A new strategy for the discovery of epimedium metabolites using high-performance liquid chromatography with high resolution mass spectrometry

Chen

Journal of Analytical Methods in Chemistry

et al. 2017

Icaritin is a naturally bioactive flavonoid with several significant effects. This study aimed to clarify the metabolite profiling, pharmacokinetics, and glucuronidation of icaritin in rats. An ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) assay was developed and validated for qualitative and quantitative analysis of icaritin. Glucuronidation rates were determined by incubating icaritin with uridine diphosphate glucuronic acid- (UDPGA-) supplemented microsomes. Kinetic parameters were derived by appropriate model fitting. A total of 30 metabolites were identified or tentatively characterized in rat biosamples based on retention times and characteristic fragmentations, following proposed metabolic pathway which was summarized. Additionally, the pharmacokinetics parameters were investigated after oral administration of icaritin. Moreover, icaritin glucuronidation in rat liver microsomes was efficient with CLint (the intrinsic clearance) values of 1.12 and 1.56 mL/min/mg for icaritin-3-O-glucuronide and icaritin-7-O-glucuronide, respectively. Similarly, the CLint values of icaritin-3-O-glucuronide and icaritin-7-O-glucuronide in rat intestine microsomes (RIM) were 1.45 and 0.86 mL/min/mg, respectively. Taken altogether, dehydrogenation at isopentenyl group and glycosylation and glucuronidation at the aglycone were main biotransformation process in vivo. The general tendency was that icaritin was transformed to glucuronide conjugates to be excreted from rat organism. In conclusion, these results would improve our understanding of metabolic fate of icaritin in vivo.

Section: Introductionmentioning

confidence: 99%

Metabolite Profiling, Pharmacokinetics, and In Vitro Glucuronidation of Icaritin in Rats by Ultra-Performance Liquid Chromatography Coupled with Mass Spectrometry

Chen

Journal of Analytical Methods in Chemistry

et al. 2017

“…These HRMS-based data-mining technologies were developed originally for the detection and identification of drug metabolites in complex biologic systems (Bateman et al, 2007;Ma and Zhu 2009;Zhu et al, 2011;Ma and Chowdhury, 2012;Geng et al, 2014;Du et al, 2015). In addition, mass spectral trees similarity filter (MTSF) technology (Jin et al, 2013) is employed for the detection and identification of TCM metabolites on the basis of the similarity of their product ion spectra to those of their precursor species. These targeted data-mining approaches are capable of searching for metabolites of individual TCM prototypes on the basis of the metabolite's predicted mass defect (MDF), fragmentation pattern (NLF and PIF), or molecular weight (EIC).…”

Section: Introductionmentioning

confidence: 99%

An Integrated Approach for Studying Exposure, Metabolism, and Disposition of Multiple Component Herbal Medicines Using High-Resolution Mass Spectrometry and Multiple Data Processing Tools

Drug Metabolism and Disposition

Wang

et al. 2016

A typical prescription of traditional Chinese medicine (TCM) contains up to a few hundred prototype components. Studying their absorption, metabolism, distribution, and elimination (ADME) presents great challenges. The objective of this study was to develop a practical approach for investigating ADME of individual prototypes in TCM. An active fraction of Xiao-Xu-Ming decoction (AF-XXMD) as a model TCM prescription was orally administered to rats. AF-XXMD-related components in plasma, urine, bile, and feces were detected using high-resolution mass spectrometry and background subtraction, an untargeted data-mining tool. Components were then structurally characterized on the basis of MS n spectral data. Connection of detected AF-XXMD metabolites to their precursor species, either prototypes or upstream metabolites, were determined on the basis of mass spectral similarity and the matching of biotransformation reactions. As a result, 247 AF-XXMD-related components were detected and structurally characterized in rats, 134 of which were metabolites. Among 198 AF-XXMD prototypes dosed, 65 were fully or partially absorbed and 13 prototypes and 34 metabolites were found in the circulation. Glucuronidation, isomerization, and deglycosylation followed by biliary and urinary excretions and direct elimination of prototypes via kidney and liver were the major clearance pathways of AF-XXMD prototypes. As an example, the ADME profile of H56, the single major AF-XXMD component in rat plasma, was elucidated on the basis of profiles of H56-related components in plasma and excreta. The results demonstrate that the new analytical approach is a useful tool for rapid and comprehensive detection and characterization of TCM components in biologic matrix in a TCM ADME study.

Evidence-Based Complementary and Alternative Medicine

“…Epimedium has been used in China to treat erectile dysfunction, postmenopausal syndrome, and osteoporosis for thousands of years [12]. Icariin is a major component of Epimedium [13, 14]. Based on findings in clinical pharmacodynamic studies on Epimedium , Shindel et al have demonstrated that icariin can promote bone formation and has neurotrophic effects in both in vivo and in vitro experiments [15].…”

Section: Introductionmentioning

confidence: 99%

EpimediumExtract Promotes Peripheral Nerve Regeneration in Rats

Kou

Wang

et al. 2013

Effects of Epimedium extract and its constituent icariin on peripheral nerve repair were investigated in a crush injury rat model. Animals were divided into four groups: sham, control, Epimedium extract, and icariin groups. At postoperative weeks 1, 2, 4, and 8, nerve regeneration and functional recovery were evaluated by sciatic functional index (SFI), nerve electrophysiology, nerve pinch test, and muscle wet weight. Results showed that at 2 and 4 weeks after surgery rats in the Epimedium group displayed a better recovery of nerve function than that in the icariin and control groups, with better recovery in the icariin group than in the control group. The nerve pinch test showed that nerve regeneration was greater in the Epimedium group and the icariin group as compared to the control group. In addition, the muscle wet weight in the Epimedium group was significantly improved when compared with the icariin group, and the improvement in the icariin group was better than that in the control group at 8 weeks after operation. Our findings suggest that Epimedium extract effectively promotes peripheral nerve regeneration and improves the function of damaged nerves.