Specific reversal of multidrug resistance to colchicine in CEM/VLB(100) cells by Gynostemma pentaphyllum extract.

P-glycoprotein (P-gp)-mediated multiple drug resistance (MDR) is perhaps the most thoroughly studied cellular mechanism of cytotoxic drug resistance. Its efflux function can be circumvented by a wide range of pharmacological agents in vitro and in vivo. Most of these agents are pharmaceuticals used clinically for conditions other than cancer. However, their use in alleviating MDR is limited because the concentrations required for inhibition of the pump surpass their dose-limiting toxicity. The aim of this research is to study the role of gypenosides, isolated from Gynostemma pentaphyllum, as modulators of P-gp-mediated MDR in tumor cells, at both cellular and plasma membrane level. In the presence of total gypenoside preparation (0.1 mg/ml), an approximately 15-fold reversal of colchicine (COL) resistance was observed in P-gp-overexpressed CEM/VLB(100) cells. However, the gypenoside sample showed no reversal effect in cells treated with vinblastine and taxol. A purified gypenoside sample (gypenoside fraction 100) exhibited even more significant reversal of COL resistance (approximately 42-fold) in the CEM/VLB(100) cells. Further examination of the reversal effect of fraction 100 in membrane vesicles derived from CEM/VLB(100) cells using the continuous fluorescence method found that gypenoside fraction 100 at 0.1 mg/ml completely abolished the transport of fluorescein-COL.

The stability of gingerol and shogaol in aqueous solutions.

Gingerols, pungent principles of ginger (the rhizome of Zingiber officinale), are biologically active components that may make a significant contribution towards medicinal applications of ginger and some products derived from ginger. Gingerols, however, are thermally labile due to the presence of a beta-hydroxy keto group in the structure, and undergo dehydration readily to form the corresponding shogaols. This study investigated the stability of [6]-gingerol [5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)decan-3-one] at temperatures ranging from 37 to 100 degrees C in aqueous solutions, at pH 1, 4, and 7. Quantitative measurements of [6]-gingerol and its major degradation product [6]-shogaol [1-(4-hydroxy-3-methoxyphenyl)decan-4-ene-3-one] were performed by HPLC. Kinetics of [6]-gingerol degradation was characterized by least square fitting of a rate equation. It was found that gingerol exhibited novel reversible kinetics, in which it undergoes dehydration-hydration transformations with shogaol, the major degradation product. Degradation rates were found to be pH dependent with greatest stability observed at pH 4. The reversible degradation of [6]-gingerol at 100 degrees C and pH 1 was relatively fast and reached equilibrium within 2 h. Activation energies for the forward and reverse reactions for [6]-gingerol were calculated from the Arrhenius equation using reaction rates obtained at temperatures ranging from 37 to 100 degrees C.