Hepatic Glucuronidation of Isoneochamaejasmin A from the Traditional Chinese MedicineStellera ChamaejasmeL. Root

Abstract

Isoneochamaejasmin A (INCA), a biflavonoid, is one of main active ingredients in the dried root of Stellera chamaejasme L., a widely used traditional Chinese medicine. In the present study, we identified the glucuronidation metabolite of INCA and characterized the UDP glucuronosyltransferases (UGTs) responsible for INCA glucuronidation. 7-O-glucuronide (M1) and 49-O-glucuronide (M2) were identified by incubation of INCA with human liver microsomes (HLMs) in the presence of UDP glucuronic acid, and their structures were confirmed by high-resolution mass spectrometry and nuclear magnetic resonance analyses. Although INCA is a single enantiomer molecule, its M1 metabolite showed two equal-size peaks on a pNAP stationary phase but only one peak on a C 18 stationary phase, indicating that the 7-/799-and 49-/4999-hydroxyl groups of INCA were in different spatial configurations relative to each other.Among the recombinant human UGT isoform test and correlation analysis, UGT1A1, UGT1A3, and UGT1A9 were found to mediate M1 formation, whereas only UGT1A3 mediated M2 formation. Kinetic studies showed obvious species differences between human, mouse, rat, dog, and pig liver microsomes. UGT1A1, HLMs, and human intestinal microsomes, but not human kidney microsomes, exhibited substrate inhibition for the formation of M1. UGT1A1-mediated formation of M1 showed a 6-and 11-fold higher V max than did UGT1A3-and UGT1A9-mediated formation of M1, respectively. The results of the relative activity factor assay showed that UGT1A1 contributed approximately 75% in the formation of M1. These findings collectively indicate that UGT1A1 is the major enzyme in the formation of M1, whereas UGT1A3 is the major enzyme in the formation of M2.

Study on Gas Chromatographic Fingerprint of Essential Oil from Stellera chamaejasme Flowers and Its Repellent Activities against Three Stored Product Insects

“…In addition, the chromatographic fingerprint data of S. chamaejasme flowers EO were systematically clustered to evaluate the consistency and differences of the samples. In the past, research on the S. chamaejasme plant mainly focused on the chemical composition and pharmacological activities of the medical root part, while studies on the above-ground parts of this herb, particularly the research into the flowers of S. chamaejasme were rarely reported [28,29]. In the light of the toxicity and the reported insecticidal effects of the root [30,31], our research team extracted the EOs of S. chamaejasme flowers from various natural sites and evaluated their repellent activities against three worldwide pests (T. castaneum, L. serricorne, and L. bostrychophila).…”