Potential modulation of microglial ferroptosis by Linggui Zhugan decoction in Alzheimer's disease through IL-17 and

Peng Tang1, Danjie Zhao2, Haixia Lin2

  • 1Department of Pharmacy, Chengdu Integrated TCM & Western Medicine Hospital, Chengdu 610000, China.

PubMed

Insights

Traditional Chinese Medicine

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Alzheimer's Disease (AD) involves cognitive decline and ferroptosis.
  • Microglial ferroptosis is implicated in AD pathogenesis.
  • Interleukin-17 (IL-17) and Tumor Necrosis Factor (TNF) signaling pathways are relevant.

Purpose of the Study:

  • To investigate the effects of Linggui Zhugan Decoction (LZD) on microglial ferroptosis in AD.
  • To explore the role of IL-17 and TNF signaling pathways in LZD's modulation of ferroptosis.
  • To assess LZD's therapeutic potential in an AD mouse model.

Main Methods:

  • Single-cell RNA sequencing in AD mice.
  • Network pharmacology analysis.
  • In vitro experiments with Aβ1-42-treated microglia.
  • In vivo behavioral tests and ferroptosis marker analysis.

Main Results:

  • LZD components potentially modulate ferroptosis-related pathways.
  • LZD treatment reduced IL-17 and TNF levels in microglia.
  • In vivo administration of LZD improved behavioral outcomes and modulated ferroptosis markers.
  • Alterations in microglial populations and ferroptosis gene expression were observed in AD mice.

Conclusions:

  • LZD shows potential in attenuating ferroptosis-associated pathology in AD.
  • Modulation of inflammatory pathways (IL-17, TNF) may underlie LZD's effects.
  • Further research is needed to confirm causal mechanisms of LZD in AD treatment.