King Oyster Mushroom, Pleurotus eryngii, Inhibits Microglia Activation via the Interplay of NLRP3 to Alleviate Neuroinflammation

Background: Mushrooms have gained attention for their potential to improve brain health. We evaluated extracts of king oyster mushroom, as well as two of its bioactive compounds—ergothioneine (ERG) and N-acetyltryptamine (NAT)—for their ability to prevent microglia activation by reducing neuroinflammation and oxidative stress. Methods: HAPI microglial cells were pretreated with king oyster extracts (crude powder, acetone, ethanol, and methanol extracts at 100 μg/mL) and pure bioactive molecules of ergothioneine (ERG, 500 μM) and N-acetyl-tryptamine (NAT,50 μM) before stimulation with LPS. The effects on nitrite; TNF-α; and expressions of the inflammatory proteins iNOS, NOX2, and NLRP3 were compared with those of a blueberry extract (BB, 500 μg/mL) as a positive control. Results: All extracts and bioactive molecules significantly reduced nitrite production, similar to the BB. Overall, the best results for reducing inflammation and inflammatory protein expression were obtained with the extracts rich in NAT (acetone and ethanol), as well as pure NAT. Furthermore, through their inhibitory target effect on NLRP3, these two extracts and the bioactive compounds (NAT and ERG), like BB, are attractive therapeutic molecules to reduce mood disorders related to brain aging, due to evidence of enhanced Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome activity in common neurodegenerative diseases. Further interventional studies are needed to confirm mushrooms’ brain health properties.