Effects of four different ginsenosides on the Vivid® CYP3A4 red assay (A) and green assay (B).

<p>Each point is the mean value of triplicate samples, with error bars representing RSD values.</p

Effects of four different ginsenosides on the formation of carbamazepine 10,11-epoxide (A) and oxidized nifedipine (B).

<p>Data are avereages of triplicate samples.</p

Shape-based pharmacophore model of the inhibition of Vivid® CYP3A4 green activity by ginsenosides.

<p>The model was generated from the 3D structure of PPT and its activities against CYP3A4. PPT fitted into the model was shown in the figure. Blue represents the shape space, black represents carbon atoms, red represents oxygen atoms, and white represents hydrogen atoms.</p

Parameters of the enzymatic reactions used to determine the activities of P450 enzymes.

<p><b>Note:</b><b><i>a</i></b>. The linear range was determined by visual inspection; parameters for substrate concentration, wavelength and CYP450 concentration were provided by the kit manufacturer.</p

IC₅₀ values of the ginsenosides and sapogenins against P450 enzymes.

<p><b>Note:</b><b><i>a</i></b>. The percent inhibition of ginsenosides against the respective P450 enzymes is shown when its IC₅₀ value is greater than the maximum concentration assayed.</p><p><b><i>b</i></b>. The maximum concentration of ginsenosides evaluated for their effects on CYP2C9 and CYP2D6 were 50 µM due to the marked solvent effect of 1% methanol on these two P450 enzymes (inhibition by 42.4% and 27.5%, respectively). When the final concentration of methanol was decreased to 0.5%, the solvent effects were acceptable for these two enzymes (10.1% and 18.9%, respectively). 1% methanol had no inhibition against CYP1A2 and CYP3A4 and had an acceptable inhibitory effect on CYP2C19 (9.7%).</p><p><b><i>c</i></b>. Positive control compounds were α-naphthoflavone (for CYP1A2), sulfaphenazole (CYP2C9), miconazole nitrate salt (CYP2C19), quinidine (CYP2D6), and ketoconazole (CYP3A4), respectively.</p><p><b><i>d</i></b>. A.A. = apparent activation. 100 µM 25-OH-PPD and 25-OH-PPT increased the turnover of Vivid® CYP3A4 red by more than 100%.</p

Functional Hydrogen-Bonded Supramolecular Framework for K⁺ Ion Sensing

A luminescent metal–organic framework was assembled by using 3,3′-((6-hydroxy-1,3,5-triazine-2,4-diyl)­bis­(azanediyl))­dibenzoic acid and Zn­(II), which exhibits a 2D layer architecture, and the adjacent layers are further stacked via hydrogen-bonding and N···N van der Waals interactions to form a 3D supramolecular framework. This material can be used as fluorescent probe of K⁺ ion

Dihydroartemisinin Exerts Its Anticancer Activity through Depleting Cellular Iron via Transferrin Receptor-1

<div><p>Artemisinin and its main active metabolite dihydroartemisinin, clinically used antimalarial agents with low host toxicity, have recently shown potent anticancer activities in a variety of human cancer models. Although iron mediated oxidative damage is involved, the mechanisms underlying these activities remain unclear. In the current study, we found that dihydroartemisinin caused cellular iron depletion in time- and concentration-dependent manners. It decreased iron uptake and disturbed iron homeostasis in cancer cells, which were independent of oxidative damage. Moreover, dihydroartemisinin reduced the level of transferrin receptor-1 associated with cell membrane. The regulation of dihydroartemisinin to transferrin receptor-1 could be reversed by nystatin, a cholesterol-sequestering agent but not the inhibitor of clathrin-dependent endocytosis. Dihydroartemisinin also induced transferrin receptor-1 palmitoylation and colocalization with caveolin-1, suggesting a lipid rafts mediated internalization pathway was involved in the process. Also, nystatin reversed the influences of dihydroartemisinin on cell cycle and apoptosis related genes and the siRNA induced downregulation of transferrin receptor-1 decreased the sensitivity to dihydroartemisinin efficiently in the cells. These results indicate that dihydroartemisinin can counteract cancer through regulating cell-surface transferrin receptor-1 in a non-classical endocytic pathway, which may be a new action mechanism of DHA independently of oxidative damage.</p> </div

DHA induced disturbance of iron homeostasis could not be reversed by NAC.

<p>(A) MCF7 cells were pretreated with 20 mM NAC or left untreated for 30 min and then DHA (25 µM) were added to further treatment. After 24 hours, cell lysates were prepared and immunoblotted. (B) HepG2 cells were pretreated with NAC or not and further incubated with 25 µM DHA for 24 hours. Quantitative RT-PCR was performed to detect the mRNA level. **, <i>P</i><0.01. Data are represented as mean ±SD of three different experiments.</p

DHA induced TfR1 internalization in a lipid rafts/caveolae mediated way.

<p>(A) After pretreatment with CPZ (20 µM) or nystatin (25 µg/ml) or left untreated for 30 min, HepG2 cells were incubated with 25 µM DHA for another 4 hours. Cells were harvested and the membrane-associated TfR1 was determined by flow cytometric analysis. *, <i>P</i><0.05 compared with DMSO-treated cells. Data are represented as mean ±SD of two different experiments. (B) HEK293 cells expressed GFP-TfR1 were treated with DMSO or 25 µM DHA for 24 hours and subjected to confocal microscope analysis. Scale bar, 5 µm. (C) HepG2 cells were treated with DMSO or 25 µM DHA for 24 hours and the endogenous TfR1 protein was immunoprecipitated to perform the palmitoylation assay as described in Materials and Methods.</p

The proposed mechanisms by which DHA disrupts iron homeostasis.

<p>The proposed mechanisms by which DHA disrupts iron homeostasis.</p