Global Research Initiative 2013/2014 - Bionorica SE · Consorzio Ferrara Ricerche for research on thalassemia. She was awarded a two-year fellowship and a post-doctoral grant from

Global Research Initiative 2013/2014

Phytoneering Award Winners

Information Kit

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Introduction

July 27, 2014

Dear Laureates, Honorable Guests, Dear Friends of Bionorica,

I initiated the Global Research Initiative (GRI) to mark the 80th anniversary of Bionorica. Starting in the fall of last year, we invited scientists from all over the world to submit their research projects to the competition, which we aptly named 'Phytoneering – one Step ahead in Thinking and Research'. We were pleased with what we consider an overwhelming response of over 130 entries. The members of the esteemed jury were greatly impressed with the quality and density of research that they were presented with.

With the GRI, I wanted to give young researchers the necessary space to carry out their research ideas in plant medicine without financial pressure. But we also expect new impulses for advanced innovation in plant medicine. This involves, in particular, identifying specific starting points for the development of new herbal preparations that improve patients’ quality of life and sustainably protects their health.

What has always fascinated me is the correlation of the healing power of nature and the opportunities advanced methods of science and technology provide. Therefore, I want to congratulate each and every one of our 20 laureates for his or her outstanding effort – I am looking forward to read and consider the results of your ambitious works. It is your courage and curiosity that we need in modern phytomedicine to offer ever more cutting-edge and breakthrough healthcare solutions.

Yours sincerely,

Prof. Dr. Michael A. Popp CEO Bionorica SE

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Content Bergonzi, C.: Innovative formulations to enhance oral bioavailability of herbal extracts. ....... 4

Brandner, J. M.: Effects of Arnebia euchroma extracts on different stages of wound healing in wounds with normal and impaired healing ...................................................................... 5

Clarke, R.: A novel human in vitro model to study the modulatory properties of plant-based medicines on physical and chemical irritant activation of airway sensory nerves .................. 6

Dansranjavin, T.: Characterization of epigenetic regulation in prostatitis and prostate cancer by a herbal preparation ................................................................................................ 7

Kalinina, S: Verbascum nigrum extract as a new complex phytotherapeutic agent ............... 8

Katarbayev, A.: New indications for a herbal preparation - “acute intestinal infections of bacterial etiology” ........................................................................................................ 9

Koeberle, A.: Bioactive lipid networks in phytomedicine.................................................. 10

Kraus, B.: Correlating the structure of differently substituted chalcones with transcriptome data and bioactivity in liver cells .................................................................................. 11

Krohn, M.: St John’s Wort extracts – ways to treat Alzheimer’s disease? .......................... 12

Quave, C.: Phytoneering Cosmeceuticals for Acne Vulgaris ............................................. 13

Margină, D.: Studies of some of the biological effects of encapsulated vegetal extracts from plants with known positive cardiovascular actions .......................................................... 14

Pérez Novo, C. A.: Molecular targets mediating the effect of a specific herbal preparation on chronic rhinosinusitis ................................................................................................. 15

Sadofsky, L.: How natural plant extracts modulate airway irritant receptor hypersensitivity 16

Savilova, A.: Investigation of the effects of a herbal preparation on endometrial mesenchymal stromal cells ............................................................................................................. 17

Schwaiger, S.: Natural products with effects on the Neuropeptide S system...................... 18

Stute, P.: Impact of black cohosh on brain after menopause ........................................... 19

Szczepanski, M. J.: Anti-cancer effect of a herbal preparation in head and neck squamous cell carcinoma................................................................................................................. 20

Wild, J.: Bactericidal/permeability-increasing protein (BPI) as a potential new target for the antimicrobial and immunomodulatory activities of herbal extracts.................................... 21

Zabolotna, D.: Study of the adjuvant effects of phytoproducts on the formation of antibodies against influenza virus antigens in the mucous membranes of the upper airways ............... 22

Zierau, O./Keiler, A: Effects of a hops extract on bone in a rat model of estrogen deficiency-induced osteoporosis.................................................................................................. 23

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Bergonzi, C.: Innovative formulations to enhance oral bioavailability of herbal extracts.

Dr Maria Camilla Bergonzi, Researcher, Department of Chemistry, University of Florence, Italy.

Title of Study Innovative formulations to enhance oral bioavailability of herbal extracts

Biography Graduated with Full Honors Degree (cum laude) in Pharmaceutical Chemistry and Technology from the University of Pisa in 1997. She gained her PhD in Science and Technology of Medicinal Plants in 2002.

Since 2005 she has held a tenured position of Assistant Professor at the Faculty of Pharmacy, University of Florence. She has received several contracts from the University of Pisa and from Consorzio Ferrara Ricerche for research on thalassemia. She was awarded a two-year fellowship and a post-doctoral grant from the University of Florence in 2002 and 2003. She is author of over 45 scientific papers, a number of congress communications, one patent, and a chapter in a book. Since 2010 she has led the Course of Pharmaceutical Technology for ungraduated students of the Faculty of Pharmacy. In 2011 she received a Research Incentivization Award from the University of Florence for intense teaching activity in the academic year 2010-2011.

Major Target of Study The project aims to assess the potential for preparation and easy industrial-scale production of new and innovative oral formulations able to overcome the limited oral bioavailability of herbal drugs and herbal extracts to increase their therapeutic efficacy.

Major Benefit of Study The study should lead to increases in the solubility, bioavailability, activity, and stability of extracts, allowing their pharmacokinetics and biodistribution to be modified. By applying these approaches, the project aims to improve patients’ quality of life and protect human health.

Abstract The project will study a phytopharmaceutical product well established from the point of view of its effectiveness and safety and to seek ways of making it more effective and safer by using technological strategies to overcome the disadvantages associated with conventional formulations. New drug delivery systems which are technologically simple, allowing rapid industrial scale-up, will be evaluated. In particular, the proposed strategies will include formulation of microemulsions, complexation with cyclodextrin, solid-state simultaneous mechanochemical activation, and co-crystallization and amorphization complexation.

My quote after learning about being a laureate: I appreciate receiving the award because it gives me the chance to pursue my research on the formulation of herbal extracts and to realize pharmaceutical preparations of industrial interest. I think the GRI is a great idea because it provides an excellent opportunity for young researchers to carry out their projects and in this way to increase the knowledge in the field of phytomedicines.

E-mail: [email protected]

Phone: +39-0554573678

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Brandner, J. M.: Effects of Arnebia euchroma extracts on different stages of wound healing in wounds with normal and impaired healing

Prof. Johanna M. Brandner, Researcher, Department of Dermatology and Venereology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany.

Title of Study Effects of Arnebia euchroma extracts on different stages of wound healing in wounds with normal and impaired healing

Biography Johanna Brandner is a PI in the Department of Dermatology and Venereology at the Hamburg-Eppendorf University Medical Center. She obtained her diploma in Biochemistry at the University of Regensburg and earned her PhD supervised by Prof. Werner W.

Franke at the German Cancer Research Center Heidelberg, focusing on structure-associated nuclear proteins. In 1998 she started research on skin barrier function and wound healing, and since 2013 a collaboration with the Hanse-Merkur-Zentrum for Traditional Chinese Medicine led to her interest in Arnebia euchroma.

With the outcome of the study, she plans to develop new wound healing treatment strategies.

Major Target of Study This study is expected to provide us with knowledge as to whether two extracts of A. euchroma used alone or in combination at different time points can improve various aspects of wound healing.

Major Benefit of Study Based on this study – if the outcome is positive - we hope to generate patient-tailored wound treatment by combining two extracts from a traditional herb.

Abstract Wounding of the skin impairs the protective barrier of the body and facilitates the entry of harmful substances and pathogens. Thus, timely regeneration of acute wounds is essential and acceleration of wound healing is therefore desirable to avoid the formation of chronic wounds. Chronic wounds are a substantial and global healthcare problem. Traditional Chinese Medicine (TCM) is based on thousands of years of experience in the field of treatment of wounds with medicinal plants and shows convincing results. However, molecular understanding of the effects is often incomplete. In this project, we want to use two extracts from a Chinese herb (A. euchroma) known from TCM and elucidate their effects on various phases/aspects of wound healing with the aim finding a time- and patient dependent combination of the two extracts for optimal wound healing.

My quote after learning about being a laureate: I appreciate receiving the award because it gives us the opportunity to contribute to the science-based acceptance of phytomedicine.

E-mail: [email protected] Phone: +49-40-7410-55819

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Clarke, R.: A novel human in vitro model to study the modulatory properties of plant-based medicines on physical and chemical irritant activation of airway sensory nerves

Ms Rebecca Clarke, PhD Student, Centre for Infection & Immunity, Queen’s University Belfast, Northern Ireland.

Title of Study A novel human in vitro model to study the modulatory properties of plant-based medicines on physical and chemical irritant activation of airway sensory nerves

Biography Rebecca is a PhD student at Queen’s University Belfast. She obtained a Bachelor’s degree in Biochemistry with Immunology at Trinity

College Dublin and began her PhD under the supervision of Dr Fionnuala Lundy and Dr Lorcan McGarvey, focusing on the development of an in vitro model of human sensory neurons from neural crest stem cells obtained from human dental pulp and validation of the model for the study of human neuronal ion channels capable of sensing nociceptive stimuli. Rebecca will complete her PhD in September 2014 and continue her work with the neuronal model as a Postdoctoral Researcher in Queen’s University Belfast Rebecca is also a recipient of the John Widdicombe award and Postgraduate IADR Hatton Award Irish Division.

Major Target of Study An in vitro model of whole functional human sensory neurons will be used for a detailed study of transient receptor potential (TRP) channels, an important family of nociceptors responsible for pain sensation and irritant airway reflexes such as cough.

Major Benefit of Study Examination of the effects of environmental irritants such as low temperature, acid pH and chemicals in cigarette smoke on the activation of neuronal TRP channels will be used to assess the potential of plant-based medicines to modulate irritant responses.

Abstract Airway sensory nerves control protective reflexes but in asthma and following respiratory viral infections these reflexes become hyperactive, causing troublesome cough and wheeze. These abnormal responses, typically triggered by environmental irritants such as cigarette smoke and cold air, are what disturb patients most about their condition. Discovering new treatments for excessive coughing is made harder because human airway nerves are extremely difficult to study. To overcome this we use novel techniques to differentiate human dental pulp stem cells into peripheral neuron equivalents. Using this model we can examine the effects of environmental irritants on sensory nerve activation and its potential modulation with plant based medicines.

My quote after learning about being a laureate: I am aware that many important medicines are plant-based and this award gives me the opportunity to understand how they work and explore the possibility of developing new treatments in the future.


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Dansranjavin, T.: Characterization of epigenetic regulation in prostatitis and prostate cancer by a herbal preparation

Dr Temuujin Dansranjavin, Dept. of Molecular Urology and Andrology, Justus-Liebig-Universität Gießen, Germany.

Title of Study Characterization of epigenetic regulation in prostatitis and prostate cancer by a herbal preparation

Biography Temuujin Dansranjavin is a research fellow in the Department of Molecular Urology and Andrology at Justus Liebig University, Gießen. He studied biology (diploma 1996) at the Martin Luther

University, Halle, and subsequently obtained his doctorate (Drrer.nat.) in 2000 with a thesis on the regulation of apoptosis in germ cell tumors. Since 2008 he has been working on epigenetic regulation of tumor-associated genes in prostate cancer (PCa). His current project, dealing with the characterization of metastasis-associated CpG-methylation in PCa, is funded by a Research Grant from the University Medical Center Gießen and Marburg (UKGM). Dr Dansranjavin is an elected member of the Working Group on Urological Research (AuF) of the German Society of Urology (DGU).

Study Development of chronic prostatic diseases such as BPH and PCa are significantly linked to prostatic inflammation. One specific herbal preparation is widely used as an anti-inflammatory treatment; however, little is known about molecular mechanisms and pathways in prostate diseases. Epigenetic deregulation of tumor suppressor genes and oncogenes plays a fundamental role in malignant tumor progression. We want to characterize the genes affected by a specific treatment and evaluate the role of the epigenetic regulation of these genes. This approach will provide novel insights into the molecular mechanisms underlying the actions of the study medication and will contribute to the development of new molecular markers for refining the treatment of prostate diseases.

E-mail: [email protected] Phone: +49-641-9939753

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Kalinina, S: Verbascum nigrum extract as a new complex phytotherapeutic agent

Dr Svetlana A. Kalinina, Researcher, Perm State Pharmaceutical Academy, Russia.

Title of Study Verbascum nigrum extract as a new complex phytotherapeutic agent: Our pharmaceutical studies include preparation of dried ethanolic and aqueous extracts of herbs, roots, flowers, leaves and stems, as well as extraction of fractions containing various classes of compounds (flavonoids, iridoids, phenolic acids) from V. nigrum. The biological activities of these extracts and fractions are evaluated. Overall, all extracts other than the root extract were found to demonstrate anticoagulant, hypotensive and diuretic activities.

Biography Svetlana Kalinina is a research fellow at Perm State Pharmaceutical Academy. She obtained her Diploma with honors in Pharmacy in 2009. As one of the leading PhD students she was awarded a “Training Abroad” grant under the President of the Russian Federation Program. As part of a research team at the School of Pharmacy, Curtin University of Technology, Australia, she took part in research on the synthesis of new purine derivatives. In 2013 she finished her PhD in medicinal chemistry and pharmacognosy. She continued her research on plant materials and extracts and the separation of biologically active natural compounds.

Major Target of Study This study will provide the first demonstration of the hypotensive, anticoagulant and diuretic effects of V. nigrum extracts. The experiments reveal links between the pharmacological activities and quantitative contents of biologically active compounds.

Major Benefit of Study The detailed pharmacological study of the extract should lead to a significant expansion of knowledge in the field of herbal medicine, in turn opening up an avenue for the creation of new promising and safe natural drugs.

Abstract An extract of the aerial part of V. nigrum has been shown to have significant antihypertensive and diuretic activities, which were attributed mainly to the actions of flavonoids. Taking phytochemical and pharmacological results and economic data into consideration, the optimal technology for producing dry extract from V. nigrum herb has been developed and studied in an experimental industrial environment.

My quote after learning about being a laureate: I appreciate receiving the award, as I believe that it will support a crucial step in the development of V. nigrum extract as a future remedy in the combined treatment of blood clotting disorders, hypertension and renal diseases.

E-mail: [email protected] Phone: +7-9194630863

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Katarbayev, A.: New indications for a herbal preparation - “acute intestinal infections of bacterial etiology”

Dr Adyl Katarbayev, Director of the Pediatrics Teaching Department and Head of the Department of Pediatric Infectious Diseases, S. D. Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.

Title of Study Preclinical studies of a herbal preparation in acute intestinal infection.

Biography In 1996 – PhD dissertation entitled "Particularities of the clinical course of acute mixed enteric infections in small children". In 2010 –doctoral dissertation entitled “Correlation of medical-demographic indicators with contagious diseases in children and development of

preventive measures”. Senior Doctor. Member of Research Council, Chairman of Scientific Task Group for Pediatric Problems, member of Ethical Council, internal auditor of Quality Management System at Kazakh National Medical University. Author of 88 scientific articles, 22 abstracts, 2 monographs (co-author), 5 guidance manuals (co-author), 1 certificate of authorship and 1 patent.

Major Target of Study This will be the first preclinical study (laboratory and histomorphological data) to suggest new indications for a specific herbal preparation – “acute intestinal infections of bacterial etiology”

Major Benefit of Study Based on this study, it will be possible to correct the quantitative and qualitative composition of the drug. It will identify the conditions for the formation of new drugs with direct actions treating and preventing acute intestinal infections.

Abstract The efficacy of a specific herbal preparation in acute intestinal infection in laboratory animals will be addressed by:

1. Assessing the sensitivity of different strains of pathogenic enterobacteria (genera Salmonella, Shigella, Escherichia).

2. Conducting laboratory and histomorphological evaluations of the efficacies of different doses and formulations in acute intestinal infection in laboratory animals.

My quote after learning about being a laureate: This award will help me translate my own research ideas into medical practice (initially in the treatment of infectious diseases in children).

E-Mail: [email protected] Phone: +7-777-681-09-19

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Koeberle, A.: Bioactive lipid networks in phytomedicine

Dr Andreas Koeberle, Junior research group leader, Professorial Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of Jena, Germany.

Title of Study Targeting of bioactive lipid networks: a novel pharmacological strategy for anti-inflammatory phytomedicine

Biography Andreas Koeberle is junior research group leader at the Chair of Medicinal/Pharmaceutical Chemistry, University of Jena, Germany, with a research focus on bioactive lipid profiling and molecular

pharmacology. After studying biochemistry, Koeberle completed his PhD studies at the University of Tübingen, Germany, in 2009 and spent two years as postdoctoral fellow at the University of Tokyo, Japan. His research is funded by grants from the Deutsche Forschungsgemeinschaft, Takeda Science Foundation, the University of Jena, and the Phospholipid Research Center, Heidelberg, and he is recipient of the Klaus-Grohe-Award for Medicinal Chemistry.

With the outcome of the study, he plans to evaluate the potential of novel identified anti-inflammatory mechanisms for (phyto)pharmacotherapy.

Major Target of Study The study will extend our understanding of how some of the most prominent plant-derived drugs modulate bioactive lipid networks and whether this might be relevant for their anti-inflammatory features.

Major Benefit of Study By providing insights into the anti-inflammatory principle of phytopharmaceuticals, the study will help to estimate their pharmacological potential and provide a mechanistic basis for their optimization.

Abstract Emerging evidence shows that the interplay of multiple bioactive lipids shapes their biological response. Koeberle speculates that distinct phytopharmaceuticals may exert anti-inflammatory activity by modulating the bioactive lipid network of immune cells. His study will employ a comprehensive lipidomics approach to determine how this network is affected by selected phytopharmaceuticals and to address whether changes observed in the lipid pattern impact immune cell function.

My quote after learning about being a laureate: I highly appreciate receiving support for my efforts in unraveling the molecular mechanisms of phytomedicine – a research field that has been neglected for a long time despite its indispensable importance to exploiting the full power of nature for human health.


Phone: +49-3641-949815

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Kraus, B.: Correlating the structure of differently substituted chalcones with transcriptome data and bioactivity in liver cells

Dr Birgit Kraus, Pharmaceutical Biology, Institute of Pharmacy, University of Regensburg, Germany.

Title of Study Correlating the structure of differently substituted chalcones with transcriptome data and bioactivity in liver cells.

Biography Birgit Kraus is a research fellow at the Institute of Pharmacy at the University of Regensburg, Germany. She obtained a degree in Biology at the Technical University, Munich (TUM), and earned her PhD under Prof. Elstner at the Center of Life and Food Sciences,

Weihenstephan (TUM), focusing on the influence of St John`s Wort (Hypericum perforatum) extract on the immunological functions of microglial cells. In 2007, she moved as a postdoctoral fellow to the group of Prof. Heilmann at the Institute of Pharmacy at the University of Regensburg. Since 2010, she has been Assistant Professor (Habilitandin). Her main research interests are hepatotoxicity, hepatoprotection, and chemoprevention by natural products and their metabolites.

Major Target of Study This will be the first study addressing correlations between results from cellular assays and transcriptome data and the molecular structures of compounds. This will give new insights into the cellular mechanisms of action of chalcones.

Major Benefit of Study The outcome of the study will lead to a better understanding of how chalcones act on the liver (in a positive or negative manner). It could further reveal entirely new applications and indications for chalcones and chalcone metabolites.

Abstract Chalcones possess a wide range of biological activities. Moreover, they offer an interesting basic structure that allows investigation of structure-activity relationships and creation of derivatives with altered and enhanced pharmacological properties. We have previously analyzed the impact of different chalcones on cellular structures and functions of liver cells. In this study, we will perform an in-depth data analysis with the aim of correlating our previously obtained results from multi-parametric cellular assays with the structural characteristics of chalcones. Furthermore, the results from the cellular assays will be complemented with data from ultra-high-throughput mRNA sequencing of the transcriptome of chalcone-treated liver cells.

My quote after learning about being a laureate: I appreciate receiving the award because this award is exactly what is needed to foster research in the current times of reduced government funding and tight budgets at academic institutions.


Phone: +49-941-943-4494

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Krohn, M.: St John’s Wort extracts – ways to treat Alzheimer’s disease?

Dr Markus Krohn, Researcher, Neurodegeneration Research Lab (NRL), Department of Neurology, University of Magdeburg, Germany

Title of Study Defining specific extracts from St John’s Wort for the treatment of Alzheimer’s disease

Biography Markus Krohn is a research fellow at the Neurodegeneration Research Lab in Magdeburg. He obtained a diploma in animal physiology at the University of Greifswald and earned his PhD under

Prof. Jens Pahnke at the University of Rostock, focusing on ABC transporter function in Alzheimer’s disease. In 2005 he started research on Alzheimer’s disease and soon focused on the role of transport proteins in the development of this disease. After elucidating the importance of the transporters ABCC1 and ABCB1, the NRL started searching for activators. During the following years phytopharmaceuticals became one focus of his research.

Major Target of Study This study will provide the first assessment of St John’s Wort extracts to identify the components responsible for ABCC1 transporter activation. It will also raise awareness of the usefulness of phytomedicines for human diseases.

Major Benefit of Study This study will not only be the first step tin defining extraction methods that can be used to produce phytopharmaceuticals from St John’s Wort with the potential to treat Alzheimer’s disease, but it is also a first step in shedding light on its other mechanisms of action.

Abstract Alzheimer’s disease (AD) is thought to be triggered by pathological aggregation of the protein amyloid-beta (Aβ) in the brain. Most current treatment approaches therefore aim to reduce the amounts of Aβ present. Our previous studies found that a defect in transport protein ABCC1 can lead to a more-than-12-fold increase in brain Aβ concentrations in a mouse model of AD (PMID: 21881209). To exploit this mechanism to develop a treatment, we tested different extracts of various medicinal plants to test their capabilities to activate ABCC1. An extract of St John’s Wort was effective independently of the hyperforin and hypericin concentrations, which are historically regarded as the main active substances in this herb (PMID: 24156265). This study now aims to further define a method for producing an extract which is effective in activating ABCC1 transport function and potential as an effective treatment option for AD.

My quote after learning about being a laureate: Yeah, that’s great! Finally a research award esteeming the value of phytomedicine.


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Quave, C.: Phytoneering Cosmeceuticals for Acne Vulgaris

Dr Cassandra Quave, Assistant Professor, Department of Dermatology and Center for the Study of Human Health, Emory University, USA

Title of Study Botanical natural product inhibitors of acne biofilms

Biography Cassandra L. Quave, PhD holds a joint appointment as Assistant Professor of Dermatology in the Emory University School of Medicine and Center for the Study of Human Health in the Emory

College of Arts and Sciences, where she leads drug discovery research initiatives and teaches undergraduate courses on medicinal plants, food and health. She is also the Curator of the Emory University Herbarium and is currently leading a revitalization effort for the collection. Trained as a medical ethnobotanist, her research is focused on the documentation and analysis of botanical remedies used in the treatment of infectious disease, with special interest in natural product inhibitors of pathogenic bacterial cell signaling pathways.

Major Target of Study For the first time, this study will assess the anti-acne biofilm activity of medicinal plants used in traditional medicine for the treatment of skin and soft tissue infections in the Mediterranean.

Major Benefit of Study This study has the potential to lead to the discovery of novel botanical products for use in future acne formulations.

Abstract Acne vulgaris is a common skin disorder, which affects >85% of teenagers. Propionibacterium acnes is implicated in its pathogenesis and biofilm formation within the skin follicles plays a critical role in this process. Like many other bacteria, P. acnes is also subject to emerging antibiotic resistance and novel therapies are in high demand. Medicinal plants may represent a unique source of new therapeutic options. Our lab has already demonstrated interesting anti-staphylococcal activity in a library of medicinal plant extracts. However, these extracts have never been evaluated for their efficacy in targeting P. acnes biofilms. The overall aim of this study is to evaluate these extracts and identify potential leads for the development of new topical acne therapies.

My quote after learning about being a laureate: With this award, Bionorica is supporting my growth and career development as a phyto-scientist. I am deeply appreciative of their generous support and will use these funds to undertake the important first steps in identifying novel therapies for an important medical condition.

E-mail: [email protected] Phone: +1-404- 727 7065

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Margină, D.: Studies of some of the biological effects of encapsulated vegetal extracts from plants with known positive cardiovascular actions

Dr Denisa Margină, Carol Davila University of Medicine and Pharmacy, Faculty of Pharmacy, Bucharest, Romania

Title of Study: Studies of some of the biological effects of encapsulated vegetal extracts from plants with known positive cardiovascular actions.

Biography Dr Denisa Margină is an Associate Professor with habilitation at the Department of Biochemistry, Faculty of Pharmacy, Bucharest, Romania. She earned her PhD in 2006 with the thesis “Studies of the biochemical and immunological implications of endothelial dysfunction”. Between 2010 and

2012 she was a post-doctoral fellow and conducted research on the positive effects induced by certain polyphenols on cellular mechanisms involved in the development of complications of chronic hyperglycemia. As a result, she published a number of papers in high-impact-factor journals: Food and Chemical Toxicology, Journal of Proteomics, Aging Clinical and Experimental Research, International Journal of Molecular Sciences, General Physiology and Biophysics.

Major Target of Study The study aims to assess some of the biological properties of vegetal extracts (Aesculus Hippocastanum semen, Vitis vinifera L. folium and Curcuma Longa rhizoma) known for their positive cardiovascular actions, in encapsulated forms.

Major Benefit of Study The results from this study should show whether or not encapsulated forms have effects similar to those observed for plant extracts and whether encapsulation has potential to be used either for preparing nutraceuticals or in the manufacture of functional foods.

Abstract The major drawbacks in using polyphenols as medicines include low bioavailability and instability at the pH levels reached in the digestive tract. The use of encapsulated polyphenols could efficiently alleviate these deficiencies. The plants identified above were chosen for evaluation of their potential antioxidant and anti-inflammatory properties. The effects will be assessed in vitro and in vivo and compared to their non-encapsulated forms and to other substances known to have antioxidant and vasoprotective effects: quercetin, curcumin, and vitamin C. The project will evaluate the quality of the extracts and their biological effects in a standardized cell culture model and in vivo using invertebrates such as Daphnia magna.

My quote after learning about being a laureate: It is a great honor for me to be a GRI Bionorica laureate, and I consider this prize not only an award, but also an exceptional opportunity. This will be a good starting point for more elaborate studies of vegetal extracts with potential beneficial cardiovascular actions. I am working in a young research team and this GRI Bionorica project could be a challenge not only for me, but also for other young researchers to approach and deepen pharmaceutical research in the field of natural compounds.


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Pérez Novo, C. A.: Molecular targets mediating the effect of a specific herbal preparation on chronic rhinosinusitis

Dr Claudina Angela Pérez Novo, post-doctoral Researcher at the Upper Airways Research Laboratory, Ghent University, Belgium.

Title of Study: Genome-wide transcriptome analysis for the elucidation of the molecular mechanisms involved in the anti-inflammatory action of a specific herbal preparation in chronic rhinosinusitis

Biography Claudina Pérez Novo obtained her PhD in Medical Sciences in 2006 under the supervision of Prof. Claus Bachert and Prof. Paul Van Cauwenberge at the

University of Ghent, Belgium. Her research work is focused in the role of lipid mediators/eicosanoids in the pathogenesis of chronic rhinosinusitis and aspirin-exacerbated respiratory disease. At present she is a senior post-doctoral researcher in the same department. Her research topic has currently been extended to the role of epigenetic events in the initiation and persistence of inflammation in chronic airway diseases. The data obtained in this study will provide an extensive gene expression/regulatory targets database linked to the pharmacological action of a specific herbal preparation that will be the start point for further mechanistic studies of the drug.

Major Target of Study This study intends to elucidate the signaling pathways mediating the anti-inflammatory action of a specific herbal preparation in chronic rhinosinusitis by comparing the entire transcriptome expressed in inflamed nasal tissue before and after drug interference.

Major Benefit of Study This study will provide the first gene reference database containing molecular targets, pathways and regulatory networks linked to the pharmaco-molecular mechanisms of a specific herbal preparation in chronic rhinosinusitis.

Abstract Chronic rhinosinusitis (CRS) is one of the most common healthcare problems worldwide. One specific herbal preparation has been proven to alleviate clinical symptoms of this disease in both children and adults. However, very little is known about the signaling mechanisms and molecular targets mediating its action. This study intends to elucidate the signaling pathways mediating the anti-inflammatory action of a specific herbal preparation in CRS. To achieve our goal, sinunasal tissue from patients suffering from CRS will be collected and incubated with the specific herbal preparation and then used for genome-wide analysis of expression. This approach will identify differentially expressed gene targets and regulatory networks involved in the mechanism of action of this compound.

My quote after learning about being a laureate For me is a great honor to be selected as one of the laureates of the Bionorica Global Research Initiative. This prize will not only allow me to contribute to consolidating and extending our knowledge of the molecular mechanisms of a specific herbal preparation in chronic rhinosinusitis, but will also enrich my knowledge in the field of phytomedicine in the management of inflammatory airways disease.


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Sadofsky, L.: How natural plant extracts modulate airway irritant receptor hypersensitivity

Dr Laura Sadofsky, Lecturer, Hull York Medical School, University of Hull, UK.

Title of Study In vitro effects of natural agonists and antagonists of airway irritant receptors

Biography Laura Sadofsky is a lecturer at Hull York Medical School, University of Hull. She gained a BSc in Biochemistry and an MSc in Toxicology from the University of Birmingham and then moved to Hull to study

for a PhD in medicine under Prof. Morice, focusing on the molecular pharmacology of the capsaicin receptor. On completing her PhD she worked as a post-doctoral researcher in respiratory medicine at the University of Hull before becoming a lecturer in 2011. Her research focuses on the molecular pharmacology of thermo-transient receptor potential channels in cough and airways inflammation. She plans to publish the outcome of the study and to provide an assay platform to verify the modulation of irritant receptors by phytopharmaceuticals.

Major Target of Study This study will provide the first demonstration of whether chronic exposure to a range of naturally occurring compounds affects irritant (TRP) channel expression or sensitivity and the mechanism involved.

Major Benefit of Study

The study will identify changes in irritant channel expression/sensitivity in airways after chronic exposure to plant products and show how these can be used to treat chronic cough or other conditions involving these channels.

Abstract Herbal remedies have been used for many years to treat cough. We wish to explore the mechanism of modulation of irritant receptor (thermo-TRP) hypersensitivity by plant extracts to understand the therapeutic basis for such remedies. We hypothesize that the expression/sensitivity of TRP channels can be influenced by chronic exposure to their agonists via the LTB4 pathway. To this end, qPCR, western blotting and calcium signaling studies using primary cells and cell lines will be employed to obtain pharmacological and biochemical evidence of modulation of TRP channels altering responses to tussive agents. We will show how natural compounds can be used to treat chronic cough and conditions where TRP channels are important, such as itch and pain.

My quote after learning about being a laureate: This award will help me establish myself as an independent researcher and allow me to pursue my interest in the pharmacology of natural plant-derived products.


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Savilova, A.: Investigation of the effects of a herbal preparation on endometrial mesenchymal stromal cells

Dr Anastasia Savilova, Head of Cell Technology Laboratory, FSBI "Research Center for Obstetrics, Gynecology and Perinatology," Ministry of Health of the Russian Federation, Moscow, Russia.

Title of Study Investigation of the mechanism of action of a specific herbal medicine on eutopic and ectopic endometrial mesenchymal stromal cells.

Biography Anastasia Savilova is head of the Cell Technology Laboratory at

"Research Center for Obstetrics, Gynecology and Perinatology". She obtained a Specialist degree in Biochemistry in 1998 at Moscow State University, and earned her PhD under supervision of prof. V. M. Stepanov in 2001, focusing on the study of proteinase precursors of microorganisms. In 2010, she started research for eutopic and ectopic endometrial mesenchymal stromal cells at the Cell Technology Laboratory. With the outcome of the study, she plans to continue the work using endometrial mesenchymal stromal cells as a model for studies of the effects of various substances on normal and ectopic human endometrium.

Major Target of Study This study for the first time looks into the interaction of a specific herbal preparation and human endometrium by investigating its effects on eutopic and ectopic endometrial mesenchymal stromal cells, comparing its action with estradiol.

Major Benefit of Study This study will allow the mechanisms of action of a specific herbal preparation on human normal and ectopic endometrial mesenchymal stromal cells to be proposed.

Abstract The aims of the project are to study the effect of a specific herbal preparation on endometrial cells from healthy women and to compare its action to that of estradiol, as well as to evaluate the effect of a specific herbal preparation on ectopic endometrial cells from endometriotic lesions. The possible effects on endometrial MSCs will be studied using different concentrations of Vitex agnus castus extract, followed by evaluation of changes in cell phenotype (by flow cytometry) and gene and protein expression (by real-time PCR and ELISA), followed by comparison with gene/protein expression in cells exposed to estradiol and unexposed cells/vehicle control cells.

My quote after learning about being a laureate: I appreciate receiving the award because it is a great opportunity for our laboratory to begin investigations of endometrial cells as a model for studying the effects of various substances on normal and ectopic human endometrium.


Phone: +7-917-561-05-36

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Schwaiger, S.: Natural products with effects on the Neuropeptide S system

Dr Stefan Schwaiger, senior-postdoc, Institute of Pharmacy/ Pharmacognosy, University of Innsbruck, Austria.

Title of Study Natural products with effects on the NPS/NPSR system

Biography Stefan Schwaiger is a senior-postdoc at the University of Innsbruck/Institute of Pharmacy/Pharmacognosy. He obtained his master's degree in pharmacy at 2001 and earned his PhD under the supervision of Univ. Prof. Dr Hermann Stuppner in 2005, focusing on phytochemical studies of edelweiss (Leontopodium nivale ssp.

alpinum). Afterwards, he continued his work at the same department, isolating and elucidating the structures of secondary metabolites from higher plants with anti-inflammatory and other pharmacological activities, resulting in contributions to 40 publications. Major Target of Study This proposal is the first attempt to use a ligand-based pharmacophore model of the NPS receptor for the discovery of natural products interfering with this target.

Major Benefit of Study Natural products with effects on the NPS/NPSR system will be of paramount importance for understanding which biological functions are controlled by the NPS/NPSR system and for defining the therapeutic potential of selective non-peptidic NPSR ligands.

Abstract Exploration of the neuropeptide S (NPS)/NPS receptor (NPSR) system, including as a therapeutic target, is limited due to the lack of non-peptidic ligands (agonists). Thus, there is a strong need to identify small, non-peptide molecules interacting with this system. Since the 3D structure of the NPSR is unknown, a ligand-based pharmacophore model has been generated based on known NPSR ligands. This model was used for 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 evaluation of their ability to interact with the NPS/NPSR-system. The most promising compounds will be analyzed in vivo.

My quote after learning about being a laureate: This initiative is a great idea to support upcoming researchers in their careers.


Phone: +43-512-507-58409

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Stute, P.: Impact of black cohosh on brain after menopause

Dr Petra Stute, Head of Menopause Clinic and Gynecological Endocrinology, Deputy Head of Gynecological Endocrinology and Reproductive Medicine Section, Department of Obstetrics and Gynecology, Inselspital Bern, Switzerland.

Title of Study Impact of black cohosh on hippocampal and hypothalamic gene expression profiles in ovariectomized rats.

Biography Petra Stute is a specialist in gynecological endocrinology and reproductive medicine. She completed her medical training in Germany and became Deputy Head of the Gynecological Endocrinology and Reproductive Medicine

Section, Department of Obstetrics and Gynecology, Inselspital Bern, Switzerland, in 2009. She started her scientific training as a postdoc at the Department of Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, USA. Since then her research activities have focused on the menopause. The study will lead to deeper insight into gene regulation in the brain before and after menopause, with and without medical intervention.

Major Target of Study Cognitive decline is a major concern in postmenopausal women. However, although estrogens have shown some promising effects on cognitive function, they are neither approved for this indication nor recommended for long-term use, due to potential major health risks such as thromboembolism. Thus, a drug with positive impact on cognition but without increasing health risks would be ideal.

Major Benefit of Study This study may demonstrate that black cohosh has a positive impact on the brain after menopause.

Abstract Menopause-related estrogen decline affects the aging process of the female brain and is accompanied by progressive decline in cognition and memory. Furthermore, estrogen decline also leads to dysfunction of temperature-sensitive neurons in the hypothalamic preoptic area and other hypothalamic nuclei areas, which may explain the reduced ability to adapt to changes in ambient temperature resulting in hot flushes, the most common menopausal symptom. The hippocampus plays a major role in learning and memory. However, it also contributes to attention, arousal, and emotional states, including stress, as well as to adaptive and reproductive behavior. Hippocampal outputs are predominantly inhibitory on downstream neuroendocrine activity. During the peri- and postmenopausal periods, estrogens or herbs such as black cohosh are often used to treat hot flushes. One explanation may be that estrogens and black cohosh increase the density of cells in the hypothalamic nuclei expressing c-fos protein (a marker of neuronal activity). Furthermore, black cohosh also interacts with the hypothalamic-pituitary-adrenal axis such that it alleviates the acute stress response in rats. Its neuroprotective effect was recently studied using Sprague-Dawley rats, with comparison of the impact of estradiol and black cohosh on the hypothalamic nuclei in ovariectomized and intact rats.

My quote after learning about being a laureate: I think the GRI is a great idea providing the opportunity to focus on research in phytomedicine.

E-Mail: [email protected] Phone: +41-31-632-1303

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Szczepanski, M. J.: Anti-cancer effect of a herbal preparation in head and neck squamous cell carcinoma

Dr Miroslaw J. Szczepanski, MD, PhD, assistant professor, Department of Otorhinolaryngology, Faculty of Medicine and Dentistry, Medical University of Warsaw, Poland.

Title of Study Anti-cancer effect of a herbal preparation in head and neck squamous cell carcinoma

Biography Dr Miroslaw J. Szczepanski is an Otolaryngologist certified by the Polish Board. He received his MD from Poznan University of Medical Sciences (Poland). He completed his Residency in Otorhinolaryngology at the Department of Otorhinolaryngology (Warsaw, Poland). He

received his PhD in tumor immunology in 2010 under Professor Grzegorz Dworacki. He spent a 3.5-year postdoctoral fellowship at the University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA in Dr Theresa Whiteside's laboratory (2006-2009). He has authored a number of publications on tumor immunology. Recent honors include the Polish Ministry of Health Award and the Professor Miodonski Research Award for young laryngologist-scientists. In addition to work, his passion is scuba diving.

Major Target of Study This study is the first investigation of the possible in vitro anti-cancer effects of a specific herbal preparation.

Major Benefit of Study The information derived from these studies will allow the possible usefulness of a specific herbal preparation in the chemoprevention or adjuvant treatment of HNSCC to be evaluated.

Abstract Head and neck squamous cell cancers (HNSCC) are a group of upper respiratory/digestive tract neoplasms with a substantial clinical and socio-economic relevance. An association between the development of cancer and inflammation has long-been appreciated. Recently, attention has been paid to herbal medicines in the treatment of various disorders including chronic inflammation and cancers. The study focuses on a frequently used herbal medicine that possesses anti-inflammatory effects. We hypothesize that this medicinal product might inhibit in vitro tumor development/progression via inhibition of proliferation and induction of apoptosis in HNSCC cell lines.

My quote after learning about being a laureate: I think the GRI is a great idea because it will help young scientists to start their own research projects and translate their research ideas to practical reality.


Phone: +48-669-757-552

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Wild, J.: Bactericidal/permeability-increasing protein (BPI) as a potential new target for the antimicrobial and immunomodulatory activities of herbal extracts.

Dr Jens Wild, Scientist, Institute of Medical Microbiology & Hygiene, University of Regensburg, Regensburg, Germany.

Title of Study Bactericidal/permeability-increasing protein (BPI) as a potential new target for the antimicrobial and immunomodulatory activities of herbal extracts.

Biography Jens Wild obtained a diploma in biology at the Saarland University, Saarbrücken, and earned his PhD at the University of Ulm. In 2000, he started working on the development and improvement of innovative

HIV-specific vaccine candidates at the Institute of Medical Microbiology & Hygiene at the University of Regensburg, where he received habilitation in 2012. In recent years he has focused on characterizing the in vitro and in vivo functions of bactericidal/permeability-increasing protein (BPI) as well as T-cell regulation in infectious diseases in mouse models.

Major Target of Study The study will evaluate the effects of herbal extracts in regulating the production, release, and biological function of bactericidal/permeability-increasing protein (BPI), one of the most potent substances of the body’s antimicrobial defense.

Major Benefit of Study The study will provide an understanding of a possible novel mode of action among the documented antimicrobial activities of plant compounds, as well as the opportunity to evaluate effects in vitro and in vivo in well-defined models.

Abstract The respiratory tract is permanently exposed to inhaled airborne particles, including potentially harmful pathogens. The first line of host defense is built by innate immune responses, e.g., infiltrating polymorphonuclear leukocytes (PMNs) which contain a broad range of pre-stored antimicrobial proteins and peptides, including BPI, which is one of the body's most potent defense substances. This project will systematically test if and how various herbal extracts are able to stimulate the degranulation of BPI from PMNs. For in vitro experiments, human whole blood samples, as well as stem cell-derived murine granulocytes, will be evaluated; promising extracts will then be tested in vivo in transgenic mouse models.

My quote after learning about being a laureate: We are very happy about receiving the award because this allows us to provide further insights into the function of BPI and novel modes of action of herbal extracts.


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Zabolotna, D.: Study of the adjuvant effects of phytoproducts on the formation of antibodies against influenza virus antigens in the mucous membranes of the upper airways

Dr Diana Zabolotna, Senior Research Fellow, Department of Clinical Allergology, State Institution “O. S. Kolomiychenko Institute of Otolaryngology, Ukrainian National Academy of Medical Sciences”, Kiev, Ukraine.

Title of Study Study of the adjuvant effects of phytoproducts on the formation of antibodies against influenza virus antigens in the mucous membrane of the upper airways (a clinical-experimental study).

Biography Education: graduated from the medical faculty of Bogomolets National Medical University in 1997 (with honors, number 001011, July 4 1997)

• Specialty - medicine, with 16 years' experience. • Graduate Education: Internship in Otorhinolaryngology at Bogomolets National Medical University,

1999 • Academic degree and title: PhD in Medicine (2002), Doctor of Medicine ("Clinical and experimental

justification for the use of probiotics in the treatment of chronic nonspecific inflammatory and allergic diseases of the upper respiratory tract") in 2010

• She plans to continue medical research on the efficacy of phytoproducts

Major Target of Study

This study will explore local monovaccination in the upper airways area against infections entering via the upper airways and will address the use of immunomodulators for augmenting the effects of vaccination.

Major Benefit of Study

Our data confirm the activating effects of phytoproducts on immune reactions and their anti-inflammatory and adaptogenic properties; the study will identify whether the concomitant use of phytoproducts and mucosal vaccines against influenza promotes effective prevention and treatment of viral infections.

Abstract

Study goal and tasks:

- to identify a suitable vector and the extent of immunomodulation of protective antibody formation against influenza virus by phytoproducts in patients with inflammatory airway diseases and in experimental animals, both normal and immunodeficient

- to determine the efficacy of immunomodulation (with phytoproducts) of the response to influenza virus antigens depending on administration time (before or after antigenic stimulation).

- to study a mucosal vaccination method in an optimized regimen (topical only, parenteral only, combined) in combination with phytoproducts.

- to assess the intensity of antibody formation against influenza virus in patients suffering from chronic inflammatory diseases undergoing topical or systemic vaccination and using phytoproducts.

My quote after learning about being a laureate:

My laboratory and I appreciate receiving this honorable award because it represents serious recognition of the work of our scientific group.

E-Mail: [email protected]

Phone: +380505068004

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Zierau, O./Keiler, A: Effects of a hops extract on bone in a rat model of estrogen deficiency-induced osteoporosis

Dr Oliver Zierau, Researcher, Department of Biology, Faculty of Science, Institute of Zoology, Technische Universität Dresden, Germany

Biography Dr Zierau graduated from the School of Veterinary Medicine, Hanover, in 1996, did his thesis work at the Institute for Molecular Medicine at the Medical University in Lübeck. His doctoral thesis (1999) was: “Influence of

antiestrogens on the expression of estradiol-regulated genes in the endometrial adenocarcinoma cell line RUCA-I” and his habilitation thesis (2012) at the TU Dresden, was “Endocrine effects of plant-derived secondary metabolites and synthetic derivatives of naringenin”. His main research topics at the Department of Molecular Cell Physiology and Endocrinology at the TU Dresden are the characterization of the cellular and molecular effects of phytoestrogens in vitro and in vivo as well as the role of estrogens in carcinogenesis and development. The study will determine whether a hops extract possesses bone sparing effects in a situation of estrogen deficiency.

My quote after learning about being a laureate: This award will help us to find and test an alternative to the classical hormone replacement therapy and to test the efficacy and safety of a hops extract in this situation.

E-mail: [email protected] Phone: + 49-351-463-378-41

Annekathrin Keiler, Researcher, Department of Biology, Faculty of Science, Institute of Zoology, Technische Universität Dresden, Germany

Biography Annekathrin Keiler graduated from the Technical University of Dresden in 2009. At the moment, she is finishing her PhD thesis at the Department of Molecular Cell Physiology and

Endocrinology at the TU Dresden. Her main research topics are further characterization of a preclinical model of postmenopausal osteoporosis and the bone-sparing effects of plant secondary metabolites using the ovariectomized rat. The study will determine whether a hops extract possesses bone sparing effects in a situation of estrogen deficiency.

My quote after learning about being a laureate: I appreciate receiving the Global Research Initiative Award because it might help us find alternatives for classical hormone replacement therapy.

E-mail: [email protected] Phone: +49-351-463-347-33

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Title of Study Effects of a hops extract on bone in a rat model of estrogen deficiency-induced osteoporosis.

Major Target of Study This study represents the first investigation of the potential of a hops extract in the prophylaxis and treatment of estrogen deficiency-induced bone loss.

Major Benefit of Study This study will evaluate hops extracts as an alternative to classical HRT in terms of the efficacy and safety of potential bone-sparing effects in an animal model of estrogen deficiency-induced osteoporosis.

Abstract From the health perspective, the most important results of menopause are osteoporosis and its consequences. Unfortunately, hormone replacement therapy is associated with increases in the incidence of breast cancer and cardiovascular diseases. This has led to rising interest in plant-derived treatment alternatives. Humulus lupulus L. (hops) has a long history as a medicinal plant e.g., in alleviating gynecological disorders. We plan to use a small-animal model of osteoporosis to test the potential of a hops extract in estrogen deficiency-induced bone loss. We also plan to analyze the cancerogenic potential of the hops extract. These studies should therefore allow us to evaluate the potential of the hops extract as a herbal remedy for preventing postmenopausal osteoporosis, as well as its safety.

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MEDIA CONTACT BIONORICA GLOBAL RESEARCH INITIATIVE

Thomas Eibenberger Senior Referent Corporate Communications Tel.: +49 9181 231-450 [email protected]

For more information please visit: www.bionorica.de/research.initiative2013

DISCLAIMER

English:

The information about the scientists and the studies rewarded were made directly by the winners. Bionorica assumes no responsibility for the accuracy, completeness, timeliness or quality of the information provided. All contents are non-binding.

Deutsch:

Die Informationen zu den Wissenschaftlern und den ausgezeichneten Studien stammen direkt von den Preisträgern. Bionorica übernimmt keine Gewähr für Korrektheit, Vollständigkeit, Aktualität oder Qualität der bereitgestellten Informationen. Alle Inhalte sind unverbindlich.

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Documents

Global Research Initiative 2013/2014 - Bionorica SE · Consorzio Ferrara Ricerche for research on thalassemia. She was awarded a two-year fellowship and a post-doctoral grant from