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      KCI등재 SCOPUS SCIE

      Malus toringoides (Rehd.) Hughes Ameliorates Nonalcoholic Fatty Liver Disease with Diabetes via Downregulation of SREBP-1c and the NF-κB Pathway In Vivo and In Vitro

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      https://www.riss.kr/link?id=A108472056

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      다국어 초록 (Multilingual Abstract)

      Diabetic patients are more prone to developing nonalcoholic fatty liver disease (NAFLD) compared with healthy people. As a plant homologous to both medicine and food, Malus toringoides (Rehd.) Hughes has been used as an intervention for both NAFLD and...

      Diabetic patients are more prone to developing nonalcoholic fatty liver disease (NAFLD) compared with healthy people. As a plant homologous to both medicine and food, Malus toringoides (Rehd.) Hughes has been used as an intervention for both NAFLD and diabetes. However, the effect and mechanism of M. toringoides on NAFLD on type 2 diabetes mellitus (T2DM) is unclear. The current investigation was designed to evaluate the ameliorative effects and mechanism of M. toringoides ethanol extract (CBTM-E375) on T2DM, and to identify the compounds in these extracts. The effects of CBTM-E375 on T2DM were verified using a high-fat diet-/streptozotocin-induced diabetic rat and free fatty acid (0.5 mM)-induced human hepatocellular carcinoma cell (HepG2) models. The components of CBTM-E375 were identified by high performance liquid chromatography-mass spectrometry/mass spectrometry. Our results demonstrate that CBTM-E375 ameliorated lipid accumulation (total cholesterol, triglyceride), oxidative stress (superoxide dismutase, catalase, malondialdehyde, glutathione peroxidase), and inflammation (tumor necrosis factor-α [TNF-α], interleukin [IL]-1β, IL-6, C-reactive protein [CRP]) in vivo and in vitro, these effects were associated with a CBTM-E375-mediated downregulation of SREBP-1c (sterol regulatory element binding protein 1c) and the NF-κB (nuclear factor κB) signaling pathway. A total of 20 chemical compounds were identified in CBTM-E375, including phlorizin, isoquercitrin, chlorogenic acid, quercetin, naringenin, and trigonelline, which have been reported to have positive effects on diabetes or on NAFLD.

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      참고문헌 (Reference) 논문관계도

      1 Yinyan Li, "Trigonelline reduced diabetic nephropathy and insulin resistance in type�2 diabetic rats through peroxisome proliferator‑activated receptor‑γ" Spandidos Publications 2019

      2 Sheng Zhong, "The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease" Ovid Technologies (Wolters Kluwer Health) 96 (96): e9061-, 2017

      3 John Baptist Nzukizi Mudumbi, "The role of pollutants in type 2 diabetes mellitus (T2DM) and their prospective impact on phytomedicinal treatment strategies" Springer Science and Business Media LLC 190 (190): 2018

      4 Megan Gow, "The Effectiveness of Different Diet Strategies to Reduce Type 2 Diabetes Risk in Youth" MDPI AG 8 (8): 486-, 2016

      5 Xu HF, "Sterol regulatory element binding protein-1 (SREBP-1)c promoter: Characterization and transcriptional regulation by mature SREBP-1 and liver X receptor a in goat mammary epithelial cells" 99 (99): 1595-1604, 2016

      6 S. Tatulashvili, "Socioeconomic inequalities and type 2 diabetes complications: A systematic review" Elsevier BV 46 (46): 89-99, 2020

      7 Ahmed Elgebaly, "Resveratrol Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-analysis" Romanian Society of Gastroenterology and Hepatology 26 (26): 59-67, 2017

      8 Neda Laiteerapong, "Response to Comment on Laiteerapong et al. The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (The Diabetes & Aging Study). Diabetes Care 2019;42:416–426" American Diabetes Association 42 (42): e46-e47, 2019

      9 Li D, "Quercetin alleviates ferroptosis of pancreatic b cells in type 2 diabetes" 12 (12): 2954-, 2020

      10 Huazhen Liu, "Phloridzin Ameliorates Lipid Deposition in High-Fat-Diet-Fed Mice with Nonalcoholic Fatty Liver Disease via Inhibiting the mTORC1/SREBP-1c Pathway" American Chemical Society (ACS) 69 (69): 8671-8683, 2021

      1 Yinyan Li, "Trigonelline reduced diabetic nephropathy and insulin resistance in type�2 diabetic rats through peroxisome proliferator‑activated receptor‑γ" Spandidos Publications 2019

      2 Sheng Zhong, "The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease" Ovid Technologies (Wolters Kluwer Health) 96 (96): e9061-, 2017

      3 John Baptist Nzukizi Mudumbi, "The role of pollutants in type 2 diabetes mellitus (T2DM) and their prospective impact on phytomedicinal treatment strategies" Springer Science and Business Media LLC 190 (190): 2018

      4 Megan Gow, "The Effectiveness of Different Diet Strategies to Reduce Type 2 Diabetes Risk in Youth" MDPI AG 8 (8): 486-, 2016

      5 Xu HF, "Sterol regulatory element binding protein-1 (SREBP-1)c promoter: Characterization and transcriptional regulation by mature SREBP-1 and liver X receptor a in goat mammary epithelial cells" 99 (99): 1595-1604, 2016

      6 S. Tatulashvili, "Socioeconomic inequalities and type 2 diabetes complications: A systematic review" Elsevier BV 46 (46): 89-99, 2020

      7 Ahmed Elgebaly, "Resveratrol Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-analysis" Romanian Society of Gastroenterology and Hepatology 26 (26): 59-67, 2017

      8 Neda Laiteerapong, "Response to Comment on Laiteerapong et al. The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (The Diabetes & Aging Study). Diabetes Care 2019;42:416–426" American Diabetes Association 42 (42): e46-e47, 2019

      9 Li D, "Quercetin alleviates ferroptosis of pancreatic b cells in type 2 diabetes" 12 (12): 2954-, 2020

      10 Huazhen Liu, "Phloridzin Ameliorates Lipid Deposition in High-Fat-Diet-Fed Mice with Nonalcoholic Fatty Liver Disease via Inhibiting the mTORC1/SREBP-1c Pathway" American Chemical Society (ACS) 69 (69): 8671-8683, 2021

      11 Guang-Hui Chen, "PPARα, PPARγ and SREBP-1 pathways mediated waterborne iron (Fe)-induced reduction in hepatic lipid deposition of javelin goby Synechogobius hasta" Elsevier BV 197 : 8-18, 2017

      12 Qiang Ye, "Optimization of Ultrasound-Assisted Extraction on Antioxidative Activity of Malus toringoides Using Response Surface Methodology" MDPI AG 7 (7): 270-, 2019

      13 Mohamed A. Lounis, "Oleate activates SREBP-1 signaling activity in SCD1-deficient hepatocytes" American Physiological Society 313 (313): E710-E720, 2017

      14 Enoch Cobbina, "Non-alcoholic fatty liver disease (NAFLD) – pathogenesis, classification, and effect on drug metabolizing enzymes and transporters" Informa UK Limited 49 (49): 197-211, 2017

      15 M. G. Radaelli, "NAFLD/NASH in patients with type 2 diabetes and related treatment options" Springer Science and Business Media LLC 41 (41): 509-521, 2017

      16 Scott L. Friedman, "Mechanisms of NAFLD development and therapeutic strategies" Springer Science and Business Media LLC 24 (24): 908-922, 2018

      17 Josephine M. Forbes, "Mechanisms of Diabetic Complications" American Physiological Society 93 (93): 137-188, 2013

      18 Neal Barnard, "Meat Consumption as a Risk Factor for Type 2 Diabetes" MDPI AG 6 (6): 897-910, 2014

      19 Victoria Jideonwo, "Impact of silencing hepatic SREBP-1 on insulin signaling" Public Library of Science (PLoS) 13 (13): e0196704-, 2018

      20 Shan Huang ; Haifeng Liu ; Ning Meng ; Bin Li ; Jule Wang, "Hypolipidemic and Antioxidant Effects of Malus toringoides (Rehd.) Hughes Leaves in High-Fat-Diet-Induced Hyperlipidemic Rats" 한국식품영양과학회 20 (20): 258-264, 2017

      21 Xiao-Li Huang, "Hepatoprotective potential of isoquercitrin against type 2 diabetes-induced hepatic injury in rats" Impact Journals, LLC 8 (8): 101545-101559, 2017

      22 Xiaowei Huo, "Hepatoprotective Effect of Aqueous Extract from the Seeds of Orychophragmus violaceus against Liver Injury in Mice and HepG2 Cells" MDPI AG 18 (18): 1197-, 2017

      23 Ter KH, "Fructose consumption, lipogenesis, and nonalcoholic fatty liver disease" MDPI AG 9 (9): 981-, 2017

      24 Anandakumar Amutha, "Diabetes complications in childhood and adolescent onset type 2 diabetes—a review" Elsevier BV 30 (30): 951-957, 2016

      25 Álvaro de Mingo, "Cysteine cathepsins control hepatic NF-κB-dependent inflammation via sirtuin-1 regulation" Springer Science and Business Media LLC 7 (7): e2464-e2464, 2016

      26 Pedro M. Rodrigues, "Correction: Corrigendum: Inhibition of NF-κB by deoxycholic acid induces miR-21/PDCD4-dependent hepatocellular apoptosis" Springer Science and Business Media LLC 6 (6): 27828-, 2016

      27 Wei-Yu Su, "Comparison of the Effects of Fasting Glucose, Hemoglobin A1c, and Triglyceride–Glucose Index on Cardiovascular Events in Type 2 Diabetes Mellitus" MDPI AG 11 (11): 2838-, 2019

      28 Linden MA, "Combining metformin and aerobic exercise training in the treatment of type 2diabetes and NAFLD in oletf rats" 306 (306): E300-, 2013

      29 Wang Y, "Chlorogenic acid inhibits forming of diabetes mellitus in rats induced by high-fat high-sucrose and streptozotocin" 33 (33): 1063-1072, 2020

      30 Jiarui Nie, "Caffeic Acid Phenethyl Ester (Propolis Extract) Ameliorates Insulin Resistance by Inhibiting JNK and NF-κB Inflammatory Pathways in Diabetic Mice and HepG2 Cell Models" American Chemical Society (ACS) 65 (65): 9041-9053, 2017

      31 Dan Li, "Antidiabetic effect of flavonoids from Malus toringoides (Rehd.) Hughes leaves in diabetic mice and rats" Elsevier BV 153 (153): 561-567, 2014

      32 Danja J. Den Hartogh, "Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol" MDPI AG 9 (9): 99-, 2019

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