Naphthodianthrones

Extract of hypericum contains at least ten constituents that may contribute to its pharmacological effect (see table 7.4) (Heiligenstein and Guenther 1998). They are categorized into six classes naphthodianthrones, flavonoids, phloroglucinols, phenolic acids, xanthones, and terpenes (Nahrstedt and Butterweck 1997 Erdelmeier 1998). The naph-... 

The oral bioavailability of hypericum may be altered and improved by a combination of its constituents. A hypericum extract containing naphthodianthrones is inactive in a water suspension, but very effective when another constituent, procyanidin, is present. Procyanidin had the effect of increasing the water solubility of naphthodianthrones, and thus increasing their pharmacokinetic availability (Butterweck et ai. 1997). Further, the facilitative effect of procyanidin exhibited an inverted U curve. 

Antidepressant effects Hypericum has been shown to have antidepressant effects in several animal models. An extract fraction high in naphthodianthrones showed antidepressant effects in the forced-swim test, and was attenuated by a dopamine antagonist (sulpiride) (Butterweck et... 

Thus, the long tradition of hypericum as a treatment for depression has been well supported by modern scientific research. Several active constituents have been identified, including naphthodianthrones (e.g., hypericin), phloroglucinols (e.g., hyperforin) and flavonoids (amentoflavone). Research has delineated its pharmacokinetic properties, and many of its neurochemical mechanisms have been identified enhancing monoamine... 

Many constituents with potential biological activity have been extracted from the flowers and leaves, the parts of the plant used for medicinal purposes. These include naphthodianthrones, flavonoids, phlorogluci-nols, and xanthones. Hypericin, one of the naphthodianthrones, has traditionally been considered the main active ingredient, but it is not known whether this is the compound with antidepressant activity. Recent data suggest that a component called hyperforin may be more important than hypericin for the antidepressant activity. 

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). 

The pharmacological activity of SJW extracts has recently been reviewed (55-58). Recent reports have shown that the antidepressant activity of Hypericum extracts can be attributed to the phloroglucinol derivative hyperforin (59-62), to the naphthodianthrones hypericin and pseudohypericin (18,63-65), and to several flavonoids (66-69). The role and the mechanisms of action of these different compounds are still a matter of debate. But, taking these previous findings together, it is likely that several constituents are responsible for the clinically observed antidepressant efficacy of SJW. 

Single- and multiple-dose pharmacokinetic studies with extracts of SJW were performed in rats and humans, which focused on the determination of plasma levels of the naphthodianthrones hypericin and pseudohypericin and the phloroglucinol derivative hyperforin. Results from pharmacokinetic... 

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). 

Women use herbal and dietary supplements at higher rates than men do. This rise in use of alternative therapies places women at increased risk of significant drug interactions, specifically drug-herb and drug-nutrient interactions (83 9). For instance, St. John s wort, a popular antidepressant, contains at least seven groups of chemical compounds. These include naphthodianthrons (hypericin and pseudohypericin), flavonoids (quercetin, hyperoside, and rutin). 

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. 

Bilia et al. reported the efficiency of two-dimensional homonuclear H- H correlated spectroscopy and two-dimensional reverse heteronuclear shift correlation spectroscopy in evaluating the composition of phloroglucinols, flavonols and naphthodianthrones in a dried extract of St John s wort. They successfully assigned carbon resonances for these three classes of compounds and also identified shikimic and chlorogenic acids, sucrose, lipid, polyphenols and traces of solvent (methanol) during the extraction process. This rapid technique is an alternative to HPLC, TLC or capillary GC for the analysis of St John s wort preparations. Another report utilized near-infrared reflectance spectroscopy (NIRS) for the... 

L., family Hypericaceae. Hypericum contains flavonoids, xanthones, naphthodianthrones such as hypericin and pseudohypericin and phloroglucinols, e.g. hyperforin. Hypericin has anti-HIV activity and is responsible for the photosensitivity reaction which has been documented for St. John s Wort in cattle and... 

Europe are impressive at 6 billion in 1999, outselling Prozac by a factor of 4. The constituents of St.John s wort include naphthodianthrones such as hypericin (96) and pseudohypericin (97), the phloroglucinol derivative hyperforin (98), and various flavonoids such as quercetin (99), rutin (100), quercitrin (101), and biapigenin. ... 

The formation of naphthodianthrones in nature most likely involves emodin anthrone 7 as intermediate which results from cyclisation of a linear polyketide. The latter is formed by condensation of eight acetyl CoA units. Emodin anthrone 7 is then dimerised to penicilliopsin 8 which undergoes oxidation to protohypericin 3, the direct precursor of hypericin 1 [17]-... 

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