The department of Pharmacognosy at the Institute of Pharmacy at the University of Innsbruck has four main research interests. They are (a) the isolation and structural elucidation of secondary metabolites from higher plants with anti-inflammatory, anti-tumor and anti-microbial activity, (b) chemosystematic investigations mainly focusing on the tribe Lactuceae, (c) analysis and quality assessment of (medicinal) plants and phyto-pharmaceuticals, as well as (d) the discovery of pharmacologically active natural products using computational methods (pharmacophore modeling, virtual screening, docking, neural networks).
The search for novel natural products, which could be used as potential drugs or serve as lead compounds is performed by using modern phytochemical and analytical techniques (gas chromatography, high performance liquid chromatography, capillary electrophoresis, capillary electrochromatography, mass spectrometry). This research is performed with special focus on European and Asian medicinal plants, or plants of the alpine region. Chemosystematic studies performed at the department aim to reveal relations between different plant taxa (or confirm them) by comparative phytochemical and analytical approaches.
Analytical tasks (standardization, method development, validation and quality assessment of plant-extracts), for which modern analytical instrumentation (e.g. LC-MS or CE-MS) is available in house, are often performed in collaboration with domestic and international companies. These collaborations, besides basic research, allow very practice- and application-oriented scientific investigations. For a target oriented search for active compounds several test models are established at the department. Computer aided pharmakophor-models utilize structural properties to detect pharmacologically active natural products (e.g. with acetylcholinesterase inhibiting activity). Enzyme assays (acetylcholinesterase, cytochromes), on the other hand, are employed for the screening of plant extracts and pure compounds.
This combination of several different approaches (analytical, chemosystematics, and pharmacology, besides “classical” phytochemistry) offers means for an extensive and efficient research on pharmacognostic issues. A number of publications in internationally renowned journals, as well as projects and cooperations indicate the significance and quality of the conducted research and underline the experience and supra-regional importance of the department of Pharmacognosy in the field of natural products research.
Project leader and Coordinator: Univ.-Prof. Dr. Hermann Stuppner Funding period: 2016 - 2019 Project description: The main goal of the MediHealth project is to introduce a novel approach for the discovery of active agents of food plants from Mediterranean diet and other global sources to promote healthy ageing. This will be achieved through a well-balanced exchange of researchers between 5 universities and 4 enterprises from EU countries and Switzerland as well as 4 universities from non-European countries. Plants from the Mediterranean diet and food plants from Africa, Asia and South America will be rationally selected and subjected to an integrated, interactive and comprehensive platform including in silico, in vitro (advanced cell-based assays), in vivo (flies and mice models) and metabolism assessment. Advanced analytical techniques will embrace the pharmacological evaluation process for the efficient isolation and identification of bioactive plant constituents. Pharmacological profiling of bioactive natural products as well as identification and synthesis of their metabolites will be carried out. Finally, to carry to the stage of development innovative products in the area of nutraceuticals/dietary supplements, process-optimization studies will be performed. Within this project, core scientific multidisciplinary knowledge from different research areas will be integrated creating valuable synergies. Expertise will be transferred by means of training of the seconded researchers in environments with different research orientation where complimentary skills are required. MediHealth aspires to comprise a successful model promoting considerably researchers’ competences and long-lasting collaboration between Industry and Academia generating innovation potential at the European and global levels.
NATPROTEC Integrated technologies for the discovery and development of cosmeceutical agents from plant biodiversity (FP7-PEOPLE-2011-IAAP, Marie Curie Actions, 286287)
Project leader:Prof. Leandros Skaltsounis Project partner: Univ.-Prof. Dr. Hermann Stuppner Funding period: 2012 - 2016 Project description: NATPROTEC is an FP7 research project (IAPP-Marie Curie actions) that aims to discover and carry to the stage of development innovative products in the area of cosmeceuticals originating from European natural resources using emerging and environmentally friendly technologies. These objectives will be implemented through an extended and balanced scheme of researchers’ exchanges and recruitments, via a mutual scientific project developed on the needs and interests of both Industry and Academia sectors.
Anti-inflammatory potential of TCM drugs – new bioactive compounds and quality issues
Project leader: Univ.-Prof. Dr. Hermann Stuppner Funding period: 2016 - 2018 Project description: This project focuses on the search for novel natural products with anti-inflammatory activity. Based on the current TCM literature constituents targeting the arachidonic acid cascade are identified by pharmacophore based virtual screening. Already available models (e.g. mPGES-1 and FLAP) ensure a most promising selection of species, which further are studied phytochemically. Pharmacological studies are conducted in collaboration with project partners and followed by the analysis of relevant compounds using state of the art analytical techniques.
Prevention and early intervention of chronic diseases by TCM: Evaluation of immunomodulatory, anti-inflammatory and neuroprotective effects
Project leader: Univ.-Prof. Dr. Hermann Stuppner Funding period: 2012 - 2015 Project description: Screening of selected TCM plants for inflammation and immune system stimulation markers; Metabolic profiling of extracts from mixtures and single herbs by MS and NMR
Searching for potential therapeutic agents for managing diabetic wounds from Vietnamese medicinal plants targeting matrix metalloproteinase-9
Cooperation Development Research- KoEF06/2019
Project leader and Coordinator: Dr. Stefan Schwaiger Funding period: 01.05.2020 - 30.04.2022 Project description: Vietnam has both the highest and fastest-growing rate of diabetes in Southeast Asia. The impaired wound healing is one of the common and dangerous complications of diabetes. Vietnamese traditional herbal medicine is a promising source for finding novel wound healing agents for diabetic patients. Matrix metalloproteinase-9 (MMP-9) has been considered as an attractive molecular target for diabetic wound healing. Aiming at finding novel MMP-9 inhibitors, in this project, fifteen Vietnamese medicinal plants will be screened utilizing MMP-9 bioassay, followed by the bio-guided isolation and determination of the active principles. These active compounds could be applied for diabetic wound healing. The results will not only shed light on the native ethnopharmacological uses of Vietnamese medicinal plants by modern research evidences but also be able to open a new stage of development of novel herbal medicine products based on scientific evidences.
Austrian Science Foundation (FWF)
Photo-activated defense strategies in fungi – an overlooked source for new photo-pharmaceuticals? (P31915)
Project leader: Dr. Bianka Siewert Funding period: 2019-2022 Project description: The splendid colors of mushrooms (Basidiomycetes) are based on a vast array of different pigments. While plenty of these colorants are chemically elucidated, their ecological function has yet to be fully uncovered. Based on the structural similarity to well-known photosensitizers (e.g. bisanthrones, anthraquinones, and harmanes) we hypothesized that fungi produce them as part of a subtle photo-activated defense mechanism. Moreover, we believe that these photosensitizers can be utilized as photopharmaceuticals. In course of this project these two hypothesis will be tested.
New ways to counter inflammation - Computer aided discovery of multi-target anti-inflammatory natural products (T942-B30)
Project leader: Mag. Veronika Temml, PhD Funding period: 2018-2021 Project description: Secondary plant metabolites often affect the human organism and show a wide array of health benefits while generally causing fewer harmful side effects than most synthetic drugs. This is due to their often poly-pharmacological mechanism of action, interacting with multiple proteins at once. This project aims to identify novel anti-inflammatory natural products with the aid of computational methods. Computational models of the interaction patterns between small molecule ligands and protein targets involved in inflammation are used to screen large compound databases to search for molecules that target multiple proteins.
Project leader: Assoc. Prof. Dr. Markus Ganzera Project partner: Dr. Anja Hartmann Funding period: 2017-2020 Project description: Extremophiles are able to survive under hostile environmental conditions because they develop mechanisms of protection, in most cases by the synthesis of specific metabolites. In the current project we will focus primarily on previously not investigated marine species and soil crust algae. All of them are potential sources of new natural products. It is our aim to select the most interesting species, to isolate, identify and analyze compounds that are induced by UV irradiation, and to study their bioactivity. Accordingly, our efforts combine aspects of biology, pharmacy, chemistry and medicine in a unique way.
Species boundaries and genetic and phytochemical diversity of Cistus creticus L. (P29305)
Project leader: Mag. Dr. Brigitte Lukas Project partner: Univ.-Prof. Dr. Hermann Stuppner Funding period: 2016 – 2019 Project description:Cistus creticus, a purple-flowering shrub widespread in the Mediterranean area, is rich in labdane-type diterpenes that showed significant cytotoxic and antitumor activity. The inconsistent naming of the taxon in floras and scientific literature and the diversity in interpretation of morphological and phytochemical variability impede progress in systematic investigations of the medicinal potential of C. creticus. The aim of this project is a comprehensive evaluation of the C. creticus complex by linking results of morphological, phytochemical and genetic investigations. Populations of various geographical origins will be sampled and individual plants will be analyzed for morphological, genetic (SNPs, sequencing) and phytochemical (GC, HPLC, metabolomic fingerprinting) characteristics.
Project leader: Assoc. Prof. Dr. Markus Ganzera Funding period: 2014 – 2018 Project description: Capillary electrochromatography (CEC) represents a separation technique which combines features of chromatography and electrophoresis in a unique way, resulting in many theoretical advantages in terms of separation efficiency and selectivity. Even so, up to now CEC is not relevant in routine analysis. This project intends to bridge this apparent discrepancy between many desired features and the (assumed) limited practical relevance of CEC. Accordingly, innovative stationary phases (e.g. of polymermonoliths with zwitterionic character) will be developed and optimized for the CEC analysis of complex matrices, i.e. natural products in plant extracts.
Project leader: Assoc. Prof. Dr. Markus Ganzera Funding period: 2012 - 2015 Project description: The term extremophile describes an organism that exists under extreme physical or geochemichal conditions. Our project systematically studies changes in the metabolic patterns of alpine high altitude green algae and cyanobacteria exposed to elevated UVA and UVB radiation. This encompasses the selection and cultivation of algae in larger scale, the identification and analysis of respective compounds, as well as studying their bioactivity focusing on anti-inflammatory and skin protecting properties. Thus, aspects of ecology, phytochemistry, analytical sciences and pharmacology are joined in a unique way, creating a stable foundation for further research on a group of organisms that largely has been overlooked by science till date.
Coordination (Project Part 01): Univ.-Prof. Dr. Hermann Stuppner Project leader (Project Part 03):Univ.-Prof. Dr. Hermann Stuppner Associate: A. Univ. Prof. Dr. Judith M. Rollinger
Project leader: Univ.-Prof. Dr. Hermann Stuppner Project partners: Univ.-Prof. Dr. Pidder Jansen-Dürr (Research Institute for Biomedical Aging Research), Roland Kohl (Cura Marketing GmbH) Funding period: 2015 - 2018 Project description: This project aims at the development of high-quality extracts from alpine plants for subsequent cosmetic applications whose effective ingredients prevent or delay the aging of human skin cells. The use of traditional knowledge will be combined with modern techniques, i.e., pharmacological models, high-tech chemical analysis and modern methods of natural product isolation, identification and quantification. We will focus on extracts and active ingredients, which specifically inhibit the production of senescence-inducing reactive oxygen species and which reverse the consequences of senescence-inducing oxidative stress in vitro. Selected natural products will be characterized in detail and their mechanisms of action will be elucidated. The effectiveness of the most promising extracts will be validated in vivo. Appropriate methods for quality control will be established.
Gut, Diet, Microbiota and Vascular Ageing (WP1.1 and WP1.2)
Project leader: Univ.-Prof. Dr. Herbert Tilg and Univ.-Prof. Dr. Hermann Stuppner Funding period: 2014 - 2018 Project description: The focus will be on the investigation of short- and long-term effects of dietary factors on metabolic inflammation, atherosclerosis, cardiovascular disease and vascular longevity. Selected food ingredients and metabolites thereof as well as endogenous substances will be determined in biofluids of participants of the Bruneck-study by sophisticated technological platforms like HPLC-TOF-MS/MS, GC-MS and NMR. Additionally, metabolomic studies using two different holistic technologies will be performed: (a) mass spectrometry (QTof, SIT) coupled to HPLC, GC, or CE and (b) NMR spectroscopy followed by cluster, PCA, and DA analyses. Metabolite identification will be achieved using open access and commercially available reference databases as well as extensive 1 and 2D NMR spectroscopy of putative biomarker hits.
Antiparasitic and anthelmintic mountain plants – HERBAL
Project leader: Dr. Stefan Martens Project partner: Univ.-Prof. Dr. Hermann Stuppner Involved Scientists of the University of Innsbruck: Mag. Veronika Temml, PhD, Dr. Bianka Siewert Funding period: 2019 - 2022
This European project aims to develop an organic antiparasitic strategy based on herbs growing in the alpine region. Parasitic infections of livestock animals, like chicken are not only a burden for animals, but also for consumers. Commonly, infected animals are treated with synthetic medications. Unfortunately, eggs laid the next two weeks after treatment have to be thrown away, because they contain drug residues. Due to the fast reproduction cycle of the worms, drug resistances are a common concern, as synthetic de-wormers additionally target only one point in the life cycle of the worm.
Alpine herbs – used for centuries to fight worm-infections by regional farmers – may contain several compounds that kill worms. Therefore it is hypothesized that an herbal extract will attack the worm via multiple routes at once, making it harder for the worm to develop a resistance. To test this hypothesis, ten herbs were selected based on the cultural knowledge of regional farmers. Extracts of these herbs will be tested against isolated worm eggs. The three most active plants will be fed to the infected chicken to test their in vivo activity. In a combined approach of activity guided isolation, focused breeding, computer aided target search and SAR analysis, in vitro and in vivo testing, we search for highly efficient natural anthelmintic treatments.
ExPoApple2 – Exploring the potential of apple dihydrochalcones
Project leader: Dr. Stefan Martens Project partner: Univ.-Prof. Dr. Hermann Stuppner Funding period: 2017 - 2020 Project description: Even though dihydrochalcones are known to be a characteristic structure class in the secondary metabolite profile of malus sp., the latter have just recently shifted into scientific focus. But still, little is known about biosynthetical aspects as well as the dihydrochalcone bioactivity. Therefore, this project aims to close these gaps of knowledge by elucidating the full biosynthtic pathway and exploring the dihydrochalcone bioactivities using phytochemical and state of the art computational methods, resulting in potential cosmetical, nutritional or pharmaceutical applications of malus-products.
Dissecting the genetic basis of negative quality traits in new disease resistant grapevines - VITISANA
Project leader: Dr. Riccardo Velasco Project partner: Univ.-Prof. Dr. Hermann Stuppner Funding period: 2016 –2019 Project description: The extraordinary quality of grapes is unfortunately accompanied by high susceptibility to pests and pathogens, meaning large volumes of chemicals must be used to control crop losses. It is known that wild species, may supply a large set of natural disease resistances, but exhibit a low quality level. This project aims for the combination of metabolic profiling data of grapes and wine (via LC-MS and NMR) and genetic data in order to decouple negative traits from resistance traits carried over by the wildtypes into breeding products. The main result of this project will then be to understand the genetics underlying negative quality traits in disease resistant grapevines, in order to pave the way to the breeding of new varieties with outstanding taste and sustainable cultivation.
Global Research Initiative / Bionorica research GmbH
Natural products with effects on the Neuropeptide S (NPS/NPSR) System
Project leader: Dr. Stefan Schwaiger Funding period: 2014 - 2015 Project description: The exploration of the neuropeptide S (NPS)/NPS receptor (NPSR) system, also as therapeutic target, is limited due to the lack of non-peptidic ligands. Thus, there is as strong need to identify small, non-peptidic molecules interacting with this system. Since the 3D structure of the NPSR is unknown, a ligand based pharmacophore model was generated based on known ligands of the NPSR. The model was used for a virtual screening of natural product (NP) libraries resulting in a hit-list of more than 250 potentially active NPs. The planned experiments will include the isolation of virtually predicted NPs and the evaluation of their ability to interact with the NPS/NPSR-system. Most promising compounds will be analyzed in vivo.
NATPROTEC
