Garlic & Health a European initiative for the development of high quality garlic and its influence on biomarkers of atherosclerosis and cancer in humans for disease prevention Chris Kik, Plant Research International, Wageningen, The Netherlands

Garlic & Health: project key facts started in February 2000 running time: 4 years budget: Euro (EU: Euro) 14 partners: 6 universities, 6 research institutes, 2 companies (and 5 subcontractors) countries involved: FR (4), GER (3), UK (2), NL (2), ISR (2) and ESP (1) human resources: 84 person years input

Garlic & Health: first annual meeting Cordoba (Spain)

Garlic & Health: management structure Every WP has a coordinator which co-ordinates the activities of the participants involved

Garlic & Health: communication Good communication is one of the most important factors for the success of a project

Garlic & Health: communication Meetings half year: 1.5 days; annual: 3 days; ad hoc Internet home page: public and restricted area monthly e-reports Presentations scientific: articles, posters, etc popular: newspapers, brochures, etc

Garlic & Health: communication Confidentiality contract consortium agreement ‘No info goes unauthorized to other parties outside the project’

Garlic & Health: rationale behind the project Garlic: quality and price of European garlic is not competitive on the world (and European) market Health: lack of studies on the precise action of garlic in the prevention of cardio-vascular diseases and cancer

Garlic & Health: main project aim ‘To improve the quality of garlic and derived products and to understand the sulphur metabolism in the plant as well as in the human body, in order to strengthen the European based garlic pharma and food industry and to increase public health’

Garlic & Health: garlic research foci WP1: Genetic resources Establishment of a unique garlic core collection (sulphur, fertility) WP 2: Breeding systems Sexual hybridization, genetic transformation, mass propagation WP 3 : Cultivation methods WP 4: Analysis of the sulphur pathway in garlic S pathway intermediates S genes localization of S pathway in plant

Sulphur metabolism in plants SOIL SO 4 2- sulfate transporters SO 4 2- APSSO 3 2- sulfite reductase ATP PP i 2e - ATP sulfurylase 6e - APS reductase S 2- serine + acetyl CoA serine acetyltransferase OAS cysteine synthetase CYS  -glutamyl cysteine synthetase  -glu- CYS glu glutathione GSH synthetase gly METHIONINE Stress, secondary metabolism

Allium - specific sulphur metabolism glutathione methyl S-me-GSH glu  -glu-me-cys Oxidase [under characterization]  -glu-me-cys sulfoxide  -glutamyl transpeptidase[cloned] methyl-cysteine sulfoxide ? Allium & crucifers Allium only Methacrylate carboxy-propyl-GSH  -glu-carboxy propyl-cysteine propyl & propenyl cysteine sulfoxide ? ?

Allium - specific sulphur metabolism ASCOs in mesophyl cells alliinase in bundle sheet cells

Garlic & Health: health research foci WP 5 and 6: Analysis of the molecular mechanisms of garlic bio-active sulphur compounds in cardio-vascular diseases and cancer WP 7: Establishment of pharmaceutical requirements for new garlic formulations WP 8: Testing of newly developed formulations in a human intervention study

Garlic & Health: cardio-vascular diseases

{ media intima fibrosis cholesterol clefts necrosis mineralisation Atherosclerosis in aorta of APOE*3-Leiden transgenic mice

Normal cell Tumoral cellsInitiated cell Programmed death of damaged cells (APOPTOSIS) DNA mutation Proliferation Normal cells Repair Garlic & Health: carcinogenesis Conversion

Preneoplastic foci induced by aflatoxin B 1 in the rat liver Control dietDiallyl disulfide (2000 ppm in the diet)

Garlic & Health: pharmaceutics Development of analytical and dissolution methods Development of new garlic dosage forms bio-availability stability

Garlic & Health: human intervention study placebo controlled three months study with 2 x 24 volunteers check on biomarkers for: atheroclerosis: ox-LDL, adhesion molecules, etc cancer: phase II enzymes, damage to lymphocytes, etc

the Garlic & Health participants wish you a pleasant symposium !! (