Herbal medicine: the science of the art

In the last 50 years science has provided new perspectives on the ancient art of herbal medicine. The present article discusses ways in which the evidence base for the professional use of 'Western' herbal medicine, as therapy to treat disease, known as phytotherapy, can be strengthened and developed. The evidence base for phytotherapy is small and lags behind that for the nutritional sciences, mainly because phytochemicals are ingested as complex mixtures that are incompletely characterised and have only relatively recently been subject to scientific scrutiny. While some methodologies developed for the nutritional sciences can inform phytotherapy research, opportunities for observational studies are more limited, although greater use could be made of patient case notes. Randomised clinical trials of single-herb interventions are relatively easy to undertake and increasing numbers of such studies are being published. Indeed, enough data are available on three herbs (ginkgo (Ginkgo biloba), St John's wort (Hypericum perforatum) and saw palmetto (Serenoa repens)) for meta-analyses to have been undertaken. However, phytotherapy is holistic therapy, using lifestyle advice, nutrition and individually-prescribed mixtures of herbs aimed at reinstating homeostasis. While clinical experience shows that this approach is applicable to a wide range of conditions, including chronic disease, evidence of its efficacy is scarce. Strategies for investigating the full holistic approach of phytotherapy and its main elements are discussed and illustrated through the author's studies at the University of Reading.

Effect of antidepressants on melatonin metabolite in depressed patients

Antidepressants increase melatonin levels, but it is still unclear whether this effect is related to the improvement of depressive symptoms or to unrelated pharmacological action of antidepressants. To answer this question, the effect of antidepressants on 6-sulphatoxymelatonin (aMT6s), the main melatonin urinary metabolite, was examined in drug-free depressed patients - most of them antidepressant-naive. aMT6s was evaluated in 34 depressed patients, before and after 8 weeks of placebo (n = 12) or antidepressant (n = 22; fluoxetine, duloxetine or Hypericum perforatum). Both groups showed an improvement of depressive symptoms after treatment compared to baseline (Hamilton Depression scores): 17.0 +/- 1.4 vs. 9.0 +/- 2.8, P = 0.007 for placebo, and 18.6 +/- 1.1 vs. 11.8 +/- 1.6, P < 0.001 for antidepressants). After treatment, aMT6s levels increased after antidepressants (P < 0.01), but not after placebo (P > 0.05). As depressive symptoms improved both in patients taking antidepressant and in those taking placebo, but an effect of antidepressants could only be seen in those taking antidepressants, we suggest that melatonin changes after antidepressants are more likely due to a pharmacological action of these drugs on melatonin secretion.

Estudo da qualidade da informação constante nas bulas dos principais medicamentos fitoterápicos registrados no Brasil

Os objetivos deste trabalho foram: fazer um levantamento das dez espécies vegetais que compõem o maior número de apresentações farmacêuticas de fitoterápicos simples registradas na ANVISA; realizar o diagnóstico da oferta e da qualidade das informações contidas nas bulas das apresentações contendo as cinco espécies vegetais mais utilizadas; e definir as informações técnicas que devem estar contidas na bula de especialidades farmacêuticas que contenham como ingredientes ativos unicamente extratos preparados a partir destas espécies. O levantamento das dez espécies vegetais abrangeu o período de 01/01/1998 a 30/06/2003 e foi realizado através de consulta ao OPTLINE (www.i-helps.com). Os medicamentos fitoterápicos representam 7,76% (1888) das apresentações de registro de medicamentos no Brasil, sendo 1311 (5,38 %) apresentações de medicamentos fitoterápicos simples. Cinqüenta e oito espécies vegetais constituíam os registros de medicamentos fitoterápicos simples, sendo as dez com maior número de apresentações Ginkgo biloba L.: 302 (23,04%); Hypericum perforatum L.: 126 (9,61%); Piper methysticum F.: 87 (6,64%); Cimicifuga racemosa Nutt: 79 (6,03%); Valeriana officinalis L.: 76 (5,80%); Vitis vinifera L.: 69 (5,26%); Echinacea purpurea L.: 58 (4,42%); Aesculus hippocastanum L.: 53 (4,04%); Panax ginseng C. A Mayer: 48 (3,66%) e Cynara scolymus L.: 31 (2,36%). O diagnóstico da oferta e da qualidade das informações contidas nos textos das bulas foi realizado comparando-se estas informações com aquelas apresentadas na base de dados Medline (PubMed - www.ncbi.nhm.nhi.gov) dos últimos 5 anos e em obras bibliográficas de referência aceitas pela ANVISA, além de outras, clássicas na área de farmacognosia e fitoterapia . Foram avaliadas vinte e oito bulas. As informações de todas as bulas apresentavam incompatibilidades com as informações da literatura consultada. Os problemas mais freqüentemente encontrados foram relativos à sinonímia popular, eficácia, via de administração, contra-indicações, uso em idosos, crianças e grupos de risco, reações adversas e interações medicamentosas. Para cada uma das cinco espécies mais citadas, as informações científicas e técnicas compiladas foram organizadas como uma proposta de bula para o Profissional de Saúde a ser incluída no Compêndio de Bulas de Medicamentos (CBM), conforme previsto na Resolução-RDC nº 140/03, o qual consiste em um conjunto de bulas de medicamentos comercializados, editado pelo órgão regulador e com conteúdo da bula para o paciente e da bula para o profissional de saúde.

Enraizamento de plantas cultivadas in vitro

The adventitious rooting process of in vitro cultured plantlets is a technique that has been employed for the vegetative propagation of a significant number of native and exotic species. Many factors are associated with the rooting stage influencing positive and/or negatively the establishment of micropropagation protocols. The objective of this work was a literature review of the main inherent factors concerning in vitro rooting process including the correlation among others the endogenous and exogenous auxins levels, juvenility, genotype, mineral nutrition, culture medium conditions, addition of growth regulators and other substances as phenolic compounds and active coal besides growth environmental conditions of in vitro cultures. Although the complete elucidation of all processes involved with rooting of in vitro cultured plants has not been achieved so far, a comprehensive study of the main factors that interfere on rooting is fundamental for the establishment of new researches that might contribute for the rooting of economically important plants.

Local clinical phototreatment of herpes infection in Sao Paulo

The clinical use of topical photodynamic therapy in herpes simplex lesions in Sao Paulo is presented and discussed. Although previous attempts utilising this type of approach in the USA were discontinued in the early 1970s due to several presentations of post-treatment Bowen's disease, none of the cases from the clinic presented here have displayed any complications on follow-up. In addition, lesion recrudescence periods are generally much longer than with conventional approaches. This is thought to be due to improvements in the treatment protocol, viz, use of the non-toxic photosensitisers methylene blue and Hypericum perforatum extract in place of proflavine and neutral red in the original trials, differences in photosensitisation pathway and illumination of the treatment site with red rather than fluorescent/UV light. Post-treatment cosmesis is also excellent. (C) 2012 Elsevier B.V. All rights reserved.

Zentrale cholinerge Wirkungen von Hyperforin, einem Inhaltsstoff des Johanniskrauts

Die vorliegende Arbeit beschreibt die Wirkung von Hyperforin, einem Johanniskraut-Inhaltsstoff, auf das zentrale cholinerge System. Da der HACU Na+-abhängig operiert und Hyperforin den transmembranären Na+-Gradienten verringert, wurde an Rattenkortex-Synaptosomen in vitro geprüft, ob der HACU durch Hyperforin gehemmt wird. Es wurde gefunden, dass Hyperforin den HACU mit einer Hemmkonstante IC50 von 8.5 µM inhibiert. Da die de novo-ACh-Synthese direkt HACU-Aktivitäts-abhängig ist, wurde in vivo mittels Mikrodialyse-Technik verifziert, ob die cholinerge Transmission beeinflusst wird. Lokale Infusionen von 100 µM Hyperforin in das Striatum resultierten in einer Reduktion der ACh-Freisetzung bei parallelem Ch-Spiegel-Anstieg bedingt durch die HACU-Inhibition. Infusionen niedrigerer Konzentration (10 und 30 µM) führten hingegen zu einer konzentrations-abhängigen Stimulation der ACh-Freisetzung bei simultaner Ch-Spiegel-Senkung. Systemische Applikation von 1 und 10 mg/kg i.p. resultierten in einer verstärkten ACh-Freisetzung im Striatum und im Hippokampus; diese Dosen führen zu therapeutisch relevanten Plasmaspiegeln. Die Ergebnisse im Striatum und im Hippokampus erklären die motilitätsverringernden Effekte im Tierexperiment bzw. die benignen Effekte in Verhaltensmodellen für Lernen und Gedächtnis. Die vergleichende Analyse der Mikrodialyse-Experimente ergab, dass eine antidepressive Johanniskraut-Begleitmedikation bei Parkinson ungünstig, jedoch Alzheimer günstig zu bewerten ist.

Post-surgical scalp wounds with exposed bone treated with a plant-derived wound therapeutic

To evaluate the efficacy of a plant-derived wound dressing, a mixture of hypericum oil (Hypericum perforatum) and neem oil (Azadirachta indica), in scalp wounds with exposed bone.

A homeopathic remedy from arnica, marigold, St. John's wort and comfrey accelerates in vitro wound scratch closure of NIH 3T3 fibroblasts

Background Drugs of plant origin such as Arnica montana, Calendula officinalis or Hypericum perforatum have been frequently used to promote wound healing. While their effect on wound healing using preparations at pharmacological concentrations was supported by several in vitro and clinical studies, investigations of herbal homeopathic remedies on wound healing process are rare. The objective of this study was to investigate the effect of a commercial low potency homeopathic remedy Similasan® Arnica plus Spray on wound closure in a controlled, blind trial in vitro. Methods We investigated the effect of an ethanolic preparation composed of equal parts of Arnica montana 4x, Calendula officinalis 4x, Hypericum perforatum 4x and Symphytum officinale 6x (0712–2), its succussed hydroalcoholic solvent (0712–1) and unsuccussed solvent (0712–3) on NIH 3T3 fibroblasts. Cell viability was determined by WST-1 assay, cell growth using BrdU uptake, cell migration by chemotaxis assay and wound closure by CytoSelect ™Wound Healing Assay Kit which generated a defined “wound field”. All assays were performed in three independent controlled experiments. Results None of the three substances affected cell viability and none showed a stimulating effect on cell proliferation. Preparation (0712–2) exerted a stimulating effect on fibroblast migration (31.9%) vs 14.7% with succussed solvent (0712–1) at 1:100 dilutions (p < 0.001). Unsuccussed solvent (0712–3) had no influence on cell migration (6.3%; p > 0.05). Preparation (0712–2) at a dilution of 1:100 promoted in vitro wound closure by 59.5% and differed significantly (p < 0.001) from succussed solvent (0712–1), which caused 22.1% wound closure. Conclusion Results of this study showed that the low potency homeopathic remedy (0712–2) exerted in vitro wound closure potential in NIH 3T3 fibroblasts. This effect resulted from stimulation of fibroblasts motility rather than of their mitosis.

Influence of an electromagnetic field on high dilutions measured by ultraviolet light spectroscopy

Background: High dilutions of various starting materials, e.g. copper sulfate, Hypericum perforatum and sulfur, showed significant differences from controls and amongst different dilution levels in ultraviolet light (UV) transmission [1,2]. Exposure of high dilutions to external physical factors such as UV light or elevated temperature (37°C) also yielded significantly different UV transmissions compared to unexposed dilutions [2,3]. In a study with highland frogs it was shown that animals incubated with thyroxine 30c but not with thyroxine 30c exposed to electromagnetic fields (EMFs) of a microwave oven or mobile phone metamorphosed more slowly than control animals [4]. Aims: The aim was to test whether the EMF of a mobile phone influences the UV absorbance of dilutions of quartz and Atropa belladonna (AB). Methodology: Commercially available dilutions of 6x, 12x, 15x, 30x in H2O and 19% ethanol of quartz (SiO2) and of 4x, 6x, 12x, 15x, 30x in H2O and 19% ethanol of AB were used in the experiments (Weleda AG, Arlesheim, Switzerland). Four samples of each dilution were exposed to the EMF of a mobile phone (Philips, Savvy Dual Band) at 900 MHz with an output of 2 W for 3 h, while control samples (4 of each dilution) were kept in a separate room. Absorbance of the samples in the UV range (from 190 to 340 nm) was measured in a randomized order with a Shimadzu UV-1800 spectrophotometer equipped with an auto sampler. In total 5 separate measurement days will be carried out for quartz and for AB dilutions. The average absorbance from 200 to 340 nm and from 200 to 240 nm was compared among dilution levels using a Kruskal-Wallis test and between exposed and unexposed samples using a Mann-Whitney-U test. Results: Preliminary results after 2 measurement days indicated that for quartz the absorbance of the various dilution levels was different from each other (except 12x and 15x), and that samples exposed to an EMF did not show a difference in UV absorbance from unexposed samples. Preliminary results after one measurement day indicated that for AB the absorbance of the various dilution levels was different from each other. The samples exposed to an EMF did not show a difference in UV absorbance from unexposed samples (except 4x in the range from 200 – 240 nm). Conclusions: These results suggest that exposure of high dilutions of quartz and AB to a mobile phone EMF as used here does not alter UV absorbance of these dilutions. The final results will show whether this holds true.

Comparison of globules prepared from high dilutions of various starting materials by ultraviolet light spectroscopy

Background: High and ultra-high dilutions of various starting materials, e.g. copper sulfate, Hypericum perforatum and sulfur, showed significant differences in ultraviolet light (UV) transmission from controls and amongst different dilution levels [1,2]. Verum and placebo globules of Aconitum napellus 30c or calcium carbonate/quercus e cortice 6x from the same packs as used in previous clinical trials and dissolved in water could be distinguished by UV spectroscopy [3]. However, it was unclear whether the differences in UV absorbance originated from specific characteristics of the starting materials, from differences in the production of verum and placebo globules, and/or other unknown interference factors. Aims: The aim of this study was to investigate whether globules produced with high and ultra-high dilutions (6x, 12x, 30c, 200c, 200CF (centesimal discontinuous fluxion), 10,000CF) of various starting materials (Aconitum napellus, Atropa belladonna, phosphorus, sulfur, Apis mellifica, quartz) could be distinguished by UV spectroscopy. Methodology: The globules were specially produced for this study by Spagyros AG (Gümligen, Switzerland) and differed only in the starting materials of the dilutions (but not in the batch of globules or ethanol used). Globules were dissolved in water at 10 mg/ml, in quadruplicates, approximately 22 h prior to the measurements. Absorbance of the samples in the UV range (from 190 to 340 nm) was measured in a randomized order with a Shimadzu double beam UV-1800 spectrophotometer equipped with an auto sampler. Samples of each starting material were prepared and measured on 5 independent days. The daily variations of the spectrophotometer as well as the drift during the measurements were corrected for. The average absorbance from 200 to 340 nm was compared among various starting materials within equal dilution levels using a Kruskal-Wallis test. Results: Statistically significant differences were found among 30c (Figure 1), 200c and 200CF dilutions of the various starting materials. No differences were found among 6x, 12x and 10,000CF dilutions. Conclusions: Globules prepared from high dilutions of various starting materials may show significantly different UV absorbance when dissolved in water. References [1] Wolf U, Wolf M, Heusser P, Thurneysen A, Baumgartner S. Homeopathic preparations of quartz, sulfur and copper sulfate assessed by UV-spectroscopy. Evid Based Complement Alternat Med. 2011;2011:692798. [2] Klein SD, Sandig A, Baumgartner S, Wolf U. Differences in median ultraviolet light transmissions of serial homeopathic dilutions of copper sulfate, Hypericum perforatum, and sulfur. Evid Based Complement Alternat Med. 2013;2013:370609. [3] Klein SD, Wolf U. Investigating homeopathic verum and placebo globules with ultraviolet spectroscopy. Forsch Komplementmed. 2013, accepted.

Pollen profiles from 8 sediment cores from the Degersee, Southern Germany

The discovery of a neolithic pile field in the shallow water near the eastern shore of the Degersee confirmed earlier palynological and sedimentological studies stating that early man was active in the region since more than 6000 years. The already available off-site data were freshly assessed, completed by additional data from old and new cores and the interpretations revised. A common time scale for the off-site data and the on-site data was obtained by AMS dating of terrestrial macro remains of the neolithic section of off-site core De_I+De_H. The ages can thus be parallelled with AMS ages of construction timber on-site. Pollen analyses from all cores provide a further time scale. The continuously and densely sampled pollen profile of the profundal zone embracing the entire Late glacial and Holocene serves as a reference. From the Boreal onwards the relative ages are transformed by AMS ages and varve counts into calibrated and absolute. A transect cored close to the neolithic pile field across the lake marl-platform demonstrates its geological architecture in the shallow water since the Lateglacial. Studies of the microfabric of thin sections of drilled cores and of box cores from the excavations demonstrate that neolithic settlements now at 2-3,5 m water depth had been erected on lake marl freshly fallen dry, thus indicating earlier lake levels dropped by 1.5-2 m. The neolithic section of the highly resolved off-site profile in the lake=s profundal zone has laminated and calcareous zones alternating with massive ones. Assemblages of diatoms and concentrations of trace elements changing simultaneously characterise the calcareous sections as deposits of low lake levels that lasted between some 40 and more than 300 years. The ages of discovered lake shore dwellings fall into calcareous segments with low lake levels. From the end of the Upper Atlantic period (F VII) appear Secondary Forest Cycles in the beech forest, a man-made sequence of repeated vegetational development with an identical pattern: With a decrease of beech pollen appear pollen of grasses, herbs and cultural indicators. These are suppressed by the light demanding hazel and birch, those again by ash, and finally by the shade demanding beech forming a new pollen peak. Seven main Forest Cycles are identified In the upper Neolithic period each comprising some 250, 450 or 800 years. They are subdivided into subcycles that can be broken down by very dense sampling in even shorter cycles of decadal length. Farming settlers have caused minor patchy clearances of the beech-mixed-forest with the use of fire. The phases of clearance coincide with peaks of charcoal and low stands of the lake levels. The Secondary Forest Cycles and the continuous occurrence of charcoal prove a continued occupation of the region. Together with the repeated restoration of the beech climax forest they point to pulsating occupation probably associated with dynamic demography. The synchronism of the many palynological, sedimentological and archaeological data point to an external forcing as the climate that affects comprehensively all these proxies. The fluctuations of the activity of the sun as manifested in the residual d14C go largely along with the proxies. The initial clearances at the begin of the forest cycles are linked to low lake levels and negative values of d14C that point to dry and warm phases of a more continental climate type. The subcycles exist independent from climatic changes, indicating that early man acted largely independent from external forces.

High-resolution multi-proxy record of the last glacial period from Lake Van, eastern Anatolian high plateau, Turkey

Detailed analyses of the Lake Van pollen, Ca/K ratio and stable oxygen isotope record allow the identification of millennial-scale vegetation and environmental changes in eastern Anatolia throughout the last glacial (~75-15 ka BP). The climate within the last glacial was cold and dry, with low arboreal pollen (AP) levels. The driest and coldest period corresponds to Marine Isotope Stage (MIS) 2 (~28-14.5 ka BP) dominated by the highest values of xerophytic steppe vegetation. Our high-resolution multi proxy record shows rapid expansions and contractions of tree populations that reflects variability in temperature and moisture availability. This rapid vegetation and environmental changes can be linked to the stadial-interstadial pattern of the Dansgaard-Oeschger (DO) events as recorded in the Greenland ice cores. Periods of reduced moisture availability were characterized by enhanced xerophytic species and high terrigenous input from the Lake Van catchment area. Furthermore, comparison with the marine realm reveals that the complex atmosphere-ocean interaction can be explained by the strength and position of the westerlies, which is responsible for the supply of humidity in eastern Anatolia. Influenced by diverse topography of the Lake Van catchment, larger DO interstadials (e.g. DO 19, 17-16, 14, 12 and 8) show the highest expansion of temperate species within the last glacial. However, Heinrich events (HE), characterized by highest concentrations of ice-rafted debris (IRD) in marine sediments, are identified in eastern Anatolia by AP values not lower and high steppe components not more abundant than during DO stadials. In addition, this work is a first attempt to establish a continuous microscopic charcoal record over the last glacial in the Near East, which documents an initial immediate response to millennial-scale climate and environmental variability and enables us to shed light on the history of fire activity during the last glacial.