Skip to main content
SpringerLink
Log in

Inhibitory effects of wogonin on catalytic activity of cytochrome P450 enzyme in human liver microsomes

  • Original Paper
  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

Wogonin, derived from the root of Scutellaria baicalensis, is a popular herb for its anticancer, anti-inflammatory, neuroprotective and anti-convulsant effects. The purpose of this study was to investigate the effect of wogonin on human hepatic cytochrome P450s (CYP450s) in vitro. Isoform-specific substrate probes of CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 were incubated in human liver microsomes with or without wogonin. IC50 and K i values were estimated and the types of inhibition were determined. Wogonin was a potent, competitive inhibitor of CYP1A2 (K i = 0.24 μM), and a weak inhibitor of CYP2C19 (IC50 = 101.10 μM), but was not able to inhibit CYP2C9, CYP2D6, CYP2E1 and CYP3A4 (IC50 > 200 μM). Wogonin could inhibit the activity of CYP1A2 and CYP2C19 with varying potency, while it is a strong inhibitor of CYP1A2. These findings suggested that it was necessary to study the potential pharmacokinetic drug interaction in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

CYP:

Cytochrome P450

HPLC:

High performance liquid chromatography

LC–MS:

High-performance liquid chromatography–electrospray spectrometry

IS:

Internal standard

IC50 :

50% inhibitory concentration

K i :

Equilibrium dissociation constant for reversible inhibitor

K m :

The Michaelis constant

References

  • Chen YC, Shen SC, Chen LG, Lee TJ, Yang LL (2001) Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase-2 gene expressions induced by nitric oxide synthase inhibitors and lipopolysaccharide. Biochem Pharmacol 61:1417–1427

    Article  PubMed  CAS  Google Scholar 

  • de Boer JG, Quiney B, Walter PB, Thomas C, Hodgson K, Murch SJ, Saxena PK (2005) Protection against aflatoxin-B1-induced liver mutagenesis by Scutellaria baicalensis. Mutat Res 578:15–22

    Article  PubMed  Google Scholar 

  • Flesch G (2004) Overview of the clinical pharmacokinetics of oxcarbazepine. Clin Drug Investig 24:185–203

    Article  PubMed  CAS  Google Scholar 

  • He N, Edeki T (2004) The inhibitory effects of herbal components on CYP2C9 and CYP3A4 catalytic activities in human liver microsomes. Am J Ther 11:206–212

    Article  PubMed  Google Scholar 

  • Hodgson E, Rose RL (2007) The importance of cytochrome P450 2B6 in the human metabolism. Pharmacol Ther 113:420–428

    Article  PubMed  CAS  Google Scholar 

  • Inaba T, Jurima M, Nakano M, Kalow W (1984) Mephenytoin and sparteine pharmacogenetics in Canadian Caucasians. Clin Pharmacol Ther 36:670–676

    Article  PubMed  CAS  Google Scholar 

  • Ito K, Satoh T, Watanabe Y, Ikarashi N, Asano T, Morita T, Sugiyama K (2008) Effects of Kampo medicines on CYP and P-gp activity in vitro. Biol Pharm Bull 31:893–896

    Article  PubMed  CAS  Google Scholar 

  • Jacobson TA (2004) Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors. Am J Cardiol 94:1140–1146

    Article  PubMed  CAS  Google Scholar 

  • Kalgutkar AS, Obach RS, Maurer TS (2007) Mechanism-based inactivation of cytochrome P450 enzymes: chemical mechanisms, structure–activity relationships and relationship to clinical drug–drug interactions and idiosyncratic adverse drug reactions. Curr Drug Metab 8:407–447

    Article  PubMed  CAS  Google Scholar 

  • Kang JJ, Chen YC, Kuo WC, Chen T, Cheng YW, Kuo ML, Ueng TH (1996) Modulation of microsomal cytochrome P450 by Scutellariae Radix and Gentianae scabrae Radix in rat liver. Am J Chin Med 24:19–29

    Article  PubMed  CAS  Google Scholar 

  • Kim BR, Kim DH, Park R, Kwon KB, Ryu DG, Kim YC, Kim NY, Jeong S, Kang BK, Kim KS (2001) Effect of an extract of the root of Scutellaria baicalensis and its flavonoids on aflatoxin B1 oxidizing cytochrome P450 enzymes. Planta Med 67:396–399

    Article  PubMed  CAS  Google Scholar 

  • Kim EH, Shim B, Kang S, Jeong G, Lee JS, Yu YB, Chun M (2009) Anti-inflammatory effects of Scutellaria baicalensis extract via suppression of immune modulators and MAP kinase signaling molecules. J Ethnopharmacol 126:320–331

    Article  PubMed  Google Scholar 

  • Krakauer T, Li BQ, Young HA (2001) The flavonoid baicalin inhibits superantigen-induced inflammatory cytokines and chemokines. FEBS Lett 500:52–55

    Article  PubMed  CAS  Google Scholar 

  • Küpfer A, Preisig R (1984) Pharmacogenetics of mephenytoin: a new drug hydroxylation polymorphism in man. Eur J Clin Pharmacol 26:753–759

    Article  PubMed  Google Scholar 

  • Lakehal F, Wurden CJ, Kalhorn TF, Levy RH (2002) Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19. Epilepsy Res 52:79–83

    Article  PubMed  CAS  Google Scholar 

  • Lim JS, Yoo M, Kwon HJ, Kim H, Kwon YK (2010) Wogonin induces differentiation and neurite outgrowth of neural precursor cells. Biochem Biophys Res Commun 402:42–47

    Article  PubMed  CAS  Google Scholar 

  • Lu N, Gao Y, Ling Y, Chen Y, Yang Y, Gu HY, Qi Q, Liu W, Wang XT, You QD, Guo QL (2008) Wogonin suppresses tumor growth in vivo and VEGF-induced angiogenesis through inhibiting tyrosine phosphorylation of VEGFR2. Life Sci 82:956–963

    Article  PubMed  CAS  Google Scholar 

  • Madgula VLM, Ali Z, Smillie TJ, Khan IA, Walker LA, Khan SI (2009) Alkaloids and saponins as cytochrome p450 inhibitors from blue cohosh (Caulophyllum thalictroides) in an in vitro assay. Planta Med 75:329–332

    Article  PubMed  CAS  Google Scholar 

  • Ohta Y, Nishida K, Sasaki E, Kongo M, Hayashi T, Nagata M, Ishiguro I (1997) Comparative study of oral and parenteral administration of shosaiko-to (xiao-chaihu-tang) extract on d-galactosamine-induced liver injury in rats. Am J Chin Med 25:333–342

    Article  PubMed  CAS  Google Scholar 

  • Oleson FB, Berman CL, Li AP (2004) An evaluation of the P450 inhibition and induction potential of daptomycin in primary human hepatocytes. Chem Biol Interact 150:137–147

    Article  PubMed  CAS  Google Scholar 

  • Pan Y, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, Pook PC, Er HM, Ong CE (2010) In vitro modulatory effects on three major human cytochrome P450 enzymes by multiple active constituents and extracts of Centella asiatica. J Ethnopharmacol 130:275–283

    Article  PubMed  CAS  Google Scholar 

  • Park HG, Yoon SY, Choi JY, Lee GS, Choi JH, Shin CY, Son KH, Lee YS, Kim WK, Ryu JH, Ko KH, Cheong JH (2007) Anticonvulsant effect of wogonin isolated from Scutellaria baicalensis. Eur J Pharmacol 574:112–119

    Article  PubMed  CAS  Google Scholar 

  • Pelkonen O, Turpeinen M, Hakkola J, Honkakoski P, Hukkanen J, Raunio H (2008) Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol 82:667–715

    Article  PubMed  CAS  Google Scholar 

  • Piao HZ, Choi IY, Park JS, Kim HS, Cheong JH (2008) Wogonin inhibits microglial cell migration via suppression of nuclear factor-kappa B activity. Int Immunopharmacol 8:1658–1662

    Article  PubMed  CAS  Google Scholar 

  • Pineau T, Fernandez-Salguero P, Lee SS, McPhail T, Ward JM, Gonzalez FJ (1995) Neonatal lethality associated with respiratory distress in mice lacking cytochrome P450 1A2. Proc Natl Acad Sci USA 92:5134–5138

    Article  PubMed  CAS  Google Scholar 

  • Sekiguchi N, Kato M, Takada M, Watanabe H, Higashida A, Sakai S, Ishigai M, Aso Y (2008) In vivo approach for the evaluation of mechanism-based inhibition of cytochrome P450 3A in rats. Xenobiotica 38:368–381

    Article  PubMed  CAS  Google Scholar 

  • Taira Z, Yabe K, Hamaguchi Y, Hirayama K, Kishimoto M, Ishida S, Ueda Y (2004) Effects of Sho-saiko-to extract and its components, Baicalin, baicalein, glycyrrhizin and glycyrrhetic acid, on pharmacokinetic behavior of salicylamide in carbon tetrachloride intoxicated rats. Food Chem Toxicol 42:803–807

    Article  PubMed  CAS  Google Scholar 

  • Taylor JR, Wilt VM (1999) Probable antagonism of warfarin by green tea. Ann Pharmacother 33:426–428

    Article  PubMed  CAS  Google Scholar 

  • Ueng YF, Shyu CC, Lin YL, Park SS, Liao JF, Chen CF (2000) Effects of baicalein and wogonin on drug-metabolizing enzymes in C57BL/6J mice. Life Sci 67:2189–2200

    Article  PubMed  CAS  Google Scholar 

  • Usia T, Iwata H, Hiratsuka A, Watabe T, Kadota S, Tezuka Y (2006) CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants. Phytomedicine 13:67–73

    Article  PubMed  CAS  Google Scholar 

  • Wallentin L (2009) P2Y(12) inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. Eur Heart J 30:1964–1977

    Article  PubMed  CAS  Google Scholar 

  • Wang LS, Zhou G, Zhu B, Wu J, Wang JG, Abd El-Aty AM, Li T, Liu J, Yang TL, Wang D, Zhong XY, Zhou HH (2004) St John’s wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Ther 75:191–197

    Article  PubMed  CAS  Google Scholar 

  • Wang W, Guo QL, You QD, Zhang K, Yang Y, Yu J, Liu W, Zhao L, Gu HY, Hu Y, Tan Z, Wang XT (2006) The anticancer activities of wogonin in murine sarcoma S180 both in vitro and in vivo. Biol Pharm Bull 29:1132–1137

    Article  PubMed  CAS  Google Scholar 

  • Welker HA, Wiltshire H, Bullingham R (1998) Clinical pharmacokinetics of mibefradil. Clin Pharmacokinet 35:405–423

    Article  PubMed  CAS  Google Scholar 

  • Xu X, Liu HY, Liu L, Xie L, Liu XD (2008) The influence of a newly developed quinolone: antofloxacin, on CYP activity in rats. Eur J Drug Metab Pharmacokinet 33:1–7

    Article  PubMed  Google Scholar 

  • Yan Z, Caldwell GW (2001) Metabolism profiling, and cytochrome P450 inhibition & induction in drug discovery. Curr Top Med Chem 1:403–425

    Article  PubMed  CAS  Google Scholar 

  • Zhou SF, Chan E, Zhou ZW, Xue CC, Lai X, Duan W (2009) Insights into the structure, function, and regulation of human cytochrome P450 1A2. Curr Drug Metab 10:713–729

    Article  PubMed  CAS  Google Scholar 

  • Zielinski JJ, Haidukewych D (1987) Dual effects of carbamazepine–phenytoin interaction. Ther Drug Monit 9:21–23

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China

    Tingting Li, Ning Li, Hui Ji, Di Zhao, Shan Xie, Xiaonan Li, Zhixia Qiu, Deen Han & Xijing Chen

  2. Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanging, 210009, Jiangsu, People’s Republic of China

    Qinglong Guo & Qidong You

  3. Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanging, 210009, Jiangsu, People’s Republic of China

    Xijing Chen

Authors
  1. Tingting Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ning Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qinglong Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hui Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Di Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shan Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaonan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhixia Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Deen Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xijing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Qidong You
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xijing Chen or Qidong You.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, T., Li, N., Guo, Q. et al. Inhibitory effects of wogonin on catalytic activity of cytochrome P450 enzyme in human liver microsomes. Eur J Drug Metab Pharmacokinet 36, 249–256 (2011). https://doi.org/10.1007/s13318-011-0050-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13318-011-0050-0

Keywords

Search

Navigation