2. Academic Validation
  3. Kaemperfol alleviates pyroptosis and microglia-mediated neuroinflammation in Parkinson's disease via inhibiting p38MAPK/NF-κB signaling pathway

Kaemperfol alleviates pyroptosis and microglia-mediated neuroinflammation in Parkinson's disease via inhibiting p38MAPK/NF-κB signaling pathway

  • Neurochem Int. 2022 Jan:152:105221. doi: 10.1016/j.neuint.2021.105221.
Meiyun Cai 1,  Wenxin Zhuang 2,  E Lv 1,  Zhan Liu 1,  Yanqiang Wang 3,  Wenyi Zhang 4,  Wenyu Fu 5
Affiliations

Affiliations

  • 1 Department of Histology and Embryology, Weifang Medical University, Weifang, 261053, Shandong, China.
  • 2 Center for Experimental Medical Research, Weifang Medical University, Weifang, 261053, Shandong, China.
  • 3 Department of Neurology, Affiliated Hospital of Weifang Medical University, Weifang, 261053, Shandong, China.
  • 4 Department of Biotechnology, Weifang Medical University, Weifang, 261053, Shandong, China.
  • 5 Department of Histology and Embryology, Weifang Medical University, Weifang, 261053, Shandong, China. Electronic address: [email protected].
PMID: 34780806 DOI: 10.1016/j.neuint.2021.105221
Abstract

The study aims to investigate whether kaemperfol (KAE) inhibits microglia Pyroptosis and subsequent neuroinflammatory response to exert neuroprotective effects, along with the underlying mechanisms. The results showed KAE could ameliorate the behavioral deficits of Parkinson's disease (PD) rats, inhibit the activation of microglia and astrocytes, reduce the loss of TH-positive neurons, down-regulate levels of pyroptosis-related NOD-like Receptor family pyrin domain containing 3 (NLRP3), GasderminD-N Term (GSDMD-NT), caspase1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), interleukin (IL)-1β, and IL-18, and decrease the levels of inflammatory molecules (inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)) and p38 mitogen-activated protein kinase/nuclear factor-kappaB (p38MAPK/NF-κB) signaling pathway molecules (p38MAPK, p-p38MAPK, NF-κB, and p-NF-κB) in the substantia nigra of PD rats. Further in vitro study indicated that KAE reversed the activation of BV2 cells and down-regulated the expressions of pyrolytic proteins, inflammatory mediators and key molecules in p38MAPK/NF-κB signaling pathway. Collectively, KAE inhibits the microglia Pyroptosis and subsequent neuroinflammatory response to exert neuroprotective effects on 6-hydroxydopamine (6-OHDA)-induced PD rats and lipopolysaccharide (LPS)-induced BV2 inflammatory cells through inhibiting p38MAPK/NF-κB signaling pathway.

Keywords

Kaempferol; Neuroinflammation; Parkinson's disease; Pyroptosis; p38MAPK/NF-κB.

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