Hypericin- A Napthodianthrone from Hypericum perforatum

Dr Amrit Pal Singh, MD (Alternative Medicine)

Medical Executive. Super Specialty Division, India ĖSwift Ltd

Address for correspondence:

Dr Amrit Pal Singh

House No: 2101 Phase-7

Mohali -160062, India

 

 

Keywords: Hypericin/Hypericum perforatum/extract.

Introduction

Hypericin is a substance isolated from a medicinal herb Hypericum perforatum, commonly known as St.Johnís Wort.1 Hypericin belongs to group of compound known as napthodianthrones. 2 Hypericin is a secondary plant metabolite of St.Johnís 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.

 

Chemistry

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 

 

Pharmacological activity

 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

 

B. Anti viral activity

In animal models hypericin has shown to prevent replication of encapsulated viruses.15

 

C. Anti-inflammatory activity 

Besides these activities, hypericin has shown anti-inflammatory activity also. It inhibits release of leukotrienes.16

 

D. Photosensitizing activity

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.

  

Pharmacokinetics 

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

Standard

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.

 

References

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 Australia. Phytochemistry 1991; 30:475-478.

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.Johnís 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 Frankfurt/Main, FRG.AAI Deustschland Gmbh & Co. KG, Neu-Ulm, FRG.

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 United States and Canada. Prentice-Hall, Inc., Englewood Cliffs, NJ. 626 p.

9. Raffa RB: Screen of receptor and uptake-site activity of hypericin component of ST. JOHN'S WORT reveals sigma receptor binding. Life Sci 1998; 62(16): PL265-70.

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, University of Frankfurt, Frankfurt/M., Germany. Pharmacopsychiatry 2001 Jul; 34 Suppl 1:S98-102.

14. Eckert GP, Muller WE. Effects of hyperforin on the fluidity of brain membranes. Department of Pharmacology, Biocenter Niederursel, University of Frankfurt, Frankfurt/Main, Germany. Pharmacopsychiatry 2001 Jul; 34 Suppl 1:S22-5.

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 USA 1989; 85:5230-5234.

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; 3:19-28.

17. Schey et al. Photo-oxidation of lens alpha-crystallin by hypericin (active ingredient in St. Johnís Wort). Photochemistry and Photobiology 72(2): 200-3. Aug 2000.

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).

 

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