Prenylated Phenolic Compounds from the Aerial Parts of Glycyrrhiza uralensis as PTP1B and α-Glucosidase Inhibitors.

Glycyrrhiza uralensis (liquorice) is a well-known medicinal plant. Its roots and rhizomes are used as the popular Chinese herbal medicine Gan-Cao. An ethanol extract of the aerial parts of G. uralensis showed antidiabetic effects on db/db mice. It decreased the blood glucose level by 30.3% and increased the serum insulin level by 41.8% compared to the control group. Eighty-six phenolic compounds (1-86) were obtained from the aerial parts, including the new prenylated isoflavanones (1-5), isoflavans (6-9), and a 2-phenylbenzofuran (10). The structures were identified by NMR and HRESIMS data analyses, and the absolute configurations were established by comparing the calculated and experimental ECD spectroscopic data. Compounds 2, 6, and 10 inhibited PTP1B with IC50 values of 5.9, 6.7, and 5.3 µM, respectively. Compound 2 and the known compounds glycycoumarin (76) and glyurallin A (79) inhibited α-glucosidase with IC50 values of 20.1, 0.1, and 0.3 µM, respectively. Compound 4 at 10 µM increased the glucose uptake rate to 95% in an insulin resistance HepG2 cell model (p < 0.01).

Selenium-containing organic nanoparticles as silent precursors for ultra-sensitive thiol-responsive transmembrane anion transport.

An anion transporter with a selenoxide group was able to form nanoparticles in water, whose activity was fully turned off due to the aggregation effect. The formed nanoparticles have a uniform size and can be readily dispersed in water at high concentrations. Turn-on of the nanoparticles by reducing molecules is proposed to be a combined process, including the reduction of selenoxide to selenide, disassembly of the nanoparticles and location of the transporter to the lipid membrane. Accordingly, a special acceleration phase can be observed in the turn-on kinetic curves. Since turn-on of the nanoparticles is quantitatively related to the amount of reductant, the nanoparticles can be activated in a step-by-step manner. Due to the sensibility of this system to thiols, cysteine can be detected at low nanomolar concentrations. This ultra-sensitive thiol-responsive transmembrane anion transport system is quite promising in biological applications.

Reversible Ca(2+) switch of an engineered allosteric antioxidant selenoenzyme.

A Ca(2+) -responsive artificial selenoenzyme was constructed by computational design and engineering of recoverin with the active center of glutathione peroxidase (GPx). By combining the recognition capacity for the glutathione (GSH) substrate and the steric orientation of the catalytic selenium moiety, the engineered selenium-containing recoverin exhibits high GPx activity for the catalyzed reduction of H2 O2 by glutathione (GSH). Moreover, the engineered selenoenzyme can be switched on/off by Ca(2+) -induced allosterism of the protein recoverin. This artificial selenoenzyme also displays excellent antioxidant ability when it was evaluated using a mitochondrial oxidative damage model, showing great potential for controlled catalysis in biomedical applications.

A dual enzyme microgel with high antioxidant ability based on engineered seleno-ferritin and artificial superoxide dismutase.

An antioxidant microgel with both glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities is reported. Using computational design and genetic engineering methods, the main catalytic components of GPx are fabricated onto the surface of ferritin. The resulting seleno-ferritin (Se-Fn) monomers can self-assemble into nanocomposites that exhibit remarkable GPx activity due to the well organized multi-GPx catalytic centers. Subsequently, a porphyrin derivative is synthesized as an SOD mimic, and is employed to construct a synergistic dual enzyme system by crosslinking Se-Fn nanocomposites into a microgel. Significantly, this dual enzyme microgel is demonstrated to display better antioxidant ability than single GPx or SOD mimics in protecting cells from oxidative damage.

Selenium/Tellurium-Containing Hyperbranched Polymers: Effect of Molecular Weight and Degree of Branching on Glutathione Peroxidase-Like Activity.

A series of novel hyperbranched polyselenides and polytellurides with multiple catalytic sites at the branching units has been synthesized via the polycondensation of A2 + B3 monomers. The GPx-like activities of these polymer mimics were assessed and it was found that the polytellurides showed higher GPx-like activities than the corresponding polyselenides. Interestingly, the polymers with higher molecular weights and degree of branching (DB) showed higher GPx-like activities than the analogous lower molecular weight polymer. The enhancement in the catalytical activity of the hyperbranched polymers with increasing molecular weight affirmed the importance of the incorporation of multiple catalytic groups in the macromolecule which increases the local concentration of catalytic sites.

Selenium-mediated micellar catalyst: an efficient enzyme model for glutathione peroxidase-like catalysis.

Mimicking the properties of the selenoenzyme glutathione peroxidase (GPx) has inspired great interest. In this report, a selenium-containing micellar catalyst was successfully constructed by the self-assembly of the cationic surfactant hexadecyltrimethylammonium bromide (CTAB) with benzeneseleninic acid (PhSeO2H) through hydrophobic and electrostatic interaction in water. The selenium-containing micellar catalyst demonstrated substrate specificity for both 3-carboxy-4-nitrobenzenethiol (ArSH, 2) and cumene hydroperoxide (CUOOH), and their complexation was confirmed by UV and fluorescence spectra. More importantly, it demonstrated high GPx activity in two assay systems. It is about 126 times more effective than the well-known GPx mimic ebselen in the classical coupled reductase assay system; however, by using hydrophobic substrate ArSH (2) as an alternative of glutathione (GSH, 1), the micellar catalyst exhibited remarkable 500-fold and 94 500-fold rate enhancements compared with that of PhSeO2H and PhSeSePh.