Natural products research is on the rise again as Irish scientists become 21st century ‘medicine hunters’ searching for ingredients for medicines, cosmetics and functional foods in Irish peatlands, coastal waters and other terrains.
The traditional use of plants in medicines, cosmetics, and food predates both Western medicine and scientific research. But when scientists began to study plants and microbes in soil and water, they found an abundance of ingredients for use in pharmaceutical drugs.
Consider paclitaxel (Taxol), the anticancer drug derived from Pacific yew; galantamine, a plant extract medicine used to treat mild to moderate Alzheimer’s disease; and the herbal Vinca alkaloids used to treat childhood leukemia, to name a few.
Today, a group of chemists from Trinity College Dublin is tasked with finding molecules with immunomodulatory, anti-inflammatory and / or analgesic properties in plants and microorganisms in Irish soils and waters.
Dr Helen Sheridan is Associate Professor of Natural Products Chemistry in the School of Pharmacy and Pharmaceutical Sciences and Academic Director of NatPro, TCD’s new natural products research center. She is a passionate natural product chemist who sees the potential of plants and microorganisms to develop for businesses in Ireland. She also has a particular interest in ethno-pharmacology, which is the study of the traditional use of plants by crops.
âAt the NatPro Center, we are examining chemicals from natural sources to find new ways to prevent disease, maintain health and compensate for the spread of disease. There is also a great consumer interest in the natural world and a growing interest in functional foods to improve people’s health. We want to be a disruptive influence by applying our multidisciplinary expertise and an innovative scientific lens to change the way of thinking about natural products and examining new ways to get things done, âshe said.
Dr Sheridan’s interest in natural products dates back to the 1980s when she studied how a fungus infected and killed trees in Irish forests. âI was examining the chemistry of the fungus at a time when the connection between chemistry and biological function was not so well established,â she explains.
Her studies took her to the laboratory of Nobel Prize-winning chemist Derek Barton at the National Center for Scientific Research in Paris, where she conducted research on anticancer molecules from the quassia plant family – and to the University of Oxford as a traveling fellow to study the chemistry of the penicillium fungus.
âWe worked with enzymologists, biologists, botanists and were a multidisciplinary team before it became fashionable,â she says. She returned to Ireland to take up a teaching post at the TCD School of Pharmacy in 1985. She is the Phytochemistry Expert for the Herbal Medicines Subcommittee of the Irish Health Products Regulatory Authority. since 2000. She was co-founder of the TCD campus. Trino Therapeutics, which has brought a new class of molecules through a long process of development, starting with a fern and progressing to phase one human clinical trials for inflammatory bowel disease. She has just been appointed a member of a government advisory committee on the bioeconomy.
According to Dr. Sheridan, there has recently been a resurgence of interest in pharmacognosy, which is the analysis of the biological, chemical, biochemical and physical properties of plants, microbes and animals for medical ingredients. âIn fact, the expertise in the field of natural product chemists is limited. We need this expertise to drive research and innovation for the rising tide in the natural products industries in Ireland, which is one of the reasons we created NatPro, âshe says.
Dr Sheridan cites the recent discovery by researchers at the School of Biomedical Sciences at the University of Ulster at Coleraine of a new culture of strephomyces in limestone prairie soil, associated with Irish folk medicine, as a new source antimicrobial investigation.
This bacteria inhibited the growth of a wide range of pathogens in vitro, including Gram-positive Staphylococcus aureus. The study demonstrated the potential of this alkaline grassland soil as a new resource for the discovery of a wide range of antimicrobial compounds, including those effective against multidrug-resistant gram-negative bacteria.
Snails also offer great hope for new treatments for intractable pain, according to Dr. Sheridan. For example, zinonotide (Prialt), a pain reliever discovered in conical snails, is more potent than morphine and has no side effects.
These new findings provide a boost to scientists bringing 21st century tools and techniques to the study of natural products. NatPro has just secured â¬ 6 million in funding for the peatland biodiscovery project, Unlocking Nature’s Pharmacy from Bogland Species. The project team, which will work with Teagasc, National Parks and Wildlife Services, Irish Peatland Council, Bord Na MÃ³na, among others, aims to identify potential therapeutic and commercial uses of native Irish peatland plants, peatland waters and the microbiome of unique peatland species. . The cultural context will also be explored.
âIreland has an established cultural use of plants in peatlands and we have extracted data from the 1930s DÃºchas [the national folklore collection] at University College Dublin for references to the use of herbal remedies in Ireland at that time, âshe explains. The NatPro center also plans to develop a transitional year module on scientific and cultural peatland research.
Combining plant metabolomics (the study of chemical variation in plant species), molecular biology and botany, researchers will search for key molecules that could be used in the treatment of inflammatory, autoimmune, viral or neurodegenerative diseases.
Carbohydrate chemist Shipra Nagar is currently studying lichens, sphagnum mosses, yellow irises and swamp myrtle at the NatPro Center. âMy job is to isolate polysaccharides, characterize their structure and send extracts to test their immunomodulatory or anti-inflammatory properties,â Nagar explains.
Dr Gaia Scalabrino, executive director of NatPro, said that outside of peatland studies, researchers at the center are exploring everything from grains and algae to food waste. âForty percent of drugs come from natural products and the natural products market is growing for drugs, cosmetics and functional foods. The regulation around natural products is complex, but we understand the entire natural products value chain and can approach the process at different stages of its development. It can take up to five years to develop a functional food or cosmetic from the lab to the market and around 12 years for drugs.
Jun Ying, specialist in microalgae, benefits from a Marie Curie grant for two years at the NatPro center. She works with Kerry-based Nutra Mara, which has licenses to harvest seaweed to develop new products in a bio-refinery. âI cultivate microalgae to examine their biological activity, the chemicals produced and to see how to cultivate them in larger quantities,â adds Jun Ying.
Dr Sheridan says it’s important for students to understand the full context of developing their research. One of the main obstacles to the commercialization of natural ingredients is that molecules in the natural world cannot be directly patented. However, the processes used to extract them can be patented. And new substances can be grown in laboratory bioreactors.
Dr Sheridan says that sometimes parts of the chemical structures of molecules isolated from plants can also be used as a chemical scaffold in the development of new drugs or if a bacteria or fungus associated with the plant produces the same ingredient, it can be grown in a bioreactor.
She would like to point out, however, that not all natural products are safe and that more research is needed to identify potentially toxic molecules in the food chain. âAn interesting example of this was captured in the movement of Hitchcock The Birds,â she notes. The film is based on an event that happened in California in 1961 when birds swooped down on people on the streets. âThe birds were confused after eating small fish contaminated with a poison called domoic acid produced by marine microalgae. In 1987, four people died and 100 were hospitalized in Prince Edward Island, Canada after eating mussels contaminated in the same way. There are many other toxins in the food chain, some of which cause neurological disease. ”
Dr Sheridan hopes the Covid-19 pandemic will give greater impetus to research for drugs and vaccines for other diseases. âWe still have unmet clinical needs in various cancers, conditions like Parkinson’s disease and multiple sclerosis – and we still don’t have a malaria vaccine. ”