Abstract
Background: Goji berry (Lycium barbarum) has been used as traditional Chinese medicine and a functional food in China. Goji tea may interact with drugs such as warfarin by inhibiting the cytochrome P450 (CYP) 2C9, and this study was undertaken to characterize the effect of Goji products on CYP2C9/19-, CYP2D6 *1/*10-, CYP3A4/5/7-, CYP19-, and flavin-containing monooxygenase (FMO) 3-mediated metabolism.
Methods: Goji juice, water, and ethanol extracts were examined for their effect on CYP2C9/19-, 2D6-, 3A4/5/7-, 4A11-, CYP19-, and FMO3-mediated metabolism by using in vitro bioassay. The mechanism-based inactivation (MBI) of Goji juice on CYP3A4 was also examined.
Results: Data indicates that both fresh juice and commercially available juice caused strong inhibition (over 75 %) of most of the major CYP450 enzymes and moderate inhibition of FMO3 (30–60 %). Compared to juice, the Goji cold/hot water extracts effected low inhibition (below 30 %) of these enzymes. Ethanol (80 %) extracts exhibit the strongest inhibition on CYP2C9 and 2C19 (over 90 %). The inhibition pattern of dried and fresh berry extract and high-performance liquid chromatography (HPLC)-UV fingerprints were similar.
Conclusions: These findings suggest that Goji products (berries, tea, tincture, and juice) can inhibit phase I drug metabolism enzymes and have the potential to affect the safety and efficacy of therapeutic products.
Acknowledgments
The authors gratefully acknowledge the support from Health Canada.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Hsu HY. Oriental materia medica: a concise guide. Long Beach, CA: Oriental Healing Arts Institute, 2005:544–5.Search in Google Scholar
2. Gao XM, Xu ZM, Li ZW. Traditional Chinese medicines. Beijing: People’s Health Publishing House, 2000:1832–50.Search in Google Scholar
3. Peng XM, Huang LJ, Qi CH, Zhang YX, Tian GY. Studies on chemistry and immuno-modulating mechanism of a glycoconjuate from Lycium barbarum L. Chin J Chem 2001;19:1190–7.10.1002/cjoc.20010191206Search in Google Scholar
4. Peng XM, Wang ZF, Tian GY. Physico-chemical properties and activity of glycoconjugate LbGp2 from Lycium barbarum L. (Goji). Yao Xue Xue Bao 2001;36:599–602.Search in Google Scholar
5. Wang JH, Wang HZ, Zhang M, Zhang SH. Anti-aging function of polysaccharides from Lycium barbarum. Acta Nutr Sin 2002;24:189–91.Search in Google Scholar
6. Gan L, Zhang SH. Effect of Lycium barbarum polysaccharides on anti-tumor activity and immune function. Acta Nutr Sin 2003;25:200–2.Search in Google Scholar
7. Gan L, Wang J, Zhang S. Inhibition the growth of human leukemia cells by Lycium barbarum (Goji) polysaccharide. Wei Sheng Yan Jiu 2001;30:333–5.Search in Google Scholar
8. Deng HB, Cui DP, Jiang JM, Feng YC, Cai NS, Li DD. Inhibiting effects of Achyranthes bidentata polysaccharide and Lycium barbarum (Goji) polysaccharide on nonenzyme glycation in D-galactose induced mouse aging model. Biomed Environ Sci 2003;16:267–75.Search in Google Scholar
9. Hai-Yang G, Ping S, Li JI, Chang-Hong X, Fu T. Therapeutic effects of Lycium barbarum (Goji) polysaccharide (LBP) on mitomycin C (MMC)-induced myelosuppressive mice. J Exp Ther Oncol 2004;4:181–7.Search in Google Scholar
10. Ni H, Qing D, Kaisa S, Lu J. The study on the effect of LBP on cleaning hydroxygen free radical by EPR technique. Zhong Yao Cai 2004;27:599–600.Search in Google Scholar
11. Gong H, Shen P, Jin L, Xing C, Tang F. Therapeutic effects of Lycium barbarum (Goji) polysaccharide (LBP) on irradiation or chemotherapy-induced myelosuppressive mice. Cancer Biother Radiopharm 2005;20:155–62.10.1089/cbr.2005.20.155Search in Google Scholar PubMed
12. Duan CL, Qiao SY, Wang NL, Zhao YM, Qi CH, Yao XS. Studies on the active polysaccharides from Lycium barbarum L. (Goji). Yao Xue Xue Bao 2001;36:196–9.Search in Google Scholar
13. Luo Q, Yan J, Zhang S. Effects of pure and crude Lycium barbarum (Goji) polysaccharides on immunopharmacology. Zhong Yao Cai 1999;22:246–9.Search in Google Scholar
14. Luo Q, Yan J, Zhang S. Isolation and purification of Lycium barbarum (Goji) polysaccharides and its anti-fatigue effect. Wei Sheng Yan Jiu 2000;29:115–17.Search in Google Scholar
15. Potterat O, Goji. Lycium barbarum and L. chinense: Phytochemistry, pharmacology and safety in the perspective of traditional uses and recent popularity. Planta Med 2010; 76:7–19.10.1055/s-0029-1186218Search in Google Scholar PubMed
16. Karp D. Goji taunts North American farmers. Los Angeles Times 2009 Aug;4 http://articles.latimes.com/2009/aug/05/food/fo-goji5.Search in Google Scholar
17. Li QY. Healthy functions and medicinal prescriptions of Lycium barbarum (Gou Ji Zi). Beijing: Jindun Press, 2001:1–16.Search in Google Scholar
18. Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokin 1997;32:210–58.10.2165/00003088-199732030-00004Search in Google Scholar PubMed
19. Rendic S, Di Carlo FJ. Human cytochrome P450 enzymes: a status report summarizing their reactions substrates inducers and Inhibitors. Drug Metab Rev 1997;29:413–580.10.3109/03602539709037591Search in Google Scholar PubMed
20. Leung H, Hung A, Hui AC, Chan TY. Warfarin overdose due to the possible effects of Lycium barbarum L. Food Chem Toxicol 2008;46:1860–2.10.1016/j.fct.2008.01.008Search in Google Scholar PubMed
21. Lam AY, Elmer GW, Mohutsky MA. Possible interaction between warfarin and Lycium barbarum L. Ann Pharmacother 2001;35:1195–9.10.1345/aph.1Z442Search in Google Scholar PubMed
22. Chatterjee P, Franklin MR. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos 2003;31:1391–7.10.1124/dmd.31.11.1391Search in Google Scholar PubMed
23. Zhou S, Chan E, Lim LY, Boelsterli UA, Li SC, Wang J, et al. Therapeutic drugs that behave as mechanism-based inhibitors of cytochrome P450 3A4. Curr Drug Metab 2004;5:415–42.10.2174/1389200043335450Search in Google Scholar PubMed
24. Lilja JJ, Kivistö KT, Neuvonen PJ. Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin. Clin Pharmacol Ther 2000;68:384–90.10.1067/mcp.2000.110216Search in Google Scholar PubMed
25. Flanagan D. Understanding the grapefruit-drug interaction. Gen Dent 2005;53:282–5.Search in Google Scholar
26. Schrag ML, Wienkers LC. Triazolam substrate inhibition: evidence of competition for heme-bound reactive oxygen within the CYP3A4 active site. Drug Metab Dispos 2001;29:70–5.10.1007/978-1-4615-0667-6_56Search in Google Scholar
27. Chan WK, Delucchi AB. Resveratrol a red wine constituent is a mechanism-based inactivator of cytochrome P450 3A4. Life Sci 2000;67:3103–12.10.1016/S0024-3205(00)00888-2Search in Google Scholar
28. Piver B, Berthou F, Dreano Y, Lucas D. Inhibition of CYP3A CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Toxicol Lett 2001;125:83–91.10.1016/S0378-4274(01)00418-0Search in Google Scholar
29. Chang TK, Yeung RK. Effect of trans-resveratrol on 7-benzyloxy-4-trifluoromethylcoumarin O-dealkylation catalyzed by human recombinant CYP3A4 and CYP3A5. Can J Physiol Pharmacol 2001;79:220–6.10.1139/cjpp-79-3-220Search in Google Scholar
30. Hsu MH, Savas U, Griffin JK, Johnson EF. Human cytochrome P450 family 4 enzymes: function genetic variation and regulation. Drug Metab Rev 2007;39:515–38.10.1080/03602530701468573Search in Google Scholar PubMed
31. Yu S, Rao S, Reddy JK. Peroxisome proliferator-activated receptors fatty acid oxidation steatohepatitis and hepatocarcinogenesis. Curr Mol Med 2003;3:561–72.10.2174/1566524033479537Search in Google Scholar PubMed
©2016 by De Gruyter
