Naringenin improve hepatitis C virus infection induced insulin resistance by increase PTEN expression via p53-dependent manner.

Hepatitis C virus (HCV) infection may finally lead to hepatocellular carcinoma (HCC), and also associated with insulin resistance (IR). Naringenin (NGEN), a flavonoid found in grapefruit, has anti-virus, anti-inflammation and insulin sensitization effects. In the present study we examined the effects of NGEN on HCV core protein (HCVCP) infection induced IR and investigated the mechanism involved. We found that NGEN ameliorated IR and glucose tolerance in HCVCP infected mice by increase the phosphorylation of Akt at both Ser473 and Thr308 site, and also inhibited the inflammation cytokine production and T-cell immune response. Similar to the in vivo results, NGEN also improved the insulin response and showed anti-inflammation effect in HCVCP infected Huh-7.5.1 cells. In addition, NGEN up-regulated the phosphatase and tensin homolog deleted on chromosome ten (PTEN) both in protein and mRNA levels. Furthermore, overexpress of PTEN abolished the HCVCP-stimulated IR and decreased the inflammation cytokine release. NGEN also blocked the interaction between HCVCP and p53, upregulated the endogenous p21/waf1 expression which indiacting the activation of p53. The p53 wild type could upregulate NGEN-stimulated PTEN expression while R273H mut-p53 showed no similar function. Our data reveals that NGEN increases insulin sensitivity in HCVCP infected liver by up-regulating PTEN in p53-dependent manner.

• Publication year

  2018

• Venue

  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

• Publication date

  2018-07-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.biopha.2018.04.110PMID 29684853
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Naringenin attenuates hepatitis B virus X protein-induced hepatic steatosis

  2017cited by this paper
• The citrus flavanone naringenin impairs dengue virus replication in human cells

  2017cited by this paper
• Naringenin Ameliorates Acute Inflammation by Regulating Intracellular Cytokine Degradation

  2017cited by this paper
• PTEN, Insulin Resistance and Cancer.

  2017cited by this paper
• Naringenin and quercetin – potential anti-HCV agents for NS2 protease targets

  2016cited by this paper
• Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats.

  2016cited by this paper
• Global epidemiology of hepatitis C virus infection: An up-date of the distribution and circulation of hepatitis C virus genotypes

  2016cited by this paper
• Inhibition of chikungunya virus replication by hesperetin and naringenin

  2016cited by this paper
• Effects of Naringenin on Inflammation in Complete Freund’s Adjuvant-Induced Arthritis by Regulating Bax/Bcl-2 Balance

  2015cited by this paper
• Inhibition of IRS-1 by hepatitis C virus infection leads to insulin resistance in a PTEN-dependent manner

  2015cited by this paper
• Hepatitis C virus infection and insulin resistance.

  2014cited by this paper
• Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action.

  2014cited by this paper
• Hepatitis C virus and metabolic disorder interactions towards liver damage and atherosclerosis.

  2014cited by this paper
• Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr−/− mice[S]

  2013cited by this paper
• Naringenin (Citrus Flavonone) Induces Growth Inhibition, Cell Cycle Arrest and Apoptosis in Human Hepatocellular Carcinoma Cells

  2013cited by this paper
• Hepatitis C virus core protein stimulates fibrogenesis in hepatic stellate cells involving the obese receptor

  2013cited by this paper
• Chronic HCV infection and inflammation: Clinical impact on hepatic and extra-hepatic manifestations.

  2013cited by this paper
• Hepatitis C Virus Activates the mTOR/S6K1 Signaling Pathway in Inhibiting IRS-1 Function for Insulin Resistance

  2012cited by this paper
• The Hepatitis C Virus Modulates Insulin Signaling Pathway In Vitro Promoting Insulin Resistance

  2012cited by this paper
• The functions and regulation of the PTEN tumour suppressor

  2012cited by this paper
• A humanized mouse model to study hepatitis C virus infection, immune response, and liver disease.

  2011cited by this paper
• Importance of hepatitis C virus-associated insulin resistance: therapeutic strategies for insulin sensitization.

  2010cited by this paper
• Naringenin enhances insulin-stimulated tyrosine phosphorylation and improves the cellular actions of insulin in a dietary model of metabolic syndrome

  2010cited by this paper
• Naringenin inhibits the assembly and long-term production of infectious hepatitis C virus particles through a PPAR-mediated mechanism.

  2010cited by this paper
• Naringenin Prevents Dyslipidemia, Apolipoprotein B Overproduction, and Hyperinsulinemia in LDL Receptor–Null Mice With Diet-Induced Insulin Resistance

  2009cited by this paper
• Biological activity of metal ions complexes of chromones, coumarins and flavones

  2009cited by this paper
• TNF-α Inhibits Insulin Action in Liver and Adipose Tissue: A Model of Metabolic Syndrome

  2009cited by this paper
• Naringenin has anti-inflammatory properties in macrophage and ex vivo human whole-blood models.

  2008cited by this paper
• Inhibition of T-cell inflammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin.

  2007cited by this paper
• Effects of HCV NS4B on p53 gene expression and apoptosis in hepatic cells

  2007cited by this paper
• Obesity, inflammation, and insulin resistance.

  2007cited by this paper
• HCV core protein immunization with Montanide/CpG elicits strong Th1/Th2 and long-lived CTL responses.

  2007cited by this paper
• Essential Role of Pten in Body Size Determination and Pancreatic β-Cell Homeostasis In Vivo

  2006cited by this paper
• Pten (phosphatase and tensin homologue gene) haploinsufficiency promotes insulin hypersensitivity

  2006cited by this paper
• Insulin Hypersensitivity and Resistance to Streptozotocin-Induced Diabetes in Mice Lacking PTEN in Adipose Tissue

  2005cited by this paper
• Targeting of Hepatitis C Virus Core Protein to Mitochondria through a Novel C-Terminal Localization Motif

  2004cited by this paper
• HCV NS5A abrogates p53 protein function by interfering with p53-DNA binding.

  2004cited by this paper
• Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation.

  2004cited by this paper
• The phosphoinositide 3-kinase pathway.

  2002cited by this paper
• HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis

  2002cited by this paper
• Regulation of PTEN transcription by p53.

  2001cited by this paper
• The multiple roles of PTEN in tumor suppression.

  2000cited by this paper
• Imaging transgene expression with radionuclide imaging technologies.

  2000cited by this paper
• Activation of p53 tumor suppressor by hepatitis C virus core protein.

  1999cited by this paper
• Suppression of human colorectal carcinoma cell growth by wild-type p53.

  1990cited by this paper

• Naringenin-loaded, tween 80-coated chitosan nanoparticles: a promising therapeutic for streptozotocin induced cognitive deficit in mice

  2025cites this paper
• Comparative efficacy of Naringenin and Sinomenine in facilitating the differentiation of mouse hematopoietic stem cells into immature dendritic cells to promote transplantation immunological regulation.

  2025cites this paper
• PTEN regulation in virus-associated cancers.

  2024cites this paper
• Flavonoids improve type 2 diabetes mellitus and its complications: a review

  2023cites this paper
• The protective roles of citrus flavonoids, naringenin, and naringin on endothelial cell dysfunction in diseases

  2023cites this paper
• Chiral Separation, Configuration Confirmation and Bioactivity Determination of the Stereoisomers of Hesperidin and Narirutin in Citrus reticulata Blanco

  2023cites this paper
• Four flavonoids from propolis ameliorate free fatty acids-induced non-alcoholic steatohepatitis in HepG2 cells: Involvement of enhanced AMPK activation, mTOR-NF-κBp65 interaction, and PTEN expression

  2023cites this paper
• BCL2L1 is identified as a target of naringenin in regulating ovarian cancer progression

  2022cites this paper
• Development and in vitro evaluation of pH-sensitive naringenin@ZIF-8 polymeric micelles mediated by aptamer

  2021cites this paper
• Preoperative Management of Surgical Patients Using Dietary Supplements: Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement.

  2021cites this paper
• Traditional Indian plants as the source of compounds to treat a respiratory viral infection

  2021cites this paper
• Phosphatase and Tensin Homolog in Non-neoplastic Digestive Disease: More Than Just Tumor Suppressor

  2021cites this paper
• A metabolomic study on the anti-depressive effects of two active components from Chrysanthemum morifolium

  2020cites this paper
• Naringenin ameliorates insulin resistance by modulating endoplasmic reticulum stress in hepatitis C virus-infected liver.

  2019cites this paper
• Dysregulated expressions of PTEN, NF-κB, WWP2, p53 and c-Myc in different subtypes of B cell lymphoma and reactive follicular hyperplasia.

  2019cites this paper
• The modulatory properties of Si Jun Zi Tang enhancing anticancer of gefitinib by an integrating approach.

  2019cites this paper
• Naringenin as a potential immunomodulator in therapeutics.

  2018cites this paper