Rapid re-evaluation of bioactive saponins from Paris polyphylla using affinity ultrafiltration-LC/MS with multiple drug targets

Paris polyphylla Smith var. yunnanensis (P. polyphylla) has been widely used as a traditional Chinese medicine for centuries. The Chinese Pharmacopoeia (2015) suggests that the four steroidal saponins, namely polyphyllin I, II, VI and VII, are considered to be the marker components for the quality control (QC) of this herb medicine. However, the active components responsible for the anti-cancer and anti-inflammatory effects of P. polyphylla and the underlying mechanisms of action remain elusive. In the present study, ultrafiltration HPLC-MS (UF-LC-MS) with the multiple drug targets of topoisomerase I, II (Top I, II) and cyclooxygenase 2 (COX-2) was carried out to systematically investigate the mechanisms of action in a multi-component manner. The results revealed that the polyphyllin I displayed not only higher binding affinity to the three drug targets, but also stronger inhibitory activities, as compared with the positive controls. Thus, COX-2 and Top I could be considered as the anti-cancer and anti-inflammatory targets of P. polyphylla. Further molecular docking studies partly revealed the inhibitory mechanism of action associated with the hydrogen bonds between polyphyllin I and the three target enzymes. This study showcased the high efficiency of OF-LC/MS in exploring the potential bioactive components from P. polyphylla and its possible mechanisms of action in a multi-target and multi-component manner. (C) 2018 Elsevier B.V. All rights reserved.