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-1ß 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.

Korean Red Ginseng Saponins Play an Anti-Inflammatory Role by Targeting Caspase-11 Non-Canonical Inflammasome in Macrophages.

We previously reported that Korean red ginseng (KRG) exerts an anti-inflammatory role through inhibiting caspase-11 non-canonical inflammasome in macrophages; however, the components responsible for the anti-inflammatory role remained unclear. This study explored the anti-inflammatory activity of the KRG saponin fraction (KRGSF) in caspase-11 non-canonical inflammasome-activated macrophages. KRGSF inhibited pyroptosis, pro-inflammatory cytokine secretion, and inflammatory mediator production in caspase-11 non-canonical inflammasome-activated J774A.1 cells. A mechanism study revealed that KRGSF-induced anti-inflammatory action was mediated via suppressing the proteolytic activation of caspase-11 and gasdermin D (GSDMD) in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Moreover, KRGSF increased the survival of lethal septic mice. Taken together, these results reveal KRGSF-mediated anti-inflammatory action with a novel mechanism, by inhibiting caspase-11 non-canonical inflammasome in macrophages.