Anti-Inflammatory Actions of a Micronized, Purified Flavonoid Fraction in Ischemia/Reperfusion

Abstract

It is now recognized that reperfusion after a prolonged period of reduced or absent blood flow, although necessary to salvage ischemic tissue, initiates a complex series of deleterious reactions which ultimately induce the same effects as ischemia per se, i.e., cell injury and necrosis. Work conducted over the past 15 years has uncovered the fact that postischemic leukocyte infiltration plays a major role in the reperfusion component of ischemia/reperfusion (I/R) injury. This discovery has led to a concerted research effort directed at identifying interventions that prevent post-ischemic leukocyte adhesion and emigration. Recent work indicates that flavonoids are particularly effective anti-inflammatory agents in the setting of I/R. While the mechanisms underlying the powerful protective effects of these compounds is uncertain, a growing body of evidence indicates that flavonoids are potent anti-oxidants that also act to inhibit the activity of key regulatory enzymes involved in the activation of pro-inflammatory signaling cascades. In addition, it appears that these compounds prevent the expression of specific adhesion molecules involved in leukocyte recruitment, observations which provide the molecular basis for the anti-adhesive properties of these compounds.