Study On Anti-Hepatocarcinoma And Safety Evaluation Of Rhizoma Paridis Saponins And Its Compound

Parispolyphylla var. yunnanensis as a traditional Chinese medicine has been used in the treatment of liver disease for thousands of years. Rhizoma Paridis Saponins (RPS), which is the effective part of Rhizoma Paridis, showed strong anti-hepatocarcinoma activities. In this research, we developed and validated the metabolic profiling of RPS intervention in H22 hepatocarcinoma mice. As a result, RPS displayed different pathway to decrease energy production of the mice. For the normal mice, RPS significantly decreased the concentration of lipid, glycerate, succinate and lactate, but increased glucose and valine levels. All these indicated that RPS inhibited glucose and valine to transform ketones which participated in the ATP production. For the H22 cancer mice, RPS increased the concentration of lipid and glycerate, but significantly decreased glucose, glycine and alanine levels in the serum. This phenomenon indicated that RPS inhibited the oxidation of fatty acids pathway and the gluconeogenesis pathway which participated in the energy supply for the body. RPS also inhibited glycine and alanine production to block the tumor growth. This selective effect of RPS to different condition of mice would improve understanding of the antitumor pathway of RPS involved in H22 hepatocarcinoma mice.Rhizoma paridis saponins (RPS), as the main active components of Paris polyphylla, have been used to treat liver injury. Anti-cirrhosis effect of Rhizoma paridis saponins (RPS) has not been known. We analyzed oxidative stress test and DNA fragmentation assay. Thus, the results is that mechanisms of RPS that participated in the inhibition of the fibrotic process included anti-oxidant, anti-apoptosis in DEN-induced liver tissues. In our previous research, turmeric increased antitumor effects of Rhizoma paridis saponins (RPS) through absorptive enhancement of paridis saponins. We set up a rat model of diethylnitrosamine (DEN) induced hepatoma and pulmonary metastasis to evaluate the antitumor effect of RPS combined with turmeric (LH). After 20 weeks treatment, rats were sacrificed in order to perform histopathological examinations, liver function tests, oxidative stress assays, metabonomics analyses and so forth. As a result, DEN induced hepatoma and pulmonary metastasis formation. LH alleviated levels of liver injury and inhibited pulmonary metastasis through significantly decreasing serum ALT and AST, inhibiting liver tissues of MDA and NO formation and increasing SOD production, down-regulating expression of MMP-9 and up-regulating expression of TIMP-2 in DEN-induced rats. Thus, LH effectively inhibited hepatocellular carcinoma and pulmonary metastasis.However, RPS has its own toxicity. In order to provide a reliable theoretical basis for guiding clinical medication safety, in this study, the long-term oral toxicity, the dose of 350 mg/kg RPS,50 mg/kg RPS,100 mg/kg curcumim and 350 mg/kg RPS combined with 35 mg/kg curcumin were investigatd. Biochemical analyses for liver and kidney function test, oxidative stress in the liver tissues, intracellular ROS generation in liver cells and histopathological examination were used to evaluate the toxicity on rats. As a result, under the dose of 350 mg/kg, RPS has a severe liver toxicity. Meanwhile, curcumin (100 mg/kg) group and RPS (50 mg/kg) group also can cause liver damage under different degrees on rats. Curcumin combined RPS significantly decreased the hepatotoxicity of RPS. After suspending the drug, every group can back to normal.