{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T13:52:49Z","timestamp":1782913969871,"version":"3.54.5"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2016,5,13]],"date-time":"2016-05-13T00:00:00Z","timestamp":1463097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: The aim of this study was to explore the mechanism by which amentoflavone (AME) improves insulin resistance in a human hepatocellular liver carcinoma cell line (HepG2). Methods: A model of insulin resistant cells was established in HepG2 by treatment with high glucose and insulin. The glucose oxidase method was used to detect the glucose consumption in each group. To determine the mechanism by which AME improves insulin resistance in HepG2 cells, enzyme-linked immunosorbent assay (ELISA) and western blotting were used to detect the expression of phosphatidyl inositol 3-kinase (PI3K), Akt, and pAkt; the activity of the enzymes involved in glucose metabolism; and the levels of inflammatory cytokines. Results: Insulin resistance was successfully induced in HepG2 cells. After treatment with AME, the glucose consumption increased significantly in HepG2 cells compared with the model group (MG). The expression of PI3K, Akt, and pAkt and the activity of 6-phosphofructokinas (PFK-1), glucokinase (GCK), and pyruvate kinase (PK) increased, while the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxylase kinase (PEPCK), and glucose-6-phosphatase (G-6-Pase) as well as the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-\u03b1 (TNF-\u03b1), and C reactive protein (CRP) decreased. Conclusions: The mechanism by which treatment with AME improves insulin resistance in HepG2 cells may involve the PI3K-Akt signaling pathway, the processes of glucose oxygenolysis, glycogen synthesis, gluconeogenesis and inflammatory cytokine expression.<\/jats:p>","DOI":"10.3390\/molecules21050624","type":"journal-article","created":{"date-parts":[[2016,5,13]],"date-time":"2016-05-13T11:53:16Z","timestamp":1463140396000},"page":"624","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["The Mechanism by Which Amentoflavone Improves Insulin Resistance in HepG2 Cells"],"prefix":"10.3390","volume":"21","author":[{"given":"Xiaoke","family":"Zheng","sequence":"first","affiliation":[{"name":"School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Ke","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aozi","family":"Feng","sequence":"additional","affiliation":[{"name":"Center for Artery Atheroscerosis Research, Havana University of Medical Sciences, Havana 999075, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peipei","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weisheng","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China"},{"name":"Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/B978-0-12-385116-1.00004-2","article-title":"Measurement of the increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese insulin-resistant individuals","volume":"489","author":"Boden","year":"2011","journal-title":"Methods Enzymol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/pmic.201100312","article-title":"Inter-organ proteomic analysis reveals insights into the molecular mechanisms underlying the anti-diabetic effects of cis-9, trans-11-conjugated linoleic acid in ob\/ob mice","volume":"12","author":"Rungapamestry","year":"2012","journal-title":"Proteomics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-med-061511-134747","article-title":"Application of metabolomics to diagnosis of insulin resistance","volume":"64","author":"Milburn","year":"2013","journal-title":"Annu. 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