Hypericum perforatum - European Herbal & Traditional Medicine ...

Recently more investigation of especially hyperforin was carried out. It was found that themechanism of serotonin inhibition of hyperforin differed from classical antidepressants suchas selective serotonin reuptake inhibitors and tricyclic compounds. Hyperforin representsthe first substance with a known preclinical antidepressant profile that inhibits serotoninuptake by elevating [Na(+)](i) (31)Alcoholic extracts from Hypericum perforatum L. inhibit dopamine-beta-hydroxylase with anIC50 of 0.1 mu mol/l; pure commercial hypericin inhibits with an IC50 of 21 mu mol/l. (32)So the total extract is 210 times more active than hypericin. Enzymes involved in thesynthesis of dopamine from tyrosine, namely tyrosinase and tyrosine decarboxylase, werenot influenced by hypericin.Denke et al. conclude that hypericin very likely does not to represent the main activeprinciple mediating the desirable effects. Thus, standardisation of the drug is no longerbased on the quantification of total hypericin and since several years simply thedetermination of dry matter content is used instead. Additionally, the authors report on theinhibition of myeloperoxidase-catalyzed dimerization of enkephalins by Hypericum extracts(33)Finally, citing from a recent thorough study : extracts, fractions and constituents ofHypericum perforatum were investigated for in vitro receptor binding with various ligands torecombinant CNS receptors including several opioid, serotonin, estrogen, histamine, GABAA,neurokinin and metabotropic glutamate receptors. A lipophilic Hypericum fraction revealedrelatively potent inhibition to the binding of the mu-, delta- and kappa-opioid and the 5-HT6and 5-HT7 receptors. Moreover, Hypericum constituents such as the naphthodianthrones,hypericin and pseudohypericin, and the phloroglucinole hyperforin inhibited both binding tothe opioid and serotonin receptors in the lower micromolar range. Estrogen binding was50% inhibited by the biflavonoid I3,II8-biapigenin at micromolar concentration. Thelipophilic Hypericum fraction provided a less potent inhibition of the neurokinin-1 receptorbinding compared to the opioid and serotonin receptors. A total ethanolic Hypericum extractpotently inhibited GABAA binding at approximately 3 micrograms/ml . These results supportthe hypothesis that several active constituents of Hypericum might in a synergistic waycontribute to its antidepressant effect in the central nervous system (34)Concluding, it becomes evident, that MAO inhibiting activity as the explanation of the antidepressant mechanism in H. perforatum, has become a legend. Up to date the everintensified search for single compounds responsible for this mechanism can only contributeto the understanding, that H. perforatum extract works through the synergy of its manycomponents and through the synergy of several mechanisms of action.Conclusions and DiscussionFinally, the opinion to be argued here is, why an obviously active and proved clinicallyeffective herb or the herbal remedy of the whole herb, which does not show anyconsiderable side effects at usual doses can legally be categorised as 'prescription only'.The question arises, why any Medical council of any European government at all couldconsider such a registration, reviewing the scientific literature available.Regarding the anti-tumor activity of hypericin, probably a chemotherapeutic pharmacon canbe developed after due course and registered as such, but the different criteria applied tothe development, treatment strategy and side effect monitoring of an anti-cancer drug haveno relation to the usage and dosage of the herb in Medical herbalism and do not prohibit thefree availability of the herb for the general public.Standardisation to a specific compound already proved useless, the hopes of finding the onepotent compound which can be isolated or synthesised for the treatment of depressionlessen with every new study. A herb, a plant and its total extract cannot be patented. Itcomes to mind, reviewing the vast evidence of the herbs activity, safety as well as thenumerous studies trying to pinpoint one responsible compound, that despite all such efforts,it finally has to be accepted, that the herb and its total extract work by the synergy of manycompounds and mechanisms.The only logical explanation seems to be an economical interest of the pharmaceuticalindustry. However, such interests should have no place in European legislation where such

decisions should be subject to laws confined to the interest of public health.The laws andregulations of the European Union should ideally be just- and not according to theeconomical interest of the pharmaceutical industry- but to protect the citizen, their safetyand their rights.Herbal medicine is the medicine of the people, has been for thousands of years and still is inlesser economically developed areas. Millions of people in the world depend solely on ruraland herbal medicine.To be fortunate enough to be born in more developed countries is no reason to give up, oreven have ruled out by law, the possibility to use, sell and buy perfectly safe and efficientherbal medicines.Janina Soerensen holds an MSc in phytochemistry & naturalproducts, specialising in essential oil chemistry, distillation andanalysis. In 1994 Janina helped establish a distillation plant,producing essential oils from wildcrafted herbs/plants gathered on theisland of Crete. Janina is in the final stages of study at the Danish Schoolof Herbal Medicine.References1 Her Majesty's Stationary Office, The Statutory Instrument No 1830, 19972 Blumenthal M., Ed. 1998. The Complete German Commission E Monographs pp 214-215.American Botanical Council, Boston, Massachusetts USA3 Schilling, W. 1969. Die Gattung Hypericum unter besonderer Berucksichtigung vonHypericum perforatum L. Praparative Pharmazie 5(8):125-1344 Thomas-Bradley C.J. 1992. Hypericin as a potential photosensitizer in photodynamictherapy of cancer. Diss Abstr Int [B] () 52(9):47155 Garret, B.J. et al. 1982. Consumption of poisonous plants (Seneco jacobaea, Symphytumofficinale, Pteridium aquilinum, Hypericum perforatum) by rats: Chronic toxicity, mineralmetabolism and hepatic drug-metabolizing enzymes. Toxicology Letters 10:183-3886 Woelk H Burkard G Grunwald J 1994 . Benefits and risks of the hypericum extract LI 160:drug monitoring study with 3250 patients. J Geriatr Psychiatry Neurol 7 Suppl 1:S34-87 Ernst E, Rand JI, Barnes J, Stevinson C 1998. Adverse effects profile of the herbalantidepressant St. John's wort (Hypericum perforatum L Eur J Clin Pharmacol 54(8):589-948 Vonsover A Steinbeck KA Rudich et al 1996. HIV-1 virus load in the serum of AIDSpatients undergoing long term therapy with hypericin. Int Conf AIDS (Jul 7-12) 11(1):120(abstract no. Mo.B.1377)9 Steinbeck-Klose A Wernet P 1993. Successful long term treatment over 40 months of HIVpatientswith intravenous Hypericin. Int Conf AIDS (Jun 6-11) 9(1):470 (abstract no. PO-B26-2012.10 Wichtl, M.1994. Herbal Drugs and Phytopharmaceuticals. p. 274. CRC Press Boca Raton,Ann Harbour, London, Tokyo.11 Mcauliffe V et al. 1993. A phase I dose escalation study of synthetic hypericin in HIVinfected patients. Natl Conf Hum Retroviruses Relat Infect (1st) ( 12-16):15912 Schempp CM, Winghofer B, Langheinrich M, Schopf E, Simon JC . 1999. Hypericin levelsin human serum and interstitial skin blister fluid after oral single-dose and steady-stateadministration of Hypericum perforatum extract. Skin Pharmacol Appl Skin Physiol Sep-12(5):299-30413 Bernd A, Simon S, Ramirez Bosca A et al. 1999. Phototoxic effects of Hypericum extractin cultures of human keratinocytes compared with those of psoralen. Photochem Photobiol69(2):218-21.14 Vandenbogaerde AL et al. 1998. Photocytotoxic effect of pseudohypericin versushypericin . J Photochem Photobiol B 45(2-3):87-9415 Wichtl, 1994 as above16 Blumenthal, 1999 as above17. Weiss, R.E. Lehrbuch der Phytotherapie, 7 th Ed.pp. 366-369, 1990. Hippokrates Verlag.Stuttgart, Germany.18 British Herbal Pharmacopoeia 1983, p.116, 1995. British Herbal Medicine Association,Bournemouth UK.

19 Vandenbogaerde A. L., Els M., Vantieghem A.M. et al. 1998. Cytotoxicity andAntiproliferative Effect of Hypericin and Derivatives after Photosensitization. PhotochemPhotobiol 67: 11920 Roberts J. Ozone depletion - occular effect of enhanched UVB, 1998. Abstract, 27 thAnnual Meeting of the American Society for Photobiology, July 10-15, Washington D.C. USA.21 Thomas-Bradley C.J. 1992 as above22 Suzuki O. et al. 1984. Inhibition of monoamine oxidase by hypericin. Planta Med. 42:272-7423 Josey ES, Tackett RL 1999 St. John's wort: a new alternative for depression. Int J ClinPharmacol Ther 37(3):111-924 Bladt S and Wagner H. 1994. Inhibition of MAO by fractions and constituents ofhypericum extract. J Geriatr Psychiatry Neurol 7 Suppl 1:S57-925 Thiede HM, Walper A. 1994. Inhibition of MAO and COMT by hypericum extracts andhypericin. . J Geriatr Psychiatry Neurol 7 Suppl 1:S54-626 Perovic S and Muller WE. 1995. Pharmacological profile of hypericum extract. Effect onserotonin uptake by postsynaptic receptors. Arzneimittelforschung 45(11):1145-827 Chatterjee SS, Bhattacharya SK, Wonnemann M et al. 1998. Hyperforin as a possibleantidepressant component of hypericum extracts . Life Sci;63(6):499-51028 Muller WE, Singer A, Wonnemann M et al. 1998. Hyperforin represents theneurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry31 Suppl 1:16-2129 Baureithel KH, Buter KB, Engesser A, et al. 1997. Inhibition of benzodiazepine binding invitro by amentoflavone, a constituent of various species of Hypericum. Pharm Acta Helv72(3):153-730 Raffa RB 1998. Screen of receptor and uptake-site activity of hypericin component of St.John's wort reveals sigma receptor binding. Life Sci 1998;62(16):PL265-7031 Singer A, Wonnemann M, Muller WE 1999. Hyperforin, a major antidepressantconstituent of St. John's Wort, inhibits serotonin uptake by elevating free intracellular Na+1.J Pharmacol Exp Ther ;290(3):1363-832 Kleber E, Obry T, Hippeli S et al. 1999. Biochemical activities of extracts from Hypericumperforatum L. 1st Communication: inhibition of dopamine-beta-hydroxylase .Arzneimittelforschung ;49(2):106-933 Denke A, Schneider W, Elstner EF 1999. Biochemical activities of extracts fromHypericum perforatum L. 2nd Communication: inhibition of metenkephaline- and tyrosinedimerization.Arzneimittelforschung 49(2):109-1434 Simmen U, Burkard W, Berger K, et al. 1999. Extracts and constituents of Hypericumperforatum inhibit the binding of various ligands to recombinant receptors expressed withthe Semliki Forest virus system. J Recept Signal Transduct Res;19(1-4):59-74