A Comprehensive Strategy for Component Screening and Mechanism Determination of Paris Polyphylla Var. Yunnanensis in Anti-liver Cancer

Introduction: Paris Polyphylla var. Yunnanensis (PY) is an anti-liver cancer TCM used in clinical practice, but its core components and anti-liver cancer mechanism remain unclear. This study combines animal experiments, network pharmacology, molecular docking, and cell verification to explore the core components and mechanisms of PY in combating liver cancer. Methods: The blood-entry components of PY were obtained through UPLC-QE-MS. Subsequently, network pharmacology was employed to predict the core components of anti-liver cancer and their potential targets. Molecular docking was then used to verify binding between the core components and the targets. Finally, by calculating the inhibitory rate and IC50 value of the core ingredient on HepG2 cells, the anti-liver cancer activity of the core ingredient was evaluated. results: A total of 103 compounds were identified in the drug-containing serum of rats. Through the establishment of a PY component library for screening, seven blood-entry components belonging to PY were obtained. Network pharmacology and molecular docking techniques were employed to predict the potential targets, core components, and key pathways of PY in anti-liver cancer. 20-Hydroxyecdysone, parisyunnanoside B, paris saponin II, and dichotomin are regarded as the core components of PY's anti-liver cancer effect. The in vitro activity assay of the core components demonstrated that paris saponin II exhibited a high inhibitory rate on the proliferation of HepG2 cells in a concentration-dependent manner. Results: A total of 103 compounds were identified in the drug-containing serum of rats. Seven ingredients were obtained after screening. The components, targets, and pathways of PY's antiliver cancer effect were predicted. 20-Hydroxyecdysone, parisyunnanoside B, paris saponin II, and dichotomin are considered the core components of PY's anti-liver cancer activity. The in vitro activity assay of the core components demonstrated that paris saponin II exhibited a high inhibitory effect on HepG2 cell proliferation in a concentration-dependent manner. Discussion: This study reveals PY's anti-hepatocellular carcinoma mechanisms, informing clinical applications and future research on its constituents. Conclusion: This study initially demonstrated that PY exerts therapeutic effects on liver cancer through multiple components, targets, and mechanisms, and elucidated its pharmacological basis.