Most chronic diseases cannot be associated to a single cause. Instead, at the cellular and molecular level, there are different pathways and mechanisms that undergo alterations, and some are common to different pathologies. The therapy of these diseases, as well as their prevention, can therefore take advantage of a multitarget approach which envisages the use of mixtures of bioactive compounds capable of simultaneously modulating various unregulated biochemical events.

Botanical extracts contain different and numerous classes of compounds and can exert a potential multi-target action. This often consists of the synergistic effect that characterizes the bioactivity of many natural molecules when "co-administered" as they are present within the same extract. In our opinion, this is the main advantage of the use of nutraceutical or functional food.

To date, the main challenges in the field of functional natural extracts are:

1. the chemical characterization of their components,
2. the rapid identification of new bioactive compounds, and
3. the elucidation of the molecular mechanisms of action at the basis of their functional properties.

Solving these issues is extremely ambitious if we consider the enormous chemical complexity of a multi-component mixture and the plethora of its putative interactions with a biological system. For these reasons, advanced analytical techniques that provide a holistic overview of the samples are essential. Hyphenated approaches that combine separation techniques to spectrometric methods, such as liquid or gas chromatography – mass spectrometry (LC-MS; GC-MS), are the most diffused to characterize a complex mixture. Nevertheless, also Nuclear Magnetic Resonance (NMR) has gained an important role in this field. This is mainly due to its intrinsically quantitative nature and the fact that it requires much more limited sample processing than mass spectrometry, which however has a much higher sensitivity. Furthermore, NMR does not require specific instrumental settings to allow the detection of different classes of compounds; it simply "sees" any molecule containing protons and/or carbons present at a concentration above the detection limit. It is therefore particularly suitable to perform untargeted analysis. Once the most interesting compound class(es) have been identified, a more detailed analysis inside the class(es) can be carried out using MS. The two approaches are therefore extremely complementary and allow the metabolic profiling of a plant species to be determined with precision and accuracy, both from a qualitative and quantitative point of view.

These features are also essential for determining the titer of the bioactive compounds in different extract batches. Even very large variations in the concentrations of bioactive species can in fact be due not only to extraction processes, but also to different geographical origins, growth and environmental conditions.

In addition, the two techniques can also be exploited to gather information on the mechanisms of action of the bioactive compounds present in the extracts.

MS is the technique of choice for proteomic studies which allow the identification of the molecular changes induced by treatment with natural extracts containing bioactive compounds.

NMR is instead particularly suitable for the study of molecular interactions involving small ligands and macromolecular receptors. It has recently been demonstrated that NMR can be used for the screening of mixtures of very complex compounds, including natural extracts, to identify ligands of proteins that are important biological and pharmacological targets. Once identified, NMR allows to characterize the binding mode among these molecular species from a structural point of view. Structural data, in turn, can be exploited to understand the bioactive compound(s)’ mechanism of action and/or to drive the rational design of new drugs. As a matter of fact, botanical extracts are traditionally used by medicinal chemists as inspiration for the development of new pharmacologically active compounds. Nevertheless, the aforementioned knowledge is critical for the rational understanding of natural extracts’ biological activities, for the identification of the bioactive components and for the design of new and effective molecules. Likewise, they are required to support the use of nutraceuticals and functional foods in the prevention of chronic diseases based on reliable scientific bases.

In addition, nutraceuticals can be used as “adjuvants” to drug therapies. There are experimental examples of how the co-administration of these preparations can allow a reduction in the doses of drug administered by increasing the sensitivity of the pharmacological targets towards them. This can greatly benefit not only the increase in therapeutic efficacy, but also the reduction of side effects related to a decrease in dosages. At the same time, even the intake of functional foods with a certain regularity through the diet can give beneficial effects.

In summary, our opinion is that the most recent technological advances in the analytical field have provided new tools that allow us to make the use of nutraceuticals in the field of chronic diseases’ prevention and therapy reliable because based on scientific, and not merely empirical, bases. The same tools have a key role in controlling their production chain and the asses the quality of production processes. Only the knowledge of the bioactive compounds they contain, and their concentrations (of their title) can permit their administration with dosage indications comparable to those provided for drugs.