St. John s wort constituent

St. John s wort constituent CYP enzyme Ki (pm) Mode of inhibition Approximate fold induction of CYP3A4 mRNA... 

Komoroski BJ, Zhang S, Cai H, et al. Induction and inhibition of cytochromes p450 by the St. John s wort constituent hyperforin in human hepatocyte cultures. Drug Metab Dispos 2004 32(5) 512-518. 

WangE,Barecki-RoachM, Johnson WW. Quantitative characterization of direct P-glycoprotein inhibition by St. John s wort constituents hypericin and hyperforin. J Pharm Pharmacol 2004 56 123-128. 

Komoroski BJ, Parise RA Egorin MJ, Strom SC, Venkataramanan R. Effect of the St. John s wort constituent hyperforin on docetaxel metabolism by human hepatocyte cultures. Clin Cancer Res 2005) 11,6972-9. 

Some herbs are standardized for several active constituents, while others are standardized to a single active ingredient. St. John s wort is standardized to contain 0.3% hypericin, whereas ginkgo is standardized to contain 24% flavone glycosides and 6% ter-pene lactones. However, standardizing an herb product to one or more plant component(s) that are identifiable by assay may be incorrect. Many herbalists believe that the whole plant contributes to the efficacy and that there are many unknown active compounds in each plant [6]. 

Hyperforin, the major constituent in Hypericum perforatum (St. John s Wort), inhibits the enzymatic activity of 5-lipoxygenase and COX-1 in platelets, acts as a dual inhibitor of 5-lipoxygenase and COX-1, and might have some potential in inflammatory and allergic diseases connected to eicosanoids (32), Several Hypericum species are of medicinal value in Asia and the Pacific. One of these is Hypericum erectum Thunb., the potential of which as a source of 5-lipoxygenase is given here. 

St John s Wort (Hypericum perforatum, S JW) has been on the herbal pharmacopeia for many years. It is a traditional remedy for depression which has been validated in recent randomized clinical trials. Like many herbal preparations levels of active constituents vary from one preparation to another. As a consequence of its validation as an active preparation it has been widely promoted. Recently it has been shown to interact with a variety of other substances probably through the process of drug interaction. 

Rager, I. et al., Rapid quantification of constituents in St. John s wort extracts by NIR spectroscopy, J. Pharm. Biomed. Appl, 28, 439, 2002. 

Of particular concern is that this inconsistency in product and active constituent occurs even within the same batch. As part of a clinical study with St. John s wort. Hall et al. analyzed 10 capsules of St. John s wort from the same lot (lot 13207) and found the mean total weight to be 444 mg (4.6% CV) versus 300 mg as stated on the label. In addition, the dosage form was supposed to be standardized to contain 900 pg of hypericin, but the mean content was found to be 840 pg (6.6% CV). There was also variability of the hyperforin content (mean 11 mg and 5.7 /o CV), which was not stated on the label (21). Our experience (Lam YWF, unpublished data) with two random capsules from one batch of kava-kava also showed the same extent of undesirable variance the total content of the pharmacologically active kavalactone was 47.3 mg in one capsule and 39.4 mg in the second one. 

Ginseng Much ado about nothing Consumer Reports, Nov. 1995 699. Obach RS. Inhibition of human cytochrome P450 enzymes by constituents of St. John s wort s, an herbal preparation used in the treatment of depression. J Pharmacol Expl Ther 2000 294 88-95. 

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... 

Table 2 Inhibition Constants and Fold Induction of CYP3A4 for the Principal Constituents of St. John s Wort on Human CYP Activities...

Singer A, Wonnemann M, Mueller WE. H perforin, a major antidepressant constituent of St. John s Wort, inhibits serotonin uptake by elevating free intracellular Na" ". J Pharmacol Exp Ther 1999 290 1363-1368. 

Wonnemann M, Singer A, Siebert B, Mueller WE. Evaluation of synaptosomal uptake inhibition of most relevant constituents of St. John s wort. Pharmacopsychiatry 2001 41 S148-S151. 

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. 

FIGURE 43.1 Principal constituents of Hypericum (St. John s wort). 

The herb St. John s wort (Hypericum perforatum) has a number of constituent parts, including hyperforin, which is currently being studied as the responsible constituent for the antidepressant action. The herb contains at least ten compounds that can have an unpredictable effect on the consumer. 

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