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PubMed2005

St. John's wort versus placebo in social phobia: results from a placebo-controlled pilot study.

Recognition of social anxiety disorder (social phobia) as a common and disabling condition has led to new advances in its pharmacotherapy. Limitations with selective seroton reuptake inhibitors (side effects) and behavior therapy (scarcity of trained therapists), coupled with the tendency for patients with the disorder to self-medicate with alternative treatments, have led to the interest in Saint John's wort (SJW) (Hypericum perforatum) for this disorder. Although the literature is mixed, SJW has demonstrated efficacy in several double-blind depression trials, and some open-label studies with anxiety disorders. There is pharmacokinetic evidence for the serotonergic, domaminergic, and GABAminergic activity of hypericum, all of which are implicated in social anxiety disorder. This study was designed to generate pilot data to examine the potential efficacy of SJW in generalized social anxiety disorder. Forty subjects were randomized to 12 weeks of treatment with a flexible dose (600-1800 mg) of SJW (n = 20) or placebo (n = 20). Subjects with comorbid depression (clinician HAMD > 16) were excluded. Results found no significant difference between mean change on the Liebowitz Social Anxiety Scale with SJW (11.4) and placebo (13.2), P = 0.27, effect size = -0.09. Post-hoc analyses found larger effects sizes associated with increased baseline severity, omitting patients with variable scores (+/-30%) during the first week, and use of self-report HAMD scores for exclusion. Results of the study fail to provide evidence for the efficacy of SJW in social phobia. The impact of methodologic improvements on signal detection, while suggestive of improvement, remains to be established.

Adolescent↗
PubMedDate not supplied

[Bigeminy--the result of interaction between digoxin and St. John's wort].

A case of an by digoxin under unusual circumstances is reported. An 80-year-old man, previously on long-term digoxin treatment, started consuming St John's wort herbal tea (2,000 ml/daily) because of frequent episodes of depression. After the cessation of consuming herbal tea containing Hypericum perforatum, digoxin poisoning developed in our patient. Electrocardiography revealed nodal bradicardia 36/min and bigeminy. Manifested symptoms were the consequence of interaction between digoxin and Hypericum perforatum which were consumed simultaneously, and the cessation of consuming St John's wort herbal tea afterwards. Therapy was the same as in the standard digitalis poisoning. Consumers of St John's wort combined with medical products are advised not to discontinue tea consumption on their own, without consulting their physician.

Aged↗
PubMed2000

[Phytotherapeutic drugs and sleep].

Most of the studies about phythotherapeutics and sleep confirmed only hypnotic effects on subjective sleep variables. For LI 160, a hypericum extract, an induction of slow wave sleep was demonstrated in older volunteers. In patients with major depression (MD) an increase of slow wave sleep was observed by our group after a six week therapy with hypericum extract (LI 160) and after an adjunct therapy with Ginkgo biloba LI 1370 extract. In MD sleep disturbances and hypersecretion of glucocorticoids are common features. For LI 160 beneficial effects on depressed mood and for LI 1370 effects on cognitive functioning are well documented. The potential relationship between influence on sleep structure and the hypothalamic-pituitary-adrenal axis will be discussed within the neurophysiological-neuroendocrine "extended two process model" of sleep regulation.

Ginkgo biloba↗
PubMed2004

How effective is St John's wort? The evidence revisited.

BACKGROUND: St. John's wort (Hypericum perforatum) has been identified as an effective treatment for depression in controlled studies and subsequent meta-analyses. However, 3 recently published large studies failed to demonstrate robust efficacy. Updated meta-analysis and assessment of publication bias may help determine the true effect of St. John's wort. METHOD: Meta-analysis to reevaluate the effectiveness of St. John's wort as an antidepressant, funnel plot analysis, and meta-regression to assess the impact of publication bias, small-study effects, and variation in trial characteristics were performed. We conducted 2 analyses: a reproduction of a recent meta-analysis including 15 studies (Meta-15) and a meta-analysis extended by the 3 studies published since then (Meta-18). The studies in Meta-15 were identified through MEDLINE and EMBASE searches conducted in June 2000. The search terms used were St. John's wort, hypericum, hypericin, depression, and antidepressant, and no language restrictions were applied. For both meta-analyses, we compared funnel plots, Begg's rank correlation, Egger's regression, trim and fill method, and meta-regression. RESULTS: In both analyses, effect sizes in recent studies were smaller than those reported in earlier studies; the addition of more recent studies into the analyses resulted in reduced effect size. In Meta-15, St. John's wort was significantly more effective than placebo with a risk ratio (RR) of 1.97 (CI = 1.54 to 2.53). In Meta-18, the RR was reduced to 1.73 (CI = 1.40 to 2.14). On funnel plot analysis, the Meta-18 plot proved to be much more skewed than the Meta-15 plot. Meta-regression showed that increase in effect size was associated with smaller sample size only. The impact of baseline severity of depression could not be evaluated as the studies used different versions of the Hamilton Rating Scale for Depression. CONCLUSION: St. John's wort may be less effective in the treatment of depression than previously assumed and may finally be shown to be ineffective if future trials confirm this trend.

Depressive Disorder↗
PubMed1995

The ethnopharmacology of Madeira and Porto Santo Islands, a review.

The ethnopharmacology of Madeira and Porto Santo Islands is extremely interesting because of the cultural and biogeographic features of this region, which make it a centre of medicinal plant diversity (richness of endemic flora, geographical isolation in the Atlantic sea, crosscultural influences, and past abundance of local healers). The medicinal flora of Madeira is composed of 259 species. Some noteworthy medicinal taxa, endemic or locally relevant, are: Acanthus mollis, Aeonium glandulosum, Aeonium glutinosum, Bidens pilosa, Borago officinalis, Chamaemelum nobile var. discoideum, Culcita macrocarpa, Echium nervosum, Euphorbia platiphylla, Helichrysum melaleucum, Helichrysum obconicum, Hypericum glandulosum, Hypericum humifussum, Kleinia repens, Laurus azorica, Monizia edulis, Ocotea foetens, Psoralea bituminosa, Rubus bollei, Rumex maderensis, Sambucus lanceolata, Scilla maderensis, Sedum brissemoretii, Sedum farinosum, Sedum nudum, Sibthorpia peregrina, Teucrium betonicum, Thymus caespititius, Trifolium squamosum and Vaccinium padifolium. Among the medicinal cryptogams, one can underline the parasitic fungus Laurobasidium lauri, which grows on the stems of Laurus azorica and is used as an antirheumatic, haemostatic, emmenagogue, insecticide and analeptic.

Medicine, Traditional↗
PubMed2003

Hyperforin inhibits vesicular uptake of monoamines by dissipating pH gradient across synaptic vesicle membrane.

Extracts of Hypericum perforatum (St. John's wort) have antidepressant properties in depressed patients and exert antidepressant-like action in laboratory animals. The phloroglucinol derivative hyperforin has become a topic of interest, as this Hypericum component is a potent inhibitor of monoamines reuptake. The molecular mechanism by which hyperforin inhibits monoamines uptake is yet unclear. In the present study we try to clarify the mechanism by which hyperforin inhibits the synaptic vesicle transport of monoamines. The pH gradient across the synaptic vesicle membrane, induced by vacuolar type H(+)-ATPase, is the major driving force for vesicular monoamines uptake and storage. We suggest that hyperforin, like the protonophore FCCP, dissipates an existing Delta pH generated by an efflux of inwardly pumped protons. Proton transport was measured by acridine orange fluorescence quenching. Adding Mg-ATP to a medium containing 130 mM KCl and synaptic vesicles caused an immediate decrease in fluorescence of acridine orange and the addition of 1 microM FCCP abolished this effect. H(+)-ATPase dependent proton pumping was inhibited by hyperforin in a dose dependent manner (IC(50) = 1.9 x 10(-7) M). Hyperforin acted similarly to the protonophore FCCP, abolishing the ATP induced fluorescence quenching (IC(50) = 4.3 x 10(-7) M). Hyperforin and FCCP had similar potencies for inhibiting rat brain synaptosomal uptake of [3H]monoamines as well as vesicular monoamine uptake. The efflux of [3H]5HT from synaptic vesicles was sensitive to both drugs, thus 50% of preloaded [3H]5HT was released in the presence of 2.1 x 10(-7) M FCCP and 4 x 10(-7) M hyperforin. The effect of hyperforin on the pH gradient in synaptic vesicle membrane may explain its inhibitory effect on monoamines uptake, but could only partially explain its antidepressant properties.

Adenosine Triphosphate↗
PubMed1999

Hyperforin attenuates various ionic conductance mechanisms in the isolated hippocampal neurons of rat.

Effects of hyperforin, an acylphloroglucinol derivative isolated from antidepressive medicinal herb Hypericum perforatum (St. John's Wort), on voltage- and ligand-gated ionic conductances were investigated. Whole-cell patch clamp and concentration clamp techniques on acutely isolated hippocampal pyramidal neurons and on cerebellar Purkinje neurons of rat were used. At concentrations between 3 to 100 microM hyperforin induced a dose and time dependent inward current which completely stabilized within a few seconds. Although 1 microM hyperforin inhibited virtually all investigated conductances (GABA > or = I(Ca(N)) > I(Na) > I(Ca(P) > or = AMPA > or = I(K(A)) > NMDA > I(K(DR))), its effects on several of them could not be reversed by repeated washings. Dose response studies revealed that although AMPA induced current is inhibited by hyperforin in a competitive manner, these responses are not completely blocked by very high concentration of the agent. On the contrary, however, NMDA receptor-activated ionic conductance could be completely and uncompetitively inhibited by the agent. Taken together these observation not only reconfirm that hyperforin is a major neuroactive component of hypericum extracts but also demonstrate that this structurally unique and naturally abundant molecule is a potent modulation of mechanism involved in the control of neuronal ionic conductances. Various observed effects of hyperforin do not, however, seem to be mediated by one single molecular mechanism of action of the agent.

Animals↗
PubMed1998

Photocytotoxic effect of pseudohypericin versus hypericin.

Pseudohypericin and hypericin, the major photosensitizing constituents of Hypericum perforatum, are believed to cause hypericism. Since hypericin has been proposed as a photosensitizer for photodynamic cancer therapy, the photocytotoxicity of its congener pseudohypericin has been investigated. The presence of foetal calf serum (FCS) or albumin extensively inhibits the photocytotoxic effect of pseudohypericin against A431 tumour cells, and is associated with a large decrease in cellular uptake of the compound. These results suggest that pseudohypericin, in contrast to hypericin, interacts strongly with constituents of FCS, lowering its interaction with cells. Since pseudohypericin is two to three times more abundant in Hypericum than hypericin and the bioavailabilities of pseudohypericin and hypericin after oral administration are similar, these results suggest that hypericin, and not pseudohypericin, is likely to be the constituent responsible for hypericism. Moreover, the dramatic decrease of photosensitizing activity of pseudohypericin in the presence of serum may restrict its applicability in clinical situations.

Anthracenes↗
PubMed2002

Pharmacological activity of hyperforin acetate in rats.

Hyperforin, the main antidepressant component of Hypericum extract, is not stable with regard to heat and light. Therefore, we investigated a newly synthetized derivative, hyperforin acetate. Herein we demonstrate its efficacy in animal models sensitive to antidepressant and anxiolytic drugs. In the forced swimming test, triple administration of hyperforin (5-20 mg/kg) significantly reduced the immobility time of rats, while in the learned helplessness test a daily treatment of 10 mg/kg for seven consecutive days was necessary to elicit an antidepressant effect. In the elevated plus-maze and in the light-dark test, the acute administration of hyperforin acetate (3-5 mg/kg) exerted an anxiolytic activity, which, however, was smaller than that of diazepam. The effect was inhibited by the pretreatment of rats with metergoline, a serotoninergic antagonist, but not with CGS-8216, a benzodiazepine receptor antagonist. Hyperforin acetate (3-10 mg/kg) was also able to reduce locomotion in rats without eliciting myorelaxant activity. As Hypericum extract was claimed to exert a potential influence on the liver drug metabolizing system, we showed that neither acute nor repeated oral doses of hyperforin acetate altered pentobarbital sleeping time in rats. Taken together, the present results show that hyperforin acetate is a pharmacologically active derivative of hyperforin and may be a starting point from which to develop new compounds for therapeutic purposes.

Animals↗
PubMed1996

Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin.

Single-dose and steady-state pharmacokinetics of antivirally acting hypericin (H) and pseudohypericin (PH) were studied in 13 healthy volunteers by administration of St. John's Wort extract LI 160, a plantal antidepressant. Oral administration of 250, 750, and 1,500 micrograms of H and 526, 1,578, and 3,156 micrograms of PH resulted in median peak levels in plasma (Cmax) of 1.3, 7.2, and 16.6 micrograms/liter for H and 3.4, 12.1, and 29.7 micrograms/liter for PH, respectively. The Cmax and the area under the curve values for the lowest dose were disproportionally lower than those for the higher doses. A lag time of 1.9 h for H was remarkably longer than the 0.4-h lag time for PH. Median half-lives for absorption, distribution, and elimination were 0.6, 6.0, and 43.1 h after 750 micrograms of H and 1.3, 1.4, and 24.8 h after 1,578 micrograms of PH, respectively. Fourteen-day treatment with 250 micrograms of H and 526 micrograms of PH three times a day resulted in median steady-state trough levels of 7.9 micrograms/liter for H and 4.8 micrograms/liter for PH after 7 and 4 days, respectively; the corresponding Cssmax levels were 8.8 and 8.5 micrograms/liter, respectively. Kinetic parameters after intravenous administration of Hypericum extract (115 and 38 micrograms for H and PH, respectively) in two subjects corresponded to those estimated after an oral dosage. Both H and PH were initially distributed into a central volume of 4.2 and 5.0 liter, respectively. The mean distribution volumes at steady state were 19.7 liters for H and 39.3 liters for PH, and the mean total clearance rates were 9.2 ml/min for H and 43.3 ml/min for PH. The systemic availability of H and PH from LI 160 was roughly estimated to be 14 and 21%, respectively. Treatment with Hypericum extract, even in high doses, was well tolerated.

Administration, Oral↗
PubMed2005

The anti-depressant effect of Nelumbinis semen on rats under chronic mild stress induced depression-like symptoms.

Nelumbinis Semen is a well-known traditional herbal medicine frequently used in treatment of depression in many Asian countries. In this study, its anti-depression effects in rats were investigated by comparing the test results of those treated with Nelumbinis Semen to those treated with other herbal anti-depressants, including Rehmanniae Radix Preparat, Corni Fructus, Lycii Fructus, Pinelliae Rhizoma and Hypericum Perforatum. In order to induce depression-like symptoms, the animals were placed under chronic mild stress in the form of overnight illumination for 2 consecutive days. They were treated with the respective herbal extract and forced swimming tests were conducted afterwards. The anti-depression effects of each extract were then evaluated based on a measured index, which consisted of struggling time, first latency and first rest duration. These test results show that Nelumbinis Semen provides greater anti-depression effects than the other herbal extracts. Specifically, only the rats treated with Nelumbinis Semen showed significant increases in struggling time (43.9%, p < 0.005, p = 0.0037) and in first latency time (90.2%, p < 0.05, p = 0.0116). However, the first rest duration for Nelumbinis Semen treated rats was not significantly different from the other rats. It appears that Nelumbinis Semen provides even greater anti-depression effects than Hypericum Perforatum (commonly referred to as St. John's Wort, perhaps the most widely used natural antidepressant today). The anti-depression effects of Nelumbinis Semen might be due to the modulation of the amount of neurotransmitters involved in depression.

Animals↗
PubMed1992

Development of natural crude drug resources from Taiwan (X). Pharmacognostical studies on the Chinese crude drug "han-lian-cao".

In a previous paper(1), it was reported that the drug "Han-lian-cao", in Taiwan was derived from the entire plant or aerial part of Eclipta prostrata L. and Alternanthera sessilis R. Brown. In this paper, the histological studies of "Han-lian-cao" derived from Wedelia and Hypericum plants, and of 3 species of Wedelia related plants distributed in Taiwan were made. The results showed that it was possible to classify these species by their external and internal characteristics. In addition, a key to the characteristics of the whole plants of Eclipta, Alternanthera, Wedelia and Hypericum plants are hereby given.

Botany↗
PubMed2006

Cellular mechanisms and prospective applications of hypericin in photodynamic therapy.

During the last decades, Photodynamic Therapy (PDT) has been established as a powerful alternative approved by health agencies of several countries for treatment of various malignant and some non-malignant diseases. PDT makes use of the light-induced destruction of target cells by formation of cytotoxic products in the presence of a photosensitizing agent and oxygen. The light-dependent tumor destructive properties of Hypericin have drawn attention to its promising application as a photosensitizer in the frame of PDT. Hypericin is a naturally occurring secondary metabolite in plants of the Hypericum genus, with Hypericum perforatum (St. John's wort) as it is a commonly known representative. This review focuses on the cellular mechanisms of Hypericin-based phototoxicity and provides an outlook for future application of Hypericin as a fluorescing and photosensitizing agent for diagnosis and treatment of cancerous diseases, respectively.

Anthracenes↗
PubMed2005

Hypericin--the facts about a controversial agent.

Hypericin is a naturally occurring substance found in the common St. John's Wort (Hypericum species) and can also be synthesized from the anthraquinone derivative emodin. As the main component of Hypericum perforatum, it has traditionally been used throughout the history of folk medicine. In the last three decades, hypericin has also become the subject of intensive biochemical research and is proving to be a multifunctional agent in drug and medicinal applications. Recent studies report antidepressive, antineoplastic, antitumor and antiviral (human immunodeficiency and hepatitis C virus) activities of hypericin; intriguing information even if confirmation of data is incomplete and mechanisms of these activities still remain largely unexplained. In other contemporary studies, screening hypericin for inhibitory effects on various pharmaceutically important enzymes such as MAO (monoaminoxidase), PKC (protein kinase C), dopamine-beta-hydroxylase, reverse transcriptase, telomerase and CYP (cytochrome P450), has yielded results supporting therapeutic potential. Research of hypericin and its effect on GABA-activated (gamma amino butyric acid) currents and NMDA (N-methyl-D-aspartat) receptors also indicate the therapeutic potential of this substance whereby new insights in stroke research (apoplexy) are expected. Also in the relatively newly established fields of medical photochemistry and photobiology, intensive research reveals hypericin to be a promising novel therapeutic and diagnostic agent in treatment and detection of cancer (photodynamic activation of free radical production). Hypericin is not new to the research community, but it is achieving a new and promising status as an effective agent in medical diagnostic and therapeutic applications. New, although controversial data, over the recent years dictate further research, re-evaluation and discussion of this substance. Our up-to-date summary of hypericin, its activities and potentials, is aimed to contribute to this process.

Animals↗
PubMed2002

Hypericin--a new antiviral and antitumor photosensitizer: mechanism of action and interaction with biological macromolecules.

Hypericin, a naturally occurring pigment, is found in certain species of plants from the genus Hypericum, the most common of which is Saint John's Wort (Hypericum perforatum). Recent interest in hypericin is provoked by the discovery that it possesses extremely high toxicity towards certain viruses notably the class of enveloped viruses that includes human immunodeficiency virus (HIV) and toward tumors, and that this toxicity absolutely requires light. Consequently, a detailed understanding of the interaction of hypericin with cellular components (membranes, proteins, nucleic acids) and with light is of fundamental biological importance. The antiviral and antineoplastic activities of hypericin and its derivatives and its mode of action have been widely studied, in the last two decades. This review is focused on the results obtained in the study of hypericin heteroassociations with biological macromolecules, DNA and human serum albumin in particular. An alternative type of the hypericin photosensitizing activity associated with its ability to produce a photogenerated pH drop is discussed that and discussed in connection with its potential application in photodynamic therapy. In the review, it is also presented how an interdisciplinary approach supported by sophisticated techniques of optical spectroscopy and molecular modeling can be effectively applied for the identification of the specific binding sites of the drug in some biomacromolecules as well as for the determination of the physico-chemical mechanism'of the biological activity of hypericin.

Animals↗
PubMed1999

St. John's wort: a new alternative for depression?

OBJECTIVE: The primary purpose of this article is to review the existing literature concerning the therapeutic uses, adverse effects, and possible drug interactions of St. John's wort (Hypericum perforatum) as compared to other antidepressant medications. METHODS: Reference material was obtained through database searches with time restrictions of 1985 to the present. Studies selected were those written in the English language which compared the role of St. John's wort, tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin-selective reuptake inhibitors in the treatment of depression. Other studies were selected based on their evaluation of the safety and efficacy of St. John's wort as an antidepressant for a minimum of four weeks. RESULTS: A review of existing literature recognized nine clinical trials that reported the efficacy of St. John's wort as compared to placebo and to other antidepressant medications. Of these nine, four controlled studies were chosen based upon their large patient populations and their consistency in brand and dosage of St. John's wort used. These four studies demonstrated that St. John's wort was as effective as other antidepressant medications and more effective than placebo, as the clinical symptoms of depression greatly decreased upon administration of H. perforatum. The side-effect profile of H. perforatum at this time appears to be superior to any current U.S.-approved antidepressant medication. CONCLUSIONS: From the existing literature, St. John's wort appears to be a safe and effective alternative in the treatment of depression. Tricylic antidepressants and monoamine oxidase inhibitors can produce serious cardiac side-effects, such as tachycardia and postural hypotension, and many unwanted anticholinergic side-effects, including dry mouth and constipation. St. John's wort has proven to be free of any cardiac, as well as anticholinergic, side-effects normally seen with antidepressant medications. Based upon limited studies, St. John's wort appears to be an acceptable alternative to traditional antidepressant therapy, although trials on a larger scale are warranted in this area. Hypericum is available to the lay public as an over-the-counter preparation and may be misused if not fully understood.

Antidepressive Agents↗
PubMed2004

Antiviral activity of medicinal plants of Nilgiris.

BACKGROUND & OBJECTIVES: Medicinal plants have been traditionally used for different kinds of ailments including infectious diseases. There is an increasing need for substances with antiviral activity since the treatment of viral infections with the available antiviral drugs often leads to the problem of viral resistance. Herpes simplex virus (HSV) causes a variety of life threatening diseases. Since the chemotherapeutic agents available for HSV infections are either low in quality or limited in efficiency, there is a need to search for new and more effective antiviral agents for HSV infections. Therefore in the present study 18 plants with ethnomedical background from different families were screened for antiviral activity against HSV-1. METHODS: Different parts of the plants collected from in and around Ootacamund, Tamil Nadu were extracted with different solvents to obtain crude extracts. These extracts were screened for their cytotoxicity against Vero cell line by assay microculture tetrazolium (MTT) trypan blue dye exclusion, proteins estimation and 3H labeling. Antiviral properties of the plant extracts were determined by cytopathic effect inhibition assay and virus yield reduction assay. RESULTS: Three plant extracts Hypericum mysorense, Hypericum hookerianum and Usnea complanta exhibited significant antiviral activity at a concentration non toxic to the cell line used. The extracts of Melia dubia, Cryptostegia grandiflora and essential oil of Rosmarinus officinalis showed partial activity at higher concentrations. INTERPRETATION & CONCLUSION: Some of the medicinal plants have shown antiviral activity. Further research is needed to elucidate the active constituents of these plants which may be useful in the development of new and effective antiviral agents.

Animals↗
PubMed1989

An experimental study of the anti-HSV-II action of 500 herbal drugs.

Experimental assessments were made on the anti-HSV-II action of 500 herbs by determinations of the virus inhibition logarithm (VIL). 13 highly effective herbs (VIL greater than or equal to 4.00) were screened cut, providing a rational basis for clinical therapy. Among these effective herbs, 10 were aqueous extracts of Artemisia anomala, Centella asiatica, Epimedium Sagittatum, Hibiscus mutabilis, Hosta plantaginea, Hypericum japonicum, Inula japonica, Mosla punctata, Rhododendron simsii, and Rhus chinenses, while 3 were alcohol extracts of Epimedium Sagittatum, Hypericum japonicum, and Mosla punctata.

Antiviral Agents↗