Crocin is a hydrophilic
carotenoid pigment found in the stigma of Crocus sativus or the fruit of Gardenia jasminoides. In this study, we investigated the effects of
Crocin on the activation of the
nucleotide-binding oligomerization domain,
leucine-rich repeat, and pyrin domain containing 3 (NLRP3)
inflammasome in J774A.1 murine macrophage cells and
monosodium urate (MSU)-induced
peritonitis.
Crocin significantly inhibited
Nigericin-,
adenosine triphosphate (
ATP)-, MSU-induced
interleukin (IL)-1β secretion, and caspase-1 cleavage without affecting pro-IL-1β and
pro-caspase-1.
Crocin also suppressed gasdermin-D cleavage and
lactate dehydrogenase release and enhanced cell viability, indicating that
Crocin reduces pyroptosis. Similar effects were observed in primary mouse macrophages. However,
Crocin did not affect
poly(dA:dT)-induced absent in
melanoma 2 (AIM2) and
muramyl dipeptide-induced NLRP1
inflammasomes.
Crocin decreased
Nigericin-induced oligimerization and the speck formation of apoptosis-associated speck-like
protein containing a caspase recruitment domain (ASC).
Crocin also dramatically alleviated the
ATP-induced production of mitochondrial
reactive oxygen species (mtROS). Finally,
Crocin ameliorated the MSU-induced production of IL-1β and
IL-18 and the recruitment of neutrophils during peritoneal
inflammation. These results suggest that
Crocin suppresses NLRP3
inflammasome activation by blocking mtROS production and ameliorates MSU-induced mouse
peritonitis. Thus,
Crocin may have therapeutic potential in various NLRP3
inflammasome-related inflammatory diseases.