Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Quinic Acid Alleviates Behavior Impairment by Reducing Neuroinflammation and MAPK Activation in LPS-Treated Mice

  • Yongun Park (College of Pharmacy, Chung-Ang University) ;
  • Yunn Me Me Paing (College of Pharmacy, Chung-Ang University) ;
  • Namki Cho (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University) ;
  • Changyoun Kim (Molecular Neuropathology Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health) ;
  • Jiho Yoo (College of Pharmacy, Chung-Ang University) ;
  • Ji Woong Choi (College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University) ;
  • Sung Hoon Lee (College of Pharmacy, Chung-Ang University)
  • Received : 2023.10.25
  • Accepted : 2023.12.27
  • Published : 2024.05.01
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Abstract

Compared to other organs, the brain has limited antioxidant defenses. In particular, the hippocampus is the central region for learning and memory and is highly susceptible to oxidative stress. Glial cells are the most abundant cells in the brain, and sustained glial cell activation is critical to the neuroinflammation that aggravates neuropathology and neurotoxicity. Therefore, regulating glial cell activation is a promising neurotherapeutic treatment. Quinic acid (QA) and its derivatives possess anti-oxidant and anti-inflammatory properties. Although previous studies have evidenced QA's benefit on the brain, in vivo and in vitro analyses of its anti-oxidant and anti-inflammatory properties in glial cells have yet to be established. This study investigated QA's rescue effect in lipopolysaccharide (LPS)-induced behavior impairment. Orally administering QA restored social impairment and LPS-induced spatial and fear memory. In addition, QA inhibited proinflammatory mediator, oxidative stress marker, and mitogen-activated protein kinase (MAPK) activation in the LPS-injected hippocampus. QA inhibited nitrite release and extracellular signal-regulated kinase (ERK) phosphorylation in LPS-stimulated astrocytes. Collectively, QA restored impaired neuroinflammation-induced behavior by regulating proinflammatory mediator and ERK activation in astrocytes, demonstrating its potential as a therapeutic agent for neuroinflammation-induced brain disease treatments.

Keywords

Acknowledgement

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIT) (Grant No. 2020R1C1C1008852, 2021R1C1C1012076, 2021M3E5E3080529, and 2021R1A6A1A0304429).

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