Trends in Molecular Medicine
ReviewFrom traditional Chinese medicine to rational cancer therapy
Section snippets
East meets West
Traditional Chinese medicine (TCM) has held, and still holds, an important position in primary health care in rural areas of China and is also appreciated in urban and well-developed areas because of its 5000-year-old tradition. Recently, the Chinese government has undertaken enormous efforts to modernize TCM by investing capital in scientific research and in the economical exploitation of TCM. In the Western world, interest in TCM stems from the hope that it might complement Western medicine.
TCM and pharmacology
At the pharmacological level, different areas of classical pharmacy focus on medicinal herbs, for example, phytochemistry, pharmacognosy and phytotherapy (see Glossary). Secondary metabolites, which are – in contrast to primary metabolites – not essential for the nutrition of plants, are produced by an organism as a defence against competitors, herbivores and pathogens and as signal compounds that attract insects for reproduction. Therefore, secondary metabolites represent an important part of
Classical targets for TCM-derived drugs applied in tumour therapy
Anti-cancer drugs target DNA either directly (e.g. platinum compounds and alkylating agents) or indirectly by inhibition of DNA-metabolizing functions. Other targets for anti-cancer drugs are proteins involved in cell division or in cell signalling related to proliferation or cell death. Standard tumour chemotherapy comprises several natural products, and many of them are derived from or have a direct relationship to TCM. Although this fact might not be well recognized in the Western academic
Novel targets for TCM-derived natural compounds
Natural products from TCM represent a valuable source for the identification of small-molecule inhibitors against novel targets for medicine, especially for cancer therapy (see Table 1 for a compilation of TCM-derived drugs). Recently, the number of molecular targets used for developing novel treatment options increased considerably. Among these targets are many signal-transduction proteins (e.g. kinases) that regulate malignant processes in cancer cells. Examples of TCM-derived natural
Novel TCM-derived anti-cancer drugs
Novel TCM-based drugs that are being used in cancer therapy or being applied in clinical trials are compiled in Table 2. Artesunate provides a good example of the translation of basic knowledge of purified agents of complex mixtures from TCM into the clinic. Artesunate is a semi-synthetic derivative of artemisinin, which is generated from the Chinese medicinal plant Artemisia annua (). The drug is well established worldwide for use in malaria therapy (Table 1) and is directed against Plasmodium
Clinical studies with TCM-based anticancer drugs
Although a huge number of patients are treated with TCM herbal formulations, randomized clinical trials of these preparations are still very few, and this fact was recently recognized by Chinese scientists 43, 44. In some cases where the active components of medicinal plants have been phytochemically identified and pharmacologically characterized, the situation is different. The single drug isolated from the TCM preparation can then be used for intensive efficacy investigation in clinical
Toxicity of TCM-derived compounds – attenuation of side effects?
Although TCM-derived drugs were shown to be useful in clinical studies, there is a clear caveat with regard to the safety of compounds derived from TCM. Even though natural products are sometimes regarded as ‘gentle medicines’, there are exceptions because bioactivity without side effects is hard to achieve. For instance, in the 1990s, several incidences of poisoning by aristolochic acids were noted in European countries. In these cases, herbal mixtures for slimming erroneously included the
Conclusion and perspectives
Recently, the potential of natural products from plants and especially from medicinal plants used in TCM has been recognized by the scientific community in the Western world. Disciplines such as phytochemistry and pharmacognosy have enabled scientific analyses of herbal mixtures and their bioactive molecules. Molecular biological approaches help to elucidate the underlying mechanisms of action of natural products. The fewer side effects observed in phytotherapy and natural-product-based
Acknowledgements
B.K.'s work was supported by Deutsche Forschungsgemeinschaft grant Ka724/13–3 and Stiftung Rheinland-Pfalz für Innovation.
Glossary
- Alternative medicine
- any of the various healing or disease-treatment systems that are not included in the traditional medical curricula taught in the Western world.
- Complementary medicine
- any of the practices of alternative medicine that are accepted and utilized by mainstream medical practitioners.
- Pharmacognosy
- the biochemistry and pharmacology of drugs of natural origin (e.g. medicinal plants and spices).
- Phytochemistry
- the chemistry of secondary metabolites and isolated chemical entities found in
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