Hypericin formulations

As with drugs and purified biomarkers, thermal- and photostability of botanical products are the factors that must be considered. Commercial dried extract and capsules of SJW were evaluated under harmonized test conditions (25). Photostability testing showed all the constituents to be photosensitive in the tested conditions. However, different opacity agents and pigments influenced the stability of the constituents. Amber containers had little effect on the photostability of the investigated constituents. Long-term thermal stability testing showed a shelf life of less than four months for hyperforins and hypericins, even when ascorbic and citric acids were added to the formulation. 

St. John s wort and some individual constituents of the preparations have been administered orally, topically, and intravenously in various pharmaceutical formulations, including tinctures, teas, capsules, purified components, and tablets. These botanical preparations of St. John s wort are prepared from plant components (i.e., flowers, buds, and stalk) whose content of the wide array of structurally diverse bioactive constituents may differ (Table 1 and Fig. 2). Many commercial tablet and capsule formulations of St. John s wort are standardized using the ultraviolet absorbance of the naphtho-dianthrones, hypericin, and pseudohypericin, to contain 0.3% hypericin content. Thus, a 300 mg dose of St. John s wort contains approximately 900 pg hypericin per dose. Despite the standardization of dosage forms... 

St. John s wort, also known as hypericum, contains a variety of constituents that might contribute to its claimed pharmacologic activity in the treatment of depression. Hypericin, a marker of standardization for currently marketed products, was thought to be the primary antidepressant constituent. Recent attention has focused on hyperforin, but a combination of several compounds is probably involved. Commercial formulations are usually prepared by soaking the dried chopped flowers in methanol to create a hydroalcoholic extract that is then dried. 

The hypericin fraction was initially reported to have MAO-A and -B inhibitor properties. Later studies found that the concentration required for this inhibition was higher than that achieved with recommended dosages. In vitro studies using the commercially formulated hydroalcoholic extract have shown inhibition of nerve terminal reuptake of serotonin, norepinephrine, and dopamine. While the hypericin constituent did not show reuptake inhibition for any of these systems, the hyperforin constituent did. Chronic administration of the commercial extract has also been reported to significantly down-regulate the expression of cortical 13 adrenoceptors and up-regulate the expression of serotonin receptors (5-HT2) in a rodent model. 

The most common commercial formulation of St. John s wort is the dried hydroalcoholic extract. Products should be standardized to 2-5% hyperforin, although most still bear the older standardized marker of 0.3% hypericin. The recommended dosing for mild to moderate depression is 900 mg of the dried extract per day in three divided doses. Onset of effect may take 2-4 weeks. Long-term benefits beyond 12 weeks have not been sufficiently studied. 

The hypericin constituent of St. John s wort is photolabile and can be activated by exposure to certain wavelengths of visible or UVA light. Parenteral formulations of hypericin (photoactivated just before administration) have been used investigationally to treat HIV infection (given... 

Several studies were also designed to evaluate the antioxidant properties of St. John s Wort (Hypericum perforatum L.), an herbal drug used in the treatment of burns, bruises, swelling and anxiety. Commercially available formulations of St. John s Wort, standardized to the naphthoquinone hypericin, Fig. (13), inhibit free radical production in both cell-free and human vascular tissue [136],... 

Hypericum extracts are extensively used in industry for the manufacturing of cosmetics and dermatological products, such as sun creams, antiphlogistic ointments or shampoos [173]. Investigations on the anti-irritant potential of several substances commonly employed in cosmetic formulations unraveled a protective activity of an oily Hypericum extract against croton oil induced skin irritation in the rabbit [174]. A phase II clinical study has now been initiated to evaluate synthetic hypericin 1 as a topically applied, light-activated therapy for specific skin diseases including psoriasis, cutaneous T-cell lymphoma, warts, and Kaposi s sarcoma [175]. 

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