Flavonoids: Hemorheological effects and mechanisms of action.

Flavonoids exhibit a wide range of biological activities, including antioxidant, anti-inflammatory, antidiabetic, antitumor, antiproliferative, and hemorheological effects. This review discusses the hemorheological activity of flavonoids and the underlying mechanisms. The hemorheological activity of flavonoids and flavonoid complexes has been studied in both in vitro and in vivo models of myocardial infarction, arterial hypertension, atherosclerosis, cerebrovascular insufficiency, pancreatitis, hepatitis, and rheumatoid arthritis, as well as in aging animals. Flavonoids are known to decrease whole blood viscosity, reduce red blood cell (RBC) aggregation, improve RBC deformability, and even, in some cases, decrease fibrinogen levels and plasma viscosity. The key mechanisms underlying the hemorheological effects of flavonoids are the following: (1) antioxidant protection from oxidative stress and (2) stabilization of membrane fluidity. The antioxidant effect is mediated through neutralization of reactive oxygen species outside RBCs, within the RBC membrane, and in the cytoplasm, thereby protecting RBC membranes (both lipid and protein constituents) from oxidative damage. Flavonoids also contribute to the maintenance and enhancement of endogenous antioxidant defense systems in RBCs. Clinical trials of flavonoid-based agents have demonstrated both hemorheological activity and therapeutic efficacy in patients with diabetes mellitus, coronary heart disease, venous insufficiency, dyscirculatory encephalopathy, arterial hypertension, and other conditions. The introduction of effective and low-toxicity flavonoid preparations with hemorheological activity into treatment regimens for conditions associated with hyperviscosity syndrome may enable the development of new therapeutic strategies for many diseases and improve patient outcomes.