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Polyphenols and heart diseases
Reactive oxygen species (ROS) are highly reactive molecules that are constantly produced by enzymatic reactions in
cells. In normal physiological conditions, ROS are produced at low levels, which are necessary for maintaining normal cell
functions, and the endogenous anti-oxidant defense systems of the body have the capacity to avert any harmful effects. However,
several established risk factors for cardiovascular disease have been linked to excessive generation of ROS, known as a state of
oxidative stress. For instance, in animal models of hiperlipidemia (Miller et al., 1998; Mugge et al., 1994), hypertension
(Morawietz et al., 2001; Zalba et al., 2000; Suzuki et al., 1995), and diabetes (Hink et al., 2001; Sano et al., 1998), elevated levels
of vascular superoxide anion production. Moreover, clinical studies have demonstrated that hypercholesterolemia and diabetes in
humans are also associated with increased vascular superoxide anion generation (Guzik et al., 2000). All these data strongly
suggest that increased oxidative stress is involved in the pathophysiology of cardiovascular disease.
Many epidemiological studies have shown that regular flavonoid intake is associated with a reduced risk of
cardiovascular diseases (Middleton et al., 2000). In the coronary heart disease, the protective effects of flavonoids include mainly
antithrombotic, antiischemic, anti-oxidant, and vasorelaxant (Jendekova et al., 2006). It is suggested that flavonoids decrease the
risk of coronary heart disease by three major actions: (A) improving coronary vasodilatation, (B) decreasing the ability of platelets
in the blood to clot and (C) preventing LDLs from oxidizing (Garc´ia and Castillo, 2008). Oxidation of low density lipoproteins is
believed to play an important role in the development of atherosclerosis (Witztum and Steinberg, 1991; Parthasarathy et al.,
1992). Oxidized low density lipoprotein cholesterol (LDL cholesterol) is taken up more readily by macrophages, which leads to
the formation of foam cells and atherosclerotic plaques (Palinski et al., 1989). Mechanisms that slow or prevent this chain of
events may decrease the risk of coronary heart disease (CHD) and stroke (Catapano, 1997). Flavonoids are a group of phenolic
compounds and are known to have antioxidant properties (Kandaswani and Middleton, 1994). They have been reported to be
scavengers of free radicals, including superoxide anions (Robak and Gryglewski, 1988), singlet oxygen (Husain et al., 1987), and
lipid peroxy-radicals (Sorata et al., 1982). In addition, flavonoids have been shown to prevent LDL cholesterol oxidation and
cytotoxicity in vitro (De Whalley et al., 1990).
According to Beretta et al. (2007), the experiments with endothelial cells fortified with the isolated fraction from native
honey enriched in antioxidants, exposed to peroxyl radicals from 1,1-diphenyl-2-picrylhydrazyl (AAPH, 10 mM) and to hydrogen
peroxide (H2O2, 50-100 microM), indicated that phenolic acids and flavonoids were the main causes of the protective effect. They
suggested that, through the synergistic action of its antioxidants, honey by reducing and removing ROS, may lower the risks and
effects of acute and chronic free radical induced pathologies in vivo.
Rakha et al. (2008) showed that natural wild honey may exert its cardioprotective and therapeutic effects against
epinephrine-induced cardiac disorders and vasomotor dysfunction directly, via its very pronounced total antioxidant capacity and
its great wealth of both enzymatic and nonenzymatic antioxidants involved in cardiovascular defense mechanisms.
Nagyova et al. (2004) also demonstrated that short-term and modest supplementation with a mixture of antioxidant
nutrients improves antioxidative capacity and reduces products of lipid peroxidation in plasma. Since a more pronounced effect "
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