Characterization of metabolites of five typical saponins from Caulophyllum robustum Maxim and their biotransformation in fibroblast-like synoviocytes by UHPLC-Q-Exactive-Plus-Orbitrap-MS

Abstract

Caulophyllum robustum Maxim (C. robustum) is a well-known traditional Chinese medicine (TCM) widely used for the treatment of rheumatoid arthritis (RA). Modern pharmacological studies have shown that saponins are the main material basis of C. robustum, of which Cauloside C, Cauloside D, Cauloside G, Cauloside H, and Leonticin D are typical representatives. Although they are known to enter the bloodstream as prototypes, metabolites, and sapogenins, their biotransformation in fibroblast-like synoviocytes (FLS) is not well understood. The UHPLC-Q-Exactive-Plus-Orbitrap-MS method was used to rapidly identify the prototypes and metabolites of C. robustum saponins in FLS and to explore the metabolic pathways of C. robustum saponins. As a result, deglycosylation, deacidification, deoxygenation, oxidation, sulfation, phosphorylation, hydrogenation, demethylation, and acetylation may be important pathways for saponins of C. robustum to function in FLS. Especially, we first discovered phosphorylated metabolites, oxidative metabolites, acetylated metabolites and deacidified metabolites. At the cellular level, saponins with different sugar chain structures of the same kind can be converted into each other. According to the structural analysis of the degradation products, the length of the sugar chain may affect the degradation of saponins in cells. This study aimed to analyze the degradation and transformation processes of C.robustum saponins in target cells and to provide scientific information for the discovery of new medicinal components.

Keywords

• Caulophyllum robustum Maxim
• Saponins
• Cauloside G
• Cauloside C
• Metabolic profile