RSS-Feed abonnieren
DOI: 10.1055/s-2003-38495
Plasma Levels of Hypericin in Presence of Procyanidin B2 and Hyperoside: A Pharmacokinetic Study in Rats
Publikationsverlauf
Received: November 22, 2002
Accepted: January 2, 2003
Publikationsdatum:
04. April 2003 (online)
![](https://www.thieme-connect.de/media/plantamedica/200303/lookinside/thumbnails/10.1055-s-2003-38495-1.jpg)
Abstract
The biological evaluation of hypericin in various test models is hampered by its poor water solubility. In former studies we have shown that the water solubility of hypericin was remarkably enhanced in the presence of the procyanidins or flavonol glycosides of Hypericum extract. The present pharmacokinetic study was designed to find out whether the improved water solubility in the presence of procyanidin B2 or hyperoside is correlated to increased plasma levels of hypericin. Plasma levels of hypericin in rats in the presence and absence of procyanidin B2 or hyperoside were determined by reversed phase HPLC using fluorimetric detection. Both compounds increased the oral bioavailability of hypericin by ca. 58 % (B2) and 34 % (hyperoside). Procyanidin B2 and hyperoside had a different influence on the plasma kinetics of hypericin; median maximal plasma levels of hypericin were detected after 360 min (Cmax: 8.6 ng/mL) for B2, and after 150 min (Cmax: 8.8 ng/mL) for hyperoside. It can be speculated that, when administered together with these compounds, a significant accumulation of hypericin in rat plasma in the presence of both polyphenols might be responsible for the observed increased in vivo activity.
References
- 1 Nahrstedt A, Butterweck V. Biologically active and other chemical constituents of the herb of Hypericum perforatum L. Pharmacopsychiatry. 1997; 30 129-34
-
2 Nahrstedt A. Antidepressant constituents of Hypericum perforatum
. In: Chrubasik S, Roufogalis BD (eds)
Herbal medicinal products for the treatment of pain . Southern Cross University Press Lismore; 2000: pp. 144-53 - 3 Chatterjee S, Bhattacharya S, Wonnemann M, Singer A, Müller W E. Hyperforin as a possible antidepressant component of Hypericum extracts. Life Sci. 1998; 63 499-510
- 4 Wonnemann M, Singer A, Siebert B, Müller W E. Evaluation of synaptosomal uptake inhibition of most relevant constituents of St. John's wort. Pharmacopsychiatry. 2001; 41 S148-51
- 5 Butterweck V, Petereit F, Winterhoff H, Nahrstedt A. Solubilized hypericin and pseudohypericin from Hypericum perforatum exert antidepressant activity in the forced swimming test. Planta Med. 1998; 64 291-4
- 6 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; 6 547-64
- 7 Calapai G, Crupi A, Firenzuoli F, Costantino G, Inferrera G, Campo G, Caputi A. 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; 51 723-8
- 8 Butterweck V, Jürgenliemk G, Nahrstedt A, Winterhoff H. Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test. Planta Med. 2000; 66 3-6
- 9 Jürgenliemk G, Nahrstedt A. Dissolution, solubility and cooperativity of phenolic compounds from Hypericum perforatum L. in aqueous systems. Pharmazie 2003; in press
- 10 Schilcher H. Standardisierung, Kontrolle und Qualitätsprüfung von nichttoxischen flüssigen Arzneipflanzenzubereitungen. Arzneimittelstandardisierung. 1965; 6 649-55
- 11 Menßen H G. Standardisierte Arzneien aus Heilpflanzen und ihre Bedeutung für die moderne Phytotherapie. Therapiewoche. 1968; 18 1432-3
- 12 Eder M, Mehnert W. Pflanzliche Begleitstoffe - wertvolle Hilfsstoffe oder überflüssiger Ballast?. Pharm Unserer Zeit. 2000; 29 377-84
- 13 Yata N, Sugihara N, Yamajo R, Murakami T, Higashi Y, Kimata H, Nakayama K, Kuzuki T, Tanaka O. Enhanced small intestinal absorption of β-lactam antibiotics in rats in presence of monodesmosides from pericaps of Sapindus mukurossi (Ennmei-hi). J Pharmacobio-Dyn. 1986; 9 211-7
- 14 Hänsel R, Sticher O, Steinegger E. Pharmakognosie - Phytopharmazie. Springer-Verlag Berlin, Heidelberg; 1999
- 15 Keledjian J, Duffield P H, Jamieson D D, Lidgard R O, Duffield A M. Uptake into mouse brain of four compounds present in the psychoactive beverage Kava. J Pharm Sci. 1988; 77 1003-6
- 16 Biber A, Nöldner M, Schlegelmilch R. Development of a formulation of Kava-Kava extract through pharmacokinetic experiments in animals. Naunyn Schmiedeberg's Arch Pharmacol. 1992; 345 R24
- 17 Vinson J A, Bose P. Comparative bioavailability to humans of ascorbic acid alone or in a citrus extract. Am J Clin Nutr. 1988; 48 601-4
- 18 List P H, Schmid W, Weil E. Reinsubstanz oder galenische Zubereitung. Arzneim Forsch. 1969; 19 181-5
- 19 Ploss O, Petereit F, Nahrstedt A. Procyanidins from the herb of Hypericum perforatum . Pharmazie. 2001; 56 509-11
- 20 Kerb R, Brockmöller J, Staffeldt B, Ploch M, Roots I. Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin. Antimicrobial Agents and Chemotherapy. 1996; 40 2087-93
- 21 Perrier D, Gibaldi M. General derivation of the equation for time to reach a certain fraction of steady state. J Pharm Sci. 1982; 71 474-5
Dr. Veronika Butterweck
Institute of Pharmacology and Toxicology
Universitätsklinikum Münster
Domagkstr. 12
48149 Münster
Germany
eMail: butterv@uni-muenster.de