Anti-inflammatory role of Artemisia argyi methanol extract by targeting the caspase-11 non-canonical inflammasome in macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE

Artemisia argyi possesses pharmacological activities against various immunopathological conditions associated with inflammation.

AIM OF THE STUDY

This study explored the inhibitory role of Artemisia argyi methanol extract (Aa-ME) in inflammatory responses and the underlying mechanism in macrophages.

MATERIALS AND METHODS

Caspase-11 non-canonical inflammasome was activated in J774A.1 macrophage by Pam3CSK4 treatment and lipopolysaccharide (LPS) transfection. Aa-ME-mediated in vitro anti-inflammatory action was examined using MTT assay, lactate dehydrogenase (LDH) activity assay, enzyme-linked immunosorbent assay (ELISA), nitric oxide (NO) generation assay, and quantitative real-time polymerase chain reaction (qPCR). Aa-ME-mediated in vivo anti-inflammatory action was examined in LPS-stimulated lethal septic mice.

RESULTS

Aa-ME inhibited caspase-11 non-canonical inflammasome-stimulated pyroptosis and the secretion of IL-1β and IL-18 in J774A.1 macrophages. Aa-ME also inhibited NO generation by downregulating inducible NO synthase (iNOS) expression in LPS-primed and caspase-11 non-canonical inflammasome-triggered J774A.1 cells. The mechanism study revealed Aa-ME suppressed the auto-proteolytic activation of caspase-11 and gasdermin D (GSDMD) in J774A.1 cells and also interfered with caspase-11-mediated direct recognition of LPS. Moreover, Aa-ME alleviated LPS-induced lethal sepsis in mice by increasing their survival rate without significant toxicity.

CONCLUSION

These results suggest a novel mechanism by which Aa-ME alleviates inflammatory responses by deactivating caspase-11 non-canonical inflammasome in macrophages.