Seminar with Associated Professor Thomas Vogt and Professor Emeritus Rob Verpoorte
Piperamide biosynthesis in black pepper
by Thomas Vogt, Associated Professor
Leibniz Institute of Plant Biochemistry, Dept. Cell and Metabolic Biology, D-06120 Halle(Saale)
Symposium abstract: The Piperales with more than 4000 species are the most diverse group of magnoliids and can be viewed as a model clade outside the monocot and eudicot radiation. Among the Piperaceae, commercially grown black pepper (Piper nigrum) is used worldwide for its pungent principle, piperine. Despite the use of black pepper as a common spice and the abundance of piperine in fruits, the biosynthesis of this alkaloid and of related piperamides is largely unknown. Based on a differential RNA-Seq approach we initiated a program to identify genes and corresponding enzymes of the piperamide biosynthetic pathway.
I have been working on Phenylpropanoids at the IPB since 1994 and I am group Leader: Phenylpropanoid Biosynthesis since 2003. Major interests are identification and characterization of enzymes and genes involved in the biosynthesis and transport of plant natural products, preferentially phenylpropanoids.
Synergy? Easier to say than to prove
by Rob Verpoorte, Professor emeritus
Natural Products Laboratory, IBL, Leiden University, Leiden, the Netherlands
Symposium abstract: In the discussion on medicinal plants often synergy is used as an argument to explain activity, and even to argue that they superior to single pure compounds. But how much real evidence is there for synergy? Synergy in simple words means that 1+1>2. To proof synergy between two compounds for a certain biological activity isobolograms are used in which one can see that the activity of the mixtures of two compounds is higher than the sum of the two. Most papers on synergy describe this method to proof synergy of two compounds, however, this requires that one knows the active compound(s) of a medicinal plant. If these are not known it becomes difficult, particularly when in bioassay guided fractionation the activity is lost, e.g. when activity is fully dependent on the presence of two or more compounds. The only solution is a systems biology approach. By measuring the metabolic profile of different extracts of a medicinal plant or fractions thereof and combining that information with the results of the bioassays of these samples one may identify the signals that correlate with activity. These signals may be due to one or more compounds. After identification of these compounds, e.g. after isolation via metabolomics guided fractionation, one can test these compounds for synergy.
If synergy would play an important role in medicinal plants, the synergistic effect is on the system as a whole, and thus may have many forms. That means for studies on synergism one should use preferably in-vivo bioassays, and if possible even apply this approach in clinical trials, as besides synergy also prodrugs may be present in medicinal plants.
Synergy is an important aspect for the quality of a medicinal plant or mixture of medicinal plants. Considering the present practice of quality control (QC) one can distinguish different levels of control. First of all the pharmacopeia assays are the standard for the identification of medicinal plants. In case of known active compounds such assays include the analysis of the active compounds. The next level of QC is on the level of contaminations, with other plants, with residues of soil contaminants and agrochemicals. This concerns the safety of the material. However, in case of unknown active compounds and prodrugs and synergy might be involved, there is no method yet available. For QC one could develop metabolomics methods like fingerprinting and correlated these with in-vivo assays. This could lead to signals that can act as markers for activity. But finding the right in-vivo assays will be a major challenge. In fact in personalized medicine, like in TCM, the ultimate level of QC is in the hands of the practitioner. First of all after prescribing the personal therapy the practitioner is monitoring the effect of the medication and may change this in case of insufficient or unwanted effects. Eventually also the side effects toxicity of a certain treatment will be observed by the practitioner. In fact it means that the practitioner is doing a sort of n=1 clinical experiment, which may generate interesting results for the better understanding of the effect of the traditional treatments
With the idea of synergy in mind we can thus make an interesting discoveries. Altogether the lesson is that with all the novel omics tools used in systems biology type of approaches, there is a lot we can learn from nature. This knowledge will be very useful for novel applications, e.g. to find new medicines, or at least come to evidence based use of traditional medicine.
Pharmacists degree (1972), PhD (1976) Leiden. Lecturer Leiden University 1976-1987, 1987 professor and head department of Pharmacognosy. 2011 Emeritus professor. Guest professor in London (UK), Uppsala (Sweden), Amiens (France), Reims (France), Florence (Italy), Seoul (Korea) and Hilo (USA). 1992-1998 Vice-Chairman and Chairman committee of the Phytochemical Society of Europe (PSE).