PerspectivesAre you interested in submitting a Perspective Article? Be sure to read The Science Advisory Board's Editorial Guides for Perspective Articles. Click here. St. John’s Wort: Quality Control & Assurance Issues by Amrit Pal Singh, M.D. Hypericum perforatum (St.John’s Wort) is an important phyto-medicine used in the treatment of mild to moderate depression. Hypericum perforatum is one of the most extensively studied medicinal herbs. The use of this drug in treating diseases likes mania, anxiety and depression is well-documented in the texts of herbal medicines. Studies across the world have demonstrated that Hypericum perforatum is equivalent to synthetic antidepressants like Tricyclic antidepressants (Imipramine and Amitrptyline) and Selective Serotonin Reuptake Inhibitors (Fluoxetine and Sertraline) and has a good safety profile. Herbal medicines are becoming increasingly popular and more patients are visiting alternative medicine clinics. Under these circumstances it is imperative that people be made aware of the efficacy and safety of the drug. Given the increasing use of herbal medicines, efforts to identify the markers in these extracts have been ongoing. Markers are chemically defined constituents of a herbal drug, which are of interest for control purposes. They do not need to have any therapeutic activity. They serve to calculate the quantity of an herbal drug in the finished product provided that marker has been quantitatively determined in the herb. Consequently, many pharmaceutical companies have introduced standardized extracts of Hypericum perforatum for the treatment of depression. Standardized extracts are more scientific than crude drugs as they provide a definite percentage of the active constituent of the drug. Standardized extracts of Hypericum perforatum are available in the market and fortunately the labels do often show that the product is standardized. However, when these extracts are subjected to analytical tests for determination of active constituents, one of the constituents is often missing. Today, Hypericin 0.3% and Hyperforin 2.8% are considered to be the standards for a typical standardized Hypericum perforatum extracts. The majority of the extracts fail these testing parameters with hyperforin content varying from 2 % to 5 %, or it may be completely absent. Even though both of the constituents are considered equally important, the active ingredient of Hypericum perforatum is not yet known. Hypericin has shown weak antidepressant activity. It is being used as a marker compound and has a significant role to play in quality control. Initially Hypericin was shown as an antidepressant constituent of Hypericum perforatum. It weakly inhibits the enzyme Monoamine oxidase (MAO). In addition, Hypericin has been shown to have antiviral activity and will inhibit succinoxidase, NADPH-oxidase, tyrosinkinase and protein kinase C. Hypericin belongs to a group of compounds known as napthodianthrones, which constituent 0.1-0.15% of the dried herb. Hypericin content varies from 0.02-2.5%. Standardization to the marker compound is important for quality control and consistency. The companies usually take 0.3% Hypericin as standard. Hyperforin in animal studies has shown the ability to inhibit the uptake of neurotransmitters, and accumulated data strongly favors hyperforin as the possible antidepressant constituent of Hypericum perforatum. Hyperforin belong to acylphloroglucinol group of compounds and it is highly unstable compound. Hyperforin not only inhibits the neuronal uptake of serotonin, norepinephrine and dopamine like many other antidepressants, but it also inhibits GABA and L-glutamate uptake. The present scenario is such that companies have shifted to standardized extracts containing 2.8% of hyperforin. Some companies are marketing Hypericum perforatum extract standardized to contain 2.8 % of hyperforin and 0.3 % of hypericin. Another factor to consider is the part of the herb used in medicine. Hypericin and hyperforin exists in the flowering tops of Hypericum perforatum with very little or negligible amounts in other parts. Hypericin content varies from 0.02% - 2.5% and the extract present in the market contains 0.3% of hypericin. The Hyperforin content of the fresh plant is not known but the dried herb contains Hyperforin up to 2.8%. The percentage of hyperforin varies substantially with stages of development of Hypericum Perforatum. It is necessary to know the growth phase of the plant in order to determine which active constituents are present and their maximum percentage in Hypericum perforatum. Under these circumstances it is necessary to buy quality extract that is standardized to both hypericin and hyperforin. The use of the raw drug has been reported to have side effects. Thus, it is vital that manufacturers ensure the quality of the product and that consumers look for the percentage of active constituents of Hypericum perforatum. Bedsides hypericin and hyperforin, Hypericum perforatum contains flavonoids, xanthones and volatile oil. These additional compounds have not yet been thoroughly investigated as to their biological activities in humans. Therefore, they cannot be ruled out in contributing antidepressant activity of Hypericum perforatum extract. In animal models, it has been observed that xanthones potentiate the antidepressant activity of hyperforin. As researchers strove to understand the compound’s antidepressant mechanism, it was concluded that possibly Xanthones present in Hypericum perforatum contributed to the antidepressant activity. The Xanthone content varies from was 2.6%-4%. Out of two different Xanthones, 1,3,6,7-tetrahydroxy-xanthone has been shown to be more active. Xanthones also possess serotonin receptor binding inhibiting activity in animal models. Based upon these results, it was concluded that the antidepressant activity of Hypericum is not limited to one of the constituents, but is probably the result of a mixtures of the constituents. This plant is akin to a biosynthetic laboratory, not only for chemical compounds, but also a multitude of compounds like glycosides, alkaloids etc. These compounds exert physiological and therapeutic effects. The compounds that are responsible for medicinal property of the drug are usually the secondary metabolites. Additional investigations in determination of the actual constituent must be undertaken. #### Amrit Pal Singh, M.D. (Alternative Medicine) Medical Executive Ind –Swift Ltd A Science Advisory Board Member Since February 2002 Address for correspondence: Dr. Amrit Pal Singh House No: 2101 Phase-7 Mohali-160062. Email amritpal2101@yahoo. com ### << Previous Next >> [ View All Perspectives ] |
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