SUMMARY
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.
KEY WORDS
Hypericum perforatum; antidepressant; pharmacology; toxicology
REFERENCES
Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray
SD, Kuszynski CA, Joshi SS, Pruess HG:
Free radicals and grape seed proanthocyanidin
extract: importance in human health and disease
prevention. Toxicology 148:187-197, 2000.
Baureithel KH, Buter KB, 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.
Bennet GJ, Lee HH: Xanthones from the
Guttiferae. Phytochemistry 28:967-998, 1989.
Bennett DA Jr., Phun L, Polk JF, Voglino SA,
Zlotnik V, Raffa RB: Neuropharmacology of
St. John's Wort (Hypericum). Ann
Pharmacother 32:1201-1208, 1989.
Berghoefer R, Hoelzl J: Biflavonoids in Hypericum
perforatum; Part 1. Isolation of I3,II8-biapigenin.
Planta Med 53:216-217, 1987.
Berghoefer R, Hoelzl J: Isolation of I3',II8-biapigenin (amentoflavone) from Hypericum
perforatum. Planta Med 55: 91, 1989.
Bladt S, Wagner H: Inhibition of MAO by
fractions and constituents of hypericum extract.
J Geriatr Psychiatry Neurol 7, Suppl 1:S57-59, 1994.
Brantner A, Kartnig T, Quehenberger F:
Vergleichende phytochemische Untersuchungen
an Hypericum perforatum L. und Hypericum
maculatum Crantz. Scient Pharm 62:261-276, 1994.
Brockman H: Photodynamisch wirksame
Pflanzenfarbstoffe. In: Zechmeister L: Fortschr
Chem Org Naturstoffe, Bd. XIV, Springer
Verlag, Wien 1957.
Brockmoller J, Reum T, Bauer S, Kerb R,
Hubner W-D, Roots I: Hypericin and
pseudohypericin: Pharmacokinetics and effects
on photosensitivity in humans.
Pharmacopsychiatry 30, Suppl:94-101, 1997.
Cardona L, Fernandez I, Pedro JR, Serrano A:
Xanthones from Hypericum reflexum.
Phytochemistry 29:3003-3006, 1990.
Chatterjee SS, Bhattacharya SK, Wonnemann M,
Singer A,. Muller WE: Hyperforin as a possible
antidepressant component of hypericum extracts.
Life Sci 63:499-510, 1998a.
Chassevent F: Chlorogenic acid, physiological and
pharmacological activity (Article in French) Ann
Nutr Aliment 23, Suppl 1: 1-14, 1969.
Chatterjee SS, Biber A, Weibezahn C:
Stimulation of glutamate, aspartate and gammaaminobutyric
acid release from synaptosomes by
hyperforin. Pharmacopsychiatry 34, Suppl 1:S11-S19, 2001.
Chatterjee SS, Noldner M, Koch E, Erdelmeier
C: Antidepressant activity of hypericum
perforatum and hyperforin: the neglected
possibility. Pharmacopsychiatry 31, Suppl. 1:7-15, 1998b.
Cellarova E, Daxnerova Z, Kimakova K,
Haluskova J: The variability of the hypericin
contents in the regenerants of Hypericum
perforatum. Act Biotechnol 14:267-274, 1994.
De Bruyne T, Pieters L, Witvrouw M, De Clercq
E, Vanden Berghe D, Vlietinck AJ: Biological
evaluation of proanthocyanidin dimers and
related polyphenols. J Nat Prod 62:954-958, 1999.
Falk H, Schmitzberger W: On the nature of
"soluble" hypericin in Hypericum species.
Monatshefte Chem. 123:731-739, 1992.
Ghelardini C, Galeotti N, Mazzanti G: Local
anaesthetic activity of monoterpenes and
phenylpropanes of essential oils. Planta Med 67:564-566, 2001.
Giese A: Hypericism. Photochem Photobiol Rev
5:229-255, 1980.
Haeberlain H, Tschiersch K-P, SchAfer HL:
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.
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.
Hegnauer R: Chemotaxonomie der Pflanzen, Vol.
VII. BirkHAuser Verlag, Berlin 1989.
Jurgenliemk G, Nahrstedt A: Phenolic compounds
from Hypericum perforatum. Planta Med 68:88-91, 2002.
Kim HK, Son KH, Chang HW, Kang SS, Kim
HP: Amentoflavone, a plant biflavone: a new
potential anti-inflammatory agent. Arch Pharm
Res 21:406-410, 1998.
Klusa V, Germane S, Noldner M, Chatterjee SS:
Hypericum extract and hyperforin: memory-enhancing
properties in rodents. Pharmacopsychiatry, Suppl 1:S61-S69, 2001.
Koch E, Chatterjee SS: Hyperforin stimulates
intracellular calcium mobilisation and enhances
extracellular acidification in DDT1-MF2 smooth
muscle cells. Pharmacopsychiatry 34, Suppl 1:S70-S73, 2001.
Maisenbacher P, Kovar K-A: Adhyperforin: A
homologue of hyperforin from Hypericum
perforatum. Planta Med 58:291-293, 1992.
MacGregor JT: Genetic toxicology of dietary
flavonoids. Prog Clin Biol Res 206:33-43, 1986.
Medina JH, Viola H, Wolfman C, Marder M,
Wasowski C, Calvo D, Paladini AC: Overview
- flavonoids: a new family of benzodiazepine
receptor ligands. Neurochem Res 22:419-425, 1997.
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.
Morales MA, Lozoya X: Calcium-antagonist
effects of quercetin on aortic smooth muscle.
Planta Med 60:313-317, 1994.
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.
Muller WE, Singer A, Wonnemann M:
Hyperforin - antidepressant activity by a novel
mechanism of action. Pharmacopsychiatry 34,
Suppl 1:S98-S102, 2001.
Nahrstedt A, Butterweck V: Biologically active
and other chemical constituents of the herb of
Hypericum perforatum L. Pharmacopsychiatry
30, Suppl 2:129-134, 1997.
Nielsen H, Arends P: Structure of the xanthone
lignoid kielcorin. Phytochemistry 17:2040-2041, 1978.
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.
Niesel S, Schilcher H: Vergleich der Freisetzung
von Hypericin und Pseudohypericin in
Abhangigkeit verschiedener
Extraktionsbedingungen. Arch Pharm 323:755, 1990.
Peebles KA, Baker RK, Kurz EU, Schneider
BJ, Kroll DJ: Catalytic inhibition of human
DNA topoisomerase IIalpha by hypericin, a
naphthodianthrone from St. John's wort
(Hypericum perforatum). Biochem Pharmaco
62:1059-1070, 2001.
Pietta P, Gardana C, Pietta A: Comparative
evaluation of St. John's wort from different
Italian regions. Farmaco 56:491-496, 2001.
Poginski B, Westendorf J, Prosenc N, Kuppe M,
Marquard H: Johannis kraut (Hypericum
perforatum L.). Genotoxicitat bedingt durch den
Quercetingehalt. Dtsch Apoth Ztg 128:1364-1366, 1988.
Raffa RB: 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.
Rueff J, Laires A, Borba H, Chaveca T, Gomes
MI, 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.
Scalbert A: Antimicrobial properties of tannins.
Phytochemistry 30:3875-3883, 1991.
Scalbert A, Deprez S, Mila I, Albrecht AM,
Huneau JF, Rabot S: Proanthocyanidins and
human health: systemic effects and local effects
in the gut. Biofactors 13:115-120, 2000.
Schempp CM, Kirkin V, Simon-Haarhaus B,
Kersten A, Kiss J, Termeer CC, Gilb B,
Kaufmann T, Borner C, Sleeman JP, Simon
JC: 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.
Scholz E: Pflanzliche Gerbstoffe. Dtsch Apoth
Ztg 134:3167-3179, 1994.
Sparenberg B, Demisch BL, Hoelzl J:
Untersuchungen uber antidepressive Wirkstoffe
von Johanniskraut. Phar Ztg Wiss 6/138:50-54, 1993.
Stavric B: Quercetin in our diet: From potent
mutagen to probable anticarcinogen. Clin
Biochem 27:245-248, 1994.
Stock S, Hoelzl J: Ist Johanniskraut phototoxisch?
Med Mod Pharm 14:304-306, 1991.
Takahashi I, Nakanishi S, Kobayashi ., 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.
Takhtajan A: Evolution und Ausbreitung der
Blutenpflanzen. G. Fischer, Stutgart 1973.
Thiede HM, Walper A: Inhibition of MAO and
COMT by hypericum extracts and hypericin. J
Geriatr Psychiatry Neurol 7, Suppl 1:S54-S56, 1994.
Vandenbogaerde AL. Kamuhabwa A, Delaey E,
Himpens BE, Merlevede WJ, de Witte PA:
Photocytotoxic effect of pseudohypericin versus
hypericin. J Photochem Photobiol B45:87-94, 1998.
Viola H, Wolfman C, Destein ML, Wasowski C,
Pena C, Medina JH, Paladini AC: Isolation
of pharmacologically active benzodiazepine
receptor ligands from Tilia tomentosa.
J Ethnopharmacol 44:47-53, 1994.
Volz HP: Controlled clinical trials of hypericum
extracts in depressed patients - an overview.
Pharmacopsychiatry 30, Suppl 2:72-76, 1997.
Wall ME, Wani MC, Hughes TJ, Taylor H:
Plant antimutagens. In: Kuroda Y, Shankel
DB, Waters MD: Antimutagenesis and
anticarconogenesis mechanism. II. Plenum Publ.
Corp, New York 1990, p. 61-78.
Wu QL, Wang SP, Du LJ, Yang JS, Xiao PG:
Xanthones from Hypericum japonicum and H.
henryi. Phytochemistry 49:1395-1402, 1998.
|
CITED
Cirak C, Radusiene J, Stanius Z, Camas N, Caliskan O, Odabas MS. Secondary metabolites of Hypericum orientale L. growing in Turkey: variation among populations and plant parts. Acta Physiol Plantarum. 34: 1313-1320, 2012.
Mendoza-Urbina FA, Gutierrez-Miceli FA, Ayora-Talavera TR, Rincon-Rosales R. Scarification of seeds of Hypericum silenoides Juss. and its effect on germination. Gayana Botanica. 69: 1-6, 2012.
Camas N, Radusiene J, Stanius Z, Caliskan O, Cirak C. Secondary Metabolites of Hypericum leptophyllum Hochst., an Endemic Turkish Species. Sci World J. Art No: 501027, 2012.
Assadi A, Zarrindast MR, Jouyban A, Samini M. Comparing of the Effects of Hypericin and Synthetic Antidepressants on the Expression of Morphine-Induced Conditioned Place Preference. Iran J Pharm Res. 10: 619-626, 2011.
Bhatia A, Arora S, Singh B, Kaur G, Nagpal A. Anticancer potential of Himalayan plants. Phytochem Rev. 10: 309-323, 2011.
Kizil G, Kizil M, Ceken B, Yavuz M, Demir H. Protective ability of ethanol extracts of Hypericum scabrum L. and Hypericum retusum Aucher against the protein oxidation and DNA damage. Int J Food Prop. 14: 926-940, 2011.
Anyzewska M, Kowalczuk A, Lozak A, Jablczynska R, Fijalek Z. Determination of total hypericins in St. John's wort and herbal medicinal product. ActaPol Pharm. 67: 586-592, 2010.
Tonk FA, Giachino RRA, Sonmez C, Yuce S, Bayram E, Telci I, Furan MA. Characterization of various Hypericum perforatum clones by hypericin and RAPD analyses. Int J Agric Biol. 13: 31-37, 2011.
Bejaoui A, Boulila A, Messaoud C, Rejeb MN, Boussaid M. Genetic diversity and population structure of Hypericum humifusum L. (Hypericacae) in Tunisia: Implications for conservation. Plant Biosystems. 144: 592-601, 2010.
Oluk EA, Orhan S, Karakas O, Cakir A, Gonuz A. High efficiency indirect shoot regeneration and hypericin content in embryogenic callus of Hypericum triquetrifolium Turra. Afr J Biotechnol. 9: 2229-2233, 2010.
Caccia S, Gobbi M. St. John's Wort Components and the Brain: Uptake, Concentrations Reached and the Mechanisms Underlying Pharmacological Effects. Curr Drug Met. 10: 1055-1065, 2009.
Odabas MS, Radusiene J, Cirak C, Camas N. Models of estimation of the content of secondary metabolites in some Hypericum species. Pharm Biol. 47: 1117-1122, 2009.
Geng XT, Ren P, Pi GP, Shi RF, Yuan Z, Wang CH. High selective purification of flavonoids from natural plants based on polymeric adsorbent with hydrogen-bonding interaction. J Chromatogr A. 1216: 8331-8338, 2009.
Ayan AK, Radusiene J, Cirak C, Ivanauskas L, Janulis V. Secondary metabolites of Hypericum scabrum and Hypericum bupleuroides. Pharm Biol. 47: 847-853, 2009.
Cirak C, Ivanauskas L, Janulis V, Radusiene J. Chemical constituents of Hypericum adenotrichum Spach, an endemic Turkish species. Nat Prod Research. 23: 1189-1195, 2009.
Toker Z. Variation of total hypericin, phenolic and flavonoid compounds in Hypericum triquetrifolium during its phenological cycle. Pharm Biol. 47: 285-288, 2009.
Mccue PP, Phang JM. Identification of Human Intracellular Targets of the Medicinal Herb St. John's Wort by Chemical-Genetic Profiling in Yeast. J Agric Food Chem. 56: 11011-11017, 2008.
Odabas MS, Radusiene J, Cirak C, Camas N. Prediction models for the phenolic contents in some Hypericum species from Turkey. Asian J Chem. 20: 4792-4802, 2008.
Kacar O, Goksu E, Azkan N. Effects of morphogenetic and diurnal variability on the hypericin content in St. John's Wort (Hypericum perforatum L.). African J Biotechnol. 7: 2163-2168, 2008.
Cirak C, Radusiene J, Camas N. Pseudohypericin and hyperforin in two Turkish Hypericum species: Variation among plant parts and phenological stages. Biochem Syst Ecol. 36: 377-382, 2008.
Ayan AK, Cirak C. Hypericin and pseudohypericin contents in some Hypericum species growing in Turkey. Pharm Biol. 46: 288-291, 2008.
Cirak C, Radusiene J, Arslan B. Variation of bioactive substances in Hypericum montbretii during plant growth. Nat Prod Res. 22: 246-252, 2008.
Cirak C, Radusiene J, Janullis V, Lvanauskas L, Arslan B. Chemical constituents of some Hypericum species growing in Turkey. J Plant Biol. 50: 632-635, 2007.
Cirak C, Radusiene J. Variation of hyperforin in Hypericum monthretii during its phenological cycle. Nat Prod Res. 21: 1151-1156, 2007.
Jung HJ, Park K, Lee IS, Kim HS, Yeo SH, Woo ER, Lee DG. S-Phase accumulation of Candida albicans by anticandidal effect of amentoflavone isolated from Selaginella tamariscina. Biol Pharm Bull. 30: 1969-1971, 2007.
Cirak C, Radusiene J, Ivanauskas L, Janulis V. Variation of bioactive secondary metabolites in Hypericum origanifolium during its phenological cycle. Acta Physiologiae Plantarum. 29: 197-203, 2007.
Cirak C, Radusiene J, Janulis V, Ivanauskas L. Secondary metabolites in Hypericum perfoliatum: variation among plant parts and phenological stages. Bot Helv. 117: 29-36, 2007.
Cirak C, Radugien J, Karabuk B, Janulis V. Variation of bioactive substances and morphological traits in Hypericum perforatum populations from Northern Turkey. Biochem Syst Ecol. 35: 403-409, 2007.
Sosa S, Pace R, Bornancin A, Morazzoni P, Riva A, Tubaro A, Della Loggia R. Topical anti-inflammatory activity of extracts and compounds from Hypericum perforatum L. J Pharm Pharmacol. 59: 703-709, 2007.
Cirak C, Radusiene J, Karabuk B, Janulis V, Ivanauskas L. Variation of bioactive compounds in Hypericum perforatum growing in turkey during its phenological cycle. J Integrat Plant Biol. 49: 615-620, 2007.
Tsaplev YB, Vasil'ev RF. The nature of chemiluminescence of the photolyzed anthrone solutions. Russ J Phys Chem. 80: 795-798, 2006.
Cirak C, Ayan AK, Kevseroglu K. Direct and indirect regeneration of plants from internodal and leaf explants of Hypericum bupleuroides gris. J Plant Biol. 50: 4-28, 2007.
Ayan AK, Cirak C, Yanar O. Variations in total phenolics during ontogenetic, morphogenetic, and diurnal cycles in Hypericum species from Turkey. J Plant Biol. 49: 432-439, 2006.
Cirak C. Hypericin in Hypericum lydium Boiss. growing in Turkey. Biochem Syst Ecol. 34: 897-899, 2006.
Cirak C, Saglam B, Ayan AK, Kevseroglu K. Morphogenetic and diurnal variation of hypericin in some Hypericum species from Turkey during the course of ontogenesis. Biochem Syst Ecol. 34: 1-13, 2006.
Ang CYW, Hu LH, Heinze TM, Cui YY, Freeman JP, Kozak K, Luo WH. Instability of St. John's Wort (Hypericum perforatum L.) and degradation of hyperforin in aqueous solutions and functional beverage. J Agric Food Chem. 52: 6156-6164, 2004.
|
