Formation of lignans in plant cell culture of Schisandra chinensis

Abstract

The fruit of Schisandra chinensis, a woody liana, has been used for centuries in traditional Chinese medicine. The fruit is prescribed for the treatment of hepatitis in China. The active principles are lignans with unusual structures derived from dibenzo[a,c]cyclooctadiene. These lignans have been shown to possess a broad range of biological activities. Recently, it has been found that lignan gamma-schizandin strongly inhibits P-glycoprotein, the overexpression of which is the most frequent cause for cancer multidrug resistance. S. chinensis cultures derived from immature zygotic embryos were developed on Murashige and Skoog and VW5 medium. Embryogenic cultures were established on the medium containing thidiazuron, 2,4-dichlorophenoxyacetic acid and benzylaminopurine. An analytical method based on HPLC-UV was used for the determination of six lignans in plant cell cultures. Our previous results showed that the concentration of lignans in plant cell cultures was mostly lower than that in fruit and leaves. We also detected the lignans in liquid culture media, but the amount of lignans inside the cells was substantially higher. In order to release the lignans stored within the cells, we explored the cultivation of five cell lines with neutral polymeric resin, Amberlite XAD2. We found that the addition of Amberlite XAD2 not only notably enlarged portions of extracellular lignans, but also greatly enhanced the production of lignan deoxyschizandrin, whereas the formation of other lignans was increased only moderately (less than 5fold). Importantly, Amberlite XAD-2 did not reduce the growth of cell cultures. Deoxyschizandrin adsorbed on the polymeric resin can be easily recovered and purified without destruction of the cells.