Hypericum perforatum naphthodianthrones

Hypericum perforatum (Clusiaceae), commonly known as SJW, is used in many countries for the treatment of mild-to-moderate forms of depression. Several clinical studies provide evidence that SJW is as effective as conventional synthetic antidepressants (46-51). From a phytochemical point of view, H. perforatum belongs to one of the best-investigated medicinal plants. A series of bioactive compounds have been detected in the crude material, namely phenylpropanes, flavonol derivatives, biflavones, proanthocyani-dins, xanthones, phloroglucinols, some amino acids, naphthodianthrones, and essential oil constituents (Fig. 3) (52-54). 

To ensure lot-to-lot consistency, standardization of extracts often relies on constituents as biomarkers for plant identity and potency. SJW Hypericum perforatum), a perennial shrub traditionally used as a mood enhancer and mild antidepressant, has been tested in dozens of clinical trials, with mixed results for efficacy. Some of its purported bioactive constituents include naphthodianthrones, including hypericin flavonoids phloroglucinols, including hyperforin and essential oils. For many years, hypericin was presumed to be the active component. As a result most extracts were standardized based on hypericin concentration. Recent data, however, support other components such as hyperforin and the flavanoids, that may also contribute to the therapeutic efficacy of the SJW extracts (33-35). Because these secondary components were previously unaccounted for in the standardization of the former clinical test articles, and because these constituents are chemically unrelated to and their content within the plant varies independently of hypericin, it has been argued that the potency of these constituents in any particular batch was unlikely to be similar to that of other batches. This variability between batches could explain the observed differences in the clinical trial results (36). 

Hypericum perforatum (devil s scourge, goat weed, rosin rose, St. John s wort, Tipton weed, witch s herb) contains the naphthodianthrones hypericin and pseudohypericin, flavonoids, such as hyperoside, isoquercitin, and rutin, and phloroglucinols, such as adhyperforin and hyperforin. It is effective in mUd to moderate depression (1). 

Peebles KA, Baker RK, Kurz EU, Schneider BJ, Kroll DJ. Catalytic inhibition of human DNA topoisomerase Ila by hypericin, a naphthodianthrone from St. John s wort (Hypericum perforatum). Biochem Pharmacol 2001 62 1059-1070. 

For a hydroalcoholic extract of Hypericum perforatum, produced by successive extraction of dried aerial parts with petroleum ether, 1,2-dichlorethane and ethanol (50 % v/v), a sedative effect in mice has been reported [123]. The authors observed a bell-shaped dose-response effect on spontaneous motility with maximal activity at an oral dose of 26.5 mg/kg p.o, while pentobarbital-induced sleeping time was most significantly prolonged at the lowest dose applied (13.25 mg/kg p.o.). No effect on neuromuscular transmission was observed in three different test models (chimney test, traction test and rota-rod test). After separation of the crude extract in fractions containing mainly flavones, naphthodianthrones or amino acids, it was not possible to clearly attribute the effect of the native extract to a particular group of constituents. Thus, the authors conclude that activity of the hydroalcoholic extract may results form the cumulative effects of different compound, but they do not offer any explanation for the lower activity of the extract at higher doses. 

Hypericin and pseudohypericin (Fig. 21) are naphthodianthrones and occur in St. John s wort Hypericum perforatum, Clusiaceae). These dark-red compounds are accumulated in glands on the margin oiK perforatum leaves and petals. It was assumed for a long time that they represent the antidepressant principle in extracts of St. John s wort. Recently, however, it became evident that the prenylated acylphloroglucinols hyperforin and adhyperforin are responsible for most of the pharmacological effects. 

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