Synergy Research: Approaching a New Generation of Phytopharmaceuticals

Synergy Research: Approaching a New Generation of Phytopharmaceuticals

Prof. Dr. Hildebert Wagner
Center of Pharma Research, Department of Pharmacy, University of Munich, Germany

The successful use of herbal drug combinations in Traditional Medicine e.g. in European phytotherapy, traditional Chinese medicine or medicines of Ayurveda makes it necessary to find a rational for the pharmacological and therapeutic superiority of many of them in comparison to single constituents.

Which mechanisms my underlying this therapeutic superiority? A first approach towards rationalizing this synergy effect was made by Berenbaum [1]. He developed the isobol method as pharmacological tool to differentiate between real synergistic and additional effects of a mixture of two plant constituents or two plant extracts. Among the possible mechanisms underlying these synergy effects, the multitarget effect seems to be the most important and interesting one. Since recently molecular biological support for this hypothesis
can be obtained from the new genomic microchip array method.

Meanwhile pharmacological evidence for synergy effects has been documented of monoextracts such as Ginkgo biloba [2], Hypericum perforatum [3], Cannabis sativa along with many other herbal extracts and also their combinations [4]. Recently in many publications very effective synergy effects were reported when antibiotics are combined with natural products or plant extracts (essential oils, polyphenols, terpenoids) to combat the worldwide increasing bacterial multiresistance (MBR) [5]. Here polyphenols e.g. Epigallocatechingallate of green tea or the curcuminoids of Curcuma spec. have found great attention at present as pure compounds or enriched in standardized extracts alone or in combinations with chemotherapeutics.

These polyphenols as monomers or oligomers are able to induce apoptosis, arrest the cell cycle of tumor cells, inhibit insulin – like growth factors, detoxify some enzymes and delay as antioxidants the appearance of several markers of aging and oxidative stress – to offer only a few examples. In combination with anticancer drugs they can inhibit ABC-cassette transporter proteins in tumor cells and thereby enhance the efficacy of anticancer drugs. Meanwhile several clinical trials do exist, which show that standardized mono or multiherbal drugs possess therapeutic equivalence with chemotherapeutics at less or lacking side effects. In summarizing the results available so far, we can conclude that progress in synergy research will not only provide a new legitimation for phytotherapy, but also enhance the possibility to use new phytodrugs alone or in combination with chemotherapeutics for the treatment of diseases which have been treated previously through chemotherapy only.