The Inhibition of the Components from Shengmai Injection Towards UDP-Glucuronosyltransferase

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2014 Dec 23

PMID 25530784

Citations 2

Authors

Li-Peng Jiang

Jin Zhao

Yun-Feng Cao

Mo Hong

Dong-Xue Sun

Xiao-Yu Sun

Jun Yin

Zhi-Tu Zhu

Zhong-Ze Fang

Affiliations

Soon will be listed here.

Abstract

The mechanism of shengmai injection- (SMI-) related drug-drug interaction remains unclear. Evaluation of the inhibition potential of SMI's ingredients towards UDP-glucuronosyltransferases (UGTs) activity will provide a new insight to understand SMI-related drug-drug interaction. In vitro incubation system to model UGT reaction was used. Recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation reactions were employed to phenotype the inhibition profile of maidong's components towards the activity of UGT isoforms. Different inhibition potential of maidong's components towards various UGT isoforms was observed. Based on the inhibition kinetic investigation results, ophiopogonin D (OD) noncompetitively inhibited UGT1A6 and competitively inhibited UGT1A8, ophiopogonin D' (OD') noncompetitively inhibited UGT1A6 and UGT1A10, and ruscorectal (RU) exhibited competitive inhibition towards UGT1A4. The inhibition kinetic parameters were calculated to be 20.6, 40.1, 5.3, 9.0, and 0.02 μM, respectively. In combination with our previous results obtained for the inhibition of UGT isoforms by ginsenosides and wuweizi components, the important SMI ingredients exhibiting strong inhibition towards UGT isoforms were highlighted. All the results obtained in the present study provide a new insight to understand SMI-related drug-drug interaction.

Citing Articles

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References

Zheng C, Hao H, Wang X, Wu X, Wang G, Sang G . Diagnostic fragment-ion-based extension strategy for rapid screening and identification of serial components of homologous families contained in traditional Chinese medicine prescription using high-resolution LC-ESI- IT-TOF/MS: Shengmai injection as.... J Mass Spectrom. 2008; 44(2):230-44. DOI: 10.1002/jms.1502. View

Uchaipichat V, Mackenzie P, Elliot D, Miners J . Selectivity of substrate (trifluoperazine) and inhibitor (amitriptyline, androsterone, canrenoic acid, hecogenin, phenylbutazone, quinidine, quinine, and sulfinpyrazone) "probes" for human udp-glucuronosyltransferases. Drug Metab Dispos. 2005; 34(3):449-56. DOI: 10.1124/dmd.105.007369. View

Liu C, Cao Y, Fang Z, Zhang Y, Hu C, Sun X . Strong inhibition of deoxyschizandrin and schisantherin A toward UDP-glucuronosyltransferase (UGT) 1A3 indicating UGT inhibition-based herb–drug interaction. Fitoterapia. 2013; 83(8):1415-9. DOI: 10.1016/j.fitote.2012.08.004. View

Lee H, Gonzalez F, Yoon M . Ginsenoside Rf, a component of ginseng, regulates lipoprotein metabolism through peroxisome proliferator-activated receptor alpha. Biochem Biophys Res Commun. 2005; 339(1):196-203. DOI: 10.1016/j.bbrc.2005.10.197. View

Wang Y, Liu H, Zhang X, Xiao Y, Lu B, Ma Z . [Screening of pregnane X receptor activation from ginsenosides]. Yao Xue Xue Bao. 2013; 48(1):144-8. View

Gall W, Zawada G, Mojarrabi B, Tephly T, Green M, Coffman B . Differential glucuronidation of bile acids, androgens and estrogens by human UGT1A3 and 2B7. J Steroid Biochem Mol Biol. 1999; 70(1-3):101-8. DOI: 10.1016/s0960-0760(99)00088-6. View

Bigo C, Caron S, Dallaire-Theroux A, Barbier O . Nuclear receptors and endobiotics glucuronidation: the good, the bad, and the UGT. Drug Metab Rev. 2013; 45(1):34-47. DOI: 10.3109/03602532.2012.751992. View

Hu Q, He G, Zhao J, Soshilov A, Denison M, Zhang A . Ginsenosides are novel naturally-occurring aryl hydrocarbon receptor ligands. PLoS One. 2013; 8(6):e66258. PMC: 3679084. DOI: 10.1371/journal.pone.0066258. View

Sneitz N, Krishnan K, Covey D, Finel M . Glucuronidation of the steroid enantiomers ent-17β-estradiol, ent-androsterone and ent-etiocholanolone by the human UDP-glucuronosyltransferases. J Steroid Biochem Mol Biol. 2011; 127(3-5):282-8. PMC: 3234363. DOI: 10.1016/j.jsbmb.2011.08.008. View

10.

Su Q, Li Y . Interaction between warfarin and the herbal product Shengmai-yin: a case report of intracerebral hematoma. Yonsei Med J. 2010; 51(5):793-6. PMC: 2908877. DOI: 10.3349/ymj.2010.51.5.793. View

11.

Nishida H, Kushida M, Nakajima Y, Ogawa Y, Tatewaki N, Sato S . Amyloid-beta-induced cytotoxicity of PC-12 cell was attenuated by Shengmai-san through redox regulation and outgrowth induction. J Pharmacol Sci. 2007; 104(1):73-81. DOI: 10.1254/jphs.fp0070100. View

12.

Meza-Junco J, Chu Q, Christensen O, Rajagopalan P, Das S, Stefanyschyn R . UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib. Cancer Chemother Pharmacol. 2009; 65(1):1-4. DOI: 10.1007/s00280-009-1096-4. View

13.

King C, Rios G, Green M, Tephly T . UDP-glucuronosyltransferases. Curr Drug Metab. 2001; 1(2):143-61. DOI: 10.2174/1389200003339171. View

14.

Fang Z, Cao Y, Hu C, Hong M, Sun X, Ge G . Structure-inhibition relationship of ginsenosides towards UDP-glucuronosyltransferases (UGTs). Toxicol Appl Pharmacol. 2013; 267(2):149-54. DOI: 10.1016/j.taap.2012.12.019. View

15.

Mu Y, Zhang J, Zhang S, Zhou H, Toma D, Ren S . Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther. 2005; 316(3):1369-77. DOI: 10.1124/jpet.105.094342. View

16.

Zucker S, Qin X, Rouster S, Yu F, Green R, Keshavan P . Mechanism of indinavir-induced hyperbilirubinemia. Proc Natl Acad Sci U S A. 2001; 98(22):12671-6. PMC: 60112. DOI: 10.1073/pnas.231140698. View