Yibin Wei

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

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 bodys iron homeostasis. Modulation of metal homeostasis and the inhibition of Fenton chemistry may be one of the possible mechanisms for herbal medicine.

A Turn‐on Fluorescent Sensor for Imaging Labile Fe3+ in Live Neuronal Cells at Subcellular Resolution

An eye for an iron: A highly sensitive, selective and reversible turn-on Fe(3+) sensor for imaging labile Fe(3+) in live cells at subcellular resolution is reported. The sensor can respond to changes in intracellular Fe(3+) levels and was used to image endogenous chelatable Fe(3+) in live human neuroblastoma SH-SY5Y cells, with two Fe(3+) pools being identified in mitochondria and endosomes/ lysosomes for the first time.

A novel profluorescent probe for detecting oxidative stress induced by metal and H2O2 in living cells

A profluorescent probe that has no fluorescent response to H(2)O(2), iron or copper ions but can be readily activated in the presence of both H(2)O(2) and Fe (or Cu) ion has been developed; the probe is capable of detecting oxidative stress promoted by Fe (or Cu) and H(2)O(2) (i.e. the Fenton reaction conditions) in living cells.

Direct observation of internalization and ROS generation of amyloid β-peptide in neuronal cells at subcellular resolution.

Seeing in many colors: Confocal images acquired using fluorescently labeled amyloid β-peptide revealed its efficient internalization by endocytosis into endosomes/lysosomes of human neuronal cells with a small portion reaching mitochondria, inducing marked cellular and mitochondrial reactive oxygen species production.

A novel H2O2-triggered anti-Fenton fluorescent pro-chelator excitable with visible light.

A chelator and a pro-chelator that can be activated by H(2)O(2) and subsequently sequesters iron and attenuates the Fenton reaction have been developed; both molecules are fluorescent excitable by visible light, and H(2)O(2)-activation, as well as iron-chelation, induces remarkable changes in fluorescence.