Flavonoids hypericum

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-... 

Although the individual inhibition of either MAO or COMT may be comparatively minor in isolation, their combined inhibition along with other monoamine or nonmonoamine actions could have additive if not synergistic effects. For example, a fraction with combined hypericin and flavonoids had antidepressant effects in an animal model (Butterweck et al. 1997). Hypericum is a particular case wherein a single isolated principle may be sufficient for the desired effect, but less effective than the entire plant extract. 

Opioid A recent study has shown activity of hypericum extracts at opioid receptors (Simmen et al. 1998). Extracts displace naloxone from p and x opioid receptors in the micromolar range (IC50 25 and 90 pg/ml, respectively). In contrast, extracts of the sedative herb Valeriana officinalis do not have this effect. This effect is due to unidentified constituents and not by the flavonoids quercetin or kaemferol. Opioids are known to have effects on emotion, so it is conceivable that activity of hypericum at p and k receptors contributes to its therapeutic effects (Gerra et al. 1998 Tejedor-Real et al. 1995 Walker and Zacny 1998). Although they are not conventional treatment for depression, opioids such as buprenorphine have been effective in treatment of refractory depression (Bodkin et a. 1995). However, for any further conclusions to be drawn, it would be necessary to further e uddate the opioid effects of hypericum to determine what functional effect, if any, hypericum has on the receptors. 

Cytotox/c/ty There has been some concern raised over cytotoxic and mutagenic in-vitro effects of hypericum, which have been ascribed to the constituent quercetin (Tyler 1994). However, quercetin is a flavonoid that is present in many plants and vegetables, and it is estimated that the average person consumes 50 mg per day. Consumption of hypericum would not significantly add to this (1 mg in commonly used amounts). The German Commission E has concluded that this is not of great concern. 

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... 

Flavonoids in the diet have been widely promoted as important antioxidant contributors. Their neuroprotective properties, because of this effect, have been demonstrated by several workers. However, they have also been demonstrated to have MAOI activity and this has been proposed as part of the explanation of the use of the common herb, St Johns Wort, Hypericum perforatum L., as an antidepressant. This dual role has now been proposed for a variety of flavonoids, such as kaempferol (22) from the leaves of Ginkgo biloba L., a widely used herbal product which has been suggested as a preventative agent against neurodegeneration. Quercetin (23), similarly, has also shown to inhibit MAO-B " and reverse the effects of induced catalepsy, which mimics the bradykinesia associated with PD. Tangeretin (24) also inhibits MAO-B and crosses the blood brain barrier in a rat model. 

Other applications include the online coupling of capillary isotachophoresis and CZE for the quantitative determination of flavonoids in Hypericum perforatum (Guttiferae) leaves and flowers. This method involved the concentration and preseparation of the flavonoid fraction before introduction into the CZE capillary. The limit of detection for quercetin 3-0-glycosides was 100 ng/ml. ... 

Urbanek, M. et al., On-line coupling of capillary isotachophoresis and capillary zone electrophoresis for the determination of flavonoids in methanolic extracts of Hypericum perforatum leaves or flowers, J. Chromatogr. A, 958, 261, 2002. 

Rocha, L. et ak. Antibacterial phloroglucinols and flavonoids from Hypericum brasiliense, Phytochemistry, 40, 1447, 1995. 

Dias, A.C.P. et al.. Unusual flavonoids produced by callus of Hypericum perforatum, Phytochemistry, 48, 1165, 1998. 

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. 

Butterweck V, Jurgenliemk G, Nahrstedt A, Winterhoff H. Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test. Planta Med 2000 66 3-6. 

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). 

Rutin extraction from buckwheat was optimally performed using between 50% and 60% ethanol with a 3-hr maceration (Kreft et al., 1999). Repeating the extraction two times was sufficient to extract most of the rutin. Lie et al. (2000) demonstrated the optimization of influencing factors such as extraction temperatures, extraction times, and solvent concentrations in a conventional extraction of dry powdered material of Hypericum perforatum. Applied extraction conditions caused variations to favor different components in the mixture. Higher extraction efficiency was achieved with moderately polar solvents to extract flavonoids such as rutin, isoquercitrin, and quercetin. The optimum extraction conditions for dry Hypericum perforatum leaf powder were determined as 44% to 69% ethanol in acetone with a 5.3- to 5.9-hr maceration at 55°C. 

The active ingredients for hypericum include cyclopseudohypericin, hypericin, hyperforin, isohypericin, protohypericin, and pseudohypericin. Other active ingredients include the following flavonoids hyperin, hyperoside, isoquercitrin, kaempferol, luteolin, quercetin, quercitrin, rutin, and the following biflavonoids amentoflavone and 13,118-biapigenin. Although the flavonoids, the essential oils, and the phenolic acids are common plant constituents, the hypericins,... 

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). 

The exact mechanism of action responsible for St. John s wort s neurological effects is not known. Additionally, it is not known if any one chemical constituent is responsible for its activity or if it is a combination of multiple components. It is known that the extracts of H. perforatum appear to inhibit the synaptic uptake of several neurotransmitters including norepinephrine, serotonin (5-HT), and dopamine (3,11-13). Rats that were fed high doses of hypericum extracts standardized to flavonoids (50%), hypericin (0.3%), and... 

HostanskaK, Bommer S, Weber M, Krasniqi B, Sailer R. Comparison of the growth-inhibitory effect of Hypericum perforatum L. extracts, differing in the concentration of phloroglucinols and flavonoids, on leukaemia cells. J Pharm Pharmacol 2003 55 973-980. 

Naphtodianthrones, phloroglucinols, flavonoids, phenolic acids Hypericum perforatum (St. John s wort) LC/DAD/SPE/NMR, 1H NMR, COSY, TOCSY 48... 

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... 

A compositional analysis of flavonoids from other species of Hypericum, namely H. hirsutum, H. maculatum, H. tatrapterum, H. montanum and H. humifusum [64], H. patulum and H. olympicum [68], has also been carried out. 

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