Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

LC-MS/MS Method Development and Validation for the Determination of Ilexsaponin A1 and Its Application in Intestinal Bacterial Metabolic Study

Author(s): Liang Wu*, An Kang, Yujie Lin, Chenxiao Shan, Zhu Zhou, Xuqin Shi and Bin Yu

Volume 16, Issue 6, 2020

Page: [774 - 781] Pages: 8

DOI: 10.2174/1573412915666190304141416

Price: $65

Abstract

Background: Ilexsaponin A1, one of the most representative triterpene saponin components in the roots of I. pubescens, showed its effects in anticoagulation and antithrombosis, attenuating ischemia-reperfusion-induced myocardial, angiogenesis and inhibiting phosphodiesterase.

Objective: Reveal the key intestinal bacterial strains responsible for ilexsaponin A1 metabolism, and clarify their metabolic behavior.

Methods: An accurate and sensitive LC-MS/MS method for the determination of “ilexsaponin A1 in General Anaerobic Medium (GAM) broth” was established and systematically validated. Then it was applied to screen and study the metabolic potential of the intestinal bacterial strains in an anaerobic incubation system.

Results: Quantitation of ilexsaponin A1 could be performed within an analytical run time of 14.5 min, in the linear range of 2 - 2000 ng/ml. Enterobacter sakazakii, Bifidobacterium breve, Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Bifidobacterium angulatum were identified to have a potential effect to metabolize ilexsaponin A1 to different extents; and further bacterial metabolic studies were performed to clarify their metabolic capacity and behavior.

Conclusion: This paper contributes to a better understanding of the intestinal bacterial metabolism of ilexsaponin A1 and provides scientific evidence for its clinical application. Additionally, the importance of intestinal bacterial strains in the disposition of natural products was also highlighted.

Keywords: Ilexsaponin A1, intestinal bacteria, LC-MS/MS, method validation, quantitative analysis, metabolic study.

Graphical Abstract

[1]
Han, Y.N.; Baik, S.K.; Kim, T.H.; Han, B.H. Antithrombotic activities of saponins from Ilex pubescens. Arch. Pharm. Res., 2009, 10(2), 115-120.
[http://dx.doi.org/10.1007/BF02857777]
[2]
Wang, J.R.; Zhou, H.; Jiang, Z.H.; Wong, Y.F.; Liu, L. In vivo anti-inflammatory and analgesic activities of a purified saponin fraction derived from the root of Ilex pubescens. Biol. Pharm. Bull., 2008, 31(4), 643-650.
[http://dx.doi.org/10.1248/bpb.31.643] [PMID: 18379056]
[3]
Miao, M.S.; Guo, L.; Li, R.Q.; Ma, X. Radix Ilicis Pubescentis total flavonoids combined with mobilization of bone marrow stem cells to protect against cerebral ischemia/reperfusion injury. Neural Regen. Res., 2016, 11(2), 278-284.
[http://dx.doi.org/10.4103/1673-5374.177736] [PMID: 27073381]
[4]
Zhou, Y.; Li, N.; Zhang, J.Y.; Jiang, Y.; Tu, P.F. Simultaneous determination of four triterpenoid saponins and two liganoids in the roots of Ilex pubescens by RP-HPLC-DAD. J. Chin. Pharm. Sci., 2014, 23(12), 866-872.
[http://dx.doi.org/10.5246/jcps.2014.12.110]
[5]
Yang, Y.Y.; Huang, S.H.; Feng, F.; Guo, P.R.; Chen, J.X. Determination of Ilexgenin A and Ilexsaponin A1 in Radix Ilicis Pubescentis by accelerated solvent extraction followed with HPLC-MS. J. Inst. Anal., 2009, 28(8), 966-969.
[6]
Liu, Z.C.; Xian, S.X.; Wang, L.J. Simultaneous determination of four chlorogenic acids and four triterpene saponins in Radix Ilicis Pubescentis by HPLC. Yaowu Fenxi Zazhi, 2017, 37(10), 1865-1870.
[7]
Qin, G.W.; Chen, Z.X.; Xu, R.S.; Jiang, Z.F.; Liang, J.G. Studies on the chemical constituents of Ilex pubescens Hook et Arn, II. the structure of ilexsaponin A. Acta Chimi. Sin., 1987, 45, 249-255.
[8]
Zhou, Y.; Xiong, T.Q.; Lin, C.Z.; Zhao, Z.X.; Qin, C.Y.; Cao, Y. Mao Dong Qing Zao Gan ilexsaponin A1 De Zhi Bei Ji Qi Yao Li Huo Xing Yan Jiu. Chin. Med. Mat., 2011, 34(5), 765-767.
[9]
Zhang, S.W.; Liu, Y.; Wang, F.; Qiang, J.; Liu, P.; Zhang, J.; Xu, J.W. Ilexsaponin A attenuates ischemia-reperfusion-induced myocardial injury through anti-apoptotic pathway. PLoS One, 2017, 12(2) e0170984
[http://dx.doi.org/10.1371/journal.pone.0170984] [PMID: 28182689]
[10]
Li, J.; Zhang, J.; Zou, L.; Lee, S.M.; Yang, C.; Seto, S.W.; Leung, G.P. Pro-angiogenic effects of Ilexsaponin A1 on human umbilical vein endothelial cells in vitro and zebrafish in vivo. Phytomedicine, 2017, 36, 229-237.
[http://dx.doi.org/10.1016/j.phymed.2017.10.006] [PMID: 29157819]
[11]
Liu, Z.; Lin, Z.; Chen, S.; Wang, L.; Xian, S. Rapid Screening of Potential Phosphodiesterase Inhibitors from the Roots of Ilex pubescens Hook. et Arn. Using a Combination of Ultrafiltration and LC-MS. Evid. Based Complement. Alternat. Med., 2017, 2017, 2749643
[http://dx.doi.org/10.1155/2017/2749643] [PMID: 28424739]
[12]
Li, M.F.; Zhao, Z.X.; Lin, C.Z.; Xiong, T.Q.; Chi, Y.G.; Zhu, C.C. Pharmacokinetic Studies of Ilexsaponin A1 in Rats. Zhongyao Xinyao Yu Linchuang Yaoli, 2011, 22(2), 187-189.
[13]
Zhao, Z.X.; Li, M.F.; Lin, C.Z.; Xiong, T.Q.; Zhu, C.C. Metabolic transformation of ilexsaponin A1 by intestinal flora. Zhongguo Yaoke Daxue Xuebao, 2011, 42(4), 329-332.
[14]
Sousa, T.; Paterson, R.; Moore, V.; Carlsson, A.; Abrahamsson, B.; Basit, A.W. The gastrointestinal microbiota as a site for the biotransformation of drugs. Int. J. Pharm., 2008, 363(1-2), 1-25.
[http://dx.doi.org/10.1016/j.ijpharm.2008.07.009] [PMID: 18682282]
[15]
Snijders, A.M.; Langley, S.A.; Kim, Y.M.; Brislawn, C.J.; Noecker, C.; Zink, E.M.; Fansler, S.J.; Casey, C.P.; Miller, D.R.; Huang, Y.; Karpen, G.H.; Celniker, S.E.; Brown, J.B.; Borenstein, E.; Jansson, J.K.; Metz, T.O.; Mao, J.H. Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome. Nat. Microbiol., 2016, 2, 16221.
[http://dx.doi.org/10.1038/nmicrobiol.2016.221] [PMID: 27892936]
[16]
Valdes, A.M.; Walter, J.; Segal, E.; Spector, T.D. Role of the gut microbiota in nutrition and health. BMJ, 2018, 361, k2179.
[http://dx.doi.org/10.1136/bmj.k2179] [PMID: 29899036]
[17]
Yip, L.Y.; Chan, E.C. Investigation of host-gut microbiota modulation of therapeutic outcome. Drug Metab. Dispos., 2015, 43(10), 1619-1631.
[http://dx.doi.org/10.1124/dmd.115.063750] [PMID: 25979259]

© 2024 Bentham Science Publishers | Privacy Policy