Nature

Medicinal Plants Produce Neuroprotective Compounds Also Effective Against Cancer

Mark Hoffman
First Posted: May 14, 2013 02:39 PM EDT

Many medicinal plants contain compounds that are now scientifically proven to be effective against many diseases, including cancer and central nervous system disorders such as Parkinson's and Alzheimer's disease. That's why an European research project scoured the tissues of two wild flowering plants for terpenoids, an astonishingly diverse group of molecules that are effective in this way, which could ultimately lead to novel drugs sourced from these natural compounds. The challenge is to then mass-produce these compounds, which necessitates the decryption of the biosynthetic pathways that make these compounds in plants and was the objective of this research.

Look on any uncultivated hillside and you are likely to find these medicinal plants. In particular, feverfew (Tanacetum parthenium) and rosemary (Rosmarinus officinalis) can both be found growing wild in southern Europe, and feverfew, with its cold tolerance, is indigenous throughout northern Europe.

Both feverfew and rosemary produce chemicals of the terpenoid class that are well known for a variety of health-promoting properties such as their anti-bacterial, anti-inflammatory, neuroprotective and anti-cancer abilities. The EU-funded TERPMED project focuses on two types of terpenoids that can be isolated from feverfew and rosemary: sesquiterpene lactones (SLs) and phenolic diterpenes (PDs).

TERPMED scientists developed analytical tools that targeted SLs and PDs, as well as hundreds of other metabolites in order to establish the chemical diversity of these medicinal plant species. The SL and PD compounds were subsequently tested for biological activity. After determining where the molecules of interest were predominantly produced and stored in the plants, sequencing data was generated from ribonucleic acid (RNA) to pinpoint the genes and enzymes responsible for their production.

The genes are used to reconstruct the biosynthetic pathways of the bioactive compounds in other plant systems, which will become pilot-scale green factories. The genetic sequences are also being used to generate new functional molecules using combinatorial biosynthesis approaches. All information about genes, enzymes and the hundreds of compounds isolated from the plants is stored in the project database, which is continuously updated with new data generated in the project and is available through the project website (https://www.terpmed.eu).

TERPMED achievements stand to be able to supply the pharmaceutical industry with new drugs to treat many diseases including central nervous system disorders and cancer.

Background, from https://medicinalplantgenomics.msu.edu/ :

"Natural products from plants serve as rich resources for drug development with almost 100 plant-derived compounds in clinical trials in 2007. Plant derived natural products have had a profound and lasting impact on human health and include compounds successfully used for decades such as digitalis, Taxol, vincristine, and morphine isolated from foxglove, periwinkle, yew, and opium poppy, respectively. The enormous structural diversity and biological activities of plant-derived compounds suggest that additional, medicinally relevant compounds remain to be discovered in plants.

While plant natural products continue to be a prime target for drug development, as evidenced by the number of ongoing clinical trials, the clinical potential of these compounds is often curtailed due to low production levels in plant species. For example, use of the blockbuster drug Taxol almost stopped in the early 1990's because the primary source, yew tree bark, could not be used as a sustainable source of the drug. In this particular instance, a Taxol precursor happened to be more readily available in a renewable part of the tree, and a semi-synthetic protocol could be developed to convert it into the drug. While fortuitous, more generalized solutions, such as metabolic engineering of effective plant and microbial production platforms, are urgently needed to ensure that the wealth of bioactive compounds found in plants enter the clinical pipeline and find widespread use in medicine."

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