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University of Heidelberg – natural substances to combat cancer and excess weight

It is difficult for natural substances to enter the drug industry. With the aim of enabling secondary plant substances to reach consumers, the Department of Biology at the Institute of Pharmacy and Molecular Biotechnology at the University of Heidelberg has joined the Bioactive Plant Products network.

Chelidonium majus (greater celandine; in Europe tetterwort) belongs to the poppy family and contains numerous alkaloids. © Wink

Prof. Dr. Michael Wink has spent half his working life investigating the effect of natural compounds. He has worked at the University of Heidelberg for more or less the last 21 years. He is the Director of the Department of Biology of the Institute of Pharmacy and Molecular Biotechnology (IPMB) and the Steinbeis Transfer Centre for Biopharmacy and Analytics. "We focus in particular on natural plant compounds, their occurrence, chemistry and pharmacology," said Wink. The department's research naturally focuses on food crops, nutraceuticals and functional foods. In the field of phytochemistry, the IPMB researchers are currently investigating complex plant mixtures using gas chromatography, HPLC, mass spectrometry, NMR and other analytical tools. The department offers small- and medium-sized companies analytics services, which include the analysis of plant ingredients. "We are a university institute that covers all areas of analytics," said Wink.

The effectiveness of the mixtures is a key element

The researchers are also interested in finding out about the pharmacological characteristics of the plant components. They are increasingly using bioassays to find out which compounds have an anti-bacterial, anti-viral or cytotoxic effect. “In terms of bacteria, we are mainly interested in multiresistant species,” said Prof. Wink. In the area of medicine and food supplements, the researchers are investigating the mechanisms that lead to the death of cells and looking into which cellular target structures are affected. An important factor in these investigations is the anti-inflammatory effect of plant compounds.

Annual mugwort (Artemisia annua) compounds are used to treat malaria and inhibit the growth of tumour cells. © Wink

The mode of action of mixtures produced by plants also plays a key role in the researchers' investigations. "The most interesting modes of action are the mixtures' synergistic effects, i.e. those that enhance their effect," said Wink. With regard to cytotoxic substances, the researchers have already obtained interesting results with cell cultures and using mice as experimental animals. Unfortunately, the investigations cannot enter the next clinical step as virtually no financing partners can be found for clinical Phase I studies. "This is a problem that affects almost the entire range of pharmaceutical research carried out at German university institutes," said Wink pointing out that particularly affected areas are research into tropical diseases like malaria and sleeping sickness which are not very common in Europe. The researchers have already investigated traditional medicinal plants and discovered compounds that are not toxic for human cells, and extremely toxic for trypanosomes, the pathogens that cause sleeping sickness. However, once again the researchers have not yet been able to prove the clinical effectiveness of the compounds due to lack of financing for clinical studies.

Classical vegetable plant as functional food

Quinoa (Chenopodium quinoa) was grown by the Incas © Wink

The "Bioactive Plant Products" network specifically focuses on excess weight and adiposity. Prof. Wink believes that medicinal and food plants are excellently suited to counteracting excess weight and adiposity. Metabolic syndrome refers to a number of metabolic risk factors that come together in a single individual, including diabetes mellitus, adiposity and disorders of blood pressure regulation. Certain food compounds have been shown to improve blood values (cholesterol or lipids in the blood), which is why they are of great interest to the researchers. Of course, some plant compounds also act as appetite suppressants. "We already know quite a lot about these compounds," said Wink explaining that appetite suppressants include terpenes, polyphenols and flavonoids that have an antioxidative effect and also act on cellular targets. "Many metabolic disorders are associated with inflammatory reactions," said Wink.

Although the scientists have already investigated numerous herbal active ingredients, they find it difficult to transfer their knowledge to industry. "We have discovered many things in the laboratory, but find it difficult to translate these findings to industry for economic implementation," said Prof. Wink. There are numerous reasons for this. In the majority of cases, the investigated compounds are already known compounds for which the researchers are trying to find ways to treat new indications. As this raises patent protection issues, Prof. Wink is convinced that this is one reason why the pharmaceutical industry is considerably less interested than it could be. The investment costs for clinical studies and for obtaining marketing authorisation are so high in the pharmaceutical industry that companies are only interested in a substance if it can be protected with patents. "Unfortunately, in Europe, these conditions considerably hinder the translation of research to industry," said Wink. Nevertheless, the IPMB has already carried out several projects with Willmar Schwabe GmbH & Co. KG and other pharmaceutical companies.

In the field of functional food, the ability to patent a substance is not such a decisive issue. Wink points out that cooperation with small- and medium-sized companies has great potential for success. "This is why I find the topic so exciting," said the pharmaceutical biologist. Prof. Wink believes that artichokes have a great future as functional food because the plant's bittering substances are known to reduce the blood fat values and have an anti-inflammatory effect. The network now faces the challenge of combining artichokes or another vegetable plant with another functional plant compound and bringing the mixture to market.


Green tea for the treatment of Alzheimer’s

Camellia sinensis is the species of plant whose leaves and leaf buds are used to produce Chinese tea © Wink

Green tea is a functional food that has been used for many centuries. The scientists from Heidelberg have been able to show with the threadworm Caenorhabditis elegans, a popular laboratory animal, that one of the main ingredients of green tea, i.e. epigallocatechin gallate (EGCG), prolonged the worm's life by around 15 per cent. "This of course correlates with epidemiology. It has been shown that people in Asian countries where green tea is a popular drink often live longer than Europeans," said Wink. The researchers have been able to show that the worms' oxidative stress is considerably reduced with the consumption of the polyphenol. In another project, which also involves Caenorhabditis elegans as model organism, the researchers have been able to show that green tea also has a positive effect on the development of Alzheimer's. "Since green tea is a food item, further studies will very probably be carried out," said Wink who also believes that the "Bioactive Plant Products" network has a lot to contribute to such projects. "In the field of functional food we are finally able to apply knowledge we have acquired," said Wink.

Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/university-of-heidelberg-natural-substances-to-combat-cancer-and-excess-weight