Costunolide enhances sensitivity of K562/ADR chronic myeloid leukemia cells to doxorubicin through PI3K/Akt pathway.

Costunolide, a sesquiterpene lactone, a small molecular monomer extracted from Inula helenium, has been reported to possess antiproliferative effects on several cancer cell lines. The current study was designed to evaluate the effect of costunolide on sensitivity of K562/ADR chronic myeloid leukemia cells to doxorubicin. The antiproliferative effect of costunolide was assessed by CCK-8 assay. Flow cytometry and Western blot were used to examine the mechanisms of antileukemia action. Costunolide dramatically enhanced doxorubicin-induced antiproliferative activity against K562/ADR cells through inhibition of PI3K/Akt pathway, activation of caspases 3, cleavage of poly (ADP-ribose) polymerase, and downregulation of p-glycoprotein expression. These results demonstrate that costunolide may be a potent therapeutic agent against CML.

Pharmacokinetic Characterizations of Ginsenoside Ocotillol, RT5 and F11, the Promising Agents for Alzheimer's Disease from American Ginseng, in Rats and Beagle Dogs.

BACKGROUND: Ocotillol, RT5 and F11, the main active components of ocotillol type ginsenosides, have attracted a lot of attention due to their beneficial effects on neurodegenerative disease models of Alzheimer's disease. Pharmacokinetic (PK) is a bridge linking the herbal medicines and their pharmacological responses. However, few data are available regarding PK behaviors of ocotillol type ginsenosides. METHODS: The liquid chromatography-tandem mass spectrometry methods were developed and validated to calculate the concentrations of 3 ginsenosides in different biological matrices. Rat and beagle dog plasma samples were deproteinized with methanol and separated on Shim-pack GIST C18 column. All of the analytes were detected in positive ion mode using multiple reaction monitoring. RESULTS: The methods showed good linearity (r > 0.996) in the established concentration range. All validated data, such as specificity, intra- and inter-day precision, accuracy, extraction recovery, matrix effect, and stability were within required limits. The values of Cmax and AUC(0-t) indicated ocotillol type ginsenosides had low systemic exposure and poor absorption into blood. T1/2 and MRT(0-t) demonstrated the elimination process of ocotillol type ginsenosides might be slow. Double peaks were observed in the mean plasma concentration versus time profiles of ocotillol, RT5, and F11 after oral intake. CONCLUSIONS: This was the first PK investigation of the ocotillol type ginsenosides in rats and beagle dogs. The results we found here were helpful to our understanding of the absorption mechanism of ocotillol type ginsenosides and provided the scientific basis for further pre-clinical research.