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Biflavonoid Methylchamaejasmin and Khaya grandifoliola Extract Inhibit NLRP3 Inflammasome in THP-1 Cell Model of
Brice Ayissi Owona1,2, Arnaud Mary3, Angelique N Messi4
1Laboratory of Pharmacology and Toxicology, Department of Biochemistry, Faculty of Science, University of Yaoundé I, AEFAS, P.O. Box 812, Yaoundé, Cameroon. vincent-brice.owona@facsciences-uy1.cm.
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.
Insights
This study shows that a biflavonoid (M8) and Khaya grandifoliola extract (KG) can inhibit neuroinflammation by blocking NLRP3 inflammasome activation. These natural compounds also restored amyloid-beta phagocytosis, offering potential Alzheimer
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Neuroinflammation, driven by NLRP3 inflammasome activation in microglia, is a key feature of Alzheimer's disease (AD).
- Identifying natural compounds that modulate inflammasome activity is crucial for developing AD therapeutics.
Purpose of the Study:
- To investigate the anti-neuroinflammatory effects of a novel biflavonoid (M8) and a Khaya grandifoliola (KG) extract.
- To determine their impact on NLRP3 inflammasome activation and related pathways in a cellular model of neuroinflammation.
Main Methods:
- Human macrophage-like THP-1 cells were used to assess cytotoxicity and nitric oxide production.
- NLRP3 inflammasome components (NFκB, NLRP3, Caspase-1, IL-1β, IL-18) were analyzed at mRNA and protein levels.
- ASC speck formation and amyloid-beta phagocytosis were evaluated following M8 and KG treatments.
Main Results:
- M8 and KG extracts demonstrated no cytotoxicity and reduced nitric oxide production.
- Both M8 and KG inhibited the production of IL-1β and IL-18 by downregulating key inflammasome components.
- Treatments prevented further ASC speck formation and restored amyloid-beta phagocytic activity impaired by inflammasome activation.
Conclusions:
- Biflavonoids and Khaya grandifoliola extract show significant potential in inhibiting NLRP3 inflammasome activation.
- These natural compounds may offer a protective role against neuroinflammation, a critical factor in Alzheimer's disease pathogenesis.
- Further research into M8 and KG as therapeutic agents for AD is warranted.
