Protective effect of hypoxylonol C and 4,5,4',5'-tetrahydroxy-1,1'-binaphthyl isolated from Annulohypoxylon annulatum against streptozotocin-induced damage in INS-1 cells

Bioorg Chem. 2019 Sep:90:103053. doi: 10.1016/j.bioorg.2019.103053. Epub 2019 Jun 8.

Abstract

We evaluated the protective effects of hypoxylonol C and 4,5,4',5'-tetrahydroxy-1,1'-binaphthyl (BNT) isolated from Annulohypoxylon annulatum on pancreatic β-cell apoptosis, using the β-cell toxin streptozotocin (STZ). Hypoxylonol C and BNT restored the STZ-induced decrease in INS-1 cell viability in a dose-dependent manner. In addition, treatment of INS-1 cells with 50 μM STZ resulted in an increase in apoptotic cell death, which was observed as annexin V fluorescence intensity. Apoptotic cell death was decreased by co-treatment with 100 μM hypoxylonol C and 100 μM BNT. Similarly, STZ caused a marked increase in the expression of cleaved caspase-8, caspase-3, Bax, and poly (ADP-ribose) polymerase (PARP), as well as a decrease in the expression of B-cell lymphoma 2 (Bcl-2), which was reversed by co-treatment with 100 μM hypoxylonol C and 100 μM BNT. These findings suggest that hypoxylonol C and BNT play an important role in protecting pancreatic β-cells against apoptotic damage.

Keywords: Annulohypoxylon annulatum; Apoptosis; Pancreatic β-cells; Streptozotocin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Ascomycota / chemistry
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Cell Line, Tumor
  • Fluorenes / isolation & purification
  • Fluorenes / pharmacology*
  • Insulin-Secreting Cells / drug effects
  • Naphthols / isolation & purification
  • Naphthols / pharmacology*
  • Oxidative Stress / drug effects
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protective Agents / isolation & purification
  • Protective Agents / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Streptozocin / toxicity*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • Bcl2 protein, rat
  • Fluorenes
  • Naphthols
  • Protective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • hypoxylonol C
  • Streptozocin
  • Poly(ADP-ribose) Polymerases
  • Casp3 protein, rat
  • Casp8 protein, rat
  • Caspase 3
  • Caspase 8