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@ARTICLE{Owona:276280,
author = {Owona, Brice Ayissi and Mary, Arnaud and Messi, Angelique N
and Ravichandran, Kishore Aravind and Mbing, Josephine Ngo
and Pegnyemb, Emmanuel and Moundipa, Paul F and Heneka,
Michael},
title = {{B}iflavonoid {M}ethylchamaejasmin and {K}haya
grandifoliola {E}xtract {I}nhibit {NLRP}3 {I}nflammasome in
{THP}-1 {C}ell {M}odel of {N}euroinflammation.},
journal = {Molecular neurobiology},
volume = {62},
number = {2},
issn = {0893-7648},
address = {Totowa, NJ},
publisher = {Humana Press},
reportid = {DZNE-2025-00259},
pages = {1605 - 1619},
year = {2025},
abstract = {Neuroinflammation is a common hallmark of Alzheimer's
disease (AD), with NLRP3 inflammasome proven to be activated
in microglia of AD patients' brains. In this study, a newly
isolated biflavonoid (7,7'-di-O-methylchamaejasmin/M8) and a
crude extract of the plant Khaya grandifoliola (KG) were
investigated for their inhibitory effect on inflammasome
activation. In preliminary experiments, M8 and KG showed no
cytotoxicity on human macrophage-like differentiated THP-1
cells and exhibited anti-inflammatory inhibition of nitric
oxide produced following lipopolysaccharide stimulation.
Furthermore, M8 and KG blocked IL-1β and IL-18 production
by reducing NLRP3 inflammasome components including NFκB,
NLRP3, Caspase-1, pro-IL-1β, and pro-IL-18 at the mRNA and
protein levels. Regarding the formation of ASC
(apoptosis-associated speck-like protein containing a CARD)
specks during inflammasome activation, the size and
fluorescent intensity of the existing specks were unchanged
across all treatment conditions. However, M8 and KG
treatments were shown to prevent further speck formation. In
addition, experiments on amyloid β phagocytosis showed that
M8 and KG pretreatments can restore the phagocytic activity
of THP-1 cells, which was impaired following inflammasome
activation. Altogether, our findings describe for the first
time a promising role of biflavonoids and KG extract in
preventing inflammasome activation and protecting against
neuroinflammation, a key factor in AD development.},
keywords = {Humans / NLR Family, Pyrin Domain-Containing 3 Protein:
metabolism / Inflammasomes: metabolism / Inflammasomes: drug
effects / Plant Extracts: pharmacology / THP-1 Cells /
Biflavonoids: pharmacology / Biflavonoids: therapeutic use /
Neuroinflammatory Diseases: drug therapy / Neuroinflammatory
Diseases: metabolism / Neuroinflammatory Diseases: pathology
/ Amyloid beta-Peptides: metabolism / Lipopolysaccharides:
pharmacology / Meliaceae: chemistry / Phagocytosis: drug
effects / Nitric Oxide: metabolism / Interleukin-1beta:
metabolism / Khaya grandifoliola (Other) /
7,7′-di-O-Methylchamaejasmin (Other) / Biflavonoid (Other)
/ NLRP3 inflammasome (Other) / THP-1 cells (Other) / NLR
Family, Pyrin Domain-Containing 3 Protein (NLM Chemicals) /
Inflammasomes (NLM Chemicals) / Plant Extracts (NLM
Chemicals) / Biflavonoids (NLM Chemicals) / Amyloid
beta-Peptides (NLM Chemicals) / Lipopolysaccharides (NLM
Chemicals) / Nitric Oxide (NLM Chemicals) /
Interleukin-1beta (NLM Chemicals)},
cin = {AG Heneka},
ddc = {570},
cid = {I:(DE-2719)1011303},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39012444},
doi = {10.1007/s12035-024-04365-4},
url = {https://pub.dzne.de/record/276280},
}