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. 2016 Dec 5;16(1):504.
doi: 10.1186/s12906-016-1472-7.

Preparation and structural determination of four metabolites of senkyunolide I in rats using ultra performance liquid chromatography/quadrupole-time-of-flight tandem mass and nuclear magnetic resonance spectra

Qiang Ma  1 , Cong Ma  1 , Fei Wu  1 , Yao-Kun Xiong  2 , Yi Feng  3 , Shuang Liang  4
Affiliations

Preparation and structural determination of four metabolites of senkyunolide I in rats using ultra performance liquid chromatography/quadrupole-time-of-flight tandem mass and nuclear magnetic resonance spectra

Qiang Ma et al. BMC Complement Altern Med. .

Abstract

Background: Senkyunolide I (SEI) is one of the most important bioactive phthalides of Ligusticum chuanxiong Hort. (Umbelliferae), a Traditional Chinese Medicine. Our previous studies suggested that it might be developed as a potential treatment for migraine.

Methods: In this paper, we aimed to isolate and characterize the main metabolites of SEI after gavage feeding in rats. Their structures were identified precisely on the basis of nuclear magnetic resonance (NMR) spectroscopy and UPLC/Q-TOF-MS spectrometry. We also established the main metabolic pathways of SEI in rats.

Results: Four metabolites (M1-M4) were isolated, for the first time, from bile samples of rats by preparative high-performance liquid chromatography. Their structures were determined as SEI-6S-O-β-D-glucuronide (M1), SEI-7S-O-β-D-glucuronide (M2), SEI-7S-S-glutathione (M3) and SEI-7R-S-glutathione (M4) on the basis of the molecular mass of the analytes, using ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry and 1D and 2D NMR.

Conclusions: The results demonstrated that glucuronide and glutathione conjugation were the major pathways of SEI metabolism in vivo, and the configuration at the 7th-position could be inverted during glutathione conjugation.

Keywords: In vivo; Metabolites; NMR; Senkyunolide I; UPLC/Q-TOF-MS.

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Figures

Fig. 1
Fig. 1
Chemical structures of the SEI and its metabolites M1–M4
Fig. 2
Fig. 2
Chromatograms for the analysis of the four metabolites of SEI in rat bile. (A) HPLC-UV chromatograms of control bile; (B) HPLC-UV chromatograms of M1-M4 and SEI standards without bile; (C) Bile samples from rats after oral administration 100 mg/ml of SEI
Fig. 3
Fig. 3
MS spectra of M1-M4
Fig. 4
Fig. 4
Representative UPLC/MS chromatograms of M1-M4
Fig. 5
Fig. 5
The major metabolic pathways of SEI in rat bile samples after oral administration of 100 mg/kg SEI, including glucuronidation (1) and glutathione conjugation (2)
See this image and copyright information in PMC

References

    1. Pharmacopoeia NCoC . Pharmacopoeia of the People’s Republic of China. Beijing: Chemical Industry Press; 2015.
    1. HZ Z, ZH D, J S. Modern Study of Traditional Chinese Medicine. Beijing: Xueyuan Press; 1997.
    1. Chan SS, Choi AO, Jones RL, Lin G. Mechanisms underlying the vasorelaxing effects of butylidenephthalide, an active constituent of Ligusticum chuanxiong, in rat isolated aorta. Eur J Pharmacol. 2006;537(1–3):111–117. doi: 10.1016/j.ejphar.2006.03.015. - DOI - PubMed
    1. Chan SS, Cheng TY, Lin G. Relaxation effects of ligustilide and senkyunolide A, two main constituents of Ligusticum chuanxiong, in rat isolated aorta. J Ethnopharmacol. 2007;111(3):677–680. doi: 10.1016/j.jep.2006.12.018. - DOI - PubMed
    1. Chan SK, Li SL, Lin G. Pitfalls of the selection of chemical markers for the quality control of medicinal herbs. J Food Drug Anal. 2007;15(4):365–371.

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