Ergosta-7,9(11),22-trien-3β-ol Rescues AD Deficits by Modulating Microglia Activation but Not Oxidative Stress

Molecules. 2021 Sep 2;26(17):5338. doi: 10.3390/molecules26175338.

Abstract

Ergosta-7,9(11),22-trien-3β-ol (EK100) was isolated from the Taiwan-specific medicinal fungus Antrodia camphorata, which is known for its health-promotion and anti-aging effects in folk medicine. Alzheimer's disease (AD) is a major aging-associated disease. We investigated the efficacy and potential mechanism of ergosta-7,9(11),22-trien-3β-ol for AD symptoms. Drosophila with the pan-neuronal overexpression of human amyloid-β (Aβ) was used as the AD model. We compared the life span, motor function, learning, memory, oxidative stress, and biomarkers of microglia activation and inflammation of the ergosta-7,9(11),22-trien-3β-ol-treated group to those of the untreated control. Ergosta-7,9(11),22-trien-3β-ol treatment effectively improved the life span, motor function, learning, and memory of the AD model compared to the untreated control. Biomarkers of microglia activation and inflammation were reduced, while the ubiquitous lipid peroxidation, catalase activity, and superoxide dismutase activity remained unchanged. In conclusion, ergosta-7,9(11),22-trien-3β-ol rescues AD deficits by modulating microglia activation but not oxidative stress.

Keywords: Alzheimer’s disease; Drosophila; EK100; ergosta-7,9(11),22-trien-3β-ol.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Disease Models, Animal
  • Drosophila
  • Humans
  • Microglia / drug effects*
  • Microglia / metabolism
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • Polyporales / chemistry

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents

Supplementary concepts

  • Taiwanofungus camphoratus