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Cost International Projects National Projects Bilateral Scientific Cooperation Национални пројекти HORIZON-RIA ИДЕЈЕ позив Proof of Concept Доказ концепта

New Varieties of Faba Bean and Their Dry Seed Extracts for Use in Subjects Suffering from Neurodegenerative and Cardiovascular Disorders

Project leader: Dr. Jelena M. Aleksić

Project collaborators: Dr. Nevena Mihailović-Stanojević, Dr. Zoran Miloradović, Dr. Milan Ivanov, Dr. Una-Jovana Vajić, Dr. Danijela Karanović, Dr. Jasmina Milenković, Dr. Ivana Živković

Duration of the project: 27.06.2024-26.02.2025.

Leading institution: Institute for Medical Research, University of Belgrade

Collaborating institutions: Institute for Forage Crops, Kruševac, Institute for Multidisciplinary Research, University of Belgrade

Description of the project:

Dopamine deficiency is a key factor in neurodegenerative and movement disorders such as Parkinson’s disease and restless legs syndrome, as well as in depression. Conventional treatments for these conditions use synthetic L-dopa, which causes numerous side effects. Natural L-dopa, which is present in certain plant species including faba bean, is a suitable alternative. On the other hand, in the nutraceutical and functional food industry, there is a rapidly growing demand for natural, bioactive compounds that have positive effects on human health, especially antioxidants such as polyphenols.

The project proved the concept that local faba bean populations from the Republic of Serbia differ in the content of L-dopa, polyphenols and other bioactive compounds, and that the content of desirable bioactive compounds can be increased in dry seed extracts by applying a cost-effective and scalable technology that, in addition, enables modeling of the composition of extracts for the purpose of optimization for various healthcare applications and market needs.

Faba bean extracts naturally enriched with desirable bioactive compounds represent natural dietary supplements that have positive effects on neurological health, dopamine regulation, and general well-being, and can also be used to increase the nutritional value of food products through enrichment with natural bioactive compounds and the production of functional foods. In addition to the beneficial effects of natural dietary products for neurological and chronic human conditions, additional benefits of their production include organic faba bean cultivation with improved soil health and reduced chemical inputs, as well as lower CO₂ emissions and reduced soil, air and water pollution through environmentally friendly agricultural practices.

Тип пројекта:

Proof of Concept

Examination of the Antihypertensive and Renoprotective Potential of Substances of Natural and Synthetic Origin in Experimental Models of Cardiovascular and Renal Diseases

Project leader: Dr. Đurđica Jovović

Project collaborators: Dr. Zoran Miloradović, Dr. Nevena Mihailović-Stanojević, Dr. Jelica Grujić Milanović, Dr. Milan Ivanov, Dr. Dinko Sušić, Dr. Slađan Milanović, Dr. Dijana Jovanović, Dr. Dragana Dekanski, Dr. Anamarija Simić, Dr. Jasmina Varagić, Dr. Danijela Karanović, Dr. Una-Jovana Vajić

Project number: 175096

Duration of the project: 2011-2019.

Leading institution: Institute for Medical Research, University of Belgrade

Collaborating institutions: Faculty of Medicine, University of Belgrade, “Galenika” A.D.

Description of the project:

The results of the project demonstrated that therapy with olive leaf extract has a beneficial effect on cardiovascular and renal parameters. It reduced oxidative stress, arterial blood pressure (systolic, diastolic, and mean), and total peripheral resistance in a rat model of essential hypertension. In the same experimental model, the olive leaf extract led to an improvement in renal circulation, a reduction in renal vascular resistance, and a decrease in the synthesis of harmful reactive oxygen species.

Similarly to the olive leaf extract, therapy with resveratrol—an active ingredient found in grapes—led to a reduction in arterial blood pressure and vascular resistance in an animal model of essential hypertension. In an experimental model of malignant hypertension, this therapy resulted in even greater improvements in hemodynamic parameters compared to essential hypertension, as well as the prevention of degenerative changes in the arterioles.

Angiotensin 2 receptor blockade, applied in a rat model of post-ischemic acute renal failure associated with hypertension, led to the improvement of systemic and renal hemodynamic parameters and reduced damage to the glomeruli and tubules. Additionally, therapy with synthetic analogues of the enzyme superoxide dismutase in the same experimental model reduced renal vascular resistance.

Тип пројекта:

National Projects

Subproject: “Investigation of the Role of Active Components of Thymus serpyllum L. and Urtica dioica L. from Serbia in Experimental Models of Cardiovascular Diseases,” within the project: “Development of Novel Encapsulation and Enzymatic Technologies for the Production of Biocatalysts and Biologically Active Food Components to Improve Competitiveness, Quality and Safety”

Project leader: Dr. Nevena Mihailović-Stanojević

Project collaborators: Dr. Đurđica Jovović, Dr. Zoran Miloradović, Dr. Jelica Grujić Milanović, Dr. Milan Ivanov

Project number: III 46010

Duration of the project: 2011-2019.

Leading institution: Institute for Medical Research, University of Belgrade

Description of the project:

The subproject was designed with the aim to explore the possible role of the active components of Thymus serpyllum L. and Urtica dioica L. from Serbia in the prevention and treatment of cardiovascular diseases. In this subproject, the in vivo effects of extracts of Thymus serpyllum L. and Urtica dioica L. on blood pressure, peripheral circulation resistance, lipid peroxidation, and oxidative stress were studied in the model of essential and malignant hypertension in rats with congenital hypertension. These results formed the basis for further research into the chronic effects of biologically active substances from Thymus serpyllum L. and Urtica dioica L. and for their application as dietary supplements in the therapy of cardiovascular diseases.

Тип пројекта:

National Projects

Effect of Dietary Lipids on Cardiovascular Parameters, Lipogenesis, and Antioxidant Status in Hypertensive Rats

Project leader: Dr. Jelica Grujić Milanović

Project collaborators: Dr. Nevena Mihailović-Stanojević, Dr. Danijela Karanović, Dr. Kristina Starčević, Dr. Tomislav Mašek, Dr. Maja Maurić

Project number: 337-00-205/2019-09/32

Duration of the project: 2019-2022.

Leading institution: Institute for Medical Research, University of Belgrade

Collaborating institution: Faculty of Veterinary Medicine, University of Zagreb, Croatia

Description of the project:

The main objective of this project was to determine the mechanism of action of high-fat foods of different origins (animal/plant) and the possibility of preventing the metabolic syndrome by modulating the n6/n3 ratio of dietary fats on the oxidative status and expression of various transcription factors that are part of the blood pressure regulatory system. The reason for this approach lies in the general public health interest in developing new strategies for the prevention and treatment of the metabolic syndrome and, consequently, of cardiovascular diseases, with the aim of reducing the number of people affected. Therefore, the aim of this project was to study the effects of a diet containing vegetable/animal fats with different ratios of n6/n3 lipids on the cardiovascular system and lipogenesis in different tissues under both physiological and pathological conditions.

Тип пројекта:

Bilateral Scientific Cooperation

Cardiac Remodelling Down the Calmodulin Kinase 2 Cascade

Project leader: Dr. Milan Ivanov

Project collaborators: Dr. Zoran Miloradović, Dr. Nevena Mihailović-Stanojević, Dr. Đurđica Jovović, Dr. Una-Jovana Vajić, Dr. Danijela Karanović, Dr. Senka Holcer, Dr. Simon Sedej, Dr. Nataša Đalinac

Project number: 451-03-02141/2017-09/44

Duration of the project: 2018-2020.

Leading institution: Institute for Medical Research, University of Belgrade

Collaborating institution: Medical University of Graz, Austria

Description of the project:

The main objective of this project was to characterize the spatial and temporal activation of signaling pathways for Ca2+/CaM/CaMKIIδC- and δB-kinases in defined subcellular areas of isolated adult ventricular cardiomyocytes and their influence on the initiation and progression of hypertrophy and heart failure. The project was performed on isolated rat cardiomyocytes and healthy and diseased human cardiomyocytes. This project enabled multidisciplinary collaboration of biologists, molecular biologists, biotechnologists and physicians from Austria and Serbia, which in the future will serve as a basis for the creation of a network of institutions for the development of modern approaches in experimental cardiovascular physiology. Complementarity of methods as well as scientific work and topics under in vivo and in vitro conditions of scientists from Austria and Serbia resulted in improvement of approach to solving problems in the field of cardiovascular physiology.

Тип пројекта:

Bilateral Scientific Cooperation

The Role of Nitric Oxide, Free Radicals, and Ang II Peptide in Vascular Structure and Function in Experimental Hypertension

Project leader: Dr. Zoran Miloradović

Project collaborators: Dr. Đurđica Jovović, Dr. Nevena Mihailović-Stanojević, Dr. Jelica Grujić Milanović, Dr. Kristek František, Dr. Soňa Čačányiová

Project number: СК-СРБ-0026-29

Duration of the project: 2010-2011.

Leading institution: Institute for Medical Research, University of Belgrade

Collaborating institution: Institute of Normal and Pathological Physiology SAS, Bratislava, Slovakia

Description of the project:

A chronic decrease in nitric oxide synthesis caused by blockade of the enzyme constitutive nitric oxide synthase results in a permanent increase in blood pressure associated with hypertrophy of the heart and arterial blood vessels. The aim of the study was to investigate the comparative effects of nitric oxide synthase inhibitors associated with vascular and cardiac changes. The long-term effects of the combined action of two types of nitric oxide synthase inhibitors on the heart and on the structure and function of blood vessels, as well as their effects on the cellular and extracellular components of the walls of conducting blood vessels in terms of the role of free radicals and the renin-angiotensin system, were investigated. The results obtained represent a contribution to the understanding of the basic regulatory mechanisms in hypertension and to the development of new approaches for the prevention and therapy of this disease.

Тип пројекта:

Bilateral Scientific Cooperation

Characterization of Extracts Isolated from Plants of the Lamiaceae Family and Evaluation of Their Antioxidant, Antilipemic, and Antihypertensive Effects In Vivo

Project leader: Dr. Nevena Mihailović-Stanojević

Project collaborators: Dr. Zoran Miloradović, Dr. Jelica Grujić Milanović, Dr. Đurđica Jovović, Dr. Milan Ivanov

Project number: 69-00-49/2010-02

Duration of the project: January 2011-December 2012.

Leading institution: Institute for Medical Research, University of Belgrade

Description of the project:

Extraction procedures for the preparation of plant extracts suitable for intravenous use under acute experimental conditions were developed to clarify the possible role of polyphenols and flavonoids from plants of the Lamiaceae family in the prevention and treatment of cardiovascular diseases. In addition, the qualitative and quantitative composition of bioactive compounds, especially polyphenols in the studied extracts, and the in vitro biological activity of the plant extracts in cell cultures were determined. Besides, the antihypertensive, antioxidant, and antiflipemic effects of extracts isolated from plants of the Lamiaceae family were studied in an experimental model of essential hypertension. Since the plant species studied are those that have long been used as beverages or herbal preparations, the aim of this project was to combine two complementary areas of research to define the composition and effects of plant extracts from the Lamiaceae family so that their consumption can ensure an adequate supply of biologically active compounds that may have beneficial effects on human health.

Тип пројекта:

Bilateral Scientific Cooperation

Investigation of the Antihypertensive and Renoprotective Potential of Natural and Synthetically Derived Substances in Experimental Models of Cardiovascular and Renal Diseases

Project leader: Dr. Đurđica Jovović

Project collaborators: Dr. Zoran Miloradović, Dr. Nevena Mihailović-Stanojević, Dr. Jelica Grujić Milanović, Dr. Milan Ivanov, Dr. Danijela Karanović, Dr. Una Jovana Vajić

Project number: OI175096

Duration of the project: January 2011-December 2019.

Leading institution: Institute for Medical Research, University of Belgrade

Description of the project:

One of the main objectives of the project was to investigate the effects of natural and synthetic antioxidant substances in hypertension and acute and chronic renal failure. The effects of using olive extract (which contains potent antioxidants) on animal models of essential hypertension and kidney disease were also studied. Part of the project also included testing the beneficial effects of resveratrol, a potent antioxidant molecule isolated from grapes, in models of experimental essential and malignant hypertension. The relationship between the renin-angiotensin system and oxidative stress in the development of post-ischemic acute renal failure and chronic kidney disease was investigated. We used rats with essential hypertension in which we induced acute kidney injury or adriamycin-induced renal glomerulosclerosis and administered angiotensin-2 receptor blockers and synthetic analogues of the enzyme superoxide dismutase. The results of these studies have revealed to us inadequately known mechanisms of action of oxidative stress and the renin-angiotensin system in hypertension, acute renal failure, and chronic kidney disease.

Тип пројекта:

National Projects