Euterpe oleracea Mart. Bioactive Molecules: Promising Agents to Modulate the NLRP3 Inflammasome.

Davidson, Carolina Bordin; El Sabbagh, Dana El Soufi; Machado, Amanda Kolinski; Pappis, Lauren; Sagrillo, Michele Rorato; Somacal, Sabrina; Emanuelli, Tatiana; Schultz, Júlia Vaz; Augusto Pereira da Rocha, João; Santos, André Flores dos; Fagan, Solange Binotto; Silva, Ivana Zanella da; Andreazza, Ana Cristina; Machado, Alencar Kolinski

Simple Summary: This paper reports the interaction between flavonoids, identified in the chemical matrix of açaí extract, and NLRP3 PYD through computational simulation, as well as the in vitro safety profile and anti-inflammatory effect in macrophages and monocytes of three flavonoids, isolated and combined, via the modulation of the NLRP3 inflammasome. Inflammation is a vital mechanism that defends the organism against infections and restores homeostasis. However, when inflammation becomes uncontrolled, it leads to chronic inflammation. The NLRP3 inflammasome is crucial in chronic inflammatory responses and has become a focal point in research for new anti-inflammatory therapies. Flavonoids like catechin, apigenin, and epicatechin are known for their bioactive properties (antioxidant, anti-inflammatory, etc.), but the mechanisms behind their anti-inflammatory actions remain unclear. This study aimed to explore the ability of various flavonoids (isolated and combined) to modulate the NLRP3 inflammasome using in silico and in vitro models. Computer simulations, such as molecular docking, molecular dynamics, and MM/GBSA calculations examined the interactions between bioactive molecules and NLRP3 PYD. THP1 cells were treated with LPS nigericin to activate NLRP3, followed by flavonoid treatment at different concentrations. THP1-derived macrophages were also treated following NLRP3 activation protocols. The assays included colorimetric, fluorometric, microscopic, and molecular techniques. The results showed that catechin, apigenin, and epicatechin had high binding affinity to NLRP3 PYD, similar to the known NLRP3 inhibitor MCC950. These flavonoids, particularly at 1 µg/mL, 0.1 µg/mL, and 0.01 µg/mL, respectively, significantly reduced LPS nigericin effects in both cell types and decreased pro-inflammatory cytokine, caspase-1, and NLRP3 gene expression, suggesting their potential as anti-inflammatory agents through NLRP3 modulation.

ACAI palm; NLRP3 protein; FLAVONOIDS; EPICATECHIN; ANTI-inflammatory agents

Biology (2079-7737), 2024, Vol 13, Issue 9, p729

2079-7737

Academic Journal

10.3390/biology13090729