title: 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 20mM phosphate buffer, pH 7.2, with a binding constant approximately 2-9 x 10(11)M(-2), whereas a 1:1 baicalein-ferric complex was formed, under the same conditions, with an apparent binding constant approximately 1-3 x 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 Fe-promoted 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Massachusetts, Dartmouth, MA 02747-2300, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Perez
authors.forename: Yibin
authors.initials: Y
authors.lastname: Wei
authors.forename: Maolin
authors.initials: M
authors.lastname: Guo
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005297:Ferrozine / Q000378:metabolism; D044950:Flavanones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007501:Iron / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008517:Phytotherapy; D031364:Scutellaria baicalensis / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; C045076:Fenton's reagent; D044950:Flavanones; D005419:Flavonoids; D007502:Iron Chelating Agents; D005297:Ferrozine; C038044:baicalin; C006680:baicalein; D006861:Hydrogen Peroxide; D007501:Iron