Effect of bioflavonoids extracted from the bark of Pinus maritima on proinflammatory cytokine interleukin-1 production in lipopolysaccharide-stimulated RAW 264.7

Currently, bioflavonoids have been known to have strong antioxidant capacit ies, and a variety of efforts have been made to identify the utilities of b ioflavonoids in treating various diseases based on their antioxidant capaci ties. The effects of bioflavonoids extracted from the bark of Pinus maritim a Pycnogenol (PYC) on free radical formation, activation of redox sensitive transcription factors, as well as interleukin-1 beta (IL-1 beta) productio n were investigated in murine macrophage cell lines. PYC exerted strong sca venging activities against reactive oxygen species generated either by H2O2 or PMA in RAW 264.7 and IC-21 cells, respectively. lit situ ELISA, immunob lot analysis, and competitive RT-PCR demonstrated that PYC pretreatment of LPS-stimulated RAW 264.7 cells dose-dependently reduced both the production of IL-1 beta and its mRNA levels. Furthermore, in the same cells, PYC bloc ked the activation of nuclear factor kappa B (NF-kappa B) and activator pro tein-1 (AP-1), two major transcription factors centrally involved in IL-1 b eta gene expression. When RAW 264.7 cells were stimulated with LPS, the inh ibitor protein I kappa B largely disappeared from cytosolic fractions. Howe ver, pretreatment of the cells with PYC abolished the LPS-induced I kappa B degradation. These results suggest that PYC can inhibit the expression of the proinflammatory cytokine IL-1 by regulating redox-sensitive transcripti on factors. This study may support the possibility that bioflavonoids inclu ding PYC can be used as antiinflammatory and immunosuppressive drugs based on their radical scavenging activities. (C) 2000 Academic Press.