title: Combination therapy of cyclophosphamide and Rhizoma Paridis Saponins on anti-hepatocarcinoma mice and effects on cytochrome p450 enzyme expression.
abstract: 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.
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Man
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address: biochemgao@163.com.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Gao
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.
authors.forename: Changxiao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome / Q000737:chemistry; D012503:Saponins / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D012503:Saponins; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System
keywords: CYP; Cyclophosphamide; Herb–drug interactions; Rhizoma Paridis Saponins