Formulated Chinese Medicine Shaoyao Gancao Tang Reduces Nlrp1 And Nlrp3 In Alzheimer’S Disease Cell And Mouse Models For Neuroprotection And Cognitive Improvement

Ya Jen Chiu, Chih Hsin Lin, Ming Chung Lee, Hsiu Mei Hsieh-Li, Chiung Mei Chen, Yih Ru Wu, Kuo Hsuan Chang, Guey Jen Lee-Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Amyloid (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.

Original languageEnglish
Pages (from-to)15620-15637
Number of pages18
JournalAging
Volume13
Issue number11
DOIs
Publication statusPublished - 2021 Jun 15

Keywords

  • Alzheimer's disease
  • anti-inflammation
  • neuroprotection
  • therapeutics

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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