There is increasing evidence for the involvement of dietary bioactive compounds in the cross-talk modulation of endocannabinoid system and some of the key regulators of transcriptional control for adipogenesis. METHODS We aimed to characterize the expression of cannabinoid CB1/CB2 receptors and fatty acid amide hydrolase (FAAH) along with selected adipogenesis-related genes (PPARγ, SREBP-1c and PREF-1), adipocyte-secreted factors (leptin and adiponectin), mitochondrial bioenergetic modulators (PGC-1A and UCP-2), and transient receptor potential vanilloid subtype 1 (TRPV1) and 2 (TRPV2) channels in visceral adipose tissue of rats fed with a high-fat diet (HFD) containing either tart cherry seeds alone or tart cherry seeds and juice for 17 weeks. The visceral adipose tissue was weighed and checked the expression of different markers by qRT-PCR, Western blot and immunohistochemistry. RESULTS Tart cherry supplements were able to downregulate the HFD-induced mRNA expression of CB1 receptor, SREBP-1c, PPARγ, leptin, TRPV1 and TRPV2 resulting in potential anti-adipogenic effects. CONCLUSION The present study points out that the intake of bioactive constituents of tart cherry may attenuate the effect of adipogenesis by acting directly on the adipose tissue and modulating the interplay between CB1, PPARγ and TRPV channel gene transcription.
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Affiliation(s)
- Paolo Cocci
- School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III Da Varano, 62032, Camerino, MC, Italy
| | - Michele Moruzzi
- Department of Medicine, University of Leipzig, Leipzig, Germany
| | | | - Federica Maggi
- Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
| | | | - Carlo Cifani
- School of Pharmacy, University of Camerino, Camerino, Italy
| | - Gilberto Mosconi
- School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III Da Varano, 62032, Camerino, MC, Italy
| | | | - Silvia Damiano
- School of Pharmacy, University of Camerino, Camerino, Italy
| | - Giulio Lupidi
- School of Pharmacy, University of Camerino, Camerino, Italy
| | - Consuelo Amantini
- School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III Da Varano, 62032, Camerino, MC, Italy
| | - Daniele Tomassoni
- School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III Da Varano, 62032, Camerino, MC, Italy
| | - Francesco Alessandro Palermo
- School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III Da Varano, 62032, Camerino, MC, Italy.
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33
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Hussain M, Li X, Liu L, Wang L, Qayum A, Purevsuren B, Hussain A. Characterization and anti-hyper-lipidemic effect of micro encapsulated phytosterol enriched cheddar cheese. Lebensm Wiss Technol 2020. [DOI: 10.1016/j.lwt.2020.110114] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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34
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Gómez-Zorita S, González-Arceo M, Trepiana J, Aguirre L, Crujeiras AB, Irles E, Segues N, Bujanda L, Portillo MP. Comparative Effects of Pterostilbene and Its Parent Compound Resveratrol on Oxidative Stress and Inflammation in Steatohepatitis Induced by High-Fat High-Fructose Feeding. Antioxidants (Basel) 2020; 9:1042. [PMID: 33114299 PMCID: PMC7690896 DOI: 10.3390/antiox9111042] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 10/19/2020] [Accepted: 10/21/2020] [Indexed: 12/17/2022] Open
Abstract
Different studies have revealed that oxidative stress and inflammation are crucial in NAFLD (Non-alcoholic fatty liver disease). The aim of this study is to analyze whether pterostilbene and resveratrol are able to either avoid or delay the progression of non-alcoholic liver steatosis towards steatohepatitis. This has been performed by examining their effects on oxidative stress, inflammation, fibrosis and pre-carcinogenic stages. Rats were distributed into five experimental groups and were fed with either a standard diet or a high-fat high-fructose diet, supplemented or not with pterostilbene (15 or 30 mg/kg/d) or resveratrol (30 mg/kg/d), for 8 weeks. Liver histological analysis was carried out by haematoxylin-eosin staining. Serum and hepatic oxidative stress-related parameters were assessed using spectrophotometry, and the expression of genes related to inflammation, fibrosis and cancer by qRT-PCR. The dietary model used in this study led to the development of steatohepatitis, where rats displayed oxidative stress, inflammation and ballooning, although not fibrosis. It also modified the expression of hepatocarcinoma-related genes. The results show, for the first time, that pterostilbene was able to partially prevent these alterations, with the exception of changes in hepatocarcinoma-related genes, mainly at 30 mg/kg/d. Pterostilbene was more effective than its parent compound resveratrol, probably due to its high bioavailability and higher anti-oxidant and anti-inflammatory activities, attributable to its different chemical structure.
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Affiliation(s)
- Saioa Gómez-Zorita
- Nutrition and Obesity group, Department of Nutrition and Food Science, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Lucio Lascaray Research Centre, 01006 Vitoria-Gasteiz, Spain; (S.G.-Z.); (M.G.-A.); (L.A.); (E.I.); (M.P.P.)
- BIOARABA Institute of Health, 01009 Vitoria-Gasteiz, Spain
- CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III (ISCIII), 01006 Vitoria-Gasteiz, Spain;
| | - Maitane González-Arceo
- Nutrition and Obesity group, Department of Nutrition and Food Science, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Lucio Lascaray Research Centre, 01006 Vitoria-Gasteiz, Spain; (S.G.-Z.); (M.G.-A.); (L.A.); (E.I.); (M.P.P.)
| | - Jenifer Trepiana
- Nutrition and Obesity group, Department of Nutrition and Food Science, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Lucio Lascaray Research Centre, 01006 Vitoria-Gasteiz, Spain; (S.G.-Z.); (M.G.-A.); (L.A.); (E.I.); (M.P.P.)
- BIOARABA Institute of Health, 01009 Vitoria-Gasteiz, Spain
- CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III (ISCIII), 01006 Vitoria-Gasteiz, Spain;
| | - Leixuri Aguirre
- Nutrition and Obesity group, Department of Nutrition and Food Science, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Lucio Lascaray Research Centre, 01006 Vitoria-Gasteiz, Spain; (S.G.-Z.); (M.G.-A.); (L.A.); (E.I.); (M.P.P.)
- BIOARABA Institute of Health, 01009 Vitoria-Gasteiz, Spain
- CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III (ISCIII), 01006 Vitoria-Gasteiz, Spain;
| | - Ana B Crujeiras
- CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III (ISCIII), 01006 Vitoria-Gasteiz, Spain;
- Epigenomics in Endocrinology and Nutrition Group, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), 15704 Santiago de Compostela, Spain
| | - Esperanza Irles
- Nutrition and Obesity group, Department of Nutrition and Food Science, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Lucio Lascaray Research Centre, 01006 Vitoria-Gasteiz, Spain; (S.G.-Z.); (M.G.-A.); (L.A.); (E.I.); (M.P.P.)
| | - Nerea Segues
- Department of Gastroenterology, University of the Basque Country (UPV/EHU), Donostia Hospital, 00685 San Sebastián, Spain; (N.S.); (L.B.)
- BIODONOSTIA Institute of Health, 00685 San Sebastián, Spain
- CIBERehd Hepatic and Digestive Pathologies, Institute of Health Carlos III (ISCIII), 01006 Vitoria-Gasteiz, Spain
| | - Luis Bujanda
- Department of Gastroenterology, University of the Basque Country (UPV/EHU), Donostia Hospital, 00685 San Sebastián, Spain; (N.S.); (L.B.)
- BIODONOSTIA Institute of Health, 00685 San Sebastián, Spain
- CIBERehd Hepatic and Digestive Pathologies, Institute of Health Carlos III (ISCIII), 01006 Vitoria-Gasteiz, Spain
| | - María Puy Portillo
- Nutrition and Obesity group, Department of Nutrition and Food Science, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Lucio Lascaray Research Centre, 01006 Vitoria-Gasteiz, Spain; (S.G.-Z.); (M.G.-A.); (L.A.); (E.I.); (M.P.P.)
- BIOARABA Institute of Health, 01009 Vitoria-Gasteiz, Spain
- CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III (ISCIII), 01006 Vitoria-Gasteiz, Spain;
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Relative contribution of fat diet and physical inactivity to the development of metabolic syndrome and non-alcoholic fat liver disease in Wistar rats. Physiol Behav 2020; 225:113040. [PMID: 32603747 DOI: 10.1016/j.physbeh.2020.113040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 06/24/2020] [Accepted: 06/26/2020] [Indexed: 01/22/2023]
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Song L, Li Y, Qu D, Ouyang P, Ding X, Wu P, Guan Q, Yang L. The regulatory effects of phytosterol esters (PSEs) on gut flora and faecal metabolites in rats with NAFLD. Food Funct 2020; 11:977-991. [PMID: 31803887 DOI: 10.1039/c9fo01570a] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Recent studies have shown that the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) can be aggravated by dysregulation of intestinal flora. We previously found that phytosterol esters (PSEs) could effectively prevent the progression of NAFLD. Here, we further investigated the regulatory effect that PSEs have on gut flora and faecal metabolites in rats with NAFLD. Adult SD (Sprague Dawley) rats were randomized into four groups: the normal chow diet (NC), high-fat diet (HFD), low-dose PSE (0.05 g per 100 g BW, PSEL) and high-dose PSE (0.10 g per 100 g BW, PSEH) groups. PSEs were intragastrically administered once a day for 12 consecutive weeks. Our work indicated that high-dose PSE treatment effectively inhibited the increase in liver and abdominal fat indexes (P < 0.01) and hepatic lipids (P < 0.01); a high dose PSE treatment effectively corrected the HFD-induced intestinal flora imbalance by changing the diversity. The relative abundances of the four phyla (Firmicutes, Proteobacteria, Actinobacteria and Verrucomicrobia) and partial bacteria at the genus level (Faecalibacterium, Akkermansia, etc.) in the PSEH group were closer to those in the NC group. High-dose PSE intervention significantly increased the relative abundance of Bacteroidetes and Anaerostipes. Compared with the HFD, PSEH treatment significantly decreased the ionic strengths of bile acid metabolism products (P < 0.05), which were positively correlated with hepatic steatosis. In conclusion, PSE treatment exerts a beneficial effect on NAFLD that is associated with its regulatory action on intestinal flora and faecal metabolites, which might present a new opportunity to develop effective and safe preventive strategies against NAFLD.
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Affiliation(s)
- Lihua Song
- Research Center for Food Safety and Nutrition, Key Laboratory of Urban Agriculture (South), Bor S. Luh Food Safety Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
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Banerjee A, Das D, Paul R, Roy S, Das U, Saha S, Dey S, Adhikary A, Mukherjee S, Maji BK. Mechanistic study of attenuation of monosodium glutamate mixed high lipid diet induced systemic damage in rats by Coccinia grandis. Sci Rep 2020; 10:15443. [PMID: 32963259 PMCID: PMC7508805 DOI: 10.1038/s41598-020-72076-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 08/25/2020] [Indexed: 12/20/2022] Open
Abstract
In the context of failure of treatment for non alcoholic fatty liver disease (NAFLD)-mediated systemic damages, recognition of novel and successful characteristic drug to combat these anomalous situations is earnestly required. The present study is aimed to evaluate protective value of ethanol extract of Coccinia grandis leaves (EECGL), naturally occurring medicinal plant, on NAFLD-mediated systemic damage induced by high lipid diet along with monosodium glutamate (HM)-fed rats. Our study uncovered that EECGL significantly ameliorates HM-induced hyperlipidemia, increased lipogenesis and metabolic disturbances (via up regulation of PPAR-α and PPAR-γ), oxidative stress (via reducing the generation of reactive oxygen species and regulating the redox-homeostasis) and inflammatory response (via regulating the pro-inflammatory and anti-inflammatory factors with concomitant down regulation of NF-kB, iNOS, TNF-α and up regulation of eNOS). Furthermore, EECGL significantly inhibited HM-induced increased population of cells in sub G0/G1 phase, decreased Bcl2 expression and thereby loss of mitochondrial membrane potential with over expression of Bax, p53, p21, activation of caspase 3 and 9 indicated the apoptosis and suppression of cell survival. It is perhaps the first comprehensive study with a mechanistic approach which provides a strong unique strategy for the management of HM-induced systemic damage with effective dose of EECGL.
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Affiliation(s)
- Arnab Banerjee
- Department of Physiology (UG & PG), Serampore College, 9 William Carey Road, Serampore, Hooghly-712201, West Bengal, India
| | - Debasmita Das
- Department of Physiology (UG & PG), Serampore College, 9 William Carey Road, Serampore, Hooghly-712201, West Bengal, India
| | - Rajarshi Paul
- Department of Physiology (UG & PG), Serampore College, 9 William Carey Road, Serampore, Hooghly-712201, West Bengal, India
| | - Sandipan Roy
- Department of Physiology (UG & PG), Serampore College, 9 William Carey Road, Serampore, Hooghly-712201, West Bengal, India
| | - Ujjal Das
- Department of Physiology, University College of Science, Technology and Agriculture, University of Calcutta, 92 Acharya Prafulla Chandra Road, Kolkata-700009, West Bengal, India
| | - Samrat Saha
- Department of Physiology, University College of Science, Technology and Agriculture, University of Calcutta, 92 Acharya Prafulla Chandra Road, Kolkata-700009, West Bengal, India
| | - Sanjit Dey
- Department of Physiology, University College of Science, Technology and Agriculture, University of Calcutta, 92 Acharya Prafulla Chandra Road, Kolkata-700009, West Bengal, India
| | - Arghya Adhikary
- Centre for Research in Nanoscience and Nanotechnology, Acharya Prafulla Chandra Roy Sikhsha Prangan, University of Calcutta, JD-2, Sector-III, Saltlake City, Kolkata-700098, West Bengal, India
| | - Sandip Mukherjee
- Department of Physiology (UG & PG), Serampore College, 9 William Carey Road, Serampore, Hooghly-712201, West Bengal, India
| | - Bithin Kumar Maji
- Department of Physiology (UG & PG), Serampore College, 9 William Carey Road, Serampore, Hooghly-712201, West Bengal, India.
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Feng X, Zhu H, Chen B, Zhu C, Gong L, Hu Z, Zhang H. Effects of phytosterols supplementation on growth performance and intestinal microflora of yellow-feather broilers. Poult Sci 2020; 99:6022-6030. [PMID: 33142521 PMCID: PMC7647796 DOI: 10.1016/j.psj.2020.07.036] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/16/2020] [Accepted: 07/25/2020] [Indexed: 01/27/2023] Open
Abstract
This research investigated effects of dietary phytosterols supplementation on growth performance and cecal gut microflora in yellow-feather broilers. A total of 360 yellow-feather broilers (1-day-old) were randomly assigned to 3 treatment groups: control group (basal diet), antibiotic group (basal diet supplemented with 200 mg/kg oxytetracycline calcium and 250 mg/kg nosiheptide), and phytosterols groups (basal diet supplemented with 25 mg/kg phytosterols). Each treatment group had 6 replicates, and there were 20 broilers within each replicate. No treatment effects on average daily feed intake, average daily gain, and food conversion rate were observed. The antibiotic group had a lower liver index compared with control group and phytosterols group. Other visceral indexes including bursa of Fabricius, spleen, and heart were not different among the 3 treatment groups. In terms of alpha diversity, no treatment effects on Shannon and Simpson indexes were observed. Supplementation of phytosterols significantly decreased the Chao1 and Ace indexes, indicating lower community richness of the gut microflora. At phylum level, the phytosterols group had a higher abundance of Bacteroidetes compared with the control group. At genus level, no treatment effect was observed on the top 10 genera. Overall, supplementation of phytosterols at 25 mg/kg level did not affect the growth performance of yellow-feather broilers, and its effect on gut microflora was limited.
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Affiliation(s)
- Xin Feng
- School of Life Science and Engineering, Foshan University, Foshan, China
| | - Hui Zhu
- School of Life Science and Engineering, Foshan University, Foshan, China
| | - Bodong Chen
- School of Life Science and Engineering, Foshan University, Foshan, China
| | - Cui Zhu
- School of Life Science and Engineering, Foshan University, Foshan, China
| | - Li Gong
- School of Life Science and Engineering, Foshan University, Foshan, China
| | - Zhiyong Hu
- College of Animal Science and Technology, Shandong Agricultural University, Shandong, China
| | - Huihua Zhang
- School of Life Science and Engineering, Foshan University, Foshan, China.
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Lim DW, Jeon H, Kim M, Yoon M, Jung J, Kwon S, Cho S, Um MY. Standardized rice bran extract improves hepatic steatosis in HepG2 cells and ovariectomized rats. Nutr Res Pract 2020; 14:568-579. [PMID: 33282120 PMCID: PMC7683207 DOI: 10.4162/nrp.2020.14.6.568] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 02/29/2020] [Accepted: 06/25/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUD/OBJECTIVES Hepatic steatosis is the most common liver disorder, particularly in postmenopausal women. This study investigated the protective effects of standardized rice bran extract (RBS) on ovariectomized (OVX)-induced hepatic steatosis in rats. MATERIALS/METHODS HepG2 cells were incubated with 200 µM oleic acid to induce lipid accumulation with or without RBS and γ-oryzanol. OVX rats were separated into three groups and fed a normal diet (ND) or the ND containing 17β-estradiol (E2; 10 µg/kg) and RBS (500 mg/kg) for 16 weeks. RESULTS RBS supplementation improved serum triglyceride and free fatty acid levels in OVX rats. Histological analysis showed that RBS significantly attenuated hepatic fat accumulation and decreased hepatic lipid, total cholesterol, and triglyceride levels. Additionally, RBS suppressed the estrogen deficiency-induced upregulation of lipogenic genes, such as sterol regulatory element-binding protein 1 (SREBP1), acetyl-CoA carboxylase 1, fatty acid synthase, glycerol-3-phosphate acyltransferase, and stearoyl-CoA desaturase 1. CONCLUSIONS RBS and γ-oryzanol effectively reduced lipid accumulation in a HepG2 cell hepatic steatosis model. RBS improves OVX-induced hepatic steatosis by regulating the SREBP1-mediated activation of lipogenic genes, suggesting the benefits of RBS in preventing fatty liver in postmenopausal women.
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Affiliation(s)
- Dong Wook Lim
- Research Division of Food Functionality, Korea Food Research Institute, Wanju 55365, Korea
| | - Hyejin Jeon
- Research Division of Food Functionality, Korea Food Research Institute, Wanju 55365, Korea
| | - Minji Kim
- Division of Food Biotechnology, University of Science & Technology, Daejeon 34113, Korea
| | - Minseok Yoon
- Research Division of Food Functionality, Korea Food Research Institute, Wanju 55365, Korea
| | - Jonghoon Jung
- Technical Assistance Center, Korea Food Research Institute, Wanju 55365, Korea
| | - Sangoh Kwon
- S&D Research and Development Institute, Cheongju 28156, Korea
| | - Suengmok Cho
- Department of Food Science and Technology, Pukyong National University, Busan 48513, Korea
| | - Min Young Um
- Research Division of Food Functionality, Korea Food Research Institute, Wanju 55365, Korea.,Division of Food Biotechnology, University of Science & Technology, Daejeon 34113, Korea
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Chen Z, Tian R, She Z, Cai J, Li H. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radic Biol Med 2020; 152:116-141. [PMID: 32156524 DOI: 10.1016/j.freeradbiomed.2020.02.025] [Citation(s) in RCA: 768] [Impact Index Per Article: 153.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 02/20/2020] [Accepted: 02/26/2020] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide and is strongly associated with the presence of oxidative stress. Disturbances in lipid metabolism lead to hepatic lipid accumulation, which affects different reactive oxygen species (ROS) generators, including mitochondria, endoplasmic reticulum, and NADPH oxidase. Mitochondrial function adapts to NAFLD mainly through the downregulation of the electron transport chain (ETC) and the preserved or enhanced capacity of mitochondrial fatty acid oxidation, which stimulates ROS overproduction within different ETC components upstream of cytochrome c oxidase. However, non-ETC sources of ROS, in particular, fatty acid β-oxidation, appear to produce more ROS in hepatic metabolic diseases. Endoplasmic reticulum stress and NADPH oxidase alterations are also associated with NAFLD, but the degree of their contribution to oxidative stress in NAFLD remains unclear. Increased ROS generation induces changes in insulin sensitivity and in the expression and activity of key enzymes involved in lipid metabolism. Moreover, the interaction between redox signaling and innate immune signaling forms a complex network that regulates inflammatory responses. Based on the mechanistic view described above, this review summarizes the mechanisms that may account for the excessive production of ROS, the potential mechanistic roles of ROS that drive NAFLD progression, and therapeutic interventions that are related to oxidative stress.
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Affiliation(s)
- Ze Chen
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Institute of Model Animals of Wuhan University, Wuhan, 430072, PR China
| | - Ruifeng Tian
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Institute of Model Animals of Wuhan University, Wuhan, 430072, PR China
| | - Zhigang She
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Institute of Model Animals of Wuhan University, Wuhan, 430072, PR China; Basic Medical School, Wuhan University, Wuhan, 430071, PR China; Medical Research Institute, School of Medicine, Wuhan University, Wuhan, 430071, PR China
| | - Jingjing Cai
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, 410013, PR China; Institute of Model Animals of Wuhan University, Wuhan, 430072, PR China
| | - Hongliang Li
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Institute of Model Animals of Wuhan University, Wuhan, 430072, PR China; Basic Medical School, Wuhan University, Wuhan, 430071, PR China; Medical Research Institute, School of Medicine, Wuhan University, Wuhan, 430071, PR China.
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Kaur Kohli S, Bhardwaj A, Bhardwaj V, Sharma A, Kalia N, Landi M, Bhardwaj R. Therapeutic Potential of Brassinosteroids in Biomedical and Clinical Research. Biomolecules 2020; 10:E572. [PMID: 32283642 PMCID: PMC7226375 DOI: 10.3390/biom10040572] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/28/2020] [Accepted: 04/03/2020] [Indexed: 12/11/2022] Open
Abstract
Steroids are a pivotal class of hormones with a key role in growth modulation and signal transduction in multicellular organisms. Synthetic steroids are widely used to cure large array of viral, fungal, bacterial, and cancerous infections. Brassinosteroids (BRs) are a natural collection of phytosterols, which have structural similarity with animal steroids. BRs are dispersed universally throughout the plant kingdom. These plant steroids are well known to modulate a plethora of physiological responses in plants leading to improvement in quality as well as yield of food crops. Moreover, they have been found to play imperative role in stress-fortification against various stresses in plants. Over a decade, BRs have conquered worldwide interest due to their diverse biological activities in animal systems. Recent studies have indicated anticancerous, antiangiogenic, antiviral, antigenotoxic, antifungal, and antibacterial bioactivities of BRs in the animal test systems. BRs inhibit replication of viruses and induce cytotoxic effects on cancerous cell lines. Keeping in view the biological activities of BRs, this review is an attempt to update the information about prospects of BRs in biomedical and clinical application.
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Affiliation(s)
- Sukhmeen Kaur Kohli
- Plant Stress Physiology Lab, Department of Botanical and Environment Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India; (S.K.K.); (A.S.)
| | - Abhay Bhardwaj
- Department of Bio-organic and Biological Chemistry, Kharkiv National Medical University, Kharkiv 61000, Ukraine; (A.B.); (V.B.)
| | - Vinay Bhardwaj
- Department of Bio-organic and Biological Chemistry, Kharkiv National Medical University, Kharkiv 61000, Ukraine; (A.B.); (V.B.)
| | - Anket Sharma
- Plant Stress Physiology Lab, Department of Botanical and Environment Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India; (S.K.K.); (A.S.)
- State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou 311300, China
| | - Namarta Kalia
- Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar 143005, Punjab, India;
| | - Marco Landi
- Department of Agriculture, Food & Environment, University of Pisa, Via del Borghetto 80, 56124 Pisa, Italy
- Interdepartmental Research Center Nutrafood “Nutraceuticals and Food for Health”, University of Pisa, Via del Borghetto 80, 56124 Pisa, Italy
| | - Renu Bhardwaj
- Plant Stress Physiology Lab, Department of Botanical and Environment Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India; (S.K.K.); (A.S.)
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Combined effect of n-3 fatty acids and phytosterol esters on alleviating hepatic steatosis in non-alcoholic fatty liver disease subjects: a double-blind placebo-controlled clinical trial. Br J Nutr 2020; 123:1148-1158. [DOI: 10.1017/s0007114520000495] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
AbstractThe aim of this study was to investigate the combined effect of n-3 fatty acids (EPA and DHA, at an EPA:DHA ratio of 150:500) and phytosterol esters (PS) on non-alcoholic fatty liver disease (NAFLD) patients. We conducted a randomised, double-blind, placebo-controlled trial. Ninety-six NAFLD subjects were randomly assigned to the following groups: the PS group (receiving 3·3 g/d PS); the FO group (receiving 450 mg EPA + 1500 mg DHA/d); the PS + FO combination group (receiving 3·3 g/d PS and 450 mg EPA + 1500 mg DHA/d) and the PO group (a placebo group). The baseline clinical characteristics of the four groups were similar. The primary outcome was liver:spleen attenuation ratio (L:S ratio). The percentage increase in liver–spleen attenuation (≤1) in the PS + FO group was 36 % (P = 0·083), higher than those in the other three groups (PS group, 11 %, P = 0·519; FO group, 18 %, P = 0·071; PO group, 15 %, P = 0·436). Compared with baseline, transforming growth factor-β (TGF-β) was significantly decreased in the three study groups at the end of the trial (PS, P = 0·000; FO, P = 0·002; PS + FO, P = 0·001) and TNF-α was significantly decreased in the FO group (P = 0·036), PS + FO group (P = 0·005) and PO group (P = 0·032) at the end of the intervention. Notably, TGF-β was reduced significantly more in the PS + FO group than in the PO group (P = 0·032). The TAG and total cholesterol levels of the PS + FO group were reduced by 11·57 and 9·55 %, respectively. In conclusion, co-supplementation of PS and EPA + DHA could increase the effectiveness of treatment for hepatic steatosis.
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Wang J, Jiang W. The Effects of RKI-1447 in a Mouse Model of Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet and in HepG2 Human Hepatocellular Carcinoma Cells Treated with Oleic Acid. Med Sci Monit 2020; 26:e919220. [PMID: 32026851 PMCID: PMC7020744 DOI: 10.12659/msm.919220] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background This study aimed to investigate the effects of RKI-1447, a selective inhibitor of Rho-associated ROCK kinases, in a mouse model of nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet, and in oleic acid-treated HepG2 human hepatocellular carcinoma cells in vitro. Material/Methods Four study groups of mice included: the control group; the high-fat diet (HFD) group; the HFD+RKI-1447 (2 mg/kg) group; and the HFD+RKI-1447 (8 mg/kg) group. Mice were fed a high-fat diet for 12 weeks. Mice in the HFD+RKI-1447 groups were fed a high-fat diet for 12 weeks and treated with RKI-1447 twice weekly for three weeks. The HepG2 human hepatocellular carcinoma cells were treated with or without RKI-1447 for 2 h and treated with oleic acid for 24 h. Results In the mouse model of NAFLD, RKI-1447 reduced insulin resistance and the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total cholesterol, triglyceride, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD). RKI-1447 reduced the histological changes in the mouse model of NAFLD in mice fed a high-fat diet and significantly inhibited the generations of triglyceride, IL-6, and TNF-α. RKI-1447 reduced the levels of oxidative stress in HepG2 cells treated with oleic acid and significantly down-regulated the expression of RhoA, ROCK1, ROCK2, toll-like receptor 4 (TLR4), p-TBK1, and p-IRF3. RKI-1447 treatment also inhibited RhoA expression. Conclusions In a mouse model of NAFLD, RKI-1447 inhibited ROCK and modulated insulin resistance, oxidative stress, and inflammation through the ROCK/TLR4/TBK1/IRF3 pathway.
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Affiliation(s)
- Jinshan Wang
- Department of Transplantation, Tianjin First Central Hospital, Tianjin, China (mainland)
| | - Wentao Jiang
- Department of Transplantation, Tianjin First Central Hospital, Tianjin, China (mainland)
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Zhang QS, Tian FW, Zhao JX, Zhang H, Zhai QX, Chen W. The influence of dietary patterns on gut microbiome and its consequences for nonalcoholic fatty liver disease. Trends Food Sci Technol 2020. [DOI: 10.1016/j.tifs.2019.12.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Song L, Zhou H, Yu W, Ding X, Yang L, Wu J, Song C. Effects of Phytosterol Ester on the Fatty Acid Profiles in Rats with Nonalcoholic Fatty Liver Disease. J Med Food 2020; 23:161-172. [PMID: 31913753 DOI: 10.1089/jmf.2019.4468] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Both serum and hepatic fatty acid (FA) compositions differ among nonalcoholic hepatic steatosis, nonalcoholic steatohepatitis, and healthy subjects. The severity of the above liver disease is closely associated with the concentration and composition of FAs. Our previous study found that phytosterol ester (PSE) could alleviate hepatic steatosis in nonalcoholic fatty liver disease rats. The aims of this work were to explore the effects of PSE (0.05/100 g·body weight) on FA profiles and the mRNA levels of FA metabolism-related genes. Compared with a high-fat diet alone group, PSE treatment significantly decreased hepatic saturated fatty acid levels (P < .05) and increased monounsaturated fatty acid (especially C16:1 n-7) levels in the liver, serum, and adipose tissue and polyunsaturated fatty acid levels in the serum and liver (P < .05) after 12 weeks of intervention. In particular, PSE treatment increased the level of C22:5 n-3, an FA that was negatively correlated with the degree of hepatic steatosis in the serum, liver, and adipose tissue. The increases in some unsaturated fatty acids are probably related to the upregulation of stearoyl-coenzyme A desaturase-1 and fatty acid desaturase-1.
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Affiliation(s)
- Lihua Song
- Department of Food Science and Technology, Bor S. Luh Food Safety Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Haiyue Zhou
- Department of Food Science and Technology, Bor S. Luh Food Safety Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Wenjuan Yu
- Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, China
| | - Xinwen Ding
- Department of Food Science and Technology, Bor S. Luh Food Safety Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Li Yang
- Department of Food Science and Technology, Bor S. Luh Food Safety Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Jiayi Wu
- Department of Food Science and Technology, Bor S. Luh Food Safety Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Chenwei Song
- Department of Food Science and Technology, Bor S. Luh Food Safety Research Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
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Hendrikx T, Binder CJ. Oxidation-Specific Epitopes in Non-Alcoholic Fatty Liver Disease. Front Endocrinol (Lausanne) 2020; 11:607011. [PMID: 33362721 PMCID: PMC7756077 DOI: 10.3389/fendo.2020.607011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 11/04/2020] [Indexed: 12/11/2022] Open
Abstract
An improper balance between the production and elimination of intracellular reactive oxygen species causes increased oxidative stress. Consequently, DNA, RNA, proteins, and lipids are irreversibly damaged, leading to molecular modifications that disrupt normal function. In particular, the peroxidation of lipids in membranes or lipoproteins alters lipid function and promotes formation of neo-epitopes, such as oxidation-specific epitopes (OSEs), which are found to be present on (lipo)proteins, dying cells, and extracellular vesicles. Accumulation of OSEs and recognition of OSEs by designated pattern recognition receptors on immune cells or soluble effectors can contribute to the development of chronic inflammatory diseases. In line, recent studies highlight the involvement of modified lipids and OSEs in different stages of the spectrum of non-alcoholic fatty liver disease (NAFLD), including inflammatory non-alcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. Targeting lipid peroxidation products shows high potential in the search for novel, better therapeutic strategies for NASH.
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Affiliation(s)
- Tim Hendrikx
- Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, Netherlands
- Department of Laboratory Medicine, Medical University Vienna, Vienna, Austria
| | - Christoph J. Binder
- Department of Laboratory Medicine, Medical University Vienna, Vienna, Austria
- Research Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM), Vienna, Austria
- *Correspondence: Christoph J. Binder,
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Yang JM, Sun Y, Wang M, Zhang XL, Zhang SJ, Gao YS, Chen L, Wu MY, Zhou L, Zhou YM, Wang Y, Zheng FJ, Li YH. Regulatory effect of a Chinese herbal medicine formula on non-alcoholic fatty liver disease. World J Gastroenterol 2019; 25:5105-5119. [PMID: 31558860 PMCID: PMC6747291 DOI: 10.3748/wjg.v25.i34.5105] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 06/14/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become a major cause of chronic liver disease. The Chinese herbal medicine (CHM) Dachaihu decoction (DCHD) has been proved to treat NAFLD with good efficacy in previous studies. Based on the TCM principle of formula formation, we divided DCHD into soothing liver part, invigorating spleen part, and dredging intestine part. Marshall officially proposed the concept of “intestinal-hepatic axis”, which systematically explains the interactions between the intestine and liver. We hypothesized that the effect of CHM on NAFLD is achieved by regulating the liver and intestine. Thus, we aimed to investigate the possible effect of a CHM formula on NAFLD in a rat model.
AIM To investigate the effects of a CHM formula (a decoction of Chinese thorowax root, scutellaria root, and white peony root) on NAFLD and its regulatory effect on the “intestinal-liver” axis.
METHODS Sixty rats were randomly divided into control, model, pioglitazone hydrochloride (PH), and CHM (a decoction of Chinese thorowax root, scutellaria root, and white peony root) groups. An NAFLD rat model was established using a high-fat high-fructose diet for 16 wk. From the 13th week, rats were administered with PH or a decoction of Chinese thorowax, scutellaria, and white peony root (CHM group) for 4 wk. Rats in the control group and model group were administered with an equal volume of distilled water. At the end of the study, blood was collected via the abdominal aorta. Liver tissues were harvested and any morphological changes were observed by hematoxylin-eosin (HE) staining, Oil red O staining, and Masson staining. In addition, blood lipids, liver function markers, and triglyceride (TG) in liver tissues were analyzed. The levels of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), Toll-like receptor-4 (TLR4), and nuclear factor-kappa B (NF-кB) in liver tissues and secreted immunoglobulin A (sIgA) in intestinal tissues were analyzed by ELISA, and protein and mRNA expression of occludin and zonula occludens-1 (ZO-1) in the intestine were measured using Western blot and reverse transcription-quantitative polymerase chain reaction, respectively. The endotoxin level in plasma was detected by endpoint chromogenic assay.
RESULTS Compared to the normal control group, the liver coefficient, serum TG, total cholesterol (TC), low density lipoprotein (LDL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), blood glucose, plasma endotoxin, and the levels of TG, TNF-α, TGF-β, NF-kB, and TLR4 in liver tissues increased significantly in the model group, while serum high density lipoprotein (HDL), intestinal sIgA, and protein and mRNA expression of occludin and ZO-1 decreased significantly in the model group (P < 0.01). PH and CHM attenuated the elevated liver coefficient, serum TG, TC, LDL, AST, and ALT, blood glucose, plasma endotoxin, and the levels of TG, TNF-α, TGF-β, NF-kB, and TLR4 in liver tissues and increased serum HDL levels compared to the model group (P < 0.01). Intestinal sIgA and the protein and mRNA expression of intestinal occludin and ZO-1 were significantly increased in the PH group compared to the model and CHM groups (P < 0.01).
CONCLUSION The decoction of Chinese thorowax root, scutellaria root, and white peony root is beneficial in regulating lipid metabolism and liver function, which indicates that it has a good effect on the liver. To a certain extent, this CHM formula can affect both the liver and intestine, while its effect on the liver is superior to that on the intestine.
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Affiliation(s)
- Jia-Min Yang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yan Sun
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Min Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xin-Lei Zhang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Shu-Jing Zhang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yu-Shan Gao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Lin Chen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Meng-Yao Wu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Lu Zhou
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yu-Mei Zhou
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yue Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Feng-Jie Zheng
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yu-Hang Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
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Ore A, Akinloye OA. Oxidative Stress and Antioxidant Biomarkers in Clinical and Experimental Models of Non-Alcoholic Fatty Liver Disease. ACTA ACUST UNITED AC 2019; 55:medicina55020026. [PMID: 30682878 PMCID: PMC6410206 DOI: 10.3390/medicina55020026] [Citation(s) in RCA: 107] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Accepted: 01/18/2019] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a term that covers a range of hepatic disorders involving fat deposits in the liver. NAFLD begins with simple steatosis and progresses into non-alcoholic steatohepatitis (NASH) characterised by inflammation, fibrosis, apoptosis, oxidative stress, lipid peroxidation, mitochondrial dysfunction and release of adipokines and pro-inflammatory cytokines. Oxidative stress and antioxidants are known to play a vital role in the pathogenesis and severity of NAFLD/NASH. A number of oxidative stress and antioxidant markers are employed in the assessment of the pathological state and progression of the disease. In this article, we review several biomarkers of oxidative stress and antioxidants that have been measured at clinical and experimental levels. Also included is a comprehensive description of oxidative stress, sources and contribution to the pathogenesis of NAFLD/NASH.
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Affiliation(s)
- Ayokanmi Ore
- Department of Biochemistry, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria.
- Biochemistry Division, Department of Chemical Sciences, Faculty of Natural Sciences, Ajayi Crowther University, Oyo, Nigeria.
| | - Oluseyi Adeboye Akinloye
- Department of Biochemistry, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria.
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Low-linoleic acid diet and oestrogen enhance the conversion of α-linolenic acid into DHA through modification of conversion enzymes and transcription factors. Br J Nutr 2018; 121:137-145. [DOI: 10.1017/s0007114518003252] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AbstractConversion of α-linolenic acid (ALA) into the longer chain n-3 PUFA has been suggested to be affected by the dietary intake of linoleic acid (LA), but the mechanism is not well known. Therefore, the purpose of this study was to evaluate the effect of a low-LA diet with and without oestrogen on the fatty acid conversion enzymes and transcription factors. Rats were fed a modified American Institute of Nutrition-93G diet with 0% n-3 PUFA or ALA, containing low or high amounts of LA for 12 weeks. At 8 weeks, the rats were injected with maize oil with or without 17β-oestradiol-3-benzoate (E) at constant intervals for the remaining 3 weeks. Both the low-LA diet and E significantly increased the hepatic expressions of PPAR-α, fatty acid desaturase (FADS) 2, elongase of very long chain fatty acids 2 (ELOVL2) and ELOVL5 but decreased sterol regulatory element binding protein 1. The low-LA diet, but not E, increased the hepatic expression of FADS1, and E increased the hepatic expression of oestrogen receptor-α and β. The low-LA diet and E had synergic effects on serum and liver levels of DHA and on the hepatic expression of PPAR-α. In conclusion, the low-LA diet and oestrogen increased the conversion of ALA into DHA by upregulating the elongases and desaturases of fatty acids through regulating the expression of transcription factors. The low-LA diet and E had a synergic effect on serum and liver levels of DHA through increasing the expression of PPAR-α.
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El-Sherbiny M, Eldosoky M, El-Shafey M, Othman G, Elkattawy HA, Bedir T, Elsherbiny NM. Vitamin D nanoemulsion enhances hepatoprotective effect of conventional vitamin D in rats fed with a high-fat diet. Chem Biol Interact 2018; 288:65-75. [PMID: 29653100 DOI: 10.1016/j.cbi.2018.04.010] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 03/27/2018] [Accepted: 04/10/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is associated with hyperlipidemia, obesity and type II diabetes. Due to increasing prevalence of these diseases globally, NAFLD is considered as a common form of chronic liver diseases. Vitamin D is a fat soluble vitamin with reported anti-inflammatory, anti-oxidant and immune modulating activity. Hypovitaminosis D often coexists with NAFLD and various studies reported beneficial role of vitamin D in modulating NAFLD. However, variable oral bioavailability, poor water solubility, and chemical degradation hinder the clinical application of vitamin D. PURPOSE We evaluated the potential protective effect of Vitamin D nanoemulsion (developed by sonication and pH-Shifting of pea protein isolate and canola oil) compared to conventional vitamin D against liver injury in rats fed with high fat diet (HFD). METHODS We analyzed liver function enzymes, lipid profile, lipid metabolism, levels and histopathology of inflammation and fibrosis in rat liver tissues. RESULTS HFD fed rats exhibited deterioration of liver function, poor lipid profile, decreased fatty acid oxidation and up-regulation of inflammatory cytokines and extracellular matrix deposition. Vitamin D administration reduced elevated liver enzymes, improved lipid profile, enhanced fatty acid oxidation and attenuated liver inflammation and fibrosis. Interestingly, vitamin D nanoemulsion was superior to conventional vitamin D with remarkable hepatoprotective effect against HFD-induced liver injury. CONCLUSION This study demonstrated vitamin D nanoemulsion as a more efficient formulation with more prominent hepatoprotective effect against HFD-induced liver injury compared to conventional oral vitamin D.
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Affiliation(s)
- Mohamed El-Sherbiny
- Anatomy Department, Mansoura Faculty of Medicine, Egypt; Almaarefa College of Medicine, Riyadh, Saudi Arabia
| | - Mohamed Eldosoky
- Medical Physiology Department, Mansoura Faculty of Medicine, Egypt
| | - Mohamed El-Shafey
- Anatomy Department, Mansoura Faculty of Medicine, Egypt; Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia
| | - Gamal Othman
- Medical Biochemistry Department, Mansoura Faculty of Medicine, Egypt; Almaarefa College of Medicine, Riyadh, Saudi Arabia
| | - Hany A Elkattawy
- Medical Physiology Department, Zagazig Obesity Management and Research Unit, Zagazig Faculty of Medicine, Egypt; Almaarefa College of Medicine, Riyadh, Saudi Arabia
| | - Tamer Bedir
- Medical Microbiology and Immunology Department, Mansoura Faculty of Medicine, Egypt
| | - Nehal Mohsen Elsherbiny
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Egypt.
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