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)

Alcohol, nutrition and health maintenance: selected aspects

In view of the developments in health care relating to the increased prevalence and incidence of chronic diseases and the continuing increase in health-care expenditure, more attention should be paid to health maintenance and disease prevention. Any strategy that can influence health maintenance is of interest, especially lifestyle factors such as nutrition, exercise or stress control. Alcohol has an important place in the daily life of many healthy as well as sick individuals. Alcohol has three major characteristics; it is a nutrient (energy source), a psycho-active drug and a toxin. Each consumer has the choice of which of the characteristics of alcohol he/she wants to utilise. Thus, alcohol represents one of the most important self-implemented disease modifiers in our modern society. The major determinants of the health effects of alcohol are the absolute amount consumed, the consumption frequency, associated lifestyle factors (e.g. smoking, nutrient intake, substrate composition, physical activity pattern) and last, but not least, the genetic background. There are few known disease conditions that have not already been associated positively or negatively with alcohol consumption. The list of diseases includes atherosclerosis, dementia, diabetes, obesity and conditions relating to Zn metabolism. Obesity represents the most important disease modifier in the world and the prevalence rates are increasing rapidly. Evidence suggests that alcohol represents a risk factor for overweight and obesity as a result of specific effects on energy metabolism and substrate metabolism. The potential role of alcohol as an important modulator for the postprandial lipidaemia and its role in the pathogenesis of modern diseases will be discusse

Alcohol and Mortality: If You Drink, Do Not Forget Fruits and Vegetables

Moderate amounts of alcohol may have cardioprotective effects. Several studies reported a higher protection by the consumption of wine. The favorable effects of wine have been attributed to different polyphenol compounds, among others. However, these biochemical compounds are also found in other beverages. In view of the present evidence, there is no "right” or "wrong” drink, only a "right” and "wrong” drinking behavior regarding absolute amounts, drinking frequency, and accompanying lifestyle and eating patter

Power sums of Coxeter exponents

Consider an irreducible finite Coxeter system. We show that for any nonnegative integer n the sum of the nth powers of the Coxeter exponents can be written uniformly as a polynomial in four parameters: h (the Coxeter number), r (the rank), and two further parameters.Comment: 14 page

An Evaluation of the area stratification used for sampling tunas in the eastern Pacific Ocean and implications for estimating total annual catches

The Inter-American Tropical Tuna Commission (IATTC) staff has been sampling the size distributions of tunas in the eastern Pacific Ocean (EPO) since 1954, and the species composition of the catches since 2000. The IATTC staff use the data from the species composition samples, in conjunction with observer and/or logbook data, and unloading data from the canneries to estimate the total annual catches of yellowfin (Thunnus albacares), skipjack (Katsuwonus pelamis), and bigeye (Thunnus obesus) tunas. These sample data are collected based on a stratified sampling design. I propose an update of the stratification of the EPO into more homogenous areas in order to reduce the variance in the estimates of the total annual catches and incorporate the geographical shifts resulting from the expansion of the floating-object fishery during the 1990s. The sampling model used by the IATTC is a stratified two-stage (cluster) random sampling design with first stage units varying (unequal) in size. The strata are month, area, and set type. Wells, the first cluster stage, are selected to be sampled only if all of the fish were caught in the same month, same area, and same set type. Fish, the second cluster stage, are sampled for lengths, and independently, for species composition of the catch. The EPO is divided into 13 sampling areas, which were defined in 1968, based on the catch distributions of yellowfin and skipjack tunas. This area stratification does not reflect the multi-species, multi-set-type fishery of today. In order to define more homogenous areas, I used agglomerative cluster analysis to look for groupings of the size data and the catch and effort data for 2000–2006. I plotted the results from both datasets against the IATTC Sampling Areas, and then created new areas. I also used the results of the cluster analysis to update the substitution scheme for strata with catch, but no sample. I then calculated the total annual catch (and variance) by species by stratifying the data into new Proposed Sampling Areas and compared the results to those reported by the IATTC. Results showed that re-stratifying the areas produced smaller variances of the catch estimates for some species in some years, but the results were not significant