Lipophilic Caffeic Acid Derivatives Protect Cells against H₂O₂-Induced DNA Damage by Chelating Intracellular Labile Iron

Abstract

Naturally occurring cinnamic acid derivatives are ubiquitously distributed in the plant kingdom, and it has been proposed that their consumption contributes to the maintenance of human health. However, the molecular mechanisms underlying their health keeping effects remain unknown. In the present investigation, we evaluated the capacity of several cinnamic acid derivatives (trans-cinnamic, p-coumaric, caffeic and ferulic acids, as well as caffeic acid-methyl and -propyl esters) to protect cells from oxidative stress-induced DNA damage. It was observed that effective protection was based on the ability of each compound to (i) reach the intracellular space and (ii) chelate intracellular "labile" iron. These results support the notion that numerous lipophilic iron chelating compounds, present abundantly in plant-derived diet components, may protect cells in conditions of oxidative stress and in this way be important contributors toward maintenance of human health.

Hydroxytyrosol inhibits hydrogen peroxide-induced apoptotic signaling via labile iron chelation

“…However, only HTy was able to prevent H 2 O 2 -induced DNA damage, while Ty was completely ineffective [20], [27]. Since the only difference in the chemical structure of the two compounds is the replacement of hydrogen at position 3 in Ty by a hydroxyl group in HTy [Scheme 1], we hypothesised that HTy could exert its protective effects by chelating intracellular labile iron through its ortho-dihydroxy moiety in the same manner as caffeic acid and its analogues did [22]. Indeed, it was observed in the present work that the degree of protection offered by HTy against H 2 O 2 -induced DNA damage correlated strongly with its ability to decrease the level of intracellular labile iron pool, as it was estimated fluorometrically by the calcein method (r=0.959, p<0.001) (Fig.…”

“…A prerequisite for effective action of a particular compound was its ability to penetrate plasma membrane in order to act in the interior of the cells. Thus, phenolic acids, like caffeic acid, which are negatively charged at neutral pH were largely ineffective, even at relatively high concentrations, although able to chelate iron [22]. On the other hand, their protective capacity was increased when the negatively charged carboxyl group was esterified, thus facilitating their penetration through plasma membrane.…”

Rosmarinic Acid-Rich Extracts of Summer Savory (Satureja hortensisL.) Protect Jurkat T Cells against Oxidative Stress

“…Indeed, in a metal-catalyst system, most phenolic compounds exhibited pro-oxidant effects at low doses and shifted to antioxidant activity at higher concentrations [33]. Furthermore, it was shown recently that high doses (2-3 mM) of caffeic acid and other phenylpropanoids protected Jurkat cells from H 2 O 2 -induced DNA damage by chelating intracellular labile iron [34]. The presence of the potent flavonoid antioxidants in the phenolic fraction, in addition to rosmarinic acid, might further strengthen its antioxidant capacity.…”

In Vivo Hepatoprotective Effect of Caffeic Acid on Mercuric Chloride-Induced Biochemical Changes in Albino Wistar Rats

“…It is easily available in several species of plants, and it also occurs in parts of fruits, vegetables, tea, coffee, and wine [15] and is regularly consumed in human diet [16,17]. In the past three decades, CA and its derivatives have a protective role that is clearly demonstrated by number of experimental works, showing that these chemicals have a variety of functions including acting as antioxidant and suppressing LPO [18][19][20]. It is a natural phenolic compound found in many plants.…”