Journal
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Volume 168, Issue -, Pages 75-82Publisher
ELSEVIER
DOI: 10.1016/j.jpba.2019.02.005
Keywords
Metabolism analysis; Metabolic pathway; Caulopphyllum robustum Maxim (CRM); Triterpene saponin
Categories
Funding
- National Nature Science Foundation of China [81373929, 81703724]
- State Key Creative New Drug Project of the 12th Five-Year Plan of China [2013ZX09102019]
- talent innovation funds from Heilongjiang University of Chinese Medicine [2012]
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Triterpenoid saponins are the main bioactive components in Caulopphyllum Robustum Maxim (CRM), and they have been reported to have extensive pharmacological properties, such as anti-inflammatory, immunomodulatory, and anti-tumor effects. Cauloside C, Cauloside D, Leonticin D and Cauloside H are the main active chemical constituents of CRM in the treatment of rheumatoid arthritis (RA). However, their metabolic processes and products remain unclear. Therefore, the purpose of this study was to analyze the metabolic components and metabolic pathways of total saponins after oral administration of CRM effective part (CRME) in rats. In this work, we collected plasma, bile, urine and feces of rats at different sampling time points after intragastric administration. The saponins and reference substances were separated from CRME and analyzed via Thermo Scientific (TM) Ultra Performance Liquid Chromatography-Orbitrap Elite Combined High resolution Mass Spectrometry. According to the structural characteristics of the compounds in CRM, the pyrolysis behavior of various components was inferred in the negative ion mode. Twenty-two components were found in rat plasma, bile, urine and stool; among these components, there were 8 prototypes and 14 metabolites. Seven prototypes and 8 metabolites were found in rat plasma; no prototype and 6 metabolites were found in bile; 5 prototypes and 8 metabolites were found in urine; and 4 prototypes and 9 metabolites were found in stool. The metabolites include deglycosylation products, sapogenin products, sulfides, and glucuronide conjugates. The same metabolites were also found in biological samples, and these products may be important metabolic pathways of triterpene saponins in rats. The current findings clarified the metabolic pathways of the main active ingredients in CRME and further elucidated the anti-RA drug-responsive substance basis of CRM. (C) 2019 Elsevier B.V. All rights reserved.
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