Antitumor pathway of Rhizoma Paridis Saponins based on the metabolic regulatory network alterations in H22 hepatocarcinoma mice

• RPS showed different metabolic alterations in normal and cancer mice.
• RPS inhibited gluconeogenesis, alanine and glycine metabolism in cancer mice.
• RPS inhibited glucose and valine to transform ketones in the normal mice.

Rhizoma Paridis Saponins (RPS), which is the effective part of Rhizoma Paridis, showed strong anti-lung cancer and anti-hepatocarcinoma activities. In this research, a gas chromatography/mass spectrometry (GC/MS) method was developed and validated for the metabolic profiling of RPS intervention in H22 hepatocarcinoma mice. Data were analyzed with partial least-squares discrimination analysis (PLS-DA). 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.