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Keywords: Hypericin/Hypericum perforatum/extract.
Hypericin is a substance isolated
from a medicinal herb Hypericum perforatum,
commonly known as St.John’s Wort.1 Hypericin belongs to group of compound known as napthodianthrones. 2 Hypericin
is a secondary plant metabolite of St.John’s Wort and the amount of Hypericin
strongly depend upon the source of the plant material. 3,4 Initially
Hypericin was considered to be the antidepressant
principle of Hypericum perforatum,
but according to latest research Hyperforin has
emerged as antidepressant principle of the herb.5 Hypericin is used as standard for identification of genuine
plant material and thus has importance from quality control point of view. The
standardization of Hypericum perforatum is
now based on both hypericin and hyperforin
content. The herb must contain 0.3% of hypericin.
Hypericin is a red dye that forms salt known as hypercinates with sodium and potassium. It is soluble in
ethanol, methanol, pyridine, acetone, ethyl acetate, butanone, aqueous alkali
solutions, but insoluble in water and methylene
chloride. 7 Hypericin produces singlet oxygen and other excited state
intermediates that indicate it should be a very efficient phototoxic agent in
the eye. It absorbs in the UV and visible range, which means it, can
potentially damage both the lens and the retina. Hypericum perforatum is known to cause
photosensitivity.8
A.
Antidepressant activity
In
experiments, hypericin has shown weak monoamine oxidase inhibiting activity. It was find that hypercin in a dose of 0.35 mg has effects similar to imipramine. 9 In other experiment hypericin in a dose of 9-28 mg/kg showed activity similar to bupropion.
10 Hyperforin in comparison inhibits the neuronal uptake of serotonin, norepinephrine and dopamine antidepressants, but also
inhibits GABA and L-glutamate uptake.11 Research on hyperforin has been intensified and most of the published
studies strongly indicate hyperforin to be the
antidepressant constituent of Hypericum perforatum. 12,13,14
In animal models hypericin has shown to prevent
replication of encapsulated viruses.15
Besides these activities, hypericin has shown
anti-inflammatory activity also. It inhibits release of leukotrienes.16
Hypericin is known to cause phototoxicity. Lens alpha-crystallin, isolated
from calf lenses, was irradiated in the presence of hypericin
and in the presence and absence of light.17 Hypericin-induced
photosensitized photo-polymerization was assessed by sodium dodecylsulfate-polyacrylamide
gel electrophoresis. Further analysis of the oxidative changes occurring in
alpha-crystallin using mass spectrometry showed
specific oxidation of methionine, tryptophan
and histidine residues, which increased with
irradiation time. Hypericin did not damage the lens
protein in the dark. Damage to alpha-crystallin could
undermine the integrity of the lens directly by protein denaturation
and indirectly by disturbing chaperone function. From the study it was
concluded that in the presence of light, hypericin
could induce changes in lens protein that could lead to the formation of
cataracts. Appropriate precautions should be taken to protect the eye from
intense sunlight while the patient is on Hypericum perforatum therapy.
In a
study, healthy volunteers were given hypercin orally
in a dose of 900, 1800 and 3600 mg and blood samples were analyzed.The
maximum plasma concentration was found after 6 hours.18
The hypericin content of Hypericum perforatum is determined by using
spectroscopic method utilizing the visible absorption characteristics of hypericin in methyl alcohol.19, 20 In atypical chromatogram of standardized Hypericum perforatum extract, absorbance occurs at
588nm and the peak.The peak at 10.67 min is
characteristic of Hypericin.
1. Hoelzl
J & Ostrowski E: Analysis of the essential
compounds of Hypericum perforatum.
Planta Med 1986; 6:531.
2. Southwell
IA & Campbell MH: Hypericin content variation in Hypericum perforatum in
3. Suzuki 0, Katsumata Y, Oya M. Inhibition of monoamine oxidase
by hypericin. Planta Med
1984; 50:272-4.
4. Wagner H, Bladt
S. Pharmaceutical quality of Hypericum extracts.
Journal of Geriatrics, Psychiatry and Neurology 1994; 7: S65-S68.
5. Cellarova,
E. et al., 1995. XIV Hypericum perforatum
(St.John’s Wort): In vitro
culture and the production of hypericin and other
secondary metabolites. Biotechnology in Agriculture and Forestry, 33:261-275.
6. Westerhoff,
K, Kaunzinger, A, Wurglics,
M, BaumeisterA, Determination of Hyperforine
and Total Hypericine Content in Hypericum
Extract Containing Herbal Medicinal Products. Institut
fur Pharamazeutische Chemie
der Univversitat
7. Michael
P. Balogh, Jeanne B.Li.
HPLC Analysis of Hypericin with Photodiode-Array and
MS Detection: The Advantage of Multispectral
Techniques.
8. Kingsbury,
J.M., 1964. Poisonous plants of the
9. Raffa RB: Screen of receptor and uptake-site activity of hypericin component of
10. Nahrstedt, A. and Butterweck V.
1997. Biologically active and other chemical constituents of Hypericum perforatum L. Pharmacopsyciat, 30: 129-134.
11.Chatterjee, S.S.,
Bhattacharya, S.K., Singer, A., Wonnemann, M., and
Mueller, W.E. 1998 Hyperforin Inhibits Synaptosomal Uptake of Neurotransmitters In Vitro and Shows
Antidepressant Activity In Vivo. Pharmazie, 53: 9.
12. Chatterjee SS, Bhattacharya SK, Wonnemann
M, Singer A, Muller WE. Hyperforin as a possible
antidepressant component of Hypericum extracts. Life Sciences 1998; 63: 499-510.
13. Muller
WE, Singer A, Wonnemann M. Hyperforin--antidepressant
activity by a novel mechanism of action. Department of
Pharmacology,
14. Eckert GP, Muller WE. Effects of hyperforin
on the fluidity of brain membranes. Department of
Pharmacology, Biocenter Niederursel,
15. Meruelo D, Lavie D & Lavie E: Therapeutic agents with dramatic antiretroviral
activity and little toxicity at effective doses. Aromatic
polycyclic diones hypericin
and pseudohypericin. Proc Natl Acad Sci
16. Panossian AG, Gabrielian E, Manvelian V et al: Immunosuppressive effects of hypericin on stimulated human leukocytes: inhibition of the
arachidonic acid release, leukotriene
B4 and interleukin-1 alpha production, and activation of nitric oxide
formation. Phytomedicine 1996;
17. Schey et al. Photo-oxidation of lens alpha-crystallin by hypericin (active
ingredient in
18. Stock S & Holz
J: Pharmacokinetic test of (14 C)-labeled hypericin
and pseudohypericin from Hypericum
perforatum and serum kinetics of hypericin
in man. Planta Med 1991; 57 Suppl
2: A61-62.
19. Butterwreck
Vet al., Isolation by MLCCC and NMR spectroscopy of hypericin,
pseudohypericin and I3, II8-biapigenin from Hypericum perforatum. In:
PM 62, abstracts of the 44th Ann Congress
of GA, 119. 1996.
20. G. Piperopolous,
R. Lotz, A.Wixforth, T.Schmierer and K.P.Zeller J,
Chromator.B695, 309-316. (1997).