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.