Biflavonoid methylchamaejasmin and Khaya grandifoliola extract inhibit inflammasome in THP-1 cells model of neuroinflammation#

Authors#

Brice Ayissi Owona, Arnaud Mary, Angelique N. Messi, Kishore Aravind Ravichandran, Josephine Ngo Mbing, Emmanuel Pegnyemb, Paul F. Moundipa, Michael Heneka

Abstract#

Neuroinflammation is a common hallmark of Alzheimer’s disease (AD) with NLRP3 inflammasome proven to be activated in microglia of AD patient’s brain. In this study, a newly isolated biflavonoid (7,7’’-di-O-methylchamaejasmin / M8) and a plant crude extract (KG) were investigated for their inhibitory effect on inflammasome activation. In preliminary experiments, M8 and KG showed no cytotoxicity on THP-1 cells and rather 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 NFkB, NLRP3, Caspase-1, pro-IL-1β and pro-IL-18 at the mRNA and protein levels. As far as ASC specks formation during inflammasome activation is concerned, the size and fluorescent intensity of the specks were unchanged across the conditions, however, M8 and KG treatments were able to prevent the increase in specks formation. In addition, experiments on Aβ phagocytosis showed that M8 and KG pretreatment can restore the phagocytic activity of human macrophage-like differentiated THP-1 cells which was impaired following inflammasome activation. Altogether, our findings for the first time describe a promising role of biflavonoids and Khaya grandifoliola extract in preventing inflammasome activation and protecting against neuroinflammation which is a key factor in AD development.