The non-peptide chemical 3,4-methylenedioxyphenol blocked lipopolysaccharide (LPS) from binding to LPS-binding protein and inhibited pro-inflammatory cytokines

Abstract

After binding to lipopolysaccharide (LPS)-binding protein, LPS is transferred to CD14 and then to the MD2—Toll-like receptor 4 complex, which results in the progression of sepsis. We investigated how 3,4-methylenedioxyphenol (sesamol), an inexpensive natural product in sesame seeds, affects the binding of LPS and LPS-binding protein and the release of pro-inflammatory cytokines. Sesamol: (i) dose-dependently inhibited LPS from binding to LPS binding protein; (ii) significantly decreased the release of tumor necrosis factor-α and interleukin-1β in LPS-challenged peritoneal macrophages in medium and in the serum of LPS-challenged rats; and (iii) significantly reduced the mortality rate in mice given a lethal dose of LPS. We hypothesize that sesamol blocks LPS from binding to LPS-binding protein and inhibits the release of pro-inflammatory cytokines, both of which are associated with a decrease of mortality in endotoxemia.

Keywords

Sesamol lipopolysaccharide (LPS)LPS-binding protein cytokine

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