|Binding and neutralization of lipopolysaccharides by plant proanthocyanidins
|DELEHANTY, JAMES B. ; JOHNSON, BRANDY J. ; HICKEY, THOMAS E. ; PONS, THOMAS ; LIGLER, FRANCES S.
|Tipo de documento:
|Proanthocyanidins (PACs), polyphenolic metabolites that are widely distributed in higher plants, have been associated with potential positive health benefits including antibacterial, chemotherapeutic, and antiatherosclerotic activities. In this paper, we analyze the binding of PACs from cranberries, tea, and grapes to lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria and the cause of several human illnesses. We demonstrate that in the case of cranberries, the most potent LPS-binding activity is contained within a PAC fraction composed of polymers with an average degree of polymerization of 21. The PAC fraction modestly inhibits the binding of LPS to the surface of HEK 293 cells expressing the full complement of LPS receptors (TLR4/MD2 and CD14), while it significantly abrogates the endocytosis of LPS. This PAC fraction also inhibits LPS-induced nuclear factor-êB activation in a manner that is not readily overcome by excess LPS. Such an effect is mediated through the inhibition of LPS interaction with TLR4/MD2 and the partial abrogation of LPS interaction with CD14. Importantly, PAC concentrations that mediate effective LPS neutralization elicit minimal in Vitro cytotoxicity. Our results identify PACs as a new class of LPS-binding compound and suggest that they have potential utility in applications that necessitate either the purification and removal of LPS or the in ViVo neutralization of LPS.
|Nota de contenido:
|En: Journal of Natural Products. -- (70) : 1718-1724 (2007)
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