http://www.nutraceut...BT_NovDec08.pdf
activate yOur mind!
The wild green oat herb extract, Neuravena, is scientifically proven to enhance stress resistance, learning ability and alertness.
Although green oat herb preparations have traditionally been used tosupport mental fitness and cognitive function since medieval times, the ability to utilize these properties in modern-day nutraceuticals, food supplements andfunctional foods is contingent on solid scientific evidence. Efficacy, safety and quality take centre stage in the herbal extractsmarket and formulators are increasingly demanding ingredients with product-specific data to substantiate health-related claims. Common bibliographic data are often not sufficient, as the pharmacological profile of different herbal extracts can vary dramatically.
Using modern scientific methods, Frutarom has been able to substantiate the beneficial effects of the wild green oat herb extract, Neuravena EFLA 955, derived from a specific oat variety. Initially, Neuravena was selected from a large range of different oat varieties, because of its superior bioactivity, using abioassay-guided development approach. Its selective effects on brain enzymes were then backed up by convincing evidence from animal studies and, most recently, from a human clinical trial. The results indicated a promising avenue for using Neuravena as a safe and natural ingredient for food supplements, nutraceuticals and functional foods targeted at improving mental fitness, stress resistance and learning abilities.
Bioassay-Guided Approach: Screening for Evidence
The clinical effect of a herbal extract cannotbe attributed to one single substance; it is the result of the synergistic interplay of allof the extract’s constituents. The genetic and phenotypic variability of a plant, as wellas the extraction and refining technologies used when developing a multicomponent herbal extract, are critical when it comes to maximizing the health benefits and minimizing the side-effects of the final product. Bioassay-guided development is a state-of-the-art research method for the rational development of efficacious and safe herbal extracts. The impact of different plant varieties and extract preparation methods on the efficacy of the extract can be assessed by screening its bioactivity profile from the raw material up tothe final product in vitro (Figure 1). Similarly, safety and tolerance aspects of possible concern, such as liver toxicity and the presence of unwanted enzyme activities (such as cytochrome P450 oxygenases) can be monitored. These are important for determiningthe extract’s drug interaction potential and safety profile. Hence, bioassay-guided development is not just used to substantiate traditional or novel areas of indication, it also provides a scientific basis for the rational selection of raw materials and processtechnologies that are best suited to design safe and efficient herbal extracts
Activity Profile
In line with Frutarom’s drive for safety and quality, dozens of different varieties of green oats were screened for their activity in various Central Nervous System (CNS) test systems that examined various targets associated with the traditional uses of green oats. The activity screening focused on 36 old and wild type varieties with high secondary or ‘traditional’ plant metabolite profiles. The bioassay screenings of these oat varieties revealed a clinically significant inhibitory effect on two enzymes that are closely connected to mental health and cognitive function: monoamine oxidase B (MAO-B) and phosphodiesterase 4 (PDE 4). Depending on which variety was used to source the raw material, the inhibitory activity of the extract on the two enzymes varied dramatically (Figure 2). Using the best performing green oat variety, Neuravena, the bioassay-oriented process was further developed: extraction procedures and key manufacturing parameters were evaluated to identify critical steps. In the meantime, the contract growing of Neuravena ensured consistent raw material quality. The dual activity profile of bioactivity-tested green oat extracts on MAO-B and PDE 4 provided a reliable, pharmacological basis on which to confirm the traditional indication profile of green oat extracts.
Animal Trial Results
To assess the activity profile of Neuravena in further detail, the impact of an oral application of the extract on the brain’s electrical activity was investigated in freely moving rats using a continuous in vivo analysis of brain field potentials (Tele-Stereo-EEG). The extract was found to attenuate brain activity in nearly all frequency ranges, indicating activated behaviour. Neuravena seems to stimulate the dopaminergic (DA) transmitter system, which is implicated in cognitive functioning and motivation and is related to depression. The main changes were observed within the hippocampus, a brain area closely connected to memory (Figure 3). In the model used in this study, the extract approached the results obtained from drugs used to treat dementia. Additionally, the results of placebo-controlled trials in rats investigating the effects of Neuravena on behaviour concluded that the extract improves general learning performance and speed of learning, ameliorates stress-coping abilities and increases alertness. Moreover, test animals clearly displayed increased social interest and improved reactions to social signals, indicating Neuravena’s positive effect on ‘soft’ skills such as social intelligence. The findings of both in vivo trials revealed a strong correlation with the pharmacological activity profile of Neuravena on MAO-B and PDE 4 found in the bioassay-guided development process, reinforcing its mode of action as well as its indications.
Human Study: Significant Changes in Brain Activity
Following the successful in vitro and animaltrials, the impact of Neuravena on mental fitness and cognitive performance under stressful situations was assessed in humans using quantitative measurements of electrical brain activity. This study was conducted in Germany by Prof. Dr Dimpfel, Neurocode AG (see sidebar), according to GCP (Good Clinical Practice). The randomized, double-blind,placebo-controlled, crossover clinical studycomprised 20 healthy men and women, aged46.5 ± 8.2 years, who ingested one single dose of 2500 mg Neuravena or a placebo. During a period of 4 hours, their baseline brainactivity signals were recorded and analysed. Brain activity was also measured while the participants were subjected to mental pressure during standardized concentration stress and performance tests.
By convention, brain activity signals are expressed in six different frequency ranges: delta, theta, alpha 1 and 2, and beta 1 and 2. As each frequency range characterizes the activity of specific signalling substances in the brain, and different brain regions are related to certain tasks, the overall pattern of how brain activity is influenced by Neuravena can be related to changes in human behaviour. Whereas delta wave brain activity seems to be modulated by the cholinergic transmitter system, theta brain activity is related to the neurotransmitter, noradrenaline. In humans, delta and theta waves have been linked to cognitive and memory performance. Neuravena was found to significantly change the brain activity of the study participants. A considerable decrease in delta and theta baseline wave activity was observed, particularly in brain regions closely connected to cognitive performance. In addition, alpha 2 wave activity increased.
These changes are related to improved concentration, learning and memory, as well as stimulatory properties. It can therefore be concluded that Neuravena improves overall mental fitness in everyday life and can help to avoid dips in cognitive performance during the course of the day. Both theta and delta wave activity was significantly increased during the concentration stress and performancetests in the Neuravena group (Figure 4). As activity levels at resting conditions are low, greater increases in delta and theta wave activity can be achieved during mental work, corresponding to better performance. This finding confirms that Neuravena positively influences brain activity under pressure and thus helps to improve concentration, learning and alertness during stressful situations.
A different way to look at the brain’s communication structure is to transform the results of the frequency analysis into spectral colours. With this special kind of “brain mapping” (see sidebar), the impact of Neuravena on brain activity during the performance of different mental tasks can be visualized in an “Electropsychogram.” The changes occurring during the performance of the concentration stress and performance testsconfirm that Neuravena specifically affects the left temple/forefront area of the brain, which is implicated in cognitive function (Figure 5).
Tailored Product Concepts for a Growing Market
Looking at the evidence presented in this article, it can be concluded that bioactivity-tested green oat extracts, such as Neuravena, are safe and natural new candidates for the emerging market of products that support mental fitness and cognitive function. Because of its strengthening and balancing effects on the brain, Neuravena offers potentially lucrative positioning possibilities for nutraceuticals, food supplements and functional foods that target cognitive support and stress coping abilities. Depending on the specific indication, there are several opportunities to combine Neuravena with other functional ingredients. For example, products targeting “Learning and Concentration” may profit from Neuravena in combination with magnesium, L-glutamine or phosphatidylserine. “Memory” could be enhanced with a Neuravena product enriched with vitamin E, omega-3 or selenium, to mention just a few possibilities.
Edited by Visionary7903, 02 January 2009 - 10:56 AM.