Formulated Chinese medicine Shaoyao Gancao Tang reduces NLRP1 and NLRP3 in Alzheimer's disease cell and mouse models for neuroprotection and cognitive improvement

Aging (Albany NY). 2021 Jun 9;13(11):15620-15637. doi: 10.18632/aging.203125. Epub 2021 Jun 9.

Abstract

Amyloid β (Aβ) plays a major role in the neurodegeneration of Alzheimer's disease (AD). The accumulation of misfolded Aβ causes oxidative stress and inflammatory damage leading to apoptotic cell death. Traditional Chinese herbal medicine (CHM) has been widely used in treating neurodegenerative diseases by reducing oxidative stress and neuroinflammation. We examined the neuroprotective effect of formulated CHM Shaoyao Gancao Tang (SG-Tang, made of Paeonia lactiflora and Glycyrrhiza uralensis at 1:1 ratio) in AD cell and mouse models. In Aβ-GFP SH-SY5Y cells, SG-Tang reduced Aβ aggregation and reactive oxygen species (ROS) production, as well as improved neurite outgrowth. When the Aβ-GFP-expressing cells were stimulated with conditioned medium from interferon (IFN)-γ-activated HMC3 microglia, SG-Tang suppressed expressions of inducible nitric oxide synthase (iNOS), NLR family pyrin domain containing 1 (NLRP1) and 3 (NLRP3), tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, attenuated caspase-1 activity and ROS production, and promoted neurite outgrowth. In streptozocin-induced hyperglycemic APP/PS1/Tau triple transgenic (3×Tg-AD) mice, SG-Tang also reduced expressions of NLRP1, NLRP3, Aβ and Tau in hippocampus and cortex, as well as improved working and spatial memories in Y maze and Morris water maze. Collectively, our results demonstrate the potential of SG-Tang in treating AD by moderating neuroinflammation.

Keywords: Alzheimer's disease; Aβ; anti-inflammation; neuroprotection; therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Cell Line
  • Cognition* / drug effects
  • Culture Media, Conditioned / pharmacology
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Memory / drug effects
  • Memory Disorders / complications
  • Memory Disorders / physiopathology
  • Mice, Transgenic
  • Microglia / drug effects
  • Microglia / metabolism
  • Models, Biological
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Neuronal Outgrowth / drug effects
  • Neuroprotection* / drug effects
  • Neuroprotective Agents / pharmacology
  • Protein Aggregates / drug effects
  • Reactive Oxygen Species / metabolism
  • Spatial Learning / drug effects
  • tau Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Amyloid beta-Peptides
  • Apoptosis Regulatory Proteins
  • Culture Media, Conditioned
  • Drugs, Chinese Herbal
  • NALP1 protein, mouse
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Neuroprotective Agents
  • Protein Aggregates
  • Reactive Oxygen Species
  • jackyakamcho-tang
  • tau Proteins
  • Green Fluorescent Proteins
  • Interferon-gamma