Head of Centre:
Professor Michael Heinrich

About the Centre:

Pharmacognosy is the discipline covering all areas of medicinal plant research, a field of study which relies on diverse methods, but is unified by an interest in securing human’s supply of safe and efficacious medicines derived of plants. Such medicines may be used as a pure compound or as a complex extract.

Our research is focused on the following themes:

Medical Ethnobotany

The uses of plants in indigenous cultures are multiple and very diverse. For many people plants still form the economic basis, and are used as medicine, food, construction material, fire wood, dyes, ornamentals and/or ritual paraphernalia. Over the last few years, we have conducted ethnobotanical studies with groups of people around the world, including Mexico (five individual groups), Italy, Spain, Guatemala, Australia and Tanzania. Our research team has called attention to the relative importance of medicinal plants within a culture (intraculturally) as well as its intercultural importance and has concentrated on evaluating the pharmacological effects of selected plants (for example, the AINP-project - see below). The goal of this research is to create a better understanding of the indigenous uses, to contribute to an improved use of resources, to find new ways for passing this knowledge to future generations and, in some instances, to search for new pharmaceuticals to be used in biomedicine.  One current focus of our research is to develop a better understanding of how historical methods can be used to understand current medicinal plant use in indigenous communities (e.g. Kufer et al 2005).

FAS-II as a target in antimalarial and antibacterial product discovery

FAS-II as a target in antimalarial and antibacterial natural product discovery;. Malaria is still the leading parasitic disease worldwide. The rapid resistance developed by parasites against most of the existing drugs except for artemisinins underscores the urgent need for new antimalarial agents. Plants have provided the most important antimalarial drugs/drug templates and continue to do so. Marine organisms are also being recognized as a valuable source for antimalarial drug candidates. Dr Deniz Tasdemir and her group focus on discovering novel antimalarials from plants, marine invertebrates, marine algae and microorganisms collected from Turkey and the UK (Tasdemir et al., 2005; Tasdemir et al., 2007). The group is particularly interested in natural products inhibiting the individual enzymes of the type II fatty acid biosynthesis system (FAS-II), e.g. enoyl-ACP reductase (FabI) of the malaria parasite, Plasmodium falciparum. The FAS-II is the first anabolic process emerged from the P. falciparum genome project and is vital for the survival of the parasite. The pathway is located in the newly identified apicoplast, a chloroplast-like organelle in P. falciparum. We also assess the species specificity of our natural inhibitors against FAS-II enzymes of different gram-positive or gram-negative bacteria (Tasdemir et al., 2007).

Antineoplastic marine natural products

Marine organisms are capable of producing secondary metabolites of extremely interesting structural diversity. The search for anticancer lead compounds has been the mainstream of marine chemistry. As a result, a number of marine natural products with unique mechanisms of action have been identified and recently entered into clinical trials in the USA and in Europe.  Dr Deniz Tasdemir and her team are interested in the discovery of potent topoisomerase- and p53/p21-dependent cytotoxic agents derived  from marine organisms. Furthermore, the group aim to investigate the impact of these compounds on signal transduction pathways (Tasdemir et al, 2002; Marshall et al, 2003).

Treatment of Menopausal Symptoms with Phytomedicines and Pure Phytoestrogens

Hormone replacement therapy (HRT) is useful in the treatment of menopausal problems, such as hot flushes.  However, due to the increased risk of endometrial/breast cancer associated with HRT, many women are seeking alternative treatments including phytomedicines and phytoestrogens.  As part of a recent collaborative project with the Centre for Toxicology (funded by industry), Dr Deniz Tasdemir is trying to identify the mechanism of anticlimacteric effect of certain phytomedicines and their active components.  These studies involve estrogen receptor alpha and beta (ERαβ) modulation, as well as neurotransmitter reuptake inhibition assays.  We also work on safety assessment of the products (and their components) that include P450 inhibition/CYP induction and apoptosis induction.

Natural products and phytotherapeutic preparations with anti-inflammatory activity

In this research area, the Centre benefits from the complementary expertise of Professor Michael Heinrich and Dr Jose Prieto on the transcription factor NF-kappaB and the COX/LOX pathways respectively.  NF-kappaB is an important mediator of immune and inflammatory response of the human body, and is induced by many pro-inflammatory stimuli including, for example, tumour necrosis factor (TNF-alpha). Ultimately, its activation triggers the induced expression of numerous target genes coding for inflammatory cytokines (cf. Bremner and Heinrich, 2005). However, there is still a need for new inhibitors of the metabolism of arachonic acid, which ideally could block both COX and LOX pathways, and recent research pointed out their future imporance as anti-inflammatory and anticancer agents.  Natural products are a unique source for this kind of drugs (Prieto et al. 2003).

Nutraceuticals with anti-oxidant activity

In Mediterranean countries, the consumption of vegetables and fruits is generally considerably higher than in most European countries and the United States; and has been termed 'the Mediterranean diet'.  In this project we are interested in locally used foods which may present a potential health benefit.  In this case, our research approach combines classical ethnobotanical methods with modern molecular biology and in pharmacology. Importantly, it also contributes to a fuller evaluation and development of the Mediterranean diet with a focus on local dietary plants (and fungi) and plant derived products.  Professor Michael Heinrich studies this local knowledge ethnobotanically and address the demand of the EU health food market for new high quality health supplements (Heinrich et al. 2005).

History of European medicinal plants

Medicinal plants have been used since ancient times in Europe.  These plants provide a unique, yet little studied resource for drug development, and are crucial for understanding the modern use of such plants in healthcare systems. The popular pharmacopeias of European countries have been influenced by many traditions (Egyptian, Islamic, Jewish, Roman, Greek, Iberian, Pre-Hispanic America). This project compares historical, ethnographical and modern ethnopharmacological sources, for better understanding the contribution of the different European traditions to the popular Materia Medica. Dr Manuel Pardo de Santayana and Professor Michael Heinrich are developing a database focusing on the Iberian Peninsula which can be used for such comparative studies. The database will contain all relevant modern ethnopharmacological research that has been published in the last three decades in Spain and Portugal and will contribute to an improved sustainable management of these local resources, and to the search for new drugs.

Medical properties of Cannabis

In recent years the medical use of Cannabis sativa has received renewed interest, particularly regarding the pain and spasticity associated with multiple sclerosis, but also it's antiinflammatory potential. These have a complex interaction with different cannabinoid receptors, and it is becoming apparent that other components of the plant can change their effects. Cannabinoid receptors have many different functions, and by selectively modifying them, it may be possible to alleviate various disease conditions. With funding from the EU we are conducting a collaborative research project (EU, FP6) to develop a high quality, high value, standardised extracts (preferably low in the psychoactive constituent THC) which are orally active and suitable for clinical use and hope to obtain an extract with a clearly defined chemical and pharmacological profile (Co-ordinator: Professor Michael Heinrich).

Equine grass sickness

Equine grass sickness (EGS) or dysautonomia is a potentially fatal disease of horses, ponies and donkeys. It primarily affects animals between the age of two and seven years that are pasture-grazed, hence its name. Visible symptoms include colic, difficulty in swallowing, drooling, muscle tremors, rapid weight loss and behavioural abnormalities. The disease, which has a high mortality rate, causes impaired intestinal activity as a result of damage to the autonomic nervous system. Incidences of the disease are more likely to occur from April to July, and on premises where there has been a previous outbreak.
While there have been a number of scientific studies investigating EGS since it was first documented in 1907, the causative agents remain speculative, hindering efforts to develop diagnostic testing and treatment. It is likely that the disease is linked to elements of the animals’ diet, either in the food or the drinking water. Currently, Dr Sarah Edwards and Dr Russhawn Aldridge under the supervision of Professor Michael Heinrich are investigating the causes of EGS, including environmental factors. 

References:

Bremner, P. and M. Heinrich (2005) Natural Products and their role as inhibitors of the pro-inflammatory transcription factor NF-κB. Phytochemistry Review 4(1): 21 – 37.

Heinrich, M. M. Leonti, S. Nebel and W. Peschel (2005) 'Local Food – Nutraceuticals': An example of a multidisciplinary research project on local knowledge. Journal of Pharmacology and Physiology (Suppl.) 56: 5-22.

Kufer, J., H. Förther, E. Pöll and M. Heinrich (2005) Historical and modern medicinal plant uses – the example of the Ch’orti’ Maya and Ladinos in Eastern Guatemala. Journal of Pharmacy and Pharmacology 57: 1127–1152.

Pardo de Santayana, M., E. Blanco and R. Morales (2005) Plants known as “té” (tea) in Spain. An ethno-pharmaco-botanical review. Journal of Ethnopharmacology 98 (1-2): 1-19.  

Tasdemir, D., R. Mallon, M. Greenstein, L.R. Feldberg, S. C. Kim, K. Collins, D. Wojciechowicz, G.C. Mangalindan, G. P. Concepcion, M. K. Harper, and Chris M. Ireland (2002) Aldisine Alkaloids from the Philippine Sponge Stylissa massa Are Potent Inhibitors of Mitogen-Activated Protein Kinase Kinase-1 (MEK-1) Journal of Medicinal Chemistry 45, 529-532.

Marshall, K.M., Matsumoto, LL., Holden, J.A., Concepcion, G.P., Tasdemir, D., Ireland, C.M., Barrows, L.R. (2003).  The Antineoplastic and Novel Topoisomerase II Mediated Cytotoxicity of Neoamphimedine, a Marine Pyridoacridine.  Biochemical Pharmacology, 66, 447-458.

Tasdemir, D., N. Deniz Guener, R. Perozzo, R. Brun, A. A. Doemez, I. Calis, P. Rueedi  (2005) Anti-protozoal and plasmodial FabI enzyme inhibiting metabolites of Scrophularia lepidota roots. Phytochemistry 66: 355–362.

Tasdemir, D., Topaloglu, B., Perozzo, R., Brun, R., O'Neill, R., Carballeira, N.M., Zhang, X., Tonge, P.J., Lindon, A., Rüedi, P. (2007).  Marine Natural Products from the Turkish Sponge Agelas oroides that Inhibit the Enoyl Reductases from Plasmodium falciparum, Mycobacterium tuberculosis and Escherichia coli.  Bioorganic and Medicinal Chemistry, 15, 6834-6845.

Prieto, J.M., Giner, R.M., Recio, M.C., Schinella, G.R., Manez, S., Rios, J.L.  (2008) In vitro and in vivo effects of Ranunculus peltatus subsp. baudotii methanol extract on models of eicosanoid production and contact dermatitis. Phytotherapy Research  Mar;22(3):297-302

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