Study On The Pharmacokinetic Characteristics And Anti-Tumor Mechanism Of Rhizoma Paridis Saponins

Rhizoma Paridis Saponins (RPS) showed strong antitumor activity. There were few researches on the pharmacokinetic or drug-interaction with RPS. Paridis Saponins Ⅱ (PSⅡ) exhibited antitumor and anti-metastasis effects in our previous research. In this research, the activity of CYP450s and the mechanism of intestinal absorption affected by RPS was studied. The anti-hepatoma effect and mechanism of PSII were studied based on the cell cycle and apoptosis. Because of the toxicity of RPS, anti-hepatoma effect by the Rhizoma Paridis Saponins I (PSI) combined with curcumin was studied by us. The aim of this study was to advance RPS for clinical application.The results of activity of CYP1A2, CYP2A6, CYP3A4, CYP2B6, CYP2C9, CYP2E1 affected by RPS showed that RPS can inhibit the activity of CYP3A4, CYP2B6 with dose of 200 mg/kg.The influence on intestinal absorption by RPS in vitro was studied by us. Results showed that RPS can inhibit intestinal absorption through inducing the activity of p-glycoprotein in the intestinal cells, and the inhibition on intestinal absorption can be reduced by combining with Curcumin with dose of 15 uM.The anti-hepatoma effect influent by PSII also been studied. The hepatocellular carcinoma HepG2 cell line’s activity measured by MTT experiment which showed that PSII had a good inhibitory effect on HepG2 cell line with dose-dependent and time-dependent. DNA ladder experiment and DAPI staining used for PSII’s apoptosis were studied. Results showed that PSII can induce apoptosis in HepG2 cell line with a time-dependent manner. The cell cycle results showed that PSII can induce S-phase arrest in HepG2 cell line. Using the 1H-NMR method, we analyzed the metabolites in the cells. Results showed that PSII can disturb the DNA synthesis in S-phase, and can disturb the carbohydrate metabolism process and the tricarboxylic acid cycle.We evaluated the anti-hepatoma effect of PSI combined with PSII and PSI combined with curcumin by MTT method. Results showed that PSI combined with PSII can be synergistic effect with the combined ratio 1:1 or 1:2. PSI combined with curcumin can promote the anti-hepatoma effect than the drug was used alone and induce S-phase arrest in HepG2 cell line.In conclusion, RPS can affect the activities of CYP450 and p-glycoprotein, and it can induce the apoptosis and S phase arrest in the HepG2 cell line.