Title:Synergy Mechanisms of Rhizoma Paridis Saponins on Non-small Cell Lung Cancer:
Segmented Solid Phase Extraction, Bioactivity Screening, and Network Pharmacology
Volume: 22
Issue: 20
Author(s): Chen Liu, Qingyun Ma, Ruikun Du, Menghan Chen, Shuyan Xing, Yong Yang*Rong Rong*
Affiliation:
- Collaborative Innovation Center for Antiviral Traditional Chinese Medicine in Shandong
Province, Jinan, China
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China;
Keywords:
Rhizoma paridis saponins, non-small cell lung cancer, segmented solid-phase extraction, bioactivity screening, network pharmacology, PI3K-Akt signaling pathway.
Abstract:
Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Rhizoma
paridis saponins (RPS), the main bioactive ingredients of Paris polyphylla Smith var. yunnanensis (PPY), have been
proved to have remarkable effects on NSCLC cell lines. However, the multi-component synergistic effects and mechanisms
of RPS on NSCLC have not been elucidated.
Objective: To decipher the multi-RPS synergistic effects and mechanisms against NSCLC based on network pharmacology
combined with segmented solid-phase extraction (SPE) and bioactivity screening method.
Methods: Firstly, segmented SPE and cytotoxicity assays were performed to screen the RPS-enrichment fraction of
PPY, and the steroidal saponins in it were identified by LC-MS/MS. Then, a network pharmacology analysis was performed
to predict the potential therapeutic targets of RPS on NSCLC. Finally, viable cell counting tests and RT-qPCR
were utilized to verify the synergistic effects and mechanisms of RPS.
Results: 48 potentially active compounds were identified from the 30% MeOH/EtOAc fraction of PPY (30% M/E
PPY). The results of the network pharmacology analysis indicated that RPS exerted joint effects by regulating six key
targets in the PI3K-AKT signaling pathway. In vitro experiments showed that due to the synergistic effects, 30% M/E
PPY at 13.90 μg/mL could exert a stronger inhibitory activity on A549 cells by reducing the overexpression of six hub
genes compared with the parallel control groups.
Conclusion: This research elaborates on the multi-RPS synergy mechanisms against NSCLC and provides a way to
develop new combination medicines for NSCLC.