J Appl Biomed 1:61-70, 2003 | DOI: 10.32725/jab.2003.010

The chemistry, pharmacology, and toxicology of the biologically active constituents of the herb Hypericum perforatum L.

Jiří Patočka
Military Medical Academy, Department of Toxicology, 502 60 Hradec Králové and Department of Radiology, Faculty of Health and Social Care, University of South Bohemia, České Budějovice, Czech Republic

St. John's wort (Hypericum perforatum) has been used as a medical herb for over 2000 years. Over the past two decades, its application as a standardized plant extract for treating depression has undergone rigorous scientific investigation, and its effectiveness has been shown in studies comparing it with other commonly used antidepressants and placebos. Safety and tolerability studies have revealed that Hypericum preparations have better safety and tolerability profiles than synthetic antidepressants. The indications for St. John's wort preparations are mild or moderate depression. The mechanism of the antidepressant action of Hypericum extract is not fully known. The view of the chemical composition and pharmaceutical a toxicological properties of biologically active substances of Hypericum perforatum is the main purpose of this paper.

Keywords: Hypericum perforatum; antidepressant; pharmacology; toxicology

Received: June 3, 2002; Published: July 31, 2003  Show citation

ACS AIP APA ASA Harvard Chicago IEEE ISO690 MLA NLM Turabian Vancouver
Patočka J. The chemistry, pharmacology, and toxicology of the biologically active constituents of the herb Hypericum perforatum L. J Appl Biomed. 2003;1(2):61-70. doi: 10.32725/jab.2003.010.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Bagchi D., Bagchi M., Stohs S.J., Das D.K, Ray S.D., Kuszynski C.A., Joshi S.S, Pruess H.G.: Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology 148: 187-197, 2000. Go to original source... Go to PubMed...
    2. Baureithel K.H, Buter K.B., Engesser A., Burkard W, Schaffner W.: Inhibition of benzodiazepine binding in vitro by amentoflavone, a constituent of various species of Hypericum. Pharm. Acta Helv. 72: 153-157, 1997. Go to original source... Go to PubMed...
    3. Bennet G.J., Lee H.H.: Xanthones from the Guttiferae. Phytochemistry 28: 967-998, 1989. Go to original source...
    4. Bennett D.A. Jr, Phun L., Polk J.F., Voglino S.A., Zlotnik V., Raffa R.B.: Neuropharmacology of St. John's Wort (Hypericum). Ann. Pharmacother. 32: 1201-1208, 1989. Go to original source...
    5. Berghoefer R., Hoelzl J.: Biflavonoids in Hypericum perforatum; Part 1. Isolation of I3,II8-biapigenin. Planta Med. 53: 216-217, 1987. Go to original source... Go to PubMed...
    6. Berghoefer R., Hoelzl J.: Isolation of I3',II8-biapigenin (amentoflavone) from Hypericum perforatum. Planta Med. 55: 91, 1989. Go to original source...
    7. Bladt S., Wagner H.: Inhibition of MAO by fractions and constituents of hypericum extract. J. Geriatr. Psychiatry Neurol. 7, Suppl 1: S57-59, 1994. Go to original source... Go to PubMed...
    8. Brantner A., Kartnig T., Quehenberger F.: Vergleichende phytochemische Untersuchungen an Hypericum perforatum L. und Hypericum maculatum Crantz. Scient. Pharm. 62: 261-276, 1994.
    9. Brockman H.: Photodynamisch wirksame Pflanzenfarbstoffe. In: Zechmeister L.: Fortschr. Chem. Org. Naturstoffe, Bd. XIV, Springer Verlag, Wien 1957. Go to original source...
    10. Brockmöller J., Reum T., Bauer S., Kerb R., Hübner W-D., Roots I.: Hypericin and pseudohypericin: Pharmacokinetics and effects on photosensitivity in humans. Pharmacopsychiatry 30, Suppl: 94-101, 1997. Go to original source... Go to PubMed...
    11. Cardona L., Fernandez I., Pedro J.R., Serrano A.: Xanthones from Hypericum reflexum. Phytochemistry 29: 3003-3006, 1990. Go to original source...
    12. Chatterjee S.S., Bhattacharya S.K., Wonnemann M., Singer A. Muller W.E.: Hyperforin as a possible antidepressant component of hypericum extracts. Life Sci. 63: 499-510, 1998a. Go to original source... Go to PubMed...
    13. Chassevent F.: Chlorogenic acid, physiological and pharmacological activity (Article in French) Ann. Nutr. Aliment. 23, Suppl 1: 1-14, 1969. Go to PubMed...
    14. Chatterjee S.S., Biber A., Weibezahn C.: Stimulation of glutamate, aspartate and gamma-aminobutyric acid release from synaptosomes by hyperforin. Pharmacopsychiatry 34, Suppl 1: S11-S19, 2001. Go to original source... Go to PubMed...
    15. Chatterjee S.S., Noldner M., Koch E., Erdelmeier C.: Antidepressant activity of hypericum perforatum and hyperforin: the neglected possibility. Pharmacopsychiatry 31, Suppl. 1: 7-15, 1998b. Go to original source... Go to PubMed...
    16. Čellarová E., Daxnerová Z., Kimaková K., Halusková J.: The variability of the hypericin contents in the regenerants of Hypericum perforatum. Act. Biotechnol. 14: 267-274, 1994. Go to original source...
    17. De Bruyne T., Pieters L., Witvrouw M. De Clercq E, Vanden Berghe D., Vlietinck A.J.: Biological evaluation of proanthocyanidin dimers and related polyphenols. J. Nat.Prod. 62: 954-958, 1999. Go to original source... Go to PubMed...
    18. Falk H., Schmitzberger W.: On the nature of "soluble" hypericin in Hypericum species. Monatshefte Chem. 123:7 31-739, 1992. Go to original source...
    19. Ghelardini C., Galeotti N., Mazzanti G.: Local anaesthetic activity of monoterpenes and phenylpropanes of essential oils. Planta Med. 67: 564-566, 2001. Go to original source... Go to PubMed...
    20. Giese A.: Hypericism. Photochem. Photobiol. Rev. 5: 229-255, 1980. Go to original source...
    21. Haeberlain H., Tschiersch K-P., Schäfer H.L.: Flavonoids from Leptospermum scoparium with affinity to the benzodiazepine receptor characterized by structure activity relationships and in vivo studies of a plant extract. Pharmazie 49: 912-922, 1994. Go to PubMed...
    22. Haeberlain H, Tschiersch K-P, Stock S, Hoelzl J: Johanniskraut (Hypericum perforatum L). Teil 1, Nachweis eines weiteren Naphthodianthrons. Pharm. Ztg. Wiss. 137: 169-174, 1992.
    23. Hegnauer R.: Chemotaxonomie der Pflanzen, Vol. VII. Birkhäuser Verlag, Berlin 1989. Go to original source...
    24. Jurgenliemk G., Nahrstedt A.: Phenolic compounds from Hypericum perforatum. Planta Med. 68: 88-91, 2002. Go to original source... Go to PubMed...
    25. Kim H.K., Son K.H., Chang H.W., Kang S.S., Kim H.P: Amentoflavone, a plant biflavone: a new potential anti-inflammatory agent. Arch. Pharm. Res. 21: 406-410, 1998. Go to original source... Go to PubMed...
    26. Klusa V., Germane S., Noldner M., Chatterjee S.S.: Hypericum extract and hyperforin: memory-enhancing properties in rodents. Pharmacopsychiatry, Suppl 1: S61-S69, 2001. Go to original source... Go to PubMed...
    27. Koch E., Chatterjee S.S.: Hyperforin stimulates intracellular calcium mobilisation and enhances extracellular acidification in DDT1-MF2 smooth muscle cells. Pharmacopsychiatry 34, Suppl 1: S70-S73, 2001. Go to original source... Go to PubMed...
    28. Maisenbacher P., Kovar K-A.: Adhyperforin: A homologue of hyperforin from Hypericum perforatum. Planta Med. 58: 291-293, 1992. Go to original source... Go to PubMed...
    29. MacGregor J.T.: Genetic toxicology of dietary flavonoids. Prog. Clin. Biol. Res. 206: 33-43, 1986.
    30. Medina J.H., Viola H., Wolfman C., Marder M., Wasowski C., Calvo D., Paladini A.C.:Overview - flavonoids: a new family of benzodiazepine receptor ligands. Neurochem. Res. 22: 419-425, 1997. Go to original source... Go to PubMed...
    31. Melzer R., Fricke U., Holzl J.: Vasoactive properties of procyanidins from Hypericum perforatum L. in isolated porcine coronary arteries. Arzneim-Forsch /Drug Res. 41: 481-483, 1991.
    32. Morales M.A., Lozoya X.: Calcium-antagonist effects of quercetin on aortic smooth muscle. Planta Med. 60: 313-317, 1994. Go to original source... Go to PubMed...
    33. Mori H., Kawabata K., Matsunaga K., Ushida J., Fujii K., Hara A., Tanaka T., Murai H.: Chemopreventive effects of coffee bean and rice constituents on colorectal carcinogenesis. Biofactors 12: 101-105, 2000. Go to original source... Go to PubMed...
    34. Müller W.E., Singer A., Wonnemann M.: Hyperforin - antidepressant activity by a novel mechanism of action. Pharmacopsychiatry 34, Suppl 1: S98-S102, 2001. Go to original source... Go to PubMed...
    35. Nahrstedt A., Butterweck V.: Biologically active and other chemical constituents of the herb of Hypericum perforatum L. Pharmacopsychiatry 30, Suppl 2: 129-134, 1997. Go to original source... Go to PubMed...
    36. Nielsen H., Arends P.: Structure of the xanthone lignoid kielcorin. Phytochemistry 17: 2040-2041, 1978. Go to original source...
    37. Nielsen M., Frokjaer S., Braestrup C.: High affinity of the naturally-occuring biflavonoid, amentoflavon, to brain benzodiazepine receptors in vitro. Biochem. Pharmacol. 37: 3285-3287, 1988. Go to original source... Go to PubMed...
    38. Niesel S., Schilcher H.: Vergleich der Freisetzung von Hypericin und Pseudohypericin in Abhängigkeit verschiedener Extraktionsbedingungen. Arch. Pharm. 323: 755, 1990.
    39. Peebles K.A., Baker R.K., Kurz E.U., Schneider B.J., Kroll D.J.: Catalytic inhibition of human DNA topoisomerase IIalpha by hypericin, a naphthodianthrone from St. John's wort (Hypericum perforatum). Biochem. Pharmaco. 62: 1059-1070, 2001. Go to original source... Go to PubMed...
    40. Pietta P., Gardana C., Pietta A.: Comparative evaluation of St. John's wort from different Italian regions. Farmaco 56 :491-496, 2001. Go to original source... Go to PubMed...
    41. Poginski B., Westendorf J., Prosenc N., Kuppe M., Marquard H.: Johannis kraut (Hypericum perforatum L). Genotoxicität bedingt durch den Quercetingehalt. Dtsch. Apoth. Ztg. 128: 1364-1366, 1988.
    42. Raffa R.B.: Screen of receptor and uptake-site activity of hypericin component of St. John's wort reveals sigma receptor binding. Life Sci. 62: PL265-PL270, 1988. Go to original source...
    43. Rueff J., Laires A., Borba H., Chaveca T., Gomes M.I., Halpern M.: Genetic toxicology of flavonoids: the role of metabolic conditions in the induction of reverse mutation, SOS functions and sister-chromatid exchanges. Mutagenesis 1: 179-183, 1986. Go to original source... Go to PubMed...
    44. Scalbert A.: Antimicrobial properties of tannins. Phytochemistry 30: 3875-3883, 1991. Go to original source...
    45. Scalbert A., Deprez S., Mila I., Albrecht A.M., Huneau J.F., Rabot S.: Proanthocyanidins and human health: systemic effects and local effects in the gut. Biofactors. 13:1 15-120, 2000. Go to original source... Go to PubMed...
    46. Schempp C.M., Kirkin V., Simon-Haarhaus B., Kersten A., Kiss J., Termeer C.C., Gilb B., Kaufmann T., Borner C., Sleeman J.P., Simon J.C.: Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis. Oncogene 21: 1242-1250, 2002. Go to original source... Go to PubMed...
    47. Scholz E.: Pflanzliche Gerbstoffe. Dtsch. Apoth. Ztg. 134: 3167-3179, 1994.
    48. Sparenberg B., Demisch B.L., Hoelzl J.: Untersuchungen über antidepressive Wirkstoffe von Johanniskraut. Phar. Ztg. Wiss. 6/138: 50-54, 1993.
    49. Stavric B.: Quercetin in our diet: From potent mutagen to probable anticarcinogen. Clin. Biochem. 27: 245-248, 1994. Go to original source... Go to PubMed...
    50. Stock S., Hoelzl J.: Ist Johanniskraut phototoxisch? Med. Mod. Pharm. 14: 304-306, 1991.
    51. Takahashi I., Nakanishi S., Kobayashi E., Nakano H., Suzuki K, Tamaoki T.: Hypericin and pseudohypericin specifically inhibit protein kinase C: possible relation to their antiretroviral activity. Biochem. Biophys. Res. Commun. 165: 207-1212, 1989. Go to original source... Go to PubMed...
    52. Takhtajan A.: Evolution und Ausbreitung der Blütenpflanzen. G. Fischer, Stutgart 1973.
    53. Thiede H.M., Walper A.: Inhibition of MAO and COMT by hypericum extracts and hypericin. J. Geriatr. Psychiatry. Neurol. 7, Suppl 1: S54-S56, 1994. Go to original source... Go to PubMed...
    54. Vandenbogaerde A.L. Kamuhabwa A., Delaey E., Himpens B.E., Merlevede W.J., de Witte P.A.: Photocytotoxic effect of pseudohypericin versus hypericin. J. Photochem. Photobiol. B 45: 87-94, 1998. Go to original source... Go to PubMed...
    55. Viola H., Wolfman C., Destein M.L., Wasowski C., Pena C., Medina J.H., Paladini A.C.: Isolation of pharmacologically active benzodiazepine receptor ligands from Tilia tomentosa. J. Ethnopharmacol. 44: 47-53, 1994. Go to original source... Go to PubMed...
    56. Volz H.P.: Controlled clinical trials of hypericum extracts in depressed patients - an overview. Pharmacopsychiatry.30, Suppl 2: 72-76, 1997. Go to original source... Go to PubMed...
    57. Wall M.E. Wani M.C., Hughes TJ., Taylor H.: Plant antimutagens. In: Kuroda Y., Shankel D.B., Waters M.D.: Antimutagenesis and anticarconogenesis mechanism. II. Plenum Publ. Corp, New York 1990, p. 61-78. Go to original source...
    58. Wu Q.L., Wang S.P., Du L.J., Yang J.S, Xiao PG: Xanthones from Hypericum japonicum and H. henryi. Phytochemistry. 49:1395-1402, 1998. Go to original source... Go to PubMed...

    Return to the content