Safety of herbal medicinal products: Echinacea and selected alkylamides do not induce CYP3A4 mRNA expression

Copyright © 2011 Maryam Modarai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.A major safety concern with the use of herbal medicinal products (HMP) is their interactions with conventional medicines, which are often mediated via the cytochrome P450 (CYP) system. Echinacea is a widely used over-the-counter HMP, with proven immunomodulatory properties. Its increasing use makes research into its safety an urgent concern. Previously, we showed that Echinacea extracts and its alkylamides (thought to be important for Echinacea's immunomodulatory activity) mildly inhibit the enzymatic activity of the main drug metabolising CYP isoforms, but to this date, there is insufficient work on its ability to alter CYP expression levels. We now report for the first time the effect of a commercial Echinacea extract (Echinaforce) and four Echinacea alkylamides on the transcription of the major drug metabolizing enzyme CYP3A4. HepG2 cells were exposed for 96 h to clinically relevant concentrations of Echinaforce (22, 11.6 and 1.16g mL-1) or the alkylamides (1.62 and 44 nM). CYP3A4 mRNA levels were quantified using real-time reverse transcription polymerase chain reaction (RT-PCR). Neither Echinaforce nor the alkylamides produced any significant changes in the steady-state CYP3A4 mRNA levels, under these conditions. In contrast, treatment with 50M rifampicin resulted in a 3.8-fold up-regulation over the vehicle control. We conclude that Echinaforce is unlikely to affect CYP3A4 transcriptional levels, even at concentrations which can inhibit the enzymatic activity of CYP3A4. Overall, our data provides further evidence for the lack of interactions between Echinacea and conventional drugs.Bioforce, Switzerland and the Maplethorpe Trust (University of London)

Transforming mesoscale granular plasticity through particle shape

When an amorphous material is strained beyond the point of yielding it enters a state of continual reconfiguration via dissipative, avalanche-like slip events that relieve built-up local stress. However, how the statistics of such events depend on local interactions among the constituent units remains debated. To address this we perform experiments on granular material in which we use particle shape to vary the interactions systematically. Granular material, confined under constant pressure boundary conditions, is uniaxially compressed while stress is measured and internal rearrangements are imaged with x-rays. We introduce volatility, a quantity from economic theory, as a powerful new tool to quantify the magnitude of stress fluctuations, finding systematic, shape-dependent trends. For all 22 investigated shapes the magnitude $s$ of relaxation events is well-fit by a truncated power law distribution $P(s)\sim {s}^{-\tau} exp(-s/s^*)$, as has been proposed within the context of plasticity models. The power law exponent $\tau$ for all shapes tested clusters around $\tau=$ 1.5, within experimental uncertainty covering the range 1.3 - 1.7. The shape independence of $\tau$ and its compatibility with mean field models indicate that the granularity of the system, but not particle shape, modifies the stress redistribution after a slip event away from that of continuum elasticity. Meanwhile, the characteristic maximum event size $s^*$ changes by two orders of magnitude and tracks the shape dependence of volatility. Particle shape in granular materials is therefore a powerful new factor influencing the distance at which an amorphous system operates from scale-free criticality. These experimental results are not captured by current models and suggest a need to reexamine the mechanisms driving mesoscale plastic deformation in amorphous systems.Comment: 11 pages, 8 figures. v3 adds a new appendix and figure about event rates and changes several parts the tex

Value Chains of Botanical and Herbal Medicinal Products: A European Perspective

In recent years, the quality of botanicals has come under increased scrutiny. Despite the availability of numerous high-quality products from reputable companies, health care professionals, patients, and consumers are understandably concerned about questionable botanical ingredients in various consumer products. In Europe, this includes products that are generally unlicensed and unregistered supplements (also referred to as “botanicals”), which are often poorly regulated, or even totally unregulated, depending on the country of jurisdiction

Exchange coupling between magnetic layers across non-magnetic superlattices

The oscillation periods of the interlayer exchange coupling are investigated when two magnetic layers are separated by a metallic superlattice of two distinct non-magnetic materials. In spite of the conventional behaviour of the coupling as a function of the spacer thickness, new periods arise when the coupling is looked upon as a function of the number of cells of the superlattice. The new periodicity results from the deformation of the corresponding Fermi surface, which is explicitly related to a few controllable parameters, allowing the oscillation periods to be tuned.Comment: 13 pages; 5 figures; To appear in J. Phys.: Cond. Matte

Medicinal plant analysis: A historical and regional discussion of Chinese publication trends and emergent complex techniques

The analysis of medicinal plants has had a long history, and especially with regard to assessing a plant’s quality. The first techniques were organoleptic using the physical senses of taste, smell, and appearance. Then gradually these led on to more advanced instrumental techniques. Though different countries have their own traditional medicines China currently leads the way in terms of the number of publications focused on medicinal plant analysis and number of inclusions in their Pharmacopoeia. The monographs contained within these publications give directions on the type of analysis that should be performed, and for manufacturers, this typically means that they need access to more and more advanced instrumentation. We have seen developments in many areas of analytical analysis and particularly the development of chromatographic and spectroscopic methods and the hyphenation of these techniques. The ability to process data using multivariate analysis software has opened the door to metabolomics giving us greater capacity to understand the many variations of chemical compounds occurring within medicinal plants, allowing us to have greater certainty of not only the quality of the plants and medicines but also of their suitability for clinical research. Refinements in technology have resulted in the ability to analyze and categorize plants effectively and be able to detect contaminants and adulterants occurring at very low levels. However, advances in technology cannot provide us with all the answers we need in order to deliver high-quality herbal medicines and the more traditional techniques of assessing quality remain as important today

Double beta decay versus cosmology: Majorana CP phases and nuclear matrix elements

We discuss the relation between the absolute neutrino mass scale, the effective mass measured in neutrinoless double beta decay, and the Majorana CP phases. Emphasis is placed on estimating the upper bound on the nuclear matrix element entering calculations of the double beta decay half life. Consequently, one of the Majorana CP phases can be constrained when combining the claimed evidence for neutrinoless double beta decay with the neutrino mass bound from cosmology.Comment: 11 pages, 3 figure

Collectors of Rhodiola species on the Sichuan-Tibetan and Sichuan-Shaanxi borders

Medicinal Rhodiola species, including Rhodiola rosea L. and Rhodiola crenulata (Hook.f. & Thomson) H.Ohba, have been widely used as traditional herbal medicines with numerous claims for their therapeutic effects. Faced with resource depletion, environment destruction and higher demand, R. rosea and R. crenulata are becoming endangered, making them economically even more valuable, but also increasing the risk of adulteration and low quality - and raising awareness for the role of often unlicensed collectors and middlemen. Although R. rosea is the most well known in Europe, R. crenulata is the recognised species in China. On the border of Sichuan and Tibet, members of the Yi minority collect R. crenulata in order to sell it to the “traditional” Chinese medicine market. Collection of this medicinal herb represents about one third of the annual income for the Yi. Three times a year they climb up to 5,000 metres in search of the plants. As it is stripped out, the Yi have to travel to more and more inhospitable places to ensure its supply. At Taibai mountain along the border of Sichuan and Shaanxi, the same medicinal plant, hongjingtian in Chinese, is growing in the wild, too. Yet, in a socioeconomic context, collectors do not have a particular ethnic background such as Yi, Tibetan or Han collectors. Here, the collectors are various unlicensed providers-cum-prescribers 'caoyi'. (The term does not mean herb-physician, as one might assume from terms such as caoyao (herbals). It means unofficial or not following the scholarly standard.) Using neither an ethnic identity nor the general botanical terms in Latin, they claim Daoism and terroir of their mountain as a sign of good quality ‘Taibai hongjingtian’. There appears to be no strategy in place to protect the species across all those socioeconomic, ethnic and provincial boundaries, and without some intervention it is likely that R. crenulata will eventually become so rare that it can no longer be collected in the current quantities. This will have consequences both for the livelihoods of the Yi and of various Caoyi, and also for the conservation of R. Crenulata and it’s sustainability