A novel mechanism of Korean red ginseng-mediated anti-inflammatory action via targeting caspase-11 non-canonical inflammasome in macrophages

• Published in: Journal of ginseng research 2022-09, Vol.46 (5), p.675-682
• Main Authors: Min, Ji-Hyun, Cho, Hui-Jin, Yi, Young-Su
• Format: Article
• Language: English
• Subjects: anti-inflammatory activity; Caspase-11; cell viability; inflammasomes; Inflammation; KRG; lactate dehydrogenase; lipopolysaccharides; Macrophage; macrophages; nitric oxide; Non-canonical inflammasome; Panax; proteolysis; pyroptosis; secretion; septic shock
• ISSN: 1226-8453; 2093-4947
• DOI: 10.1016/j.jgr.2021.12.009

Korean red ginseng (KRG) was reported to play an anti-inflammatory role, however, previous studies largely focused on the effects of KRG on priming step, the inflammation-preparing step, and the anti-inflammatory effect of KRG on triggering, the inflammation-activating step has been poorly understood. This study demonstrated anti-inflammatory role of KRG in caspase-11 non-canonical inflammasome activation in macrophages during triggering of inflammatory responses. Caspase-11 non-canonical inflammasome-activated J774A.1 macrophages were established by priming with Pam3CSK4 and triggering with lipopolysaccharide (LPS). Cell viability and pyroptosis were examined by MTT and lactate dehydrogenase (LDH) assays. Nitric oxide (NO)-inhibitory effect of KRG was assessed using a NO production assay. Expression and proteolytic cleavage of proteins were examined by Western blotting analysis. In vivo anti-inflammatory action of KRG was evaluated with the LPS-injected sepsis model in mice. KRG reduced LPS-stimulated NO production in J774A.1 cells and suppressed pyroptosis and IL-1β secretion in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Mechanistic studies demonstrated that KRG suppressed the direct interaction between LPS and caspase-11 and inhibited proteolytic processing of both caspase-11 and gasdermin D in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Furthermore, KRG significantly ameliorated LPS-mediated lethal septic shock in mice. The results demonstrate a novel mechanism of KRG-mediated anti-inflammatory action that operates through targeting the caspase-11 non-canonical inflammasome at triggering step of macrophage-mediated inflammatory response. [Display omitted]