Abstract
Five pulchinenosides (pulchinenoside B3, pulchinenoside BD, pulchinenoside B7, pulchinenoside B10, and pulchinenoside B11) isolated from Pulsatilla chinensis (Bge) Regel saponins extract exhibited strong antitumor activities but poor gastrointestinal absorption properties. The enteric induction of P-glycoprotein (P-gp) is understood to restrict the oral bioavailability of some pharmaceutical compounds and lead to adverse drug reactions. Therefore, the present investigation was intended to delineate the impacts of pulchinenosides on cellular P-gp function and expression using Sf9 membrane vesicles and LS180 cells as a surrogate of human intestinal epithelial cells. Preliminary cytotoxic studies showed that 10 μM was an acceptable concentration for cytotoxicity and antiproliferation studies for all pulchinenosides using the alamarBlue assay. The cell cycle of LS180 cells detected by flow cytometry was not significantly influenced after 48 hours of coincubation with 10 μM of pulchinenosides. In the presence of pulchinenosides, the ATP-dependent transport of N-methyl-quinidine mediated by P-glycoprotein was stimulated significantly. The upregulation of P-glycoprotein and mRNA levels was found by Western blot and real-time PCR analysis in LS180 cells. Parallel changes indicate that all pulchinenosides are exposed to pulchinenosides-mediated transcriptional regulation. In conclusion, pulchinenosides could induce P-glycoprotein expression and directly increase its functional activity.
Highlights
A febrifugal traditional Chinese medicine named Pulsatilla chinensis (Bge) Regel has been used in medicinal and traditional practices in China and other Eastern countries for centuries. ere are 13 Chinese patent medicine formulas and 49 ancient prescriptions containing Pulsatilla chinensis retrieved on the Database of Drug Intelligence NetworkTraditional Chinese medicine prescription [1]
In contrast to anemoside B4, which was described in Chinese Pharmacopeia [2], recent reports revealed that these five pulchinenosides probably explain the antitumor activity of PRS more effectively [9]
Our research has identified pulchinenosides as substrates of P-glycoprotein in rat intestinal segments [22]. Since this suggested a crucial relationship in low drug bioavailability and P-glycoprotein function, we explore the impacts of pulchinenosides on P-glycoprotein function, which could restrict their absorption
Summary
A febrifugal traditional Chinese medicine named Pulsatilla chinensis (Bge) Regel has been used in medicinal and traditional practices in China and other Eastern countries for centuries. ere are 13 Chinese patent medicine formulas and 49 ancient prescriptions containing Pulsatilla chinensis retrieved on the Database of Drug Intelligence NetworkTraditional Chinese medicine prescription [1]. Ere are 13 Chinese patent medicine formulas and 49 ancient prescriptions containing Pulsatilla chinensis retrieved on the Database of Drug Intelligence NetworkTraditional Chinese medicine prescription [1]. It has been already recorded in the Chinese Pharmacopeia for ages and portrayed as “heat-clearing and detoxification, blood-cooling, and diarrhea-preventing [2].”. Pulsatilla chinensis saponins (PRS) extract was considered to possess biologically active components that exert potential antitumor activity in nude mice without producing toxicity [8]. Some constituents of Pulsatilla were identified and isolated in ceaseless efforts to find potential biologically active constituents from the Pulsatilla chinensis saponin extract. In contrast to anemoside B4, which was described in Chinese Pharmacopeia [2], recent reports revealed that these five pulchinenosides probably explain the antitumor activity of PRS more effectively [9]
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