Isolation of P-glycoprotein inhibitors from Schisandra chinensis
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| Year of publication | 2012 |
| Type | Conference abstract |
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| Description | Schisandra chinensis (Schisandraceae) is a well-known medicinal plant in traditional Chinese medicine. Recently was found that dibenzocyclooctadiene lignans inhibit ATP binding cassette (ABC) transporters, P-glycoprotein and multidrug resistance-associated protein 1 (MRP1), which export drugs out of the cancer cells. In our previous study, we have isolated nine dibenzo[a,c]cyclooctadiene lignans, schizandrin, gomisin A, gomisin N, gomisin J, angeloylgomisin H, tigloylgomisin P, deoxyschizandrin, gamma-schizandrin and wuweizisu C from seeds of Schisandra chinensis and lignans were examined for their effect on doxorubicin-resistant human lung carcinoma COR-L23/R cell line over-expressing MRP1. We have found that two lignans, R-(+)-deoxyschizandrin and R,S-gamma-schizandrin at relatively non-toxic concentrations enhanced the accumulation of doxorubicin in COR-L23/R cells and restored the cytotoxic action of doxorubicin on drug-resistant cells (Slaninová et al.: Toxicology in Vitro 23, 2009, 1047). In order to obtain more effective lignans, the methanolic extracts of Schisandra chinensis seed and stem were screened for their effect on accumulation of doxorubicin in promyelotic leukaemia cells HL60/MDR overexpressing P-glycoprotein. The methanolic extract of both seed and stem increased intracellular doxorubicin accumulation. Activity-guided fractionation of both methanolic extracts on SPE cartridges Supelco LC 18 showed that active compounds were present in the fraction rich in lignans. The lignan fraction originated from the seeds was further purified by semi-preparative HPLC on a C18 column to give three subfraction with higher ability of doxorubicin accumulation than that of deoxyschizandrin. Further separation of one of these fractions on a semi-preparative C18 column provided two new lignans, which accumulated doxorubicin inside the HL60/MDR cells more effectively than well-known P-glycoprotein inhibitor verapamil or deoxyschizandrin. |
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