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Kaemperfol alleviates pyroptosis and microglia-mediated neuroinflammation in Parkinson's disease via inhibiting p38MAPK/NF-κB signaling pathway
- Source :
- Neurochemistry International. 152:105221
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
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.
- Subjects :
- Lipopolysaccharides
Male
MAP Kinase Signaling System
p38 mitogen-activated protein kinases
Nitric Oxide Synthase Type II
Neuroprotection
Rats, Sprague-Dawley
Cellular and Molecular Neuroscience
Pyroptosis
medicine
Animals
Oxidopamine
Protein kinase A
Neuroinflammation
Microglia
biology
Chemistry
NF-kappa B
Parkinson Disease
Cell Biology
Cell biology
Nitric oxide synthase
medicine.anatomical_structure
Neuroinflammatory Diseases
biology.protein
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 01970186
- Volume :
- 152
- Database :
- OpenAIRE
- Journal :
- Neurochemistry International
- Accession number :
- edsair.doi.dedup.....aeec110aa6ce4a20f41a8184c94b1c70