A beta-secretase (BACE1) inhibitor hispidin from the mycelial cultures of Phellinus linteus

Planta Med. 2004 Feb;70(2):143-6. doi: 10.1055/s-2004-815491.

Abstract

In the course of screening for anti-dementia agents from natural products, a beta-secretase (BACE1) inhibitor was isolated from the culture broth of Phellinus linteus and identified as hispidin. It showed an IC (50) value of 4.9 x 10 (-6) M and a Ki value of 8.4 x 10 (-6) M. The compound was a non-competitive inhibitor. Hispidin also inhibited a prolyl endopeptidase (IC (50) = 1.6 x 10 (-5) M, Ki = 2.4 x 10 (-5) M), but it was less inhibitory to alpha-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Cells, Cultured
  • Endopeptidases
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Fungi*
  • Humans
  • Inhibitory Concentration 50
  • Phytotherapy*
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Pyrones / administration & dosage
  • Pyrones / pharmacology*
  • Pyrones / therapeutic use

Substances

  • Enzyme Inhibitors
  • Plant Extracts
  • Pyrones
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • hispidin