Extract fromAcanthopanax senticosusprevents LPS-induced monocytic cell adhesion via suppression of LFA-1 and Mac-1

Abstract

A crude extract from Acanthopanax senticosus (AS) has drawn increased attention because of its potentially beneficial activities, including anti-fatigue, anti-stress, anti-gastric-ulcer, and immunoenhancing effects. We previously reported that AS crude extract exerts anti-inflammatory activity through blockade of monocytic adhesion to endothelial cells. However, the underlying mechanisms remained unknown, and so this study was designed to investigate the pathways involved. It was confirmed that AS extract inhibited lipopolysaccharide (LPS)-induced adhesion of monocytes to endothelial cells, and we found that whole extract was superior to eleutheroside E, a principal functional component of AS. A series of PCR experiments revealed that AS extract inhibited LPS-induced expression of genes encoding lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1) in THP-1 cells. Consistently, protein levels and cell surface expression of LFA-1 and Mac-1 were noticeably reduced upon treatment with AS extract. This inhibitory effect was mediated by the suppression of LPS-induced degradation of IκB-α, a known inhibitor of nuclear factor-κB (NF-κB). In conclusion, AS extract exerts anti-inflammatory activity via the suppression of LFA-1 and Mac-1, lending itself as a potential therapeutic galenical for the prevention and treatment of various inflammatory diseases.

Extract from Prunus mume Sieb. et Zucc. Fruit Prevents LPS-induced Homotypic Aggregation of Monocytic THP-1 Cells via Suppression of Nitric Oxide Production and NF-κB Activation

“…Given that homotypic aggregation of activated monocytes is regulated by NO production and CAM expression [18,32,36], it is plausible that Maesil extract regulates these mediators, thereby crucially modifying homotypic aggregation of monocytes. Previous studies have shown that the integrin A B C Fig.…”

“…It is also noteworthy that an advantage of using whole extracts seems likely to appear unexpected efficacy caused by unknown compounds in the whole extracts. Many studies have shown that such synergistic effects from unknown compounds in whole extracts occasionally render the crude extract more efficacious when comparing to a single compound isolated at the equivalent dose [8,18].…”

“…Maesil extract inhibits the NF-κB pathway through inhibition of LPS-induced phosphorylation of IκB-α and NF-κB translocation into the nucleus [15,18]. However, further studies will be required to elucidate whether inhibition of the NF-κB pathway is directly involved in Maesil extract mediated inhibition of LPS-induced THP-1 cell homotypic aggregation via NO regulation.…”

“…Under chronic inflammation, proinflammatory stimuli, such as lipopolysaccharide (LPS), activate monocytes and induce the expression of cell adhesion molecules (CAMs) and the production of nitric oxide (NO) [9,18,36]. As a result, activated monocytes move to target tissues and induce heterotypic/homotypic cell adhesion [11], indicating that CAMs and NO are key regulators of the inflammatory processes that control cell-cell adhesion [18,32,36]. During this process, increased expression of lymphocyte function-associated antigen-1 (LFA-1) is correlated with the induction of homotypic aggregation of monocytes [22,24].…”

Effects of sinomenine in LPS‐associated diseases are related to inhibition of LBP, Mac‐1, and L‐selectin levels

“…In macrophages stimulated with LPS and ATP [for inflammasome activation], LBP is observed in the close vicinity of activated caspases (Kopp, Kupsch, & Schromm, 2016 data from the present study showed that high-dose sinomenine significantly inhibited Mac-1 secretion induced by LPS. A series of PCR analyses revealed that Acanthopanax senticosus (AS) extract inhibited LPS-induced expression of the gene encoding Mac-1 in THP-1 cells (Kim, McLean, Pyee, Kim, & Park, 2014). This inhibitory effect was found to be mediated by a suppression of LPS-induced degradation of IκBα, a known inhibitor of nuclear factor (NF)-κB.…”