Hypericum perforatum Subspecies Angustifolium shows a Protective Activity on the Consequences of Unavoidable Stress Exposure at Lower Doses than Hypericum perforatum Perforatum

M. Usai; B. Leggio; S. Grappi; G. Nanni; C. Gambarana; P. Tolu; D. Giachetti; M. G. De Montis

doi:10.1055/s-2003-45114

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2003; 36(6): 283-287
DOI: 10.1055/s-2003-45114

Original Paper

Hypericum perforatum Subspecies Angustifolium shows a Protective Activity on the Consequences of Unavoidable Stress Exposure at Lower Doses than Hypericum perforatum Perforatum

M. Usai¹ , B. Leggio² , S. Grappi² , G. Nanni² , C. Gambarana² , P. Tolu² , D. Giachetti³ , M. G. De Montis^1, ²

¹Department of Scienze del Farmaco, University of Sassari, Sassari, Italy
²Department of Neuroscience, University of Siena, Siena, Italy
³Department of Environmental Sciences, University of Siena, Siena, Italy

Abstract

Clinical studies have demonstrated that the antidepressant efficacy of Hypericum perforatum extract is comparable to that of classic antidepressants, such as imipramine. The role played by its components, particularly hypericin and hyperforin, has been examined in different experimental models of depression. The present study was carried out in order to verify the hypothesis that hyperforin is the main active antidepressant component. For this purpose we evaluated the activity of a dry extract from a subspecies of H. perforatum, H. perforatum spp. angustifolium, which has a higher hyperforin content than H. perforatum perforatum, in a series of experimental models of depression. The models used are based on the development of hyporeactivity to aversive stimuli induced by unavoidable stress exposure in rats. The extract of H. perforatum angustifolium presented an efficacy that was similar to that obtained with a treatment with imipramine or H. perforatum perforatum. Furthermore, in the models used the H. perforatum angustifolium extract was active at doses eight times lower than those necessary to produce a comparable activity with H. perforatum extract.

Full Text

References

1 Battacharya S -K, Chakrabarti A, Chatterjee S -S. Activity profiles of two hyperforin-containing hypericum extracts in behavioral models. Pharmacopsychiatry. 1998; 31 Suppl 2 22-29
2 Bombardelli E, Morazzoni P. Hypericum perforatum . Fitoterapia. 1995; 66 43-68
3 Brolis M, Gabetta B, Fuzzati N, Pace R, Panzeri F, Peterlongo F. Identification by high-performance liquid chromatography-diode array detection-mass spectrometry and quantification by high-performance liquid chromatography-UV absorbance detection of active constituents of Hypericum perforatum . J Cromatography A. 1998; 825 9-16
4 Butterweck V, Wall A, Liefländer-Wulf U, Winterhoff H, Nahrstedt A. Effects of the total extract and fractions of Hypericum perforatum in animal assays for antidepressant activity. Pharmacopsychiatry. 1997; 30 Suppl 2 117-124
5 Butterweck V, Petereit F, Whinterhoff H, Nahrstedt A. Solubilized hypericin and pseudohypericin from Hypericum perforatum exert antidepressant activity in the forced swimming test. Planta Med. 1998; 64 291-294
6 Butterweck V, Jurgenliemk G, Nahrstedt A, Vinterhoff H. Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test. Planta Med. 2000; 66 (1) 3-6
7 Butterweck V, Korte B, Winterhoff H. Pharmacological and endocrine effects of Hypericum perforatum and hypericin after repeated treatment. Pharmacopsychiatry. 2001; 34 Suppl 1 2-7
8 Cappelletti C. In: ” Botanica” sistematica , UTET Torino. 1965 2: 1372
9 Chatterjee S S, Koch E, Nöldner M, Biber A, Erdelmeier C. Hyperforin and hypericum extract: Interaction with some neurotransmitter systems. Phytomedicine. 1996; 3 Suppl 1 106
10 Chatterjee S S, Bhattacharya S K, Wonnemann M, Singer A, Müller W E. Hyperforin as a possible antidepressant component of hypericum extracts. Life Sci. 1998; 63 499-510
11 Chatterjee S S, Nöldner M, Koch C, Erdelmeier C. Antidepressant activity of Hypericum perforatum and hyperforin: the neglected possibility. Pharmacopsychiatry. 1998; 31 7-15
12 De Montis M G, Gambarana C, Ghiglieri O, Tagliamonte A. Reversal of stable behavioural modifications through NMDA receptor inhibition in rats. Behav Pharmacol. 1995; 6 562-567
13 De Smet P AGM, Nolen W A. St John's wort as an antidepressant. Br Med J. 1996; 313 241-242
14 Erdelmeier C AJ. Hyperforin, possibly the major non-nitrogenous secondary metabolite of Hypericum perforatum L. Pharmacopsychiatry. 1998; 31 2-6
15 Ernst E. St. John's wort, an antidepressant? A systematic, criteria-based review. Phytomedicine. 1995; 2 7-71
16 Gambarana C, Ghiglieri O, Taddei I, Tagliamonte A, De Montis M G. Imipramine and fluoxetine prevent the stress-induced escape deficits in rats through a distinct mechanism of action. Behav Pharmacol. 1995; 6 66-73
17 Gambarana C,Ghiglieri O, Tolu P, De Montis M .G, Giachetti D, Bombardelli E, Tagliamonte A. Efficacy of an Hypericum perforatum (St. John's wort) extract in preventing and reverting a condition of escape deficit in rats. Neuropsychopharmacol. 1999; 21 247-257
18 Gambarana C, Scheggi S, Tagliamonte A, Tolu P, De Montis M G. Animal models for the study of antidepressant activity. Brain Res Prot. 2001; 7 11-20
19 Gambarana C, Tolu P L, Masi F, Rinaldi M, Giachetti D, Morazzoni P, De Montis M G. A study of the antidepressant activity of Hypericum perforatum on animal models. Pharmacopsychiatry. 2001; 34 42-44
20 Gambarana C, Grappi S, Nanni G. Dose-dependent antidepressant activity of hyperforin in rats. Soc Neurosci Abs 2001 27: Program No. 975.12
21 Gobbi M, Mennini T. Is St John's wort a ”Prozac like” herbal antidepressant?. TIPS. 2001; 22 557-559
22 Hotopf M. St. John's wort is more effective than placebo for treating depressive disorders. Evidence-Based Med. 1999; 4 82
23 Laakmann G, Schüle C, Baghai T, Kieser M. St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry. 1998; 31 Suppl 54-59
24 Linde K, Ramirez G, Mulrow C. D, Pauls A, Weidenhammer W. Melchart D. St John's wort for depression-an overview and meta-analysis of randomised clinical trials. Br Med J. 1996; 313 253-258
25 Linde K, Mulrow C D. St John's wort for depression (Cochrane Review). In: The Cochrane Library. 2002 Issue 2 Oxford;
26 Müller W E, Rolli M, Schäfer C, Hafner U. Effects of hypericum extract (Li160) in biochemicals models of antidepressant activity. Pharmacopsychiatry. 1997; 30 Suppl 2 102-107
27 Müller W .E, Singer A, Wonnemann M, Hafner U, Rolli M, Schäfer C. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry. 1998; 31 Suppl 1 16-21
28 Müller V E, Singer A, Wonnemann M. Hyperforin - antidepressant activity by a novel mechanism of action. Pharmacopsychiatry. 2001; 34 Suppl 1 98-102
29 Nahrstedt A, Butterweck V. Biological activity and other chemical constituents of the herb of Hypericum perforatum L. Pharmacopsychiatry. 1997; 30 Suppl 2 129-134
30 Nöldner M. Antidepressive Effekte von Johanniskrauteextract und wichtigen Inhaltsstoffen im Tiermodell. In: Behandlung von depressiven Patienten in der täglichen Praxis Stellenwert von Joanniskrautextrakt. W. E. Müller & M. Gatspar (Hrsg) Neu- Isenburg; LinguaMed-Verlag GmbH 2001
31 Nöldner M, Schötz K. Rutin is essential for the antidepressant activity of Hypericum perforatum extracts in the forced swimming test. Planta Med. 2002; 68 577-580
32 Philipp M, Kohnen R, Hiller K -O. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. Br Med J. 1999; 319 1534-1539
33 Shelton R C, Keller M B, Gelenberg A, Dunner D L, Hirschfeld R, Thase M E, Russell J, Lydiard R B, Crits-Cristoph P, Gallop R, Todd L, Hellerstein D, Goodnick P, Keitner G, Stahl S M, Halbreich U. Effectiveness of St John's wort in major depression: a randomized controlled trial. JAMA. 2001; 285 1978-1986
34 Tekel'ova D, Repcak M, Zemkova E, Toth J. Quantitative changes of dianthrones, hyperforin and flavonoids content in the flower ontogenesis of Hypericum perforatum . Planta Med. 2000; 66 778-780
35 Volz H P. Controlled clinical trials of hypericum extracts in depressed patients - an overview. Pharmacopsychiatry. 1997; 30 Suppl 2 72-76
36 Wheatly D. Hypericum extract-potential in the treatment of depression. CNS Drugs. 1998; 9 431-440
37 Wonnemann M, Singer A, Müller WE Inhibition of synaptosomal uptake of 3H-L-glutamate and 3H-GABA by h yperforin, a major constituent of S t. John's Wort. The role of amiloride sensitive sodium conductive patways. Neuropsychopharmacology. 2000; 23 188-197

Dr. M. G. De Montis

Department of Neuroscience

University of Siena

via A. Moro 4

53100 Siena

Italy

Email: demontis@unisi.it

Phone: 390577234069

Fax: 390577234208