Podophyllum sinense, a folk herbal medicine, possesses multiple phytochemicals and extensive pharmaceutical activities. Modern pharmacological studies have indicated that P. sinense has remarkable activities, such as anti-proliferative, anti-inflammatory, anti-viral effects, etc. However, the specific functional constituents responsible for anti-proliferative, anti-inflammatory and anti-viral activities remain unknown.  

To address this bottleneck, supervised by Prof. GUO Mingquan from the Wuhan Botanical Garden of the Chinese Academy of Sciences, FENG Huixia aimed to find out the correlations between potential bioactive components from P. sinense extracts and multiple activities.  

Affinity ultrafiltration with topoisomerase I (Topo I), Topo II, cyclooxygenase 2 (COX-2), and angiotensin-converting enzyme II (ACE2) coupled with high performance liquid chromatography - the triple quadrupole mass spectrometer electrospray ionization - mass spectrometry / mass spectrometry technology was then developed to meet this demand.    

Several active ingredients were screened out and the subsequent validation experiments in vitro indicated that two key compounds, diphyllin and podophyllotoxin, exhibited higher inhibitory rate against A549 (non-small lung cell cancer) and HT-29 (colon cancer) cells compared with 5-fluorouracil and etoposide.  

Meanwhile, diphyllin displayed significant COX-2 inhibitory activity with the IC₅₀ value at 1.29 ± 0.14 mM by comparison with indomethacin at 1.22 ± 0.08 mM.  

Furthermore, several representative components against Topo I, Topo II, COX-2, and ACE2 were also confirmed by molecular docking analysis.  

This is the first report to succeed in exploring the selective inhibitors responsible for its pharmaceutical activities correlated to multiple drug targets from P. sinense, and this study is conducive to discover more novel and curative agents from P. sinense or other medicinal plants.   

Relevant results have been published in Frontiers in Pharmacology and this study was financially supported by the National Natural Science Foundation of China and the Youth Innovation Promotion Association of CAS. 

The constructed multi-component and multi-target network incorporating the potential bioactive components screened out with multiple drug targets. (Image by WBG)