Combination therapy of cyclophosphamide and Rhizoma Paridis Saponins on anti-hepatocarcinoma mice and effects on cytochrome p450 enzyme expression

• RPS and cyclophosphamide both exhibited anti-cancer effect alone.
• CYP2B6 and CYP3A4-mediated herb-drug interactions between RPS and other drugs.
• RPS inhibited transference of cyclophosphamide into active and inactive compounds.

Rhizoma Paridis Saponins (RPS), which is the effective part of Rhizoma Paridis, showed strong activity against lung cancer and hepatocarcinoma. In this research, a combination of RPS with cyclophosphamide (CTX) was used to treat hepatocarcinoma in mice. Although no active enhancement of activity was observed, some attenuation of the toxicity of RPS in combination with CTX occurred. In order to explain this phenomenon, we carried out research on the effects of Rhizoma Paridis Saponins on the activities of cytochrome p450 enzymes CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2E1 and CYP3A4. The results indicated that RPS significantly influenced the activity of CYP2B6 and CYP3A4 through the inhibition of protein expression. However, RPS did not affect the activity of CYP1A2, CYP2A6, CYP2C9 and CYP2E1 in rats in vivo. These results suggested that RPS inhibited the conversion of cyclophosphamide into active metabolites and inactive byproducts through the reduced activities of CYP2B6 and CYP3A4. Therefore, it’s essential to pay attention to CYP2B6- and CYP3A4-mediated herb–drug interactions between RPS and other drugs.

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