Iron-binding and anti-Fenton properties of baicalein and baicalin

Abstract

Baicalein and baicalin, the major bioactive compounds found in the Chinese herb Scutellaria baicalensis, have been shown to be effective against cancer, bacterial infections and oxidative stress diseases. However, little is known about their mechanisms of action. To probe whether iron homeostasis modulation may play a role in their bioactivity, we have investigated their iron binding characteristics under physiologically relevant conditions. A 2:1 baicalein-ferrous complex was readily formed in 20 mM phosphate buffer, pH 7.2, with a binding constant ~2-9 × 10 11 M -2 , whereas a 1:1 baicalein-ferric complex was formed, under the same conditions, with an apparent binding constant ~1-3 × 10 6 M -1 . Baicalein appears to bind the ferrous ion more strongly than ferrozine, a well known iron(II) chelator. Using 1 H NMR and Zn 2+ and Ga 3+ as probes, the iron-binding site on baicalein was elucidated to be at the O6/O7 oxygen atoms of the A-ring. No binding was observed for baicalin under the same NMR conditions. Furthermore, baicalein strongly inhibits the Fepromoted Fenton chemistry via a combination of chelation and radical scavenging mechanism while baicalin can provide only partial protection against radical damage. These results indicate that baicalein is a strong iron chelator under physiological conditions and hence may play a vital role in modulating the body's iron homeostasis. Modulation of metal homeostasis and the inhibition of Fenton chemistry may be one of the possible mechanisms for herbal medicine.

A Novel Antimycobacterial Compound Acts as an Intracellular Iron Chelator

“…First, the molar stoichiometry of the complexes formed by titration of 10 M PZP with increasing amounts of Fe 2ϩ was determined by monitoring the change of absorbance at 400 nm (the wavelength where the complexes absorb while the ligand does not). The method used was previously described for the determination of the apparent binding constant of the quercetin-Fe 2ϩ complex (29). The spectroscopic measurements registered at 400 nm were used for the calculations.…”

“…Figure 5B shows a possible chemical structure of the [Fe(PZP) 3 ] ϩ complex. The conditional binding constant of the compound with Fe 2ϩ was estimated at 400 nm by applying a method established for measuring the binding constants of complexes between flavonoids and iron (29). Since a strong binding constant was determined for the [Fe(PZP) 3 ] ϩ complex (K, ϳ2 ϫ 10 11 mM), we performed competition experiments with ferrozine, a well-known Fe 2ϩ chelator (K, 3.65 ϫ 10 15 mM) (38).…”

Influence of supplementation with different oenological tannins on malvidin-3-monoglucoside copigmentation

“…In fact, the literature has attributed to oenological tannins several other features such as antioxidant activity (protection of wines against oxidation) [2], direct consumption of dissolved oxygen [3], ability to scavenge peroxyl radicals [4], ability for chelating iron (II), preventing the oxidative damage mediated by Fentonbased reactions [5], antioxidasic activity (anti-laccase activity) [6], improvement of structure and mouthfeel of wines [7], color improvement and stabilization of red wines [8], copigmentation effect [9], direct formation of new pigments [10], elimination of reduction odors [7] and even bacteriostatic effects [11].…”

Enhancing the potency of lithospermate B for inhibiting Na+/K+-ATPase activity by forming transition metal ion complexes

“…Chelation of metal ions might affect the bioactivities of phenolic compounds, such as baicalein and baicalin. These two major bioactive compounds in the Chinese herb Scutellaria baicalensis were found to form complexes with Fe 2+ and Fe 3+ that possessed distinctive anti-Fenton properties [34] . Similar iron-binding properties of quercetin, the major phenolic compound in cranberries, were also observed and were proposed to be effective at modulating cellular iron homeostasis under physiological conditions [35] .…”