Marine Bromophenol Derivative 3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-isopropoxymethyl benzyl)benzene-1,2-diol Protects Hepatocytes from Lipid-Induced Cell Damage and Insulin Resistance via PTP1B Inhibition

Mar Drugs. 2015 Jul 17;13(7):4452-69. doi: 10.3390/md13074452.

Abstract

3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-isopropoxymethyl benzyl)benzene-1,2-diol (HPN) is a bromophenol derivative from the marine red alga Rhodomela confervoides. We have previously found that HPN exerted an anti-hyperglycemic property in db/db mouse model. In the present study, we found that HPN could protect HepG2 cells against palmitate (PA)-induced cell death. Data also showed that HPN inhibited cell death mainly by blocking the cell apoptosis. Further studies demonstrated that HPN (especially at 1.0 μM) significantly restored insulin-stimulated tyrosine phosphorylation of IR and IRS1/2, and inhibited the PTP1B expression level in HepG2 cells. Furthermore, the expression of Akt was activated by HPN, and glucose uptake was significantly increased in PA-treated HepG2 cells. Our results suggest that HPN could protect hepatocytes from lipid-induced cell damage and insulin resistance via PTP1B inhibition. Thus, HPN can be considered to have potential for the development of anti-diabetic agent that could protect both hepatic cell mass and function.

Keywords: HPN; HepG2 cell; PTP1B inhibition; anti-cell damage; anti-insulin resistance; palmitate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Benzyl Compounds / pharmacology*
  • Catechols / pharmacology*
  • Cell Death / drug effects*
  • Hep G2 Cells / drug effects
  • Hepatocytes / drug effects*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin Resistance*
  • Lipids / adverse effects*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism

Substances

  • 3,4-dibromo-5-(2-bromo-3,4-dihydroxy-6-(isopropoxymethyl)benzyl)benzene-1,2-diol
  • Benzyl Compounds
  • Catechols
  • Hypoglycemic Agents
  • Lipids
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1