The NLRP3 inflammasome, which plays a central role in innate immunity, is linked to a variety of inflammatory diseases, and thus it may provide a new target for the treatment of those diseases. Biosynthesized silver nanoparticles (AgNPs), particularly those synthesized using medicinal plant extracts, have recently been shown to be a promising therapeutic option. Herein, the aqueous extract of Ageratum conyzoids was used to prepare a series of sized AgNPs (AC-AgNPs), in which the smallest mean particle size was 30 ± 1.3 nm with a polydispersity of 0.328 ± 0.009. The ζ potential value was -28.77 with a mobility of -1.95 ± 0.24 cm2/(v·s). Its main ingredient, elemental silver, accounted for about 32.71 ± 4.87% of its mass, and other ingredients included amentoflavone-7,7⁗-dimethyl ether, 1,3,5-tricaffeoylquinic acid, kaempferol 3,7,4'-triglucoside, 5,6,7,3',4',5'-hexamethoxyflavone, kaempferol, and ageconyflavone B. In LPS+ATP-stimulated RAW 264.7 and THP-1 cells, AC-AgNPs significantly inhibited the release of IL-1β, IL-18, TNF-α, and caspase-1, indicating that AC-AgNPs can inhibit the activation of the NLRP3 inflammasome. The mechanistic study revealed that AC-AgNPs could decrease the phosphorylation levels of IκB-α and p65, resulting in decreased expression of NLRP3 inflammasome-related proteins, including pro-IL-1β, IL-1β, procaspase 1, caspase 1P20, NLRP3, and ASC, and also scavenge the level of intracellular ROS to prevent NLRP3 inflammasome assembly. Furthermore, AC-AgNPs attenuated the in vivo expression of inflammatory cytokines by suppressing NLRP3 inflammasome activation in a peritonitis mouse model. Our study provides evidence that the as-prepared AC-AgNPs can inhibit the inflammatory process by suppressing NLRP3 inflammasome activation and might be used to treat NLRP3 inflammasome-driven inflammatory diseases.
Keywords: Ageratum conyzoides; NLRP3 inflammasome; activation; biosynthesis; silver nanoparticles (AgNPs).