Ginseng leaf extract ameliorates the survival of endotoxemic mice by inhibiting the release of high mobility group box 1

Abstract

High mobility group box 1 (HMGB1) is a well‐defined mediator involved in the pathophysiologic response to endotoxemia and sepsis. However, the mechanisms and therapeutic agents that could prevent its release are not fully elucidated. Here, the present study demonstrates that the ginseng leaf extract (GLE) regulates lipopolysaccharide (LPS)‐triggered release of HMGB1 in macrophages and endotoxemic animal model. Treatment of RAW264.7 macrophages with GLE significantly inhibited the release of HMGB1 stimulated by LPS. GLE also suppressed the generation of nitric oxide (NO) and expression of inducible NO synthase (iNOS) in a dose‐dependent manner. These effects of GLE were accompanied by inhibition of HMGB1 release stimulated by LPS, indicating a potential mechanism by which GLE regulates HMGB1 release through NO signaling. Furthermore, induction of suppressor of cytokine signaling 1 by GLE‐mediated GLE‐dependent suppression of HMGB1 release and NO/iNOS induction by inhibiting Janus kinase 2/signal transducer and activator of transcription 1 signal in RAW 264.7 cells exposed to LPS. Finally, administration of the GLE ameliorated the survival rate of LPS‐injected endotoxemic mice in a NO‐dependent manner. Thus, GLE may block the LPS‐stimulated release of HMGB1 by regulating cellular signal networks, thereby providing a therapeutic strategy for endotoxemia as a functional food. Practical applications High mobility group box 1 (HMGB1) is released into the extracellular milieu when immune cells are exposed to pathogen‐related molecules such as lipopolysaccharide (LPS), in which it acts as a critical mediator of lethality in sepsis and endotoxemia. The extract of ginseng leaf, which is a part that can be easily thrown away, ameliorated the survival rate of endotoxemic mice by inhibiting HMGB1 secretion in a NO‐dependent manner. Thus, this study suggests that ginseng leaf can be used as a functional food by resolving the immune responses in the pathology of endotoxemia.

Anti-inflammatory effects of two lupane-type triterpenes from leaves of Acanthopanax gracilistylus on LPS-induced RAW264.7 macrophages

“…Inflammation results in the production of proinflammatory cytokines and other inflammatory mediators such as tumor necrosis factor (TNF)-α, and IL-1β, and high mobility group box 1 (HMGB1) (Insuan et al, 2021). HMGB1 plays a critical role in the pathophysiology of inflammatory diseases like sepsis (Yang et al, 2021;Hur et al, 2021). It is a late inflammation factor that may enlarge inflammatory response by causing elevated levels of other cytokines through stimulating macrophages to synthesize pro-inflammatory cytokines, which induce and promote each other (Yang et al, 2021).…”

“…It is a late inflammation factor that may enlarge inflammatory response by causing elevated levels of other cytokines through stimulating macrophages to synthesize pro-inflammatory cytokines, which induce and promote each other (Yang et al, 2021). Moreover, recently the inhibition of HMGB1 is considered to be a promising therapeutic target for attenuating inflammatory respond (Zhou et al, 2018;Ni et al, 2020;Wang et al, 2020;Hur et al, 2021). Nuclear transcription factor-κB (NF-κB) is a key transcription factor in inflammatory response (Luo et al, 2020).…”