Abstract: The aim of this study was to screen active constituents that reverse multidrug resistance(MDR) in P-glycoprotein(Pgp) overexpressing cancer cells from plant Metaplexis hemsleyana Oliv.(Asclepiadaceae). The aerial parts of M. hemsleyana were extracted with hot ethanol. After removal of ethanol,the concentrated ethanol extract was successively extracted with petrol ether(PE),ethyl acetate(EtOAc) and n-butanol(BuOH) to yield PE,EtOAc and BuOH fractions. Chemical constituents from the BuOH fraction were isolated through silica gel and ODS chromatographic columns. The chemical structures of isolated compounds were identified by comprehensive spectroscopic analysis on their NMR and MS data. Activity of the four compounds in reversing resistance of MDR cancer cells to vinblastine,doxorubicin and paclitaxel was evaluated in Pgp-overexpressing human epidermoid carcinoma cell KB V1,leukemia cell K562/Dox,hepatoma cell HepG2/Dox and cervical carcinoma cell HeLa/Tax. Four compounds were obtained from the BuOH fraction and their structures were identified as tenacissoside H(1),marsdenoside B(2),tenacissoside A(3) and marsdenoside H(4). Compounds 1 and 2 at 5 μM,a non-cytotoxic concentration,significantly reversed the resistance to vinblastine,doxorubicin and paclitaxel in all four MDR cells. At the same concentration,compounds 3 and 4 had no or only weak reversal effect on drug resistance. This is the first report that tenacigenin B derivatives were found from M. hemsleyana and tenacissoside H and marsdenoside B showed activity in reversing MDR in Pgp overexpressing human cancer cells.

Key words: Metaplexis hemsleyana Oliv., C₂₁ steroid, cancer multidrug resistance, tenacissoside H, marsdenoside B