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Production of hypericin, pseudohypericin and flavonoids in cell cultures of various Hypericum species and their chemotypes.

Suspension cultures were established from the shoots of sterile germinated seeds of various provenances of seven Hypericum (H.) species in a half strength modified Murashige and Skoog liquid medium. In most strains of H. perforatum (18 provenances) and all strains of H. maculatum (6 provenances) as well as in the cultures of H. tomentosum, H. bithynicum, H. glandulosum and H. balearicum, hypericin and pseudohypericin could be proven, however, in extremely varying amounts. In general, the pseudohypericin content was significantly higher than that of hypericin. The flavonoid patterns, comprising monomeric quercetin derivatives and dimeric apigenin derivatives, varied among strains over a wide range.

Animals↗

A new phloroglucinol derivative from Hypericum calycinum with antifungal and in vitro antimalarial activity.

The new phloroglucinol derivative 1 has been isolated from the light petroleum ether extract of the aerial parts of Hypericum calycinum. Its structure has been established by means of 1H- and 13C-NMR spectroscopy and by nOe, MHQC, and HMBC experiments on its monomethyl ether derivative 3. Compound 1 was fungicidal against Cladosporium cucumerinum in a TLC bioassay. In addition, this new phloroglucinol derivative was also found to exert an interesting antimalarial activity in an in vitro test system.

Animals↗

Hyperforin, possibly the major non-nitrogenous secondary metabolite of Hypericum perforatum L.

An overview of the constituents of Hypericum perforatum is given, with special emphasis on the acylphloroglucinol hyperforin. Previous work on the chemistry of hyperforin and on other components derived from hyperforin in H. perforatum is reviewed. A new optimized method of isolating hyperforin on a large scale is presented, including full spectroscopic characterization of the isolate.

Bridged Bicyclo Compounds↗

Effects of the total extract and fractions of Hypericum perforatum in animal assays for antidepressant activity.

A commercially available extract of the aerial parts of Hypericum perforatum, LI 160, showed pronounced activity in selected animal bioassays. These include the forced swimming test (FST) and the tail suspension test, used to determine antidepressant activity, and tests indicating activity on the central nervous system, such as body temperature and ketamine induced sleeping time. The counteracting effects of drugs known to interfere with the central dopaminergic system strongly suggested that dopamine mediated activity is important for the activity of the extract. Dose-response experiments of the total extract and of fractions rich in flavonoids and napthodianthrones produced inverted U-shaped dose response curves.

Animals↗

Biologically active and other chemical constituents of the herb of Hypericum perforatum L.

Phenylpropanes, flavonol derivatives, biflavones, proanthocyanidins, xanthones, phloroglucinols, some amino acids, naphthodianthrones and essential oil constituents are the natural plant products known from the crude drug of Hypericum perforatum, Hyperici herba. These compounds are discussed with respect to structural features, their concentration, biological activities and their possible contribution to the clinically demonstrated antidepressant efficacy of extracts obtained from Hyperici herba.

Animals↗

Effect of benzophenones from Hypericum annulatum on carbon tetrachloride-induced toxicity in freshly isolated rat hepatocytes.

Five benzophenones and a xanthone, isolated from Hypericum annulatum Moris, were investigated for their protective effect against carbon tetrachloride toxicity in isolated rat hepatocytes. The benzophenones and the xanthone gentisein were administered alone (100 microM) and in combination with CCl4 (86 microM). CCl4 undergoes dehalogenation in the liver endoplasmic reticulum. This process leads to trichlormethyl radical (*CCl3) formation, initiation of lipid peroxidation, and measurable toxic effects on the hepatocytes. The levels of thiobarbituric acid reactive substances (TBARS) were assayed as an index of lipid peroxidation (LPO). Lactate dehydrogenase (LDH) leakage, cell viability and reduced glutathione (GSH) depletion were used as signs of cytotoxicity. CCl4 significantly decreased hepatocyte viability, GSH level and increased TBARS level and LDH leakage as compared to the control. Our data indicate that 2,3',5',6-tetrahydroxy-4-methoxybenzophenone, 2-O-alpha-L-arabinofuranosyl-3',5',6-trihydroxy-4-methoxybenzophenone and 2-O-alpha-L-3'-acetylarabinofuranosyl-3',5',6-trihydroxy-4-methoxybenzophenone showed weaker toxic effects compared to CCl4 and in combination showed statistically significant protection against the toxic agent.

Animals↗

St John's Wort (Hypericum perforatum)--a herbal antidepressant.

A number of clinical studies conducted over the past few years have indicated that whole extract of St John's wort (Hypericum perforatum L.) has antidepressant effects. The herbal antidepressant St John's wort offers promising results in the treatment of patients with mild and moderate depression (response rate of 60-70% estimated by analysis of pooled data). St John's wort preparations are well tolerated. Their use rarely leads to adverse drug reactions which, when they do occur, are mainly subjective symptoms (e.g. gastrointestinal, dizziness). The generally good tolerability of St John's wort preparations and the resulting high patient compliance in taking the prescribed medication, in conjunction with their efficacy in mild and moderate depression, make these preparations particularly suitable for use in outpatient practice. Tolerability is also very good in elderly patients. If a sufficiently high-dose course of treatment with St John's wort preparations (900 mg daily) does not lead to a clear improvement in depression after four to six weeks, therapy should be continued with an established ('classical') antidepressant.

Chemistry, Pharmaceutical↗

Neuropharmacology of St. John's Wort (Hypericum).

OBJECTIVE: To review preclinical information related to possible antidepressant mechanism(s) of action of St. John's wort in order to address the issue of whether its purported clinical effectiveness has a rational pharmacologic basis. DATA SOURCES: Primary and review articles were identified by a MEDLINE search (1966-January 1998) and through secondary sources. Many of the original German articles had English abstracts, but where necessary, German articles were translated into English. The results of a new screen of hypericin activity at receptor and uptake sites are summarized. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated and all information deemed relevant was included in this review. DATA SYNTHESIS: The neuropharmacology of St. John's wort has been examined in only a few studies. A mechanism similar to that of the synthetic antidepressants, such as the selective serotonin-reuptake inhibitors or monoamine oxidase (MAO) inhibitors, might play a role, but other mechanisms are possible. CONCLUSIONS: Hypericum extracts have only weak activity in assays related to mechanisms of the synthetic antidepressants, that is, inhibition of MAO, catechol O-methyltransferase, or serotonin reuptake. It has been postulated that the clinical efficacy of St. John's wort could be attributable to the combined contribution of several mechanisms, each one too weak by itself to account for the overall effect. The recent demonstration of a significant affinity of hypericin for sigma receptors presents new possibilities for consideration.

Animals↗

Effects of hypericum extract HYP 811 in patients with psychovegetative disorders.

The efficacy of tolerability of a 6-week course of Hypericum extract HYP 811 were investigated in a postmarketing surveillance study of 758 outpatients suffering from psychovegetative disorders. The investigations included a standardized list of typical somatic symptoms and global evaluations of the drug's efficacy and tolerability. By study end, 83.1% of patients had experienced a reduction in symptom severity, and the frequency of symptoms had improved by an average of 37.3%. After 3 weeks of treatment, the dosage could be reduced to one capsule per day in 35.8% of patients.

Adolescent↗

[The modification of a radiation lesion in animals with an aqueous extract of Hypericum perforatum L. 2].

The preparation Hypericum perforatum L. has been shown to decrease the intensity level of enzymatic and non-enzymatic processes of lipid peroxidation of rat liver microsomes in vitro and in vivo. In the mucus of the this intestine in vivo the increase of the number of non-enzymatic SH-groups is observed. Possible mechanisms of radioprotective action of the preparation is under discussion.

Animals↗

Vasoactive properties of procyanidins from Hypericum perforatum L. in isolated porcine coronary arteries.

Procanidin fractions (PC) were isolated from Hypericum perforatum L. (Guttiferae). Characterization of the main components of each fraction was performed by UV- and mass spectroscopy. Their biological activity was tested in porcine isolated coronary arteries. All PC fractions antagonized histamine- or prostaglandin F2 alpha-induced arterial contractions. In contrast, vasorelaxation was insignificant in KCl-precontracted coronary arteries except with the higher oligomeric PC fraction 3. Vasoactive properties of the PC seem to be dependent on their relative molecular mass. An inhibition of cellular phosphodiesterase might be involved in the underlying mechanism of action.

Animals↗

[Hypericum poisoning in sheep].

A report about a case of St. John's wort poisoning in German Blackface sheep is given. After the ingestion of St. John's wort (Hypericum perforatum) all slightly pigmented parts of the skin, that were rarely covered with hair, were photosensitized. In summer many sheep suffered from inflammatory skin alterations at the ears, the bridge of the nose and at the surroundings of the eyes. A literature review informs about etiology and treatment of photosensitivity disease and the St. John's wort is exactly described to facilitate recognition.

Animals↗

Studies of sheep experimentally poisoned with Hypericum perforatum.

Sheep given different dosages and frequencies of Hypericum perforatum had decreased hemoglobin, red blood cell count, packed cell volumes, total protein, glucose, cholesterol, triglycerides, and serum alkaline phosphotase activities. Blood urea nitrogen, sodium, potassium, bilrubin (total and direct), and the activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and gamma glutamyltransferase increased. Hemato-biochemical assays were useful diagnostic aids to determine the severity of this plant's toxic effects.

Animals↗