Skip to main content
SpringerLink
Log in

Hypericum Perforatum: A ‘Modern’ Herbal Antidepressant

Pharmacokinetics of Active Ingredients

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Hypericum perforatum (St John’s Wort [SJW]) counts among the most favourite herbal drugs, and is the only herbal alternative to classic synthetic antidepressants in the therapy of mild to moderate depression. Several clinical studies have been conducted to verify the effectiveness of ethanolic or methanolic extracts of SJW.

Alcoholic SJW extracts are a mixture of substances with widely varying physical and chemical properties and activities. Hyperforin, a phloroglucinol derivative, is the main source of pharmacological effects caused by the consumption of alcoholic extracts of SJW in the therapy of depression. However, several studies indicate that flavone derivatives, e.g. rutin, and also the naphthodianthrones hypericin and pseudohypericin, take part in the antidepressant efficacy.

In contrast to the amount of documentation concerning clinical efficacy, oral bioavailability and pharmacokinetic data about the active components are rather scarce.

The hyperforin plasma concentration in humans was investigated in a small number of studies. The results of these studies indicate a relevant plasma concentration, comparable with that used in in vitro tests. Furthermore, hyperforin is the only ingredient of H. perforatum that could be determined in the brain of rodents after oral administration of alcoholic extracts.

The plasma concentrations of the hypericins were, compared with hyperforin, only one-tenth and, until now, the hypericins could not be found in the brain after oral administration of alcoholic H. perforatum extracts or pure hypericin.

Until now, the pharmacokinetic profile of the flavonoids in humans after oral administration of an alcoholic H. perforatum extract has been investigated in only one study. More data are available for rutin and the aglycone quercetin after administration of pure substances or other flavonoid sources.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Table I
Fig. 3
Table II
Table III
Table IV

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. WHO. Depression: what is depression [online]? Available from URL: http://www.who.int/mental_health/management/depression/definition/en/ [Accessed 2006 Feb 28]

  2. Ayuso-Mateos JL, Vazquez-Barquero JL, Dowrick C, et al. Depressive disorders in Europe: prevalence figures from the ODIN study. Br J Psychiatry 2001; 179: 308–16

    PubMed  CAS  Google Scholar 

  3. Hale AS. ABC of mental health: depression. BMJ 1997; 315(7099): 43–6

    PubMed  CAS  Google Scholar 

  4. Thomas CM, Morris S. Cost of depression among adults in England in 2000. Br J Psychiatry Suppl 2003; 183: 514–9

    Google Scholar 

  5. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 1994; 51(1): 8–19

    PubMed  CAS  Google Scholar 

  6. Lepine JP, Gastpar M, Mendlewicz J, et al. Depression in the community: the first pan-European study DEPRES (Depression Research in European Society). Int Clin Psychopharmacol 1997; 12(1): 19–29

    PubMed  CAS  Google Scholar 

  7. Richelson E. Treatment of acute depression. Psychiatr Clin North Am 1993; 16(3): 461–78

    PubMed  CAS  Google Scholar 

  8. Conti DJ, Burton WN. The economic impact of depression in a workplace. J Occup Med 1994; 36(9): 983–8

    PubMed  CAS  Google Scholar 

  9. Richelson E. Pharmacology of antidepressants. Mayo Clin Proc 2001; 76: 511–27

    PubMed  CAS  Google Scholar 

  10. Müller WE. St. John’s Wort and its active principles in depression and anxiety. Basel: Birkhäuser, 2005

    Google Scholar 

  11. Kommission E. Monographie: Hyperici herba (Johanniskraut). Bundesanzeiger 1984: 228

  12. Kasper S. Hypericum perforatum: a review of clinical studies. Pharmacopsychiatry 2001; 34 Suppl. 1: S51–5

    PubMed  CAS  Google Scholar 

  13. Berner M, Riemann D, Berger M. The Efficacy of SJW extracts with more than 1% or less than 0.5% hyperforin content compared to placebo in the treatment of major depression [abstract]. Eur Arch Psychiatry Clin Neurosci 2002; 252 Suppl. 1: 56

    Google Scholar 

  14. Laakmann G, Schule C, Baghai T, et al. St. John’s Wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry 1998; 31 Suppl. 1: 54–9

    PubMed  CAS  Google Scholar 

  15. Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St John’s Wort in major depression: a randomized controlled trial. JAMA 2001; 285(15): 1978–86

    PubMed  CAS  Google Scholar 

  16. Linde K, Berner M, Egger M, et al. St John’s Wort for depression: meta-analysis of randomised controlled trials. Br J Psychiatry 2005; 186: 99–107

    PubMed  Google Scholar 

  17. Schwabe U, Paffrath D. Arzneiverordnungs report 2003. Berlin: Springer-Verlag, 2004

    Google Scholar 

  18. Capasso F, Gaginella TS, Grandolini G, et al. Phytotherapy: a quick reference to herbal medicine. Berlin: Springer-Verlag, 2003

    Google Scholar 

  19. St. John’s Wort. European Pharmacopoeia 2003; 4 Suppl. 4.5: 2157–8

    Google Scholar 

  20. European Medicines Agency. Guideline on quality of herbal medicinal products/traditional herbal medicinal products [online]. Available from URL: http://www.emea.eu.int/pdfs/human/qwp/281900en.pdf [Accessed 2006 Feb 28]

  21. Suzuki O, Katsumata Y, Oya M, et al. Inhibition of monoamine oxidase by hypericin. Planta Medica 1984; 50(3): 272–4

    PubMed  CAS  Google Scholar 

  22. Nöldner M, Schotz K. Rutin is essential for the antidepressant activity of Hypericum perforatum extracts in the forced swimming test. Planta Medica 2002; 68(7): 577–80

    PubMed  Google Scholar 

  23. Melzer R, Fricke U, Holzl J. Vasoactive properties of procyanidins from Hypericum perforatum L. in isolated porcine coronary arteries. Arzneimittel Forschung 1991; 41(5): 481–3

    PubMed  CAS  Google Scholar 

  24. Barnes J, Anderson LA, Phillipson JD. St John’s Wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties. J Pharm Pharmacol 2001; 53(5): 583–600

    PubMed  CAS  Google Scholar 

  25. Gambarana C, Tolu PL, Masi F, et al. A study of the antidepressant activity of Hypericum perforatum on animal models. Pharmacopsychiatry 2001; 34 Suppl. 1: S42–4

    PubMed  CAS  Google Scholar 

  26. Schulte-Lobbert S, Holoubek G, Muller WE, et al. Comparison of the synaptosomal uptake inhibition of serotonin by St John’s Wort products. J Pharm Pharmacol 2004; 56(6): 813–8

    PubMed  CAS  Google Scholar 

  27. Muller WE, Rolli M, Schafer C, et al. Effects of hypericum extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychiatry 1997; 30 Suppl. 2: 102–7

    PubMed  CAS  Google Scholar 

  28. Chatterjee SS, Bhattacharya SK, Wonnemann M, et al. Hyperforin as a possible antidepressant component of hypericum extracts. Life Sci 1998; 63(6): 499–510

    PubMed  CAS  Google Scholar 

  29. Jensen AG, Hansen SH, Nielsen EO. Adhyperforin as a contributor to the effect of Hypericum perforatum L. in biochemical models of antidepressant activity. Life Sci 2001; 68(14): 1593–605

    PubMed  CAS  Google Scholar 

  30. Muller WE, Singer A, Wonnemann M. Hyperforin: antidepressant activity by a novel mechanism of action. Pharmacopsychiatry 2001; 34 Suppl. 1: S98–102

    PubMed  CAS  Google Scholar 

  31. Singer A, Wonnemann M, Muller WE. Hyperforin, a major antidepressant constituent of St. John’s Wort, inhibits serotonin uptake by elevating free intracellular Na+l. J Pharmacol Exp Ther 1999; 290(3): 1363–8

    PubMed  CAS  Google Scholar 

  32. Wonnemann M, Singer A, Muller WE. Inhibition of synaptosomal uptake of 3H-L-glutamate and 3H-GABA by hyperforin, a major constituent of St. John’s Wort: the role of amiloride sensitive sodium conductive pathways. Neuropsychopharmacology 2000; 23(2): 188–97

    PubMed  CAS  Google Scholar 

  33. Gobbi M, Valle FD, Ciapparelli C, et al. Hypericum perforatum L. extract does not inhibit 5-HT transporter in rat brain cortex. Naunyn Schmiedebergs Arch Pharmacol 1999; 360(3): 262–9

    PubMed  CAS  Google Scholar 

  34. Gobbi M, Moia M, Pirona L, et al. In vitro binding studies with two Hypericum perforatum extracts hyperforin, hypericin and biapigenin on 5-HT6, 5-HT7, GABA (A)/benzodiazepine, sigma, NPY-Y1/Y2 receptors and dopamine transporters. Pharmacopsychiatry 2001; 34 Suppl. 1: S45–8

    PubMed  CAS  Google Scholar 

  35. Roz N, Rehavi M. Hyperforin inhibits vesicular uptake of monoamines by dissipating pH gradient across synaptic vesicle membrane. Life Sci 2003; 73(4): 461–70

    PubMed  CAS  Google Scholar 

  36. Roz N, Mazur Y, Hirshfeld A, et al. Inhibition of vesicular uptake of monoamines by hyperforin. Life Sci 2002; 71(19): 2227–37

    PubMed  CAS  Google Scholar 

  37. Eckert GP, Keller JH, Jourdan C, et al. Hyperforin modifies neuronal membrane properties in vitro. Neurosci Lett 2004; 367(2): 139–43

    PubMed  CAS  Google Scholar 

  38. Treiber K, Singer A, Müller WE. Activation of nonselective cation channels by hyperforin: a novel mechanism of antidepressant activity [abstract]. Soc Neurosci 2003; 29: 851

    Google Scholar 

  39. Calapai G, Crupi A, Firenzuoli F, et al. Effects of Hypericum perforatum on levels of 5-hydroxytryptamine, noradrenaline and dopamine in the cortex, diencephalon and brainstem of the rat. J Pharm Pharmacol 1999; 51(6): 723–8

    PubMed  CAS  Google Scholar 

  40. Yu PH. Effect of the Hypericum perforatum extract on serotonin turnover in the mouse brain. Pharmacopsychiatry 2000; 33(2): 60–5

    PubMed  CAS  Google Scholar 

  41. Serdarevic N, Eckert GP, Muller WE. The effects of extracts from St. John’s Wort and Kava Kava on brain neurotransmitter levels in the mouse. Pharmacopsychiatry 2001; 34 Suppl. 1: S134–6

    PubMed  CAS  Google Scholar 

  42. Ruschitzka F, Meier PJ, Turina M, et al. Acute heart transplant rejection due to Saint John’s Wort. Lancet 2000; 355(9203): 548–9

    PubMed  CAS  Google Scholar 

  43. Mathijssen RH, Verweij J, de Bruijn P, et al. Effects of St. John’s Wort on irinotecan metabolism. J Natl Cancer Inst 2002; 94(16): 1247–9

    PubMed  CAS  Google Scholar 

  44. Fugh-Berman A. Herb-drug interactions. Lancet 2000; 355(9198): 134–8

    PubMed  CAS  Google Scholar 

  45. Ernst E. St John’s Wort supplements endanger the success of organ transplantation. Arch Surg 2002; 137(3): 316–9

    PubMed  CAS  Google Scholar 

  46. Ernst E. Second thoughts about safety of St John’s Wort. Lancet 1999; 354(9195): 2014–6

    PubMed  CAS  Google Scholar 

  47. Ernst E, Rand JI, Barnes J, et al. Adverse effects profile of the herbal antidepressant St. John’s Wort (Hypericum perforatum L.). Eur J Clin Pharmacol 1998; 54(8): 589–94

    PubMed  CAS  Google Scholar 

  48. Mai I, Bauer S, Perloff ES, et al. Hyperforin content determines the magnitude of the St John’s Wort-cyclosporine drug interaction. Clin Pharmacol Ther 2004; 76(4): 330–40

    PubMed  CAS  Google Scholar 

  49. Wentworth JM, Agostini M, Love J, et al. St John’s Wort, a herbal antidepressant, activates the steroid X receptor. J Endocrinol 2000; 166(3): R11–6

    PubMed  CAS  Google Scholar 

  50. Watkins RE, Maglich JM, Moore LB, et al. 2.1 A crystal structure of human PXR in complex with the St. John’s Wort compound hyperforin. Biochemistry 2003; 42(6): 1430–8

    PubMed  CAS  Google Scholar 

  51. Moore LB, Goodwin B, Jones SA, et al. St. John’s Wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci U S A 2000; 97(13): 7500–2

    PubMed  CAS  Google Scholar 

  52. Nebel A, Schneider BJ, Baker RK, et al. Potential metabolic interaction between St. John’s Wort and theophylline. Ann Pharmacother 1999; 33(4): 502

    PubMed  CAS  Google Scholar 

  53. Kaminsky LS, Zhang ZY. Human P450 metabolism of warfarin. Pharmacol Ther 1997; 73(1): 67–74

    PubMed  CAS  Google Scholar 

  54. Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St John’s Wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003; 290(11): 1500–4

    PubMed  CAS  Google Scholar 

  55. Izzo AA. Drug interactions with St. John’s Wort (Hypericum perforatum): a review of the clinical evidence. Int J Clin Pharmacol Ther 2004; 42(3): 139–48

    PubMed  CAS  Google Scholar 

  56. Komoroski BJ, Zhang S, Cai H, et al. Induction and inhibition of cytochromes P450 by the St. John’s Wort constituent hyperforin in human hepatocyte cultures. Drug Metab Dispos 2004; 32(5): 512–8

    PubMed  CAS  Google Scholar 

  57. Schwarz UI, Buschel B, Kirch W. Unwanted pregnancy on self-medication with St John’s Wort despite hormonal contraception. Br J Clin Pharmacol 2003; 55(1): 112–3

    PubMed  Google Scholar 

  58. Henderson L, Yue QY, Bergquist C, et al. St John’s Wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002; 54(4): 349–56

    PubMed  CAS  Google Scholar 

  59. Pfrunder A, Schiesser M, Gerber S, et al. Interaction of St John’ s Wort with low-dose oral contraceptive therapy: a randomized controlled trial. Br J Clin Pharmacol 2003; 56(6): 683–90

    PubMed  CAS  Google Scholar 

  60. Hall SD, Wang Z, Huang SM, et al. The interaction between St John’s Wort and an oral contraceptive. Clin Pharmacol Ther 2003; 74(6): 525–35

    PubMed  CAS  Google Scholar 

  61. Johne A, Brockmoller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John’s Wort (Hypericum perforatum). Clin Pharmacol Ther 1999; 66(4): 338–45

    PubMed  CAS  Google Scholar 

  62. Wang EJ, Barecki-Roach M, Johnson WW. Quantitative characterization of direct P-glycoprotein inhibition by St John’s Wort constituents hypericin and hyperforin. J Pharm Pharmacol 2004; 56(1): 123–8

    PubMed  CAS  Google Scholar 

  63. Wang Z, Hamman MA, Huang SM, et al. Effect of St John’s Wort on the pharmacokinetics of fexofenadine. Clin Pharmacol Ther 2002; 71(6): 414–20

    PubMed  CAS  Google Scholar 

  64. Bodo A, Bakos E, Szeri F, et al. The role of multidrug transporters in drug availability, metabolism and toxicity. Toxicol Lett 2003; 140–141: 133–43

    PubMed  Google Scholar 

  65. Durr D, Stieger B, Kullak-Ublick GA, et al. St John’s Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 2000; 68(6): 598–604

    PubMed  CAS  Google Scholar 

  66. Mannel M. Drug interactions with St John’s Wort: mechanisms and clinical implications. Drug Saf 2004; 27(11): 773–97

    PubMed  CAS  Google Scholar 

  67. Nahrstedt A, Butterweck V. Biologically active and other chemical constituents of the herb of Hypericum perforatum L. Pharmacopsychiatry 1997; 30 Suppl. 2: 129–34

    PubMed  CAS  Google Scholar 

  68. Schulte-Lobbert S, Westerhoff K, Wilke A, et al. Development of a high-performance-liquid-chromatographic method for the determination of biapigenin in biorelevant media. J Pharm Biomed Anal 2003; 33(1): 53–60

    PubMed  CAS  Google Scholar 

  69. Hertog MG, Feskens EJ, Kromhout D. Antioxidant flavonols and coronary heart disease risk. Lancet 1997; 349(9053): 699

    PubMed  CAS  Google Scholar 

  70. Yochum L, Kushi LH, Meyer K, et al. Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women [published erratum appears in Am J Epidemiol 1999 Aug 15; 150 (4): 432]. Am J Epidemiol 1999; 149(10): 943–9

    PubMed  CAS  Google Scholar 

  71. Kiesewetter H, Koscielny J, Kalus U, et al. Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II): a randomized, double-blind, placebo-controlled trial. Arzneimittel Forschung 2000; 50(2): 109–17

    PubMed  CAS  Google Scholar 

  72. Ihme N, Kiesewetter H, Jung F, et al. Leg oedema protection from a buckwheat herb tea in patients with chronic venous insufficiency: a single-centre, randomised, double-blind, placebo-controlled clinical trial. Eur J Clin Pharmacol 1996; 50(6): 443–7

    PubMed  CAS  Google Scholar 

  73. Demisch L, Hölzl J, Gollnik B, et al. Identification of selective MAO-Typ A inhibition of Hypericum perforatum L [abstract]. Pharmacopsychiatry 1989; 22: 194

    Google Scholar 

  74. Thiede HM, Walper A. Inhibition of MAO and COMT by hypericum extracts and hypericin. J Geriatr Psychiatry Neurol 1994; 7 Suppl. 1: S54–6

    PubMed  Google Scholar 

  75. Cracchiolo C. Pharmacology of St. John’s Wort: botanical and chemical aspects. Sci Rev Alt Med 1998; 2: 29–35

    Google Scholar 

  76. Cott JM. In vitro receptor binding and enzyme inhibition by Hypericum perforatum extract. Pharmacopsychiatry 1997; 30 Suppl. 2: 108–12

    PubMed  CAS  Google Scholar 

  77. Butterweck V, Nahrstedt A, Evans J, et al. In vitro receptor screening of pure constituents of St. John’s Wort reveals novel interactions with a number of GPCRs. Psychopharmacology (Berl) 2002; 162(2): 193–202

    CAS  Google Scholar 

  78. Butterweck V, Jurgenliemk G, Nahrstedt A, et al. Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test. Planta Med 2000; 66(1): 3–6

    PubMed  CAS  Google Scholar 

  79. Porsolt RD. Animal model of depression. Biomedicine 1979; 30(3): 139–40

    PubMed  CAS  Google Scholar 

  80. Nöldner M. Behandlung von depressiven Patienten in der täglichen Praxis — Stellenwert von Johanniskraut. Neu-Isenburg: LinguaMed Verlags-GmbH, 2001

    Google Scholar 

  81. Butterweck V, Korte B, Winterhoff H. Pharmacological and endocrine effects of Hypericum perforatum and hypericin after repeated treatment. Pharmacopsychiatry 2001; 34 Suppl. 1: S2–7

    PubMed  CAS  Google Scholar 

  82. Butterweck V, Hegger M, Winterhoff H. Flavonoids of St. John’s Wort reduce HPA axis function in the rat. Planta Med 2004; 70(10): 1008–11

    PubMed  CAS  Google Scholar 

  83. Rubin RT, Phillips JJ, McCracken JT, et al. Adrenal gland volume in major depression: relationship to basal and stimulated pituitary-adrenal cortical axis function. Biol Psychiatry 1996; 40(2): 89–97

    PubMed  CAS  Google Scholar 

  84. Rubin RT, Phillips JJ, Sadow TF, et al. Adrenal gland volume in major depression. Increase during the depressive episode and decrease with successful treatment. Arch Gen Psychiatry 1995; 52(3): 213–8

    PubMed  CAS  Google Scholar 

  85. Holsboer F, Benkert O. Neuroendocrinologic and endocrinologic research in depressive patients [in German]. Nervenarzt 1985; 56(1): 1–11

    PubMed  CAS  Google Scholar 

  86. Holsboer F, Liebl R, Hofschuster E. Repeated dexamethasone suppression test during depressive illness: normalisation of test result compared with clinical improvement. J Affect Disord 1982; 4(2): 93–101

    PubMed  CAS  Google Scholar 

  87. Baureithel KH, Buter KB, Engesser A, et al. Inhibition of benzodiazepine binding in vitro by amentoflavone, a constituent of various species of Hypericum. Pharm Acta Helv 1997; 72(3): 153–7

    PubMed  CAS  Google Scholar 

  88. Butterweck V, Lieflander-Wulf U, Winterhoff H, et al. Plasma levels of hypericin in presence of procyanidin B2 and hyperoside: a pharmacokinetic study in rats. Planta Med 2003; 69(3): 189–92

    PubMed  CAS  Google Scholar 

  89. Butterweck V, Bockers T, Korte B, et al. Long-term effects of St. John’s Wort and hypericin on monoamine levels in rat hypothalamus and hippocampus. Brain Res 2002; 930(1–2): 21–9

    PubMed  CAS  Google Scholar 

  90. Butterweck V, Winterhoff H, Herkenham M. St John’s Wort, hypericin, and imipramine: a comparative analysis of mRNA levels in brain areas involved in HPA axis control following short-term and long-term administration in normal and stressed rats. Mol Psychiatry 2001; 6(5): 547–64

    PubMed  CAS  Google Scholar 

  91. Butterweck V, Petereit F, Winterhoff H, et al. Solubilized hypericin and pseudohypericin from Hypericum perforatum exert antidepressant activity in the forced swimming test. Planta Med 1998; 64(4): 291–4

    PubMed  CAS  Google Scholar 

  92. Brockmöller J, Reum T, Bauer S, et al. Hypericin and pseudohypericin: pharmacokinetics and effects on photosensitivity in humans. Pharmacopsychiatry 1997; 30 Suppl. 2: 94–101

    PubMed  Google Scholar 

  93. Agostinis P, Vantieghem A, Merlevede W, et al. Hypericin in cancer treatment: more light on the way. Int J Biochem Cell Biol 2002; 34(3): 221–41

    PubMed  CAS  Google Scholar 

  94. Lenard J, Rabson A, Vanderoef R. Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using hypericin and rose bengal: inhibition of fusion and syncytia formation. Proc Natl Acad Sci U S A 1993; 90(1): 158–62

    PubMed  CAS  Google Scholar 

  95. Andersen DO, Weber ND, Wood SG, et al. In vitro virucidal activity of selected anthraquinones and anthraquinone derivatives. Antiviral Res 1991; 16(2): 185–96

    PubMed  CAS  Google Scholar 

  96. Hänsel R, Keller K, Rimpler H, et al. Hager’s Handbuch der Pharmazeutischen Praxis. Berlin: Srpinger-Verlag, 1993

    Google Scholar 

  97. Hölzl J, Sattler S, Schutt H. Johanniskraut: eine Alternative zu synthetischen Antidepressiva? Pharmazeutische Zeitung 1994; 139: 3959–77

    Google Scholar 

  98. Erdelmeier CA. Hyperforin, possibly the major non-nitrogenous secondary metabolite of Hypericum perforatum L. Pharmacopsychiatry 1998; 31 Suppl. 1: 2–6

    PubMed  CAS  Google Scholar 

  99. Ostrowski E. Untersuchung zur Analytik, 14C-Markierung und Pharmakokinetik phenolischer Inhaltsstoffe von Hypericum perforatum L. Marburg: University of Marburg, 1988

    Google Scholar 

  100. Biber A, Fischer H, Romer A, et al. Oral bioavailability of hyperforin from hypericum extracts in rats and human volunteers. Pharmacopsychiatry 1998; 31 Suppl. 1: 36–43

    PubMed  CAS  Google Scholar 

  101. Franklin M, Chi J, McGavin C, et al. Neuroendocrine evidence for dopaminergic actions of hypericum extract (LI 160) in healthy volunteers. Biol Psychiatry 1999; 46(4): 581–4

    PubMed  CAS  Google Scholar 

  102. Agrosi M, Mischiatti S, Harrasser PC, et al. Oral bioavailability of active principles from herbal products in humans: a study on Hypericum perforatum extracts using the soft gelatin capsule technology. Phytomedicine 2000; 7(6): 455–62

    PubMed  CAS  Google Scholar 

  103. Cui Y, Gurley B, Ang CY, et al. Determination of hyperforin in human plasma using solid-phase extraction and high-performance liquid chromatography with ultraviolet detection. J Chromatogr B Analyt Technol Biomed Life Sci 2002; 780(1): 129–35

    PubMed  CAS  Google Scholar 

  104. Schulz HU, Schurer M, Bassler D, et al. Investigation of the bioavailability of hypericin, pseudohypericin, hyperforin and the flavonoids quercetin and isorhamnetin following single and multiple oral dosing of a hypericum extract containing tablet. Arzneimittel Forschung 2005; 55(1): 15–22

    PubMed  CAS  Google Scholar 

  105. Wurglics M, Westerhoff K, Kaunzinger A, et al. Batch-to-batch reproducibility of St. John’s Wort preparations. Pharmacopsychiatry 2001; 34 Suppl. 1: S152–6

    PubMed  CAS  Google Scholar 

  106. Wonnemann M, Singer A, Siebert B, et al. Evaluation of synaptosomal uptake inhibition of most relevant constituents of St. John’s Wort. Pharmacopsychiatry 2001; 34 Suppl. 1: S148–51

    PubMed  CAS  Google Scholar 

  107. Cervo L, Rozio M, Ekalle-Soppo CB, et al. Role of hyperforin in the antidepressant-like activity of Hypericum perforatum extracts. Psychopharmacology 2002; 164(4): 423–8

    PubMed  CAS  Google Scholar 

  108. Keller JH, Karas M, Muller WE, et al. Determination of hyperforin in mouse brain by high-performance liquid chromatography/tandem mass spectrometry. Anal Chem 2003; 75(22): 6084–8

    PubMed  CAS  Google Scholar 

  109. Liebes L, Mazur Y, Freeman D, et al. A method for the quantitation of hypericin, an antiviral agent, in biological fluids by high-performance liquid chromatography. Anal Biochem 1991; 195(1): 77–85

    PubMed  CAS  Google Scholar 

  110. Bauer S, Stornier E, Graubaum HJ, et al. Determination of hyperforin, hypericin, and pseudohypericin in human plasma using high-performance liquid chromatography analysis with fluorescence and ultraviolet detection. J Chromatogr B Biomed Sci Appl 2001; 765(1): 29–35

    PubMed  CAS  Google Scholar 

  111. Pirker R, Huck CW, Bonn GK. Simultaneous determination of hypericin and hyperforin in human plasma and serum using liquid-liquid extraction, high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 2002; 777(1–2): 147–53

    CAS  Google Scholar 

  112. Kerb R, Brockmoller J, Staffeldt B, et al. Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin. Antimicrob Agents Chemother 1996; 40(9): 2087–93

    PubMed  CAS  Google Scholar 

  113. Staffeldt B, Kerb R, Brockmoller J, et al. Pharmacokinetics of hypericin and pseudohypericin after oral intake of the hypericum perforatum extract LI 160 in healthy volunteers. J Geriate Psychiatry Neurol 1994; 7 Suppl. 1: S47–53

    Google Scholar 

  114. Weiser D. Pharmakokinetik von Hypericin nach der oralen Einnahme des Johanniskraut-Extrakte LI160. Nervenheilkunde 1991; 10: 318–9

    Google Scholar 

  115. Fox E, Murphy RF, McCully CL, et al. Plasma pharmacokinetics and cerebrospinal fluid penetration of hypericin in nonhuman primates. Cancer Chemother Pharmacol 2001; 47(1): 41–4

    PubMed  CAS  Google Scholar 

  116. Hollman PC, de Vries JH, van Leeuwen SD, et al. Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am J Clin Nutr 1995; 62(6): 1276–82

    PubMed  CAS  Google Scholar 

  117. Hollman PC, van Trijp JM, Buysman MN, et al. Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Lett 1997; 418(1–2): 152–6

    PubMed  CAS  Google Scholar 

  118. Hollman PC, Bijsman MN, van Gameren Y, et al. The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radic Res 1999; 31(6): 569–73

    PubMed  CAS  Google Scholar 

  119. Cermak R, Landgraf S, Wolffram S. The bioavailability of quercetin in pigs depends on the glycoside moiety and on dietary factors. J Nutr 2003; 133(9): 2802–7

    PubMed  CAS  Google Scholar 

  120. Wolffram S, Block M, Ader P. Quercetin-3-glucoside is transported by the glucose carrier SGLT1 across the brush border membrane of rat small intestine. J Nutr 2002; 132(4): 630–5

    PubMed  CAS  Google Scholar 

  121. Graefe EU, Wittig J, Mueller S, et al. Pharmacokinetics and bioavailability of quercetin glycosides in humans. J Clin Pharmacol 2001; 41(5): 492–9

    PubMed  CAS  Google Scholar 

  122. Day AJ, Mellon F, Barron D, et al. Human metabolism of dietary flavonoids: identification of plasma metabolites of quercetin. Free Radic Res 2001; 35(6): 941–52

    PubMed  CAS  Google Scholar 

  123. Ishii K, Furata T, Kasuya Y. Determination of rutin in human plasma by high-performance liquid chromatography utilizing solid-phase extraction and ultraviolet detection. J Chromatogr B Biomed Sci Appl 2001; 759(1): 161–8

    PubMed  CAS  Google Scholar 

  124. Manach C, Morand C, Demigne C, et al. Bioavailability of ratin and quercetin in rats. FEBS Lett 1997; 409(1): 12–6

    PubMed  CAS  Google Scholar 

  125. O’Leary KA, Day AJ, Needs PW, et al. Metabolism of quercetin-7- and quercetin-3-glucuronides by an in vitro hepatic model: the role of human beta-glucuronidase, sulfotransferase, catechol-O-methyltransferase and multi-resistant protein 2 (MRP2) in flavonoid metabolism. Biochem Pharmacol 2003; 65(3): 479–91

    PubMed  Google Scholar 

  126. Graefe EU, Derendorf H, Veit M. Pharmacokinetics and bioavailability of the flavonol quercetin in humans. Int J Clin Pharmacol Ther 1999; 37(5): 219–33

    PubMed  CAS  Google Scholar 

  127. Erlund I, Kosonen T, Alfthan G, et al. Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. Eur J Clin Pharmacol 2000; 56(8): 545–53

    PubMed  CAS  Google Scholar 

  128. Erlund I, Alfthan G, Siren H, et al. Validated method for the quantitation of quercetin from human plasma using high-performance liquid chromatography with electrochemical detection. J Chromatogr B Biomed Sci Appl 1999; 727(1–2): 179–89

    PubMed  CAS  Google Scholar 

  129. Juergenliemk G, Boje K, Huewel S, et al. In vitro studies indicate that miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is able to reach the CNS from the small intestine. Planta Med 2003; 69(11): 1013–7

    PubMed  CAS  Google Scholar 

  130. Gutmann H, Braggisser R, Schaffner W, et al. Transport of amentoflavone across the blood-brain barrier in vitro. Planta Med 2002; 68(9): 804–7

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Institute of Pharmaceutical Chemistry, ZAFES, J.W. Goethe University, Frankfurt am Main, Germany

    Mario Wurglics & Manfred Schubert-Zsilavecz

Authors
  1. Mario Wurglics
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manfred Schubert-Zsilavecz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mario Wurglics.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wurglics, M., Schubert-Zsilavecz, M. Hypericum Perforatum: A ‘Modern’ Herbal Antidepressant. Clin Pharmacokinet 45, 449–468 (2006). https://doi.org/10.2165/00003088-200645050-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-200645050-00002

Keywords

Search

Navigation