hyperoside and hypericin

The example of St. John's wort offers convincing evidence for the concept that modern methods of pharmacological and phytochemical research are effective in advancing the development of traditional herbal remedies. As a consequence of these efforts, it is known today that several compounds from different structural groups and with different mechanisms of action seem to be responsible for the observed antidepressant efficacy of St. John's Wort. Co-effectors in the extract improve the bioavailability of active constituents such as hypericin (1) (pharmacokinetic synergy). Unwanted side effects are preventable without remarkable loss of activity when the responsible constituent(s) are carefully removed during the extraction process, as demonstrated for hyperforin (3), which is responsible for the induction of cytochrome P450 (CYP)-metabolizing enzymes (CYP3A4, in particular). On the basis of our findings, it is likely that positive interactions between single compounds occur more frequently in traditionally used herbal preparations than is known presently.

Topics: Anthracenes; Antidepressive Agents; Bridged Bicyclo Compounds; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Hypericum; Molecular Structure; Perylene; Phloroglucinol; Plant Preparations; Plants, Medicinal; Terpenes

Hypericum perforatum L. (St. John's wort) is a medicinally important member of Hypericaceae. Many pharmacological activities have been mostly attributed to its hyperforin, hypericin and/or hyperoside contents. Therefore, qualitative and quantitative determinations of these ingredients are essential to justify the beneficial effects of St. John's wort on health. In the European Pharmacopoeia, the TLC and HPLC methods were given for this purpose. High performance thin layer chromatography (HPTLC) has recently become increasingly used as a suitable technique for analysing herbal drugs. This study aims to develop new and validated HPTLC methods to analyse these active components in different Hypericum spp. to find other suitable species to replace the official plant.. Three different mobile phases were developed: n-hexane-ethyl acetate (8:2) for hyperforin analysis, toluene-chloroform-ethyl acetate-formic acid (8:5:3.5:0.6) for hypericin analysis and ethyl acetate-formic acid-acetic acid-water (15:2:2:1) for hyperoside analysis. These newly developed and validated HPTLC systems were further applied to determine their concentrations in different Hypericum species.. Hyperforin concentration was found between 6.40 to 26.40 mg/g only in H. triquetrifolium, H. scabrum and two H. perforatum samples; hypericin was detected between 0.81 and 1.41 mg/g only in H. bithynicum, H. perfoliatum, H. triquetrifolium and two H. perforatum samples; and hyperoside was identified in all tested specimens ranging from 1.01 to 9.73 mg/g. The new HPTLC methods developed and validated in the present study may ensure reliable results for the qualification and quantification of hyperforin, hypericin and hyperoside contents in Hypericum species.

Topics: Anthracenes; Chromatography, Thin Layer; Hypericum; Perylene; Phloroglucinol; Plant Extracts; Quercetin; Terpenes

Accumulation of selected secondary metabolites in two Hypericum species (H. perforatum and H. annulatum) was compared in their vegetative parts (stems and leaves) and in terms of the extraction solvent (80% aq. methanol or 60% aq. ethanol). The presence of chlorogenic acid and quercitrin was not detected in stem of both species. Almost all metabolites were more accumulated in the leaves than in the stems (rutin, hyperoside, quercetin and hypericin) but epicatechin showed the opposite in both species and hyperforin in H. annulatum. Extraction solvents showed rather species-specific differences with EtOH being more suitable for the extraction of hypericin, quercetin, quercitrin, and hyperoside (on average, for both the leaves and stems, extraction increased by approximately 130, 30, 25, and 15%, respectively) while MeOH for the extraction of epicatechin, rutin, and hyperforin (increased extraction by approximately 50, 40, and 35%, respectively). On the other hand, content of total soluble phenols did not differ in relation to solvent in any organ or species. Various ages of H. annulatum plants did not show dramatic impact on the amount of metabolites. Subsequently, the usefulness of capillary electrophoresis (CE) as an alternative to HPLC for the quantification of metabolites in H. perforatum was tested and results showed non-significant differences between CE and HPLC with the methods we developed (the difference did not exceed 10%).

Topics: Anthracenes; Catechin; Chlorogenic Acid; Chromatography, High Pressure Liquid; Hypericum; Perylene; Phloroglucinol; Plant Extracts; Plant Leaves; Plant Stems; Quercetin; Rutin; Terpenes

To study the constituents of ethyl acetate fraction form Hypericum hengshanense.. The constituents were isolated and purified by chromatography on silica gel and their structures were elucidated by MS and NMR spectral analysis.. Ten compounds were isolated and identified as: hyperoside (1), hypericin (2), quercetin (3), quercitrin (4), sesamin (5), betulonic acid (6), rutin (7), kaempferol (8), beta-daucosterol (9), beta-sitosterol (10).. All compounds are obtained from this plant for the first time.

Topics: Acetates; Anthracenes; Hypericum; Kaempferols; Magnetic Resonance Spectroscopy; Perylene; Plant Components, Aerial; Plants, Medicinal; Quercetin; Rutin

 This study describes the antispasmodic, bronchodilator, and cardiovascular-modulatory activities of Hypericum perforatum Linn. (Hypericaceae) fractions and constituents..  Pharmacological investigation of H. perforatum fractions and active principles..  H. perforatum extract fractions [petroleum spirit (HpPet), chloroform (HpCHCl(3)), ethyl acetate (HpEtAc), and aqueous (HpAq)] and its compounds (hyperforin, hypericin, and hyperoside) were studied in various isolated tissue preparations..  In rabbit jejunum, HpCHCl(3), HpEtAc and HpAq, like papaverine, inhibited both spontaneous and K(+) (80 mM)-induced contractions at similar concentrations, whereas HpPet was relatively potent against K(+), as verapamil. All fractions caused rightward of Ca(2+) concentration-response curves (CRCs), similar to verapamil. HpCHCl(3), HpEtAc, and HpAq shifted isoprenaline-inhibitory CRCs to left, like papaverine, while HpPet was devoid of any such effect, as verapamil. In guinea-pig trachea, HpCHCl(3), HpEtAc, and HpAq equipotently relaxed carbachol and K(+)-induced contractions and shifted the isoprenaline-curves to the left, whereas HpPet was more effective against K(+), without potentiating isoprenaline effect. When tested in rabbit aorta, all fractions exhibited vasoconstrictor and vasodilator effects, except HpEtAc, which did not produce vasoconstriction. In guinea-pig atria HpCHCl(3), HpEtAc, and HpAq initially caused cardiac stimulation, followed by inhibition, similar to papaverine, whereas HpPet, like verapamil, caused only cardiac suppression. Hyperforin, hypericin, and hyperoside showed a similar pattern of spasmolytic effect to verapamil..  Thus, all tested fractions of H. perforatum exhibit a combination of Ca(2+) antagonist and phosphodiesterase-inhibition, except petroleum spirit which was devoid of later mechanism. The compounds tested showed only Ca(2+) channel blocking effect.

Topics: Animals; Anthracenes; Calcium; Calcium Channel Blockers; Dose-Response Relationship, Drug; Female; Guinea Pigs; Hypericum; In Vitro Techniques; Male; Perylene; Phloroglucinol; Phosphodiesterase Inhibitors; Plant Extracts; Quercetin; Rabbits; Terpenes; Verapamil

The antinociceptive profile of St. John's Wort (SJW) was investigated in mice in a condition of acute thermal and chemical pain, together with the mechanism that might underlie this effect. A dried extract of SJW induced a prolonged antinociception that persisted for 120 minutes after administration. The thermal antinociception was prevented by naloxone and by the protein kinase C (PKC) activator PMA, whereas the chemical antinociception was prevented by PMA, remaining naloxone insensitive. A chloroform (CHL) and a methanol (MET) fraction, obtained to investigate the involvement of the SJW main components, hyperforin and hypericin/flavonoid, respectively, increased pain threshold with a time course comparable to the dried extract. The CHL antinociception was prevented by naloxone, whereas the MET antinociception was antagonized by PMA. Purified hyperforin and hypericin showed an antinociceptive efficacy comparable to CHL and MET, respectively. Conversely, flavonoids were devoid of any effect. The administration of yohimbine and atropine did not modify SJW, CHL and MET antinociception. These results indicate that both CHL and MET fractions mediate the SJW-induced antinociception. In particular, the presence of hypericin was fundamental to induce both thermal and chemical antinociception through the inhibition of the PKC activity, whereas hyperforin selectively produced a thermal opioid antinociception.. This article presents evidence of a persistent thermal and chemical antinociception of SJW that is mainly mediated by PKC-inhibiting mechanisms. These findings identify important targets for a longer-acting activation of endogenous pain systems and should potentially help clinicians who seek safe, tolerable, and prolonged treatments for pain relief.

Topics: Acetic Acid; Analgesics; Analgesics, Opioid; Animals; Anthracenes; Chromatography, High Pressure Liquid; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; Drug Compounding; Hypericum; Male; Mice; Naloxone; Naltrexone; Narcotic Antagonists; Pain; Pain Measurement; Pain Threshold; Perylene; Phorbol Esters; Phytotherapy; Protein Kinase C; Quercetin; Somatostatin; Spectrometry, Mass, Electrospray Ionization; Statistics, Nonparametric; Time Factors

The phloroglucinol derivative hyperforin, the naphthodianthrones hypericin and pseudohypericin, the phenylpropane chlorogenic acid, and the flavonoids rutin, hyperoside, apigenin-7-O-glucoside, kaempferol, quercitrin, quercetin and amentoflavone were investigated in Hypericum confertum growing wild in Turkey. After drying at room temperature, the plant materials were assayed for secondary metabolite concentrations by HPLC. All the listed compounds were detected at various levels. This is the first report on the chemistry of H. confertum.

Topics: Anthracenes; Apigenin; Biflavonoids; Bridged Bicyclo Compounds; Chlorogenic Acid; Hypericum; Perylene; Phloroglucinol; Plant Components, Aerial; Quercetin; Rutin; Terpenes

The present study was conducted out to determine hyperforin, hypericin, pseudohypericin, chlorogenic acid, rutin, hyperoside, quercitrin, quercetin, kaempferol, apigenin-7-O-glucoside and amentoflavone contents of Hypericum adenotrichum, an endemic plant species to Turkey. The aerial parts representing a total of 30 individuals were collected at full flowering, dried at room temperature and assayed for secondary metabolite concentrations by HPLC. All of the chemicals were detected at various levels except for hyperforin. This is the first report on polar chemistry of this endemic species.

Topics: Anthracenes; Bridged Bicyclo Compounds; Chromatography, High Pressure Liquid; Hypericum; Kaempferols; Perylene; Phloroglucinol; Quercetin; Terpenes; Turkey

The present study was designed to get further insight into the mode of antidepressant action of extracts prepared from St. John's wort (SJW) and relevant active constituents. Down-regulation of central beta-adrenergic receptors (beta-AR's) has been widely considered a common biochemical marker of antidepressant efficacy. Although previous studies have reported a beta-AR down-regulation for SJW extracts, in vivo studies that compare the effects of SJW extracts with those of relevant active constituents on beta-AR density have not been done yet. We used quantitative radioligand receptor-binding-studies to examine in rats the effects of short-term (2 wks) and long-term (8 wks) administration of different SJW extracts and constituents on beta-AR binding in rat frontal cortex. The effects were compared to those of the standard antidepressants imipramine and fluoxetine. [125I]CYP binding to beta-AR was found to be decreased after short as well as after long-term treatment with imipramine (36%, 40%). Short-term treatment with fluoxetine decreased the number of beta-adrenergic receptors (17%) while long-term treatment with fluoxetine elicited an increase (14%) in beta-AR-binding. This effect was comparable to that of the lipophilic CO2 extract which decreased beta-AR-binding (13%) after two weeks and slightly increased the number of beta-AR's after 8 weeks (9%). Short-term treatment with the methanolic SJW extract decreased beta-AR-binding (14%), no effects for this extract were observed after 8 weeks. Treatment with hypericin led to a significant down-regulation (13%) of beta-AR's in the frontal cortex after 8-weeks, but not after 2 weeks, while hyperforin (used as trimethoxybenzoate, TMB), and hyperoside were ineffective in both treatment paradigms. Compared to the SJW extracts and single compounds the effect of imipramine on beta-AR-binding was more pronounced in both treatment paradigms.

Topics: Animals; Anthracenes; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Bridged Bicyclo Compounds; Cell Membrane; Fluoxetine; Frontal Lobe; Hypericum; Imipramine; Male; Perylene; Phloroglucinol; Plant Extracts; Quercetin; Radioligand Assay; Rats; Receptors, Adrenergic, beta; Terpenes

The biological evaluation of hypericin in various test models is hampered by its poor water solubility. In former studies we have shown that the water solubility of hypericin was remarkably enhanced in the presence of the procyanidins or flavonol glycosides of Hypericum extract. The present pharmacokinetic study was designed to find out whether the improved water solubility in the presence of procyanidin B2 or hyperoside is correlated to increased plasma levels of hypericin. Plasma levels of hypericin in rats in the presence and absence of procyanidin B2 or hyperoside were determined by reversed phase HPLC using fluorimetric detection. Both compounds increased the oral bioavailability of hypericin by ca. 58 % (B2) and 34 % (hyperoside). Procyanidin B2 and hyperoside had a different influence on the plasma kinetics of hypericin; median maximal plasma levels of hypericin were detected after 360 min (C max : 8.6 ng/mL) for B2, and after 150 min (C max : 8.8 ng/mL) for hyperoside. It can be speculated that, when administered together with these compounds, a significant accumulation of hypericin in rat plasma in the presence of both polyphenols might be responsible for the observed increased in vivo activity.

Topics: Administration, Oral; Animals; Anthracenes; Antidepressive Agents; Biflavonoids; Biological Availability; Catechin; Chromatography, High Pressure Liquid; Drug Synergism; Male; Perylene; Phytotherapy; Plant Extracts; Proanthocyanidins; Quercetin; Rats; Rats, Sprague-Dawley; Solubility

We examined two commercially available St. John's wort extracts and some of their constituents for their potential in inducing rat cytochrome P450 (CYP450) enzyme activities after oral administration. None of the extracts or pure constituents tested enhanced the hepatic cytochrome content or the activity of cytochrome P450 isozymes in rat liver microsomes. Our results demonstrated that the reported interactions between St. John's Wort and various other drugs are not mediated by CYP 450 isoforms present in rat liver.

Topics: Animals; Anthracenes; Antidepressive Agents; Bridged Bicyclo Compounds; Cytochrome P-450 Enzyme System; Ethanol; Excitatory Amino Acid Antagonists; Female; Hypericum; Liver; Male; Methanol; Microsomes; Perylene; Phenobarbital; Phloroglucinol; Plant Extracts; Quercetin; Rats; Rats, Sprague-Dawley; Sex Factors; Solvents; Terpenes

To determine the concentrations of chemical characteristic to extracts of leaves and flowers of Hypericum perforatum (St John's wort) in a number of selected samples and, following chemical characterization, to investigate the effects of these extracts on several pharmacological properties including effects of the extracts on inhibition of 5-hydroxytryptamine (5-HT) uptake and on antioxidant properties.. The samples were analyzed for the presence of characteristic chemicals by high performance liquid chromatography (HPLC) directly coupled to ultraviolet wavelength absorbance and positive or negative mode electrospray mass spectrometric detection. The effects of extracts on 5-HT uptake were determined by quantifying 3H-5-HT incorporation into rat hippocampal prisms. Estimates of effects of extracts on free radical scavenging capacity were made using a dynamic assay based on the ability of compounds to prevent the initiation of a colored reaction produced by the horseradish peroxidase catalyzed formation of hydroxyl free radicals from hydrogen peroxide using 2',2'-azinobis (3-ethylbenzthiazoline-6-sulfonic acid) as the color indicator.. The chemical profile of a number of extracts were determined and found to differ substantially from each other. Inhibition of 5-HT uptake was found to correlate with hyperforin content and free radical scavenging capacity was found to correlate with the content of several flavonoids including quercetin and hyperoside.. Standardized extracts of H perforatum varied substantially in the concentration of several characteristic chemicals. The correlation between pharmacological activity and certain characteristic chemicals found in these extracts indicates that the medicinal benefit derived from selected extracts will vary considerably depending on their chemical composition.

Topics: Animals; Anthracenes; Antioxidants; Bridged Bicyclo Compounds; Free Radical Scavengers; Hippocampus; Hypericum; Male; Perylene; Phloroglucinol; Quercetin; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Terpenes

Topics: Anthracenes; Flavones; Perylene; Plants; Quercetin