Ganoderic Acid B's Influence Towards the Therapeutic Window of Trifluoperazine (TFP)

Overview

Journal Afr Health Sci

Date 2015 Apr 3

PMID 25834543

Citations 1

Authors

Jun Guo

Chenming Ni

Xiaoyang Liu

Tao Liu

Affiliations

Soon will be listed here.

Abstract

Background: Ganoderic acid B is an important bioactive ingredient isolated from Ganoderma lucidum, and exhibits various pharmacological activities.

Aims: To investigate the influence of Ganoderic acid B towards the therapeutic window of trifluoperazine (TFP).

Methods: In vitro human liver microsomes (HLMs) incubation system was used to determine the inhibition of Ganoderic acid B towards the glucuronidation of trifluoperazine (TFP).

Results: Ganoderic acid B exerted concentration-dependent inhibition towards the glucuronidation of TFP. Furthermore, Dixon plot was used to determine the inhibition type. The intersection point was located in the second quadrant in Dixon plot, indicating the competitive inhibition of Ganoderic acid B towards TFP glucuronidation. Through fitting the data using competitive nonlinear fitting equation, the inhibition kinetic parameter was calculated to be 56.7 uM.

Conclusion: All this data indicated the potential influence of Ganoderic acid B-containing herbs towards therapeutic window of TFP. Given that the glucuronidation reaction of TFP is the probe reaction of UGT1A4, the data obtained from the present study also indicated the potential influence of Ganoderic acid-containing herbs towards the therapeutic window of drugs mainly undergoing UGT1A4-mediated metabolism.

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Tumwine J Afr Health Sci. 2015; 15(1):i-iii.

PMID: 25834569 PMC: 4370150.

References

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

Wang Z, Wong T, Hashizume T, Dickmann L, Scian M, Koszewski N . Human UGT1A4 and UGT1A3 conjugate 25-hydroxyvitamin D3: metabolite structure, kinetics, inducibility, and interindividual variability. Endocrinology. 2014; 155(6):2052-63. PMC: 4020929. DOI: 10.1210/en.2013-2013. View

Green M, Bishop W, Tephly T . Expressed human UGT1.4 protein catalyzes the formation of quaternary ammonium-linked glucuronides. Drug Metab Dispos. 1995; 23(3):299-302. 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

Fang Z, Zhang Y, Ge G, Huo H, Liang S, Yang L . Time-dependent inhibition (TDI) of CYP3A4 and CYP2C9 by noscapine potentially explains clinical noscapine-warfarin interaction. Br J Clin Pharmacol. 2010; 69(2):193-9. PMC: 2824481. DOI: 10.1111/j.1365-2125.2009.03572.x. View

Laverdiere I, Caron P, Harvey M, Levesque E, Guillemette C . In vitro investigation of human UDP-glucuronosyltransferase isoforms responsible for tacrolimus glucuronidation: predominant contribution of UGT1A4. Drug Metab Dispos. 2011; 39(7):1127-30. DOI: 10.1124/dmd.111.039040. View

Wu G, Lu J, Guo J, Li Y, Tan W, Dang Y . Ganoderic acid DM, a natural triterpenoid, induces DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells. Fitoterapia. 2011; 83(2):408-14. DOI: 10.1016/j.fitote.2011.12.004. View

Li F, Wang Y, Wang X, Li J, Cui H, Niu M . Ganoderic acids suppress growth and angiogenesis by modulating the NF-κB signaling pathway in breast cancer cells. Int J Clin Pharmacol Ther. 2012; 50(10):712-21. DOI: 10.5414/CP201663. View

Guo X, Shen X, Long J, Han J, Che Q . Structural identification of the metabolites of ganoderic acid B from Ganoderma lucidum in rats based on liquid chromatography coupled with electrospray ionization hybrid ion trap and time-of-flight mass spectrometry. Biomed Chromatogr. 2013; 27(9):1177-87. DOI: 10.1002/bmc.2924. View

10.

McGill M, Jaeschke H . Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res. 2013; 30(9):2174-87. PMC: 3709007. DOI: 10.1007/s11095-013-1007-6. View

11.

Kuok Q, Yeh C, Su B, Hsu P, Ni H, Liu M . The triterpenoids of Ganoderma tsugae prevent stress-induced myocardial injury in mice. Mol Nutr Food Res. 2013; 57(10):1892-6. DOI: 10.1002/mnfr.201200704. View

12.

Hempel C, Norenberg W, Sobottka H, Urban N, Nicke A, Fischer W . The phenothiazine-class antipsychotic drugs prochlorperazine and trifluoperazine are potent allosteric modulators of the human P2X7 receptor. Neuropharmacology. 2013; 75:365-79. DOI: 10.1016/j.neuropharm.2013.07.027. View

13.

Fang Z, Krausz K, Nagaoka K, Tanaka N, Gowda K, Amin S . In vivo effects of the pure aryl hydrocarbon receptor antagonist GNF-351 after oral administration are limited to the gastrointestinal tract. Br J Pharmacol. 2014; 171(7):1735-46. PMC: 3966752. DOI: 10.1111/bph.12576. View

14.

Ma H, Sun D, Cao Y, Ai C, Qu Y, Hu C . Herb-drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7. Toxicol Appl Pharmacol. 2014; 277(1):86-94. PMC: 6335651. DOI: 10.1016/j.taap.2014.02.021. View

15.

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