Metabolite profiles of epimedin C in rat plasma and bile by ultra‐performance liquid chromatography coupled with quadrupole‐TOF‐MS

Cui, Li; Sun, E; Zhang, Zhenhai; Tan, Xuecai; Xu, Fei; Jia, Xiao‐Bin

doi:10.1002/bmc.3174

Cited by 10 publications

(4 citation statements)

References 16 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, ultra‐performance liquid chromatography coupled with quadrupole‐time‐of‐flight mass spectrometry (UPLC/Q‐TOF‐MS) has been proved to be an efficient analytical tool for elucidating unknown metabolites from bio‐assays of complex samples such as TCM prescriptions (Su et al ., ; Cui et al ., ). Compared with conventional high‐performance liquid chromatography, UPLC provides higher sensitivity, shorter analysis time and lower consumption of samples.…”

Section: Introductionmentioning

confidence: 97%

Characterization of metabolites in rats after intravenous administration of salvianolic acid for injection by ultra‐performance liquid chromatography coupled with quadrupole‐time‐of‐flight mass spectrometry

Miao

Sun

Huang

et al. 2016

Biomedical Chromatography

View full text Add to dashboard Cite

It is an essential requirement to clarify the metabolites of traditional Chinese medicine (TCM) injections, which contain numerous ingredients, to assess their safe and effective use in clinic. Salvianolic acid for injection (SAFI), made from hydrophilic phenolic acids in Salvia miltiorrhiza Bunge, has been widely used for the treatment of cerebrovascular diseases, but information on its metabolites in vivo is still lacking. In the present study, we aimed to holistically characterize the metabolites of the main active ingredients in rat plasma, bile, urine and feces following intravenous administration of SAFI. An ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method was developed. Combining information on retention behaviors, multistage mass spectra and literature data, a total of eight prototypes and 52 metabolites were tentatively characterized. Metabolites originated from rosmarinic acid and salvianolic acid B comprised the majority of identified compounds. Meanwhile, four metabolites derived from salvianolic acid D and five from salvianolic acid B are reported for the first time. This study revealed that methylation, sulfation and glucuronidation were the major metabolic pathways of phenolic acids in SAFI in vivo. Furthermore, the developed UPLC/Q-TOF-MS method could also benefit the metabolic investigation of extracts and preparations in TCM with hydrophilic ingredients. Copyright © 2016 John Wiley & Sons, Ltd.

show abstract

Section: Introductionmentioning

confidence: 97%

Characterization of metabolites in rats after intravenous administration of salvianolic acid for injection by ultra‐performance liquid chromatography coupled with quadrupole‐time‐of‐flight mass spectrometry

Miao

Sun

Huang

et al. 2016

Biomedical Chromatography

View full text Add to dashboard Cite

show abstract

“…ICA is one of the major bioactive constituents of Herba Epimedii which is mainly metabolized via desugarization, dehydrogenation, hydrogenation, dehydroxylation, hydroxylation, demethylation and glucuronidation pathways in rodent 48 . As a natural prenylated flavonol glycoside, ICA, at the level of μM concentration, has been shown to suppress the proliferation of various types of cancer cells 12 13 14 49 .…”

Section: Discussionmentioning

confidence: 99%

Icariin displays anticancer activity against human esophageal cancer cells via regulating endoplasmic reticulum stress-mediated apoptotic signaling

Fan

Yang

Liu

et al. 2016

Sci Rep

View full text Add to dashboard Cite

In this study, we investigated the antitumor activity of icariin (ICA) in human esophageal squamous cell carcinoma (ESCC) in vitro and in vivo and explored the role of endoplasmic reticulum stress (ERS) signaling in this activity. ICA treatment resulted in a dose- and time-dependent decrease in the viability of human EC109 and TE1 ESCCs. Additionally, ICA exhibited strong antitumor activity, as evidenced by reductions in cell migration, adhesion, and intracellular glutathione (GSH) levels and by increases in the EC109 and TE1 cell apoptotic index, Caspase 9 activity, reactive oxygen species (ROS) level, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Furthermore, ICA treatments upregulated the levels of ERS-related molecules (p-PERK, GRP78, ATF4, p-eIF2α, and CHOP) and a pro-apoptotic protein (PUMA) and simultaneously downregulated an anti-apoptotic protein (Bcl2) in the two ESCC cell lines. The downregulation of ERS signaling using eIF2α siRNA desensitized EC109 and TE1 cells to ICA treatment, and the upregulation of ERS signaling using thapsigargin sensitized EC109 and TE1 cells to ICA treatment. In summary, ERS activation may represent a mechanism of action for the anticancer activity of ICA in ESCCs, and the activation of ERS signaling may represent a novel therapeutic intervention for human esophageal cancer.

show abstract

“…Herba Epimedii known as YinYangHuo in Chinese is the dried leaf of the Epimedium and has been historically used in combination with other herbs to treat skeletal diseases in traditional Chinese medicine (TCM) [1]. Metabolic pathways of other Epimedium flavonoids, namely, Epimedin A (EA) [2], Epimedin B (EB) [3], Epimedin C (EC) [4], icariin [5], and Baohuoside I (BI) [6], were well described in both mammals and adult zebrafish ( Danio rerio ) [7]. However, no data have been reported on the metabolism of Epimedium flavonoids such as Sagittatoside A (SA), Sagittatoside B (SB), and 2′′-O-rhamnosylicariside II (SC), probably attributed to the difficult separation and purification process.…”

Section: Introductionmentioning

confidence: 99%

The Toxicity and Metabolism Properties ofHerba EpimediiFlavonoids on Laval and Adult Zebrafish

Zhong

Chen

Ling

et al. 2019

Evidence-Based Complementary and Alternative Medicine

Self Cite

View full text Add to dashboard Cite

Zebrafish is being increasingly used for metabolism and toxicity assessment. The drugs consumed in zebrafish metabolism studies are far less than those used in rat studies. In our study, zebrafish embryos were exposed to icariin, Baohuoside I (BI), Epimedin A (EA), Epimedin B (EB), Epimedin C (EC), Sagittatoside A (SA), Sagittatoside B (SB), and 2′′-O-rhamnosylicariside II (SC), respectively, to examine the toxicity and metabolic profiles of these flavonoids. The order of toxicity was SC, SB > EC, SA > BI, icariin, EA, EB. After 24 h exposure to SB and SC, the mortality of zebrafish larvae reached 100% and yolk sac swollen was obvious. Both SC and SB caused severe hepatocellular vacuolization and liver cells degeneration in adult zebrafish after 15 consecutive days’ treatment. The metabolic profiles of these flavonoids with trace amount were also monitored in larvae. BI was the common metabolite shared by icariin, EA, EB, SA, and SB, via deglycosylation. Both BI and SC remained as the prototype in the medium, suggesting that it is hard for BI and SC to cleave the rhamnose residue. EC was metabolized into SC and BI in zebrafish, inferring that SC might be responsible for the toxicity observed in EC group. The metabolites of icariin, EA, EB, EC, and BI in zebrafish larvae coincided with results from rats and intestinal flora. These data support the use of this system as a surrogate in predicting metabolites and hepatotoxicity risk, especially for TCM compound with trace amount.

show abstract

Metabolite profiles of epimedin C in rat plasma and bile by ultra‐performance liquid chromatography coupled with quadrupole‐TOF‐MS

Cited by 10 publications

References 16 publications

Characterization of metabolites in rats after intravenous administration of salvianolic acid for injection by ultra‐performance liquid chromatography coupled with quadrupole‐time‐of‐flight mass spectrometry

Characterization of metabolites in rats after intravenous administration of salvianolic acid for injection by ultra‐performance liquid chromatography coupled with quadrupole‐time‐of‐flight mass spectrometry

Icariin displays anticancer activity against human esophageal cancer cells via regulating endoplasmic reticulum stress-mediated apoptotic signaling

The Toxicity and Metabolism Properties ofHerba EpimediiFlavonoids on Laval and Adult Zebrafish

Contact Info

Product

Resources

About