The non-peptide chemical 3,4-methylenedioxyphenol blocked lipopolysaccharide (LPS) from binding to LPS-binding protein and inhibited pro-inflammatory cytokines.
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-alpha and interleukin-1beta 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.
Hsu
Dur-Zong
DZ
Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan. durzonghsu@gmail.com
Chu
Pei-Yi
PY
Liu
Ming-Yie
MY
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D052117:Benzodioxoles / Q000737:chemistry / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds; D031685:Sesamum; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D052117:Benzodioxoles; D002352:Carrier Proteins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010636:Phenols; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C025583:sesamol