Olmix Symposium September, 10 th 2012 FRANCE - Palais des Congrès of Pontivy How Algae can bring solutions to Global Nutrition & Health issues « Algae : The Blue Revolution for a Sustainable Chemistry » This event is organized by Olmix with the support of its partners:
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Proceedings of the symposium "ALGAE: THE BLUE REVOLUTION FOR A SUSTAINABLE CHEMISTRY" (English)
Nearly thirty scientists of the highest level, Breton specialists in marine sciences and in algae, representatives of research labs, of CNRS Roscoff, of the University of Western Brittany, of the University of Southern Brittany, of the INRA and of the regional SMEs presented the richness and the potential of algae, especially green algae, to provide solutions to the world issues of nutrition and health, particularly of animals and plants. With the help of this impressive line-up of experts, 400 specialists in animal nutrition and breeding coming from 24 countries, discovered the future uses of these algae (green algae), available in a variety of products intended for tomorrow’s breeding, aquaculture and agriculture. This symposium was organized under the high patronage of Mr. Kobenan Kouassi Adjoumani, Minister of Animal and Halieutic Ressources of Côte d’Ivoire. It is at the invitation of Mr. Hervé Balusson, chairman and managing director of OLMIX, that the Minister of Côte d’Ivoire, accompanied by a delegation of scientists, came in parallel with SPACE to discover the expertise and the breeding techniques in Brittany, in order to develop effective industries in his country.
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Olmix SymposiumSeptember, 10th 2012
FRANCE - Palais des Congrès of Pontivy
How Algae can bring solutions to GlobalNutrition & Health issues
«Algae: The Blue Revolution
for a Sustainable Chemistry»
This event is organized by Olmix with the support of its partners:
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Dear partner,
OLMIX, pioneer in algae use for animal nutrition since 1995 has the pleasure to invite you to attend the 1st olmix algae symposium dedicated to “global nutrition and health issues”.
Using algae extract for their polysaccharides and trace-elements materials became com-mon for Olmix in the beginning of the second millennium.
It all started when OLMIX‘s R&D team had the feeling that they could increase the binding potential of Clay by including inside algae polysaccharides. The idea was to increase the interlayer space of natural montmorillonite clay thanks to the ulvans, green algae poly-saccharides. A full program was then developed with CNRS (National Center of Scientific Research) and CEVA (Center for study and valorization of algae) and gave birth to Ama-deite®, the algae based revolutionary and worldwide patented hybrid material. The first great commercial success using Algae in animal feeding was born: MTX+.
These successes encouraged OLMIX to increase its use of Algae for animal and vege-tal health and nutrition. Today ULVANS, a new R&D program, is aimed to provide even more Algae based solutions to the field with more technology inside, using enzymatic hydrolysis and separation techniques from harvest to the final product.
How Can Olmix innovate so much in Algae use? Its location, based right in the middle of a region of the world where most of the Algae scientific knowledge, supply and diversity is concentrated: BRITTANY.
To share this Algae Blue revolution for a sustainable Chemistry with its partners OLMIX organize on September 10th the 1st OLMIX ALGAE SYMPOSIUM “How algae can bring solutions to global nutrition and health issues”. Speakers from the
most recognized specialized institutions will share with us the latest knowledge on Algae science and yet more…
On behalf of Hervé Balusson, OLMIX CEO, we are looking forward to welcoming you soon in Brittany.
Olmix team
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Morning sessions under the Chairmanship of Catherine Boyen Director of the “Marine plants and biomolecules” laboratory - Roscoff Biological Station- CNRS UMR 7139 - Steering committee of Biogenouest®
8.30 Welcome reception
9.00 Welcome speechHervé Balusson Olmix Group President and CEO
Session 1 Algae: A new world to discover
9.10
Introduction - Brittany, historic region in algae valorisation• History of algae situation in the region• Sea World professional organizations and institutes - Current actionsDr. Christine Bodeau-Bellion Science et Mer Laboratory - President of the Syndicate of Seaweed and Marine Plants - Le Relecq Kerhuon
9.30Brittany an area of excellence in algae knowledge• Research organizations in Brittany - Their expertise• Present and future research programsPr. Eric Deslandes University of Western Brittany - Brest
9.50Discovering the Blue Chemistry• General information on algae, their origin and biological characteristicsDr. Philippe Potin Research Director - Roscoff Biological Station - CNRS UMR 7139 - IDEALG project coordinator
Algae: A sugared treasureDr. Mirjaml Czjzek Research Director - Roscoff Biological Station - CNRS UMR 1931
11.00 Coffee break
Session 2 Algae in the service of Health
11.30Enzymatic hydrolysis in chemistry of seaweedsPr. Nathalie Bourgougnon LBCM (Biotechnology and Marine Chemistry Laboratory) - University of Southern Brittany - Vannes
PROGRAM
«Algae: The Blue Revolution for a Sustainable Chemistry»
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How Algae can bring solutions to Global Nutrition & Health issues
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12.00Bioactivities of Marine Polysaccharides in human and animal health (Update)Dr. Henri Salmon Research Director - INRA Tours - Nouzilly (French National Institute for Agricultural Research)
12.30Marine lipids in amplifying cancers chemotherapyPr. Philippe Bougnoux Oncologist, Director of the Unit «Nutrition, growth and cancer» - INSERM(National Institute for Health and Medical Research) - Chief of cancerology service - CHU Tours(University Hospital Center)
13.00 Lunch (marine buffet)
Afternoon sessions under the Chairmanship of Dr. Christine Bodeau-BellionScience et Mer Laboratory - President of the French Syndicate of Seaweed and Marine Plants - Le Relecq Kerhuon
Session 3 Industrial applications originating from algae chemistry
14.15The algae industry in ChileEliana Henriquez Flores Agronomist - Head of the International Affairs Unit - CIREN(Centre for Renewable Natural Resources Information) - Santiago, CHILE
14.30 Algae, source of active principles in cosmeticsAlexis Rannou Deputy Managing Director in charge of Innovation - ARD Soliance - Pommacle
14.50Algae, source of nutriments for humansDr. Maria Hayes Scientific Project Manager - NutraMara - Teagasc Ashtown Food ResearchCentre - IRELANDChristine Le Tennier Algues de Bretagne - Globe Export SARL - Rosporden
15.25 Algae in the service of soils nutritionDr. Bruno Daridon Research and Development Director - PRP Technologies - Paris
16.00 Coffee break
Session 4 Industrial applications originating from algae chemistry (follow)
16.15 Algae in the service of terrestrial plants healthDr. Adeline Picot Plants Pathology Laboratory - VEGENOV BBV - St Pol de Léon
Algae, source of nutrients in animal nutritionPr. Simon Davies Professor of Aquaculture Nutrition at the University of Plymouth (UK).Member of World Aquaculture Society
17.10 Round table: From research to industrial application.
18.30 Cocktail: Marine algae in the castle20.00 Gala dinner and evening festivities - Pontivy castle - Palais des Congrès
16.40
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GUEST SPEAKERSIntroduction and presentation
Mr Hervé BalussonOlmix Group President and CEO
Hervé Balusson is the founder and Chairman of Olmix Group, specialized in the trace-elements feed additives and organic fertilizer. He has succee-ded in bringing Olmix from a regional stage into international coverage.Olmix products are now available in more than 50 countries.
Ms Catherine BoyenDirector of the “Marine plants and biomolecules” laboratory - Roscoff Biological Station- CNRS UMR 7139 - Steering committee of Biogenouest®.
Dr. Christine Bodeau-Bellion Science et Mer Laboratory - President of the Syndicate of Seaweed and Marine Plants - Le Relecq Kerhuon
Pr. Eric DeslandesUniversity of Western Brittany - Brest
Dr. Philippe PotinResearch Director - Roscoff Biological Station - CNRS UMR 7139 - IDEALG pro-ject coordinator
Philippe Potin (49), Docteur en biologie, HDR, Directeur de Recherche 2ème classe au CNRS depuis oct. 2006 (SBR, UMR 7139 CNRS-UPMC-Paris6)Dr. Philippe Potin, marine biologist and biochemist has obtained his Ph.D. from the University of Brest in 1992 and continued his post-doctoral research at the NRC Institute for Marine Biosciences in Halifax (NS Canada) and was hired by CNRS in Roscoff. P. Potin’s scientific interests (>70 primary publications) are in the bases of pathogen defense reactions and signaling in marine algae, with an emphasis of the specific traits of marine plants such as the halide metabolism. Research in his team investigates fundamental processes underlying interactions between seaweeds and pests. He was also interested in technology transfer with the Goëmar Laboratories, to develop the use of oligosaccharides for disease control in agricultural crops (4 patents, one product on the market) and during his mandate as a project manager for
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GUEST SPEAKERSIntroduction and presentation
the marine biotechnologies at the Maritime Cluster “Pôle Mer Bretagne”. He is currently the scientific coordinator of IDEALG, a 10-year national integrative pro-ject, within the framework of the French Stimuli Program Investis- sements d’Avenir, to capitalize on the recent breakthroughs in algal genomics to develop seaweed genetics and biotechnology.Philippe POTIN, Station Biologique de Roscoff, BP 74 - 29680 Roscoff, Tel.33-2. 98.29.23.75, Fax.33-2. 98.29.23.85, Mail [email protected]
Dr. Mirjaml CzjzekResearch Director - Roscoff Biological Station - CNRS UMR 1931
Mirjam Czjzek has studied chemistry at the University of Frankfurt, then at the TH Darmstadt in Germany where she has obtained her PhD in crystallography. After one year of a post-doctoral position in the ‘Labo-ratory for crystallography of biological macromolecules’ (LCMB) of Mar-seille, she has been recruited at the CNRS in October 1992. She is crys-tallographer by education and has started to work on CAZymes solving the crystal structures of cellulases and beta-glucosidases during several years in the group of Bernard Henrissat in Marseille, France. In 2005 she moved to the Station Biologique de Roscoff, where she is now ‘directrice de recherche’ of CNRS in the laboratory for ‘Marine plants and biomolecules’. Her research program entitled ‘Marine Glycobiology’ currently focuses on the structures and functions of carbohydrate-active enzymes, including their CBMs, which are involved in marine algal cell wall polysaccharide depolymerization.
Pr. Nathalie BourgougnonLBCM (Biotechnology and Marine Chemistry Laboratory) - University of Sou-thern Brittany - Vannes
Nathalie Bourgougnon has been working in the Laboratoire deBio-technologie et Chimie Marines (LBCM) at Université de Bretagne-Sud since 2001. Previously, she was lecturer at the University de la
Rochelle during 8 years. The principal thematic of her research relates to the search for marine substances with biological activities mainly extrac-ted from algae. She has a good experience in the field of the extraction, purification, characterization and evaluation of biological (antiviral, antifouling, antiprolifera-tive…) activities of marine compounds. She has published ca. 55 papers in peer-reviewed journals and book chapters, in particular on antifouling or antiviral substances extracted
from seaweeds, extraction and purification of bioactive marine substances. She has deposit two patents about antiviral substances. She has been involved in
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several Euro- pean projects (e.g. FP4 Bioactive Marine Natural Products in the Field of Antitumo- ral, Antiviral and Immunomodulant Activity, MAST III; FP5 AVINSI- Anti Viral Infection Non Specific Immunity: Basis of non specific immunity against viral diseases in aquacultured species; FP6 Valbiomar Biotechnologique valorization of the marine resources; FP7 Biotecmar: integrated transregional project for communication, technical information and technology transfer in the domain of biotechnological exploitation of marine products and by-products) and recently in OSEO program ULVANS. She has coordinated the project ASEM-DUO from MAE between France and Malaysia (2007-2009). She is member of several networks, Two French networks: BioChiMar concerning marine substances with biological activity and SEAPro (Sustanaible Exploitation of Aquatic PRO-ducts) concerning biotechnological up-grading of fish, seaweeds or aquaculture by-pro-ducts; and an international network: RAQ Quebec Aquaculture Network. At the national level, Nathalie Bourgougnon has collaborated with Dr. JL Mouget (Université du Mans) for physiological approaches of antifouling substances extracted from seaweeds, V. Stiger (Université de Bretagne Occidentale) for marine substances extracted from red seaweeds, Dr T. Renault (IFREMER, La Tremblade) for defences mechanisms of oysters against bacteria and viruses , JP Bergé (IFREMER, Nantes) for upgrading of marine resources and at the international level, she gained experience in cooperation with Morocco (University Tétouan; Pr. H. Riadi), Institute of Marine Biotechnology of University Malaysia Terengganu (Pr. Effendy) for biological compounds extracted from seaweeds, ISMER (Québec, Dr. R. Tremblay) for biological compounds extracted from seaweeds, microalgae, invertebrates. She is Vice-president of International PhD School (Coordination of Doctoral program) of the Université européenne de Bretagne (UEB) www.ueb.eu. At University de Bretagne-Sud, she is in charge of research program and Coordinator of master «Biotechnology» (www-lbcm.univ-ubs.fr).
Dr. Henri SalmonResearch Director - INRA Tours - Nouzilly (French National Institute for Agricul-tural Research)
Dr. Henri Salmon is a Research Director in the Institute of National Agro-nomic Research (INRA) in France. He earned his DVM from the National Veterinary School-Alfort in Paris and his PhD in Immunology from the University of Paris.Prior to joining INRA, he served 6 years as a Research Assistant at Col-lege of Veterinary Medicine in Alfort. Since 1984, he has served as Director of Research, INRA, laboratory of Animal Infectiology and Public Health, Tours-Nouzilly. He served one year in Transplantation Research Biology Center, Harvard Medical School and Massasuchetts General Hospital (Boston, MA).
GUEST SPEAKERSIntroduction and presentation
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GUEST SPEAKERSIntroduction and presentation
The objective of his research is an understanding of the interrela- tions («immune links») between digestive, pulmonary and mammary mucosal im- mune responses to improve protection against pathogens. He has dissected the mechanisms under-lying the migration of IgA plasma cells from the mucosae to the mammary gland in the sow ; these mechanisms substantiate the production of IgA in colostrum and milk. and hence are responsible of passive mucosal protection of the suckling piglets. Now he is looking at the means to shorten the onset of IgA response in gut of weaned piglet. To replace the anti-biotics-growth factors in food, he designed «immunoprobiotic», as vectors to enhance the neonatal gut immunity which deliver enhacing factors of IgA immune response including pre- and probiotics.
Pr. Philippe BougnouxOncologist, Director of the Unit «Nutrition, growth and cancer» - INSERM (Natio-nal Institute for Health and Medical Research) - Chief of cancerology service - CHU Tours (University Hospital Center)
Philippe Bougnoux is a medical oncologist, specialized in breast and gynaecologic cancers. He performed his trainings in medicine in Tours and in immunology at the Pasteur Institute in Paris. After a 3 years post-doctoral staying as a Fogarty fellow at the National Cancer Institute in Bethesda, MD, he became professor of cancer biology at the university of Tours, and chief of the cancer outpatient unit at the university cancer centre Henry S. Kaplan. He belongs to the Inserm research Unit 1069 « Nutrition, growth and Cancer » and has been coordina-ting a consortium of research units in chemistry and biology on marine-derived anticancer agents within the canceropôle of the western part of France, which he heads now. His research interests are to understand how diet and lipid nutrients influence the molecu-lar alterations which result in malignant tumors and how they integrate to delay breast can-cer occurrence or individual response to anticancer agents. He does translational research
in the field of dietary lipids in relation to breast cancer prevention and treatment. He is currently carrying out randomized clinical trials of dietary intervention with omega-3 poly-unsaturated fatty acids to enhance the sensitivity of tumors to radiation or chemotherapy.
Address: INSERM U1069, Henry S. Kaplan Cancer Centre, University Hospital Breton-neau, 37044 Tours, FranceTelephone: +33 (0) 2 4747 8261Email: [email protected] site: www.n2c.univ-tours.fr
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Ms Eliana Henriquez FloresAgronomist - Head of the International Affairs Unit - CIREN (Centre for Re-newable Natural Resources Information) - Santiago, CHILE
Agronomist - Head of the International Affairs Unit - CIREN (Centre for Renewable Natural Resources Information) - Santiago, CHILEIn the period between the years 2004-2008, working as Chief of Labora-tory Sub-department and Quarantine Agricultural Station, from the Agricultural and Lives-tock Service, she has made an important management of inter-agency cooperation at the national and international level with different research institutions of great renown and reco-gnized academic prestige around the world. This has enabled that SAG, at present, has signed various «Memorandum of understanding» or Agreements of International Coope-ration with institutions of Spain, Scotland, Italy and United States. Thus, all the necessary efforts were made that will, in the near future, allow to establish agreements with England, Australia, France and New Zealand.The technological horizon for Laboratory Sub-Department and Agricultural Quarantine Station was expanded through the emphasis on inter-agency, both national and foreign cooperation. In this way, one can access to the techniques implemented and developed in important centers of research around the world
M Alexis RannouDeputy Managing Director in charge of Innovation - ARD Soliance - Pommacle
Ingénieur Agricole (ISAB) 1991Ingénieur d’études ARD (Agro industrie Recherche et développement) en charge de la sélection variétale de la betterave biotechnologie pour la fabrication d’acide galacturonique.1994 Responsable du pilote industriel ARD mise au point de tension-actifs verts (Uronate de sodium et Alkyl polypentosides)1997 Directeur technique SOLIANCE & développement industriel Amadéïte avec OLMIX2000 Formation IFG CGDPME (Gestion des entreprises) 2002 Directeur Général Adjoint en charge de la production et du compte l’Oréal2007 DGA en charge de l’innovation (8 Brevets) 20 bx produits et du marketing stratégique2012 DGA en charge de l’innovation Soliance et Wheat Oléo
GUEST SPEAKERSIntroduction and presentation
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GUEST SPEAKERSIntroduction and presentation
Dr. Maria HayesScientific Project Manager - NutraMara - Teagasc Ashtown Food Re-search Centre - IRELAND
NutraMara Scientific Programme Manager & Principle Investigator - Work Package 2 and 7.Main Research Interests: • Isolation, purification and characterisation of marine derived molecules, especially peptides and phlorotannins from marine seaweeds and by-products • Fermentation • Bioassay development with a particular focus on heart and mental health disorders – i.e., renin, ACE-I, PAF-AH, PEP and inhibition of other enzymes with heart and mental health effects • Generation of chitin and chitosan from marine shellfisheries waste streams • Isolation and characterisation of enzymes (in particular chitinolytic enzymes)Short Biography:Dr Hayes obtained her BSc (Hons) in Science, specialising in Industrial Microbiology and Chemistry from University College Dublin (UCD). She carried out her PhD at the Teagasc Food Research Centre, Moorepark and University College Cork in the area of bioactive peptide isolation and characterisation from milk proteins and waste streams (whey and casein). She then carried out Post-doctoral work at the Centre of Applied Marine Biotech-nology in Donegal where she worked on the isolation of chitinolytic enzymes from shell-fisheries crab and whelk waste streams. She is currently the NutraMara Scientific Pro-gramme Manager and supervises two NutraMara PhD researchers who are funded by the Teagasc Walsh Fellowship programme. These students are Mr Ciaran Fitzgerald and Ms Michelle Tierney.
Selected publications: Fitzgerald, C., Gallagher, E., Tasdemir, D., Hayes, M., (2011), Heart Health peptides from
macroalgae and their potential use in functional foods. Journal of Agriculture and Food Chemistry, DOI: 10.1021/jf201114d Di Bernardini, R., Harnedy, P., Bolton, D., Kerry, J., O’ Neill, E., Mullen, A. M., Hayes, M., (2011), Antioxidant and antimicrobial peptidic hydrolysates from muscle protein sources and by-products. Food Chemistry, 124, 1296-1307.
Tierney, M. S., Croft, A. K., Hayes, M., (2010) A review of antihypertensive and antioxidant activities in macroalgae, Botanica Marina, 53 (2010), 387-408.
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Hayes, M., Carney, B., Slater, J., Bruck, W., (2008), Mining marine shellfish wastes for bioac- tive molecules: Chitin and chitosan; Part B: Applications. Biotech-nology Journal, 3, 7, 871-877.Hayes, M., Barrett, E., O’Connor, P., Gardiner, G., Fitzgerald, G., Hill, C., Stanton C., Ross R.P. (2007), Salivaricin P: one of a family of two component anti-listerial bacteriocins pro-duced by intestinal isolates of Lactobacillus salivarius, Appl Environ Microbiol. 73, 11, 3719-3723.
Ms Christine Le TennierAlgues de Bretagne - Globe Export SARL - Rosporden
«“I was born an entrepreneur”Christine Le Tennier is a dynamic person. An impulsive one. She is com-plete. Political cant, she does not know it. “I was born an entrepreneur.” A witticism? Not at all. Before she was 20 years old, Christine Le Tennier did not have any idea about what the wage system was. “My grandpa-rents were corporate managers.” Farmer on her paternal side, tinsmith in Alger for her maternal grandmother. When she was 20, she was hired by Hilton. As a barmaid. At age 22, she became a commercial executive. Still at Hilton. In Ontario – where she was born – and in New York State. When she was offered a big job in Africa, she turned it down. Went back to Brittany, met her future husband and went back to school to study international business.In 1986 Christine Le Tennier created Snc Glob’export with the aim of international consul-ting and trade. Globe export became Sarl Globe Export – Seaweed of Brittany in 1993, opening date of the first production factory of seaweed-based products.Today edible seaweed are lacking in Brittany, studies foresee a field for seaweed in 10 years. “But I do need seaweed here and now.” Meanwhile the development of this field, Christine Le Tennier imports a part of seaweed she transforms and makes a turnover of 2 million Euros with 13 to 15 employees. Customers of Seaweed of Brittany: industry, catering, retail, export (20%), mail order selling. The strategy developed in 2012 can be summarized in 2 major divisions: innovation and interna-tional.
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GUEST SPEAKERSIntroduction and presentation
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GUEST SPEAKERSIntroduction and presentation
Dr. Bruno DaridonResearch and Development Director - PRP Technologies - Paris
Bruno Daridon, 51 years old, integrated PRP Technologies in March 2007 as R&D manager, and then joined the executive committee. He is an agronomist (ENSAIA Nancy-1984) and Doctor in Biotechnology and Food Process Engineering (INPL Nancy- 1988). From 1993 to 1997, he created as a R&D engineer, Prabil S.A., a society of research on hire about extraction and functionalization of plant molecules and valuations of non-food agricultural products, then became its general manager in 1997. From 2004 to 2007, he was in charge of the site Novasep Brabois where he developed processes of fractionation and purification of biomolecules for the pharmaceutical industry.
Dr. Adeline PicotPlants Pathology Laboratory - VEGENOV BBV - St Pol de Léon
After graduating with a PhD in plant pathology from the University of Paris-Sud 11 in 2010, Adeline Picot has been working at Vegenov as a Plant pathology assistant for one year. Her field of research focuses on the evaluation of plant defense elicitors and the optimization of their use in several pathosystems including grey molds and powdery and downy mildews in tomato, strawberry… She is involved in the French network Elicitra which aims at understanding, developing and promoting the strategy of plant de-fense elicitors.
Pr. Simon DaviesProfessor of Aquaculture Nutrition at the University of Plymouth (UK). Member of World Aquacul-
ture Society.
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La Bretagne : Terre historique de la valorisation des algues
Christine BODEAU
Présentation dédiée à : • Jean DUGOUJON, créateur de la Chambre Syndicale des Algues et Végétaux Marins • Pierre ARZEL, Chercheur à IFREMER • Jean-Yves FLOCH, Professeur à l’Université de Bretagne Occidentale
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Olmix Algae Symposium - Sept. 10th, 2012
3 entreprises dans années 1960’
21 entreprises aujourd’hui : diversité des applications
La Chambre Syndicale des Algues et Végétaux Marins
Algae are photosynthetic organisms. Based on the pigment and food reserve, algae are classified into different types, namely, blue green algae (BGA), green algae, red algae and brown algae.
Hana-Tsunomata™ when translated from Japanese means "Flower Chondrus". Other common references to Hana-Tsunomata™ sea vegetables include Hana-nori™ ("Flower seaweed"), Cultivated Chondrus, Kaede-nori ("Maple seaweed") and Hana-sakura-sou ("Cherry blossom sea plant").
Apply knowledge of metabolic pathways and networks, enzymes, molecules, biocatalyzers, bioconversion, bioengineering and aquaculture of domesticated seaweeds, Pre-pilot scale projects and technological research
Develop basic research on brown, red and green seaweeds toward domestication of local crops and improvement of seaweeds uses in biotechnology and blue-green chemistry
Various modifications can be observed like, pyruvate groups, methylation, sulfatation, or even branching .... These modified agar components are often called agaropectins
“Marine biofilm: biological and chemical approaches” program Study of the interactions between organisms and abiotic surfaces Study of physical and chemical parameters involved in bacterial adhesion by
conceiving model substrates Development of antifouling systems combining efficiency and environmental
respect Cell-cell interfaces Complex bacterial biofilms Procaryote-eucaryote interactions and communications
Biotechnology: valorization of marine molecules
Purification and characterization of compounds of interest from invasive marine organisms (sponges, algae, bacteria, echinoderms...)
Laboratoire de Biotechnologie et Chimie Marines
15 teachers/researchers - 10 PhD students - 2 technical assistants
Protein nature Product was not consumed during the reaction Active in small proportion Do not modify the balance thermodynamics reaction Accelerate only the speed of the reaction Specific of a reaction Large-scale production
Great potential for structural variability due to their interconnections (glycosidic bonds) at several points to form a wide variety of linear or branched structures [2].
Inhibition of the replication of enveloped viruses: blocks the viral entry into the cell by binding to glycoprotein C (gC) and glycoprotein D (gD) of HSV-1(37)
-> Antiviral activity of sulfated polysaccharides increases with sulfation and their molecular weight [34]
Chemical structure of disaccharides (VI and VII) relevant for binding
In vitro inhibition of influenza A virus infection by marine microalga-derived sulfated polysaccharide p-KG03 Meehyein Kim a, Joung Han Yim , So-Yeon Kim a, Hae Soo Kim ,Woo Ghil Lee a, Sung Jin Kim ,Pil-Sung Kang b, Chong-Kyo Lee
Immuno-Inflammatory Activities of MSP: Generalities
MSP may affect multiple targets in the immune and inflammatory systems that can have impact on disease progression and outcome including tumor progression and metastasis [41]. Sulfated polysaccharides play two-edged roles, inhibitor and promoter, in immune response.
General Effects : • Stimulation of the immune response / control of immune cell activity to
mitigate associated negative effects such as inflammation [40].
• Anti-inflammatory Growing body of evidence illustrating their ability to interfere with the migration of leukocytes to sites of inflammation. [42,43].
• Inhibit tissue degradative enzymes such as heparanase and elastases that are involved in the breakdown of basement membrane integrity during inflammation [45,46].
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Olmix Algae Symposium - Sept. 10th, 2012
Intravital microscopic images of a rabbit mesenteric venule. (A)Basal leucocytes rolling along the venular endothelium (B) demonstration that the rolling was abolished 3 min after systemic administration of fucoidin (10 mg/kg).
Changes in basal rolling leucocytes flux without change in arterial blood pressure over time in the rabbit after systemic treatment with fucoidin
By binding of fucoidan to L- and P selectins, cell adhesion molecules essential in the recruitment process., Fucans also inhibit leukocyte recruitment to the abdominal cavity during acute peritonitis in rats [44].
Anti-Inflammatory Activities of MSP: Anti-migration of leukocytes to sites of inflammation
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interfering with the migration of leukocytes to sites of inflammation. [42,43].
λ-carrageenan stimulate mouse T cell cultures in a toll-like receptor-4 (TLR4) dependent manner generating a T helper 1 (Th1) patterned cytokine response. However, splenocytes prepared from TLR4-deficient mice still retain some ability to produce interferon-γ in response to λ-carrageenan suggesting that PRRs other than TLR4 are also elicited. [52]
These and other reports of algal sulfated polysaccharides directly stimulating the innate immune system [53,56,57] suggests that they may find therapeutic use in opposing T helper 2 (Th2)-based pathologies such as autoimmune disorders and allergy.
Fucans’ Superoxide radical scavenging activity correlated positively high sulfate content of the polysaccharide fractions [24,26]. Antioxidant properties of Carrageenans [24] and Ulvans [27 ] also appeared related to sulfate content.
Inhibition of lipid peroxydation of rat liver microsome
Lipid-lowering (serum triglyceride and total cholesterol) in hyperlipidemic animal models (28,29,30).
In rats fed a high cholesterol diet for 21 days, supplementation of the diet with ulvans from U. pertusa led to reductions in serum total cholesterol and LDL-cholesterol with no significant alteration in serum triglycerides . The effects of ulvans were modified when it was degraded into lower molecular weight fractions (29).
Illustration of the function of hepatic lipase as a lipolytic enzyme. Santamarina-Fojo S et al. Arterioscler Thromb Vasc Biol 2004;24:1750-1754
M.S.P
Certainly fucoidan and other algal sulfated polysaccharides may influence LPL (Lipoprotein Lipase) and HL (Hepatic Lipase) through interaction with well-characterized heparin-binding sites on these enzymes (31).
Conclusion:Algal sulfated polysaccharides are showing promising effects in addressing the hyperlipidemia associated with certain drug toxicities (32, 33).
The study of algal sulfated polysaccharides structures is challenging, because of their diversity and heterogeneity.
This may also have hindered their development as therapeutic agents to date in spite of various biological activities already demonstrated. (Immunity, inflammation, coagulation, oxidation, lipidemia….)
Due to the difficulties in identifying the precise chemical structure of algal sulfated polysaccharides, the relation between their structures and biological activities is far from fully understood.
The production of a standardized commercial product based on algal sulfated polysaccharide constituents can also be a challenge since their structural and pharmacological features may vary depending on species and on location and time of harvest [66].
Important points can already be mentioned regarding the conditions of MSP bioactivities:
Importance of understanding the structural requirements for biological activity
Do low molecular weight derivatives, which are potentially more bioavailable, remain active?
Therapeutic use by oral route can be limited due to low bioavailability given often high molecular weights of MSP(64).
At the opposite :
Advantage for the hypolipidemic effects due to bile acid sequestration in the intestinal lumen.
With regards to some immunomodulatory activities, site of activation of the immune system may also be within the intestinal lumen (e.g., at Peyer’s patches).
Hypothesized for immunomodulatory effects of polysaccharide constituents from Chlorella pyrenoidosa [65].
6. Lahaye, M.; Robic, A. Structure and functional properties of ulvan, a polysaccharide from green seaweeds. Biomacromolecules 2007, 8, 1765-1774.
5. Percival, E.; McDowell, R.H. Chemistry and Enzymology of Marine Algal Polysaccharides; Academic Press: New York, NY, USA, 1967; p. 219.
7. Lahaye, M.; Brunel, M.; Bonnin, E. Fine chemical structure analysis of oligosaccharides produced by an ulvan-lyase degradation of the water-soluble cell-wall polysaccharides from Ulva sp. (Ulvales, Chlorophyta). Carbohydr Res 1997, 304, 325-333.
2. Sharon, N., Lis, H. Scientific American, 1993, pp. 74-81.
3. Hodgson, J. Biotechnology, 1991, 9, 609-613.
1. Ooi, V.E.C; Liu, F. Immunomodulation and Anti-Cancer Activity of Polysaccharide-Protein Complexes. Current Medicinal Chemistry, 2000, 7, 715-729.
4. Lahaye, M.; Ray, B. Cell-wall polysaccharides from the marine green alga Ulva rigida (Ulvales, Chlorophyta)-NMR analysis of ulvan oligosaccharides. Carbohydr Res 1996, 283,161-173.
9. Springer, G.F.; Wurzel, H.A.; McNeal, G.M.; Ansell, N.J.; Doughty, M.F. Isolation of anticoagulant fractions from crude fucoidin. Proc Soc Exp Biol Med 1957, 94, 404-409.
10. Kusaykin, M.; Bakunina, I.; Sova, V.; Ermakova, S.; Kuznetsova, T.; Besednova, N.; Zaporozhets, T.; Zvyagintseva, T. Structure, biological activity, and enzymatic transformation of fucoidans from the brown seaweeds. Biotechnol J 2008, 3, 904-915.
11. Li, B.; Lu, F.; Wei, X.; Zhao, R. Fucoidan: structure and bioactivity. Molecules 2008, 13,1671-1695.
12. Pomin, V.H.; Mourao, P.A.S. Structure, biology, evolution, and medical importance of sulfated fucans and galactans. Glycobiology 2008, 18, 1016-1027.
13. Matsubara, K.; Matsuura, Y.; Bacic, A.; Liao, M.L.; Hori, K.; Miyazawa, K. Anticoagulant properties of a sulfated galactan preparation from a marine green alga, Codium cylindricum. Int J Biol Macromol 2001, 28, 395-399.
14. Farias, E.H.C.; Pomin, V.H.; Valente, A.P.; Nader, H.B.; Rocha, H.A.O.; Mourao, P.A.S. A preponderantly 4-sulfated, 3-linked galactan from the green alga Codium isthmocladum.Glycobiology 2008, 18, 250-259.
16. Hayakawa, Y.; Hayashi, T.; Lee, J.B.; Srisomporn, P.; Maeda, M.; Ozawa, T.; Sakuragawa, N. Inhibition of thrombin by sulfated polysaccharides isolated from green algae. Biochim Biophys Acta 2000, 1543, 86-94.
18. Farias, W.R.L.; Valente, A.P.; Pereira, M.S.; Mourao, P.A.S. Structure and anticoagulant activity of sulfated galactans. Isolation of a unique sulfated galactan from the red algaeBotryocladia occidentalis and comparison of its anticoagulant action with that of sulfated galactans from invertebrates. J Biol Chem 2000, 275, 29299-29307.
15. Mao, W.; Zang, X.; Li, Y.; Zhang, H. Sulfated polysaccharides from marine green algaeUlva conglobata and their anticoagulant activity. J Appl Phycol 2006, 18, 9-14.
17. Shanmugam, M.; Mody, K.H. Heparinoid-active sulphated polysaccharides from marine algae as potential blood anticoagulant agents. Curr Sci 2000, 79, 1672-1683.
20. Qi, H.; Zhang, Q.; Zhao, T.; Hu, R.; Zhang, K.; Li, Z. In vitro antioxidant activity of acetylated and benzoylated derivatives of polysaccharide extracted from Ulva pertusa(Chlorophyta). Bioorg Med Chem Lett 2006, 16, 2441-2445.
21. Ruparez, P.; Ahrazem, O.; Leal, J.A. Potential antioxidant capacity of sulfated polysaccharides from the edible marine brown seaweed Fucus vesiculosus. J Agric Food Chem 2002, 50, 840-845.
22. Wang, J.; Liu, L.; Zhang, Q.; Zhang, Z.; Qi, H.; Li, P. Synthesized oversulphated, acetylated and benzoylated derivatives of fucoidan extracted from Laminaria japonica and their potential antioxidant activity in vitro. Food Chem 2009, 114, 1285-1290.
23. Ruparez, P.; Ahrazem, O.; Leal, J.A. Potential antioxidant capacity of sulfated polysaccharides from the edible marine brown seaweed Fucus vesiculosus. J Agric Food Chem 2002, 50, 840-845.
24. Rocha de Souza, M.; Marques, C.; Guerra Dore, C.; Ferreira da Silva, F.; Oliveira Rocha, H.; Leite, E. Antioxidant activities of sulfated polysaccharides from brown and red seaweeds. J Appl Phycol 2007, 19, 153-160.
35. Luescher-Mattli, M. Algae, A Possible Source for New Drugs in the Treatment of HIV and Other Viral Diseases. Curr Med Chem 2003, 2, 219-225.
36. Ghosh, T.; Chattopadhyay, K.; Marschall, M.; Karmakar, P.; Mandal, P.; Ray, B. Focus on antivirally active sulfated polysaccharides: From structure-activity analysis to clinical evaluation. Glycobiology 2009, 19, 2-15.
28. Vaquez-Freire, M.J.; Lamela, M.; Calleja, J.M. Hypolipidaemic activity of a polysaccharide extract from Fucus vesiculosus. Phytother Res 1996, 10, 647-650.
30. Huang, L.; Wen, K.; Gao, X.; Liu, Y. Hypolipidemic effect of fucoidan from Laminaria japonica in hyperlipidemic rats. Pharm Biol 2010, 48, 422-426.
29. Pengzhan, Y.; Ning, L.; Xiguang, L.; Gefei, Z.; Quanbin, Z.; Pengcheng, L. Antihyperlipidemic effects of different molecular weight sulfated polysaccharides from Ulva pertusa (Chlorophyta). Pharmacol Res 2003, 48, 543-549.
31. Yokota, T.; Nagashima, M.; Ghazizadeh, M.; Kawanami, O. Increased effect of fucoidan on lipoprotein lipase secretion in adipocytes. Life Sci 2009, 84, 523-529.
32. Raghavendran, H.R.; Sathivel, A.; Devaki, T. Effect of Sargassum polycystum(Phaeophyceae)-sulphated polysaccharide extract against acetaminophen-induced hyperlipidemia during toxic hepatitis in experimental rats. Mol Cell Biochem 2005, 276, 89-96.
33. Josephine, A.; Veena, C.K.; Amudha, G.; Preetha, S.P.; Varalakshmi, P. Protective role of sulphated polysaccharides in abating the hyperlipidemic nephropathy provoked by cyclosporine A. Arch Toxicol 2007, 81, 371-379..
25. Zhao, X.; Xue, C.; Cai, Y.; Wang, D.; Fang, Y. Study of antioxidant activities of fucoidan from Laminaria japonica. High Tech Lett 2005, 11, 91-94.
26. Wang, J.; Zhang, Q.; Zhang, Z.; Song, H.; Li, P. Potential antioxidant and anticoagulant capacity of low molecular weight fucoidan fractions extracted from Laminaria japonica. Int J Biol Macromol 2010, 46, 6-12.
27. Qi, H.; Zhang, Q.; Zhao, T.; Chen, R.; Zhang, H.; Niu, X.; Li, Z. Antioxidant activity of different sulfate content derivatives of polysaccharide extracted from Ulva pertusa(Chlorophyta) in vitro. Int J Biol Macromol 2005, 37, 195-199.
34. Witvrouw, M.; De Clercq, E. Sulfated polysaccharides extracted from sea algae as potential antiviral drugs. Gen Pharmacol 1997, 29, 497-511.
37. Harden, E.A.; Falshaw, R.; Carnachan, S.M.; Kern, E.R.; Prichard, M.N. Virucidal activity of polysaccharide extracts from four algal species against herpes simplex virus. Antiviral Res2009, 83, 282-289.
47. Blondin, C.; Fischer, E.; Boisson-Vidal, C.; Kazatchkine, M.D.; Jozefonvicz, J. Inhibition of complement activation by natural sulfated polysaccharides (fucans) from brown seaweed.Mol Immunol 1994, 31, 247-253.
41. Groth, I.; Grunewald, N.; Alban, S. Pharmacological profiles of animal- and nonanimal-derived sulfated polysaccharides--comparison of unfractionated heparin, the semisynthetic glucan sulfate PS3, and the sulfated polysaccharide fraction isolated from Delesseria sanguinea. Glycobiology 2009, 19, 408-417.
42. Granert, C.; Raud, J.; Xie, X.; Lindquist, L.; Lindbom, L. Inhibition of leukocyte rolling with polysaccharide fucoidin prevents pleocytosis in experimental meningitis in the rabbit. J Clin Invest 1994, 93, 929-936.
39. Carlucci, M.J.; Scolaro, L.A.; Noseda, M.D.; Cerezo, A.S.; Damonte, E.B. Protective effect of a natural carrageenan on genital herpes simplex virus infection in mice. Antiviral Res2004, 64, 137-141.
43. Preobrazhenskaya, M.E.; Berman, A.E.; Mikhailov, V.I.; Ushakova, N.A.; Mazurov, A.V.; Semenov, A.V.; Usov, A.I.; Nifant’ev, N.E.; Bovin, N.V. Fucoidan inhibits leukocyte recruitment in a model peritoneal inflammation in rat and blocks interaction of P-selectin with its carbohydrate ligand. Biochem Mol Biol Int 1997, 43, 443-451.
45. Senni, K.; Gueniche, F.; Foucault-Bertaud, A.; Igondjo-Tchen, S.; Fioretti, F.; Colliec-Jouault, S.; Durand, P.; Guezennec, J.; Godeau, G.; Letourneur, D. Fucoidan a sulfated polysaccharide from brown algae is a potent modulator of connective tissue proteolysis.Arch Biochem Biophys 2006, 445, 56-64.
44. Cumashi, A.; Ushakova, N.A.; Preobrazhenskaya, M.E.; D’Incecco, A.; Piccoli, A.; Totani, L.; Tinari, N.; Morozevich, G.E.; Berman, A.E.; Bilan, M.I.; Usov, A.I.; Ustyuzhanina, N.E.; Grachev, A.A.; Sanderson, C.J.; Kelly, M.; Rabinovich, G.A.; Iacobelli, S.; Nifantiev, N.E. A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiology 2007, 17, 541-552.
38. Damonte, E.B.; Matulewicz, M.C.; Cerezo, A.S. Sulfated seaweed polysaccharides as antiviral agents. Curr Med Chem 2004, 11, 2399-2419.
48. Clement, M.J.; Tissot, B.; Chevolot, L.; Adjadj, E.; Du, Y.; Curmi, P.A.; Daniel, R. NMR characterization and molecular modeling of fucoidan showing the importance of oligosaccharide branching in its anticomplementary activity. Glycobiology 2010, 20, 883-894.
53. Leiro, J.M.; Castro, R.; Arranz, J.A.; Lamas, J. Immunomodulating activities of acidic sulphated polysaccharides obtained from the seaweed Ulva rigida C. Agardh. Int Immunopharmacol 2007, 7, 879-888.
49. Tissot, B.; Montdargent, B.; Chevolot, L.; Varenne, A.; Descroix, S.; Gareil, P.; Daniel, R. Interaction of fucoidan with the proteins of the complement classical pathway. Biochim Biophys Acta 2003, 1651, 5-16.
50. Tissot, B.; Daniel, R. Biological properties of sulfated fucans: The potent inhibiting activity of algal fucoidan against the human complement system. Glycobiology 2003, 13, 29G-31G.
51. Tissot, B.; Gonnet, F.; Iborra, A.; Berthou, C.; Thielens, N.; Arlaud, G.J.; Daniel, R. Mass spectrometry analysis of the oligomeric C1q protein reveals the B chain as the target of trypsin cleavage and interaction with fucoidan. Biochemistry 2005, 44, 2602-2609.
52. Tsuji, R.F.; Hoshino, K.; Noro, Y.; Tsuji, N.M.; Kurokawa, T.; Masuda, T.; Akira, S.; Nowak, B. Suppression of allergic reaction by lambda-carrageenan: toll-like receptor 4/MyD88-dependent and -independent modulation of immunity. Clin Exp Allergy 2003, 33, 249-258.
54. Nakamura, T.; Suzuki, H.; Wada, Y.; Kodama, T.; Doi, T. Fucoidan induces nitric oxide production via p38 mitogen-activated protein kinase and NF-kB-dependent signaling pathways through macrophage scavenger receptors. Biochem Biophys Res Commun2006, 343, 286-294.
55. Yang, J.W.; Yoon, S.Y.; Oh, S.J.; Kim, S.K.; Kang, K.W. Bifunctional effects of fucoidan on the expression of inducible nitric oxide synthase. Biochem Biophys Res Commun 2006,346, 345-350.
56. Do, H.; Pyo, S.; Sohn, E.H. Suppression of iNOS expression by fucoidan is mediated by regulation of p38 MAPK, JAK/STAT, AP-1 and IRF-1, and depends on up-regulation of scavenger receptor B1 expression in TNF-alpha- and IFN-gamma-stimulated C6 glioma cells. J Nutr Biochem 2010, 21, 671.
57. Kim, M.H.; Joo, H.G. Immunostimulatory effects of fucoidan on bone marrow-derived dendritic cells. Immunol Lett 2008, 115, 138-143.
58. Choi, E.M.; Kim, A.J.; Kim, Y.O.; Hwang, J.K. Immunomodulating activity of arabinogalactan and focoidan in vitro. J Med Food 2005, 8, 446-453.
59. Zhou, G.; Sun, Y.; Xin, H.; Zhang, Y.; Li, Z.; Xu, Z. In vivo antitumor and immunomodulation activities of different molecular weight lambda-carrageenans from Chondrus ocellatus.Pharmacol Res 2004, 50, 47-53.
60. Clement, M.J.; Tissot, B.; Chevolot, L.; Adjadj, E.; Du, Y.; Curmi, P.A.; Daniel, R. NMR characterization and molecular modeling of fucoidan showing the importance of oligosaccharide branching in its anticomplementary activity. Glycobiology 2010, 20, 883-894.
61. Nishino, T.; Yokoyama, G.; Dobashi, K.; Fujihara, M.; Nagumo, T. Isolation, purification, and characterization of fucose-containing sulfated polysaccharides from the brown seaweed Ecklonia kurome and their blood-anticoagulant activities. Carbohydr Res 1989,186, 119-129.
63. Pomin, V.H.; Pereira, M.S.; Valente, A.P.; Tollefsen, D.M.; Pavao, M.S.G.; Mourao, P.A.S. Selective cleavage and anticoagulant activity of a sulfated fucan: Stereospecific removal of a 2-sulfate ester from the polysaccharide by mild acid hydrolysis, preparation of oligosaccharides, and heparin cofactor II-dependent anticoagulant activity. Glycobiology2005, 15, 369-381.
66. Bourgougnon, N.; Lahaye, M.; Quemener, B.; Chermann, J.C.; Rimbert, M.; Cormaci, M.; Furnari, G.; Kornprobst, J.M. Annual variation in composition and in vitro anti-HIV-1 activity of the sulfated glucuronogalactan from Schizymenia dubyi (Rhodophyta, Gigartinales). J Appl Phycol 1996, 8, 155-161.
65. Ewart, H.S.; Bloch, O.; Girouard, G.S.; Kralovec, J.; Barrow, C.J.; Ben-Yehudah, G.; Suárez, E.R.; Rapoport, M.J. Stimulation of cytokine production in human peripheral blood mononuclear cells by an aqueous Chlorella extract. Planta Med 2007, 73, 762-768.
62. Nishino, T.; Nagumo, T. The sulfate-content dependence of the anticoagulant activity of a fucan sulfate from the brown seaweed Ecklonia kurome. Carbohydr Res 1991, 214, 193-197.
References
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Marine lipids in amplifying cancers chemotherapy
Pr. Philippe Bougnoux - INSERM U 1069, Centre Henry S. Kaplan, University Hospital, Tours, France
How was DHA identifed: an observational study in breast cancer DHA increases the sensitivity of breast cancer cell lines to anthracyclines Dietary DHA makes rat mammary tumors sensitive to anthracyclines DHA increases radiosensitivity of mammary tumors in rats
How to account for the tumor specificity of DHA action ? Loss of antioxidant defences during tumor progression Remodeling of tumor neovascular architecture
Translation: from the sea to the patient A phase I-II study of DHA supplementation in metastatic breast cancer during
chemotherapy In progress:... a randomized, phase III study
How was DHA identified as a lipid component of diet associated with tumor chemosensitivity ? An observational clinical study
Context: Breast cancer patients presenting with a tumor larger than 3 cm
receive neoadjuvant chemotherapy as their initial treatment
Some tumors will shrink, others will not
Hypothesis: If dietary lipids influence breast tumor sensitivity to chemotherapy, then patients with sensitive tumors should have past dietary intake of lipids different from that of patients with resistant tumors
Loss of antioxidant defences during tumor progression may account for the tumor specificity of DHA action
Maheo et al., Free Rad Biol & Med, 2004
Vibet et al., Free Rad Biol & Med, 2008
How to account for the tumor specificity of DHA action ?
1. Using two breast cancer cell lines at different degree of tumor progression, we found that the degree of tumor progression influenced tumor response amplification by DHA
2. DHA enhanced doxorubicine toxicity only in cell lines able to produce ROS in response to doxorubicine ….and to subsequently produce lipoperoxides
3. In these cell lines, there was a lack of GPx response to the oxidative stress
4. There was an inverse correlation between GPx1 activity and response of the cells to chemotherapy
Using Power-Doppler sonography of rat mammary tumors, sensitized with microbubles to quantify tumor vessels We found that dietary DHA led to decreased tumor vascularization, prior to any chemotherapy, and that effect of DHA was abolished by dietary Vit. E (Colas et al., Clin Cancer Res 2006)
Remodelling tumor neovessels may also account for the tumor specificity of DHA action
Denis et al., Clin Cancer Res 2003
Using polymer casts of tumor blood vessels, we found that fish oil diet induced remodeling of tumor vascularization with lower density and thiner blood vessels This led to decreased interstitial pressure within mammary tumors and increased diffusion
Evaluation of the feasibility and safety of DHA administration during chemotherapy of metastatic breast cancer
Hypothesis: 1.8 g of daily DHA should lead to an enrichment of membrane lipids of breast cancer metastases, making them more sensitive to anthracyclin-based chemotherapy
Study design: Phase I-II study, with 25 patients – monocentric (Tours) – 2 years inclusion - Patients with metastatic breast carcinoma, OMS < 2 - DHASCO (Martek Inc) 9 cp/day, 10 days prior to chemotherapy, up to the end of CT - Chemotherapy with Epirubicine, Cyclophosphamide, 5-FU, 1 cycle every 3 weeks
End points: Safety & compliance, plasma + RBC levels of DHA Time to tumor progression
Secondary end points: Survival Bougnoux et al., Proc Am Ass Cancer Res, 2006
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Olmix Algae Symposium - Sept. 10th, 2012
Interindividual variability in DHA incorporation after dietary intervention
Stratification into 2 groups
High DHA incorporators
Low DHA incorporators
DHA is rapidly incorporated after dietary intervention
No, this is premature PUFA should not be provided without defined clinical trials
A phase III randomized trial comparing the fatty acid to placebo is on-going in metastatic breast cancer patients to definitely assess the usefulness of fatty acid supplementation during chemotherapy
Finally, could dietary DHA or n-3 PUFA be provided safely during cancer treatments ?
Not with antioxidant molecules at pharmacological doses …may stimulate tumor growth
Effect may change according to the intake of other PUFA ?
EPA has been reported to alter immune response and promote melanoma growth in experimental systems
First line chemotherapy (anthracyclines, taxanes..)
Metastatic breast cancer
HER2 negative
RH positive
(Fish oil in food supplement) DHA 1.5 g / day
DHA 0 g / day
216 patients, 2 yrs inclusion
Dietary intervention, 4 to 6 months
Endpoints: Time to progression QoL Funding : PHRC 2011
15 cancer centers involved
The future… marine-derived lipids as adjuvant to breast cancer treatments Bougnoux et al, Prog Lipid Res 2010
ClinicalTrials.gov Identifier: NCT01548534
Aim of the study: To determine whether adjuvant nutrition improves the treatment of breast cancer (Dec 2011 - July 2015)
A randomized, double-blind, phase III multicentric clinical trial comparing fish oil supplementation versus vegetable oil during chemotherapy in metastatic breast cancer patients
It is an institution that provides information on renewable natural resources, which has brought together the largest database of georeferenced soil, farms, water resources, agroclimate, fruit plantations and forest that exists in Chile, and other products are developed for different MINAGRI institutions.
In Chile, seaweeds are exported as raw material, used internally as alginates and agar and to a lesser degree, are also consumed as food.
The species that accumulate polysaccharides in their walls are a source of raw material for a variety of industrial products which the agar, carrageenan and alginates are the most used.
Seaweed synthesized polysaccharides in considerable amounts constituting an important renewable resource. A limited number of red and brown algae are exploited for the production of industrial application phycocolloids. It has been found that some seaweed sulfated polysaccharides have interesting biological properties such as anticoagulant activity, antitumor and antiviral.
The production of algae (gracilarias) borders the 90 000 t per year and there are only emerging projects that seek to increase diversity in the cultivation of these plants hydrobiological.
Macrocrystis pyrifera The common name of this alga is "huiro" or "kelp". The contribution of this alga is in the production of alginates. In Chile extends from Cape Horn to Valparaiso. (SANTELICES, 1989).
Porphyra columbina Conocida como "luche rojo". Es explotado casi de toda la costa Chilena, comercializándose a nivel local para el consumo humano bajo la forma de precosido y seco. (RED ALGAS MARINAS CHILE, 1990).
Lessonia trabeculata Known as "red fight." Is exploited almost all the Chilean coast, locally marketed for human consumption in the form of pre-cooked and dry. (RED SEAWEED CHILE, 1990).
Ulva lactuca Its common name is "fight", "fight green" and "sea lettuce". One of the most common species off the coast of the Tenth Region of Chile. Consumption in the region is low, its main contribution of carbohydrates. (Ramirez, 1981.).
Gracilaria chilensis
Common name "nap". The main raw material used in production of Agar-Agar is unique to the genre Glacilaria. (SANTELICES, 1986). The main importing country of Chile is Japan, which absorbs about 80% of production. Coquimbo is the main area of export of this resource. (SANTELICES, 1990).
Durvillaea antartica
In our country known as cochayuyo. In Chile this plant is harvested for human consumption or for export as raw material for the production of alginates. Human consumption takes two forms. The conical stipe is consumed fresh, as part of salads or stews and is called "ulte".Fronds dry roasted and cooked as part of hot dishes, this is known as "cochayuyo". (SANTELICES, 1989). The main production areas are in regions VII and X. (RED, 1990).
Alginatos 1756 20,6 Fuente: Intern. Trade Center – Trade Map
Description of exportable supply of Chile
8
Chilean production of different algae and algal products for export FOB amount reached close to USD 200 million, with volumes close to the 75,000 tons.
Export supply of Chile, the most important product in volume are natural dried seaweed, especially the genus Lessonia. However, when analyzing the export earnings, are Derivatives from Algae who take the utmost importance and represent 59% of the returns.
Olmix Algae Symposium - Sept. 10th, 2012 Olmix Algae Symposium Tabla: Exportaciones de algas pardas 2010. FUENTE: Revista Aqua. Mayo 2011.
Description of exportable supply of Chile
The kelp industry has had a high growth worldwide and in this area, Chile contributes with 10% of the biomass. Of these, the ones with the greatest commercial importance are Lessonia nigrescens, Lessonia trabeculata, Macrocystis integrifolia and Macrocystis pyrifera Durvillacea Antarctic.
Some of these species are of great economic importance, since they are extracted aliginatos used in the pharmaceutical industry, food (animal and human), textile, biomedical and cultivation of land plants, among other things.
The main destination markets for natural seaweed production in Chile in 2011 were China (with 67% of the tonnage shipped), Japan, France and Norway.
Different markets have virtually remained the volumes imported during the last 5 years, except China, which doubled its imports from Chile in this period.
Chile has had an average annual growth rate of 7% in these exports over the past 5 years.
Definition: Colloids are complex polysaccharides capable of forming gels, viscous substances and stabilizers of suspensions, according to its concentration and type of colloid (agar, vegetable gums, starch, Peptinas, alginates, carrageenans, etc.). The FICO prefix means Algae (Latin).
Alginates or alginic acids: Alginic acid obtained from different types of algae (Macrocrystis, Lessonia, Fucus, etc.). Extracting with sodium carbonate and precipitating with acid treatment. The gels are formed in the presence of calcium, which must be added in a controlled manner to achieve the formation of ordered molecular associations are not reversible by heating, this property makes alginates unique among all gelling agents. It is used in canned vegetables and jams, confectionery, cakes and cookies and ice cream. Also used the development of cold meats, pates, dehydrated soups, to keep the pulp suspension in fruit nectars and soft drinks that contain as foam stabilizer in beer.
Carrageenan: Are obtained from various types of red algae (Gigartina, Gracilaria, Furcellaria). The carrageenans are acidic and form thermally reversible gels, and it is necessary to dissolve in hot. They are widely used in the preparation of desserts, and they interact very favorably with milk proteins. With concentrations of 0.025% of carrageenan, it can stabilized suspension and at around 0.15% already provide solid textures .
Agar-agar: In Chile It is obtained mainly from Gracilaria chilensis. Is a polysaccharide widely used in microbiology, as an excellent growth medium for microorganisms.
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Olmix Algae Symposium - Sept. 10th, 2012
Japan34%
USA20%
Russian Fed18%
Thailand7%
Others21%
Target markets - AGAR AGAR
Target markets: products of algae
13
Even when China is the largest importer of natural algae in Chile, that country is not important destination of the processed products derived from algae.
In the case of agar, and alginates, the main countries receiving exports from Chile are Japan and USA.
In the case of carrageenan, USA and Denmark are the main destinations of exports from Chile.
France is an importer of Natural Seaweed, alginates and carrageenan with a 9%, 6% and 8% respectively from the total export volumes from Chile.
Conclusions from the point of view of Chile's export supply
1. There has been a sharp increase in world demand for Chilean supply of algae in their natural state and also for products derived from algae, due to its quality and export capacity in the country.
2. Chile has shown a very quick and efficient ability to increase their export volumes to meet rising world demand, yet there is great potential for further growth in the country.
3. The export supply in Chile is not only crude feedstock (algae naturally), but also products derived from algae, especially Agar Agar, Alginates and Carrageenan.
4. The export prices of Chilean Offer are convenient, especially for tariff benefits with importers, thanks to the many trade agreements Chile has signed with most countries.
CHILEAN FOOD STANDARDS Chile has regularized within the aquaculture products, in the Chilean Norm 1857. Office 84, this standard applies to the algae commonly known in Chile for commercial purpose, with common and scientific nomenclature.
FOOD HEALTH REGULATIONS According to Health Regulations of food, derived from seaweed (phycocolloids) are considered as food additives as required by Title III, Paragraph I, Article 130, since they only meet a technological and nutritious. In Title III, Paragraph II The use of additives, Article 149 states that are allowed to use as thickeners and hydrocolloids with good manufacturing practices agar, alginate, ammonium, calcium and sodium, Carrageenan. In the provisions of Title II, Paragraph II of the labeling and advertising, Article 107, all food products must bear a label or tag on their packaging contain the following information: name of the product, net contents, name or business name and address of manufacturer, country of origin, number and date of the health decision, dates, and duration of the product, instructions for use and storage. (Food Health Regulations 1998).
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Thanks for your attention!
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« Algae, source of active principles in cosmetics »
Alexis Rannou - Deputy Managing Director in charge of Innovation - ARD Soliance
[C’est une substance ou une préparation destinée à être mise
en contact avec les diverses parties superficielles du corps humain, notamment l'épiderme, les systèmes pileux et capillaire, les ongles, les lèvres et les organes génitaux externes, ou avec les dents et les muqueuses buccales, en vue, exclusivement ou
principalement, de les nettoyer, de les parfumer, d'en modifier l'aspect, de les protéger, de les maintenir en bon état ou de
corriger les odeurs corporelles.]
Source: article L.5131-1 du code de la santé publique 2
La pigmentation de la peau résulte de la présence de mélanine dans l’épiderme.
Wakamine Contexte biologique
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Deux types de mélanine : • l’eumélanine, brun-noir, • et la pheomélanine, jaune-orange.
La tyrosinase est l’enzyme indispensable pour les deux premières étapes de la mélanogénèse. Wakamine est un actif blanchissant performant Il inhibe la tyrosinase, l’enzyme clé impliquée dans la production de mélanine.
Cette algue fut introduite en France en 1971 en Méditerranée (étang de Thau) et par IFREMER sur les côtes Bretonnes en 1983.
Wakamine Origine géographique
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Undaria pinnatifida : Originaire des baies de la mer du Japon à l’ouest d’Hokkaido ainsi que des baies Coréennes et Chinoises, elle est traditionnellement cultivée et largement utilisée dans la cuisine asiatique.
Olmix Algae Symposium - Sept. 10th, 2012
Wakamine Culture de l’algue
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Undaria pinnatifida est récoltée dans ses habitats naturels depuis des siècles, elle est également cultivée. Sa production est estimée entre 450 000 et 500 000 tonnes au Japon et en Corée.
Culture de l’algue sur l’île d’Ouessant Cette macroalgue est aujourd’hui cultivée sur l’île d’Ouessant en Bretagne, un site classé par l’UNESCO.
Olmix Algae Symposium
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Olmix Algae Symposium - Sept. 10th, 2012
En inhibant la tyrosinase, Wakamine limite la production de mélanine
Wakamine (100mg/ml) : Les mélanocytes sont légèrement
visibles
Wakamine Inhibition de la production de mélanine (test ex vivo)
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Protocole Les épidermes sont obtenus à partir d’explants de peau. Ils sont séparés après incubation dans du NaBr 2N pendant 100 minutes à 37°C. Les épidermes sont ensuite fixés avec une solution tampon de formaldehyde, rincés et traités avec un mélange de l’actif (100μg/ml) et d’une solution de DOPA (1mg/ ml) pendant 4 heures à 37°C. Après incubation, les épidermes sont rincés et visualisés au microscope. Une analyse quantitative est réalisée par traitement d’images.
Wakamine aussi efficace que l’Arbutine (test in vivo)
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Protocole Une solution de Wakamine 3% est appliquée sur les explants de peau à l’aide de patchs de papier Whatmann une fois par jour pendant 6 jours. Les explants sont fixés dans le formol et montés dans la paraffine. La coloration due à la mélanine sur les coupes est traitée selon la technique de Masson. L’intensité de couleur est calculée par analyse d’images.
Wakamine est plus performant que l’Arbutine (référence quasi drug au Japon)
* p< 0.001 Chaque valeur de l’index mélanique est significativement différente par rapport à la valeur de J0.
* *
La diminution est effective pour 91% du panel
Protocole L’efficacité éclaircissante de Wakamine a été évaluée sur un panel de volontaires de type asiatique (22 volontaires, d’âge moyen 43 ans). Les panélistes appliquent 2 fois/jour pendant 56 jours.
En remplaçant 1% d’arbutine par 1% de Wakamine, des résultats in vivo similaires sont obtenus.
Wakamine permet de rendre vos formules plus innovantes
Stimulation des activités du protéasome (test in vitro) Protocole Les kératinocytes sont traités avec 2,5 μg/ml d’extrait de P.tricornutum pendant 24 h. Les activités peptidases du protéasome sont évaluées dans le lysat cellulaire en utilisant 25 μM de LLVY-amc, 150 μM de LLE-na, et 40 μM de LSTR-amc comme substrat peptidique fluorescent avec 20 μg de protéines totales.
En stimulant les activités du protéasome, Megassane diminue le taux de protéines oxydées
Diminution du taux de protéines oxydées (test in vitro) Protocole Un Oxyblot est réalisé avec 10 μg de protéines issues du lysat de kératinocytes, cultivés 7 h après traitement avec 2,5 μg/ml d’extrait de Phaeodactylum.
Restauration des activités du protéasome après exposition aux UV Protocole Une culture de kératinocytes est irradiée par des UVA UVB et/ou traitée par de P.tricornutum pendant 24 h. Les activités peptidases du protéasome sont évaluées dans le lysat cellulaire.
En restaurant les activités du protéasome Megassane répare les protéines endommagées par les UV
Réparation des dommages protéiques dus aux UV Protocole Une culture de kératinocytes, préalablement exposée aux UV, est traitée avec 2,5 μg/ml d’extrait de Phaeodactylum. Un Oxyblot est réalisé avec les protéines issues du lysat.
Un actif antirides et anti-âge exceptionnel. Très facilement incorporable en formulation, Revertime® propose une solution efficace et pertinente dans la lutte contre le vieillissement cutané.
Legal restrictions, high costs and environmental problems regarding the disposal of marine processing wastes.
European legislation (EU Council Directive 1999/31/EC, 1999) specific targets for disposal at landfills.
The Marine Functional Foods Research Initiative focuses on three main marine resources (i) fish processing waste streams, (ii) seaweeds and microalgae and (iii) aquaculture sources.
The Marine Functional Foods Research Initiative aims to exploit these marine resources for functional foods/ ingredients development.
Identification of bioactive compounds to the dietary intervention level in order to make a health claim.
Hypertension is one of the major yet controllable risk factors in CVD but it can be controlled by inhibition of a number of enzymes in the Renin Angiotensin System (RAS).
Platelet activating factor acetylhydrolase (PAF-AH) is a circulating enzyme produced and secreted by inflammatory cells centrally involved in atherosclerosis.
It generates two key pro-inflammatory mediators, lysophosphatidylcholine (LPC) and oxidized nonesterified fatty acids (oxNEFAs).
Evidence exists for a regulatory role of these lipids in promoting atherosclerotic plaque development that can ultimately lead to the formation of a necrotic core, a key determinant in atherosclerotic plaque vulnerability.
PAF-AH is an enzyme that converts PAF to the biologically inactive lyso-PAF.
PAF is a biologically active phospholipid that is involved in activation of platelets, monocytes, macrophages, polymorphonuclear leukocytes.
PAF-AH is linked to atherosclerosis and may be a positive risk factor for coronary heart disease in humans.
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Figure 1: PAF-AH inhibitory activities presented as percentage inhibitory values for the trout myofibrillar protein thermolysin 10-kDa-UFH RP-HPLC fractions.
PAF-AH inhibition by RP-HPLC fractions generated from trout myofibrilar muscle hydrolysed with thermolysin and filtered
Enzyme prolyl endopeptidase (PEP) plays a role in the degradation and metabolism of biologically active peptides containing proline such as oxytocin, vasopressin, substance P, bradykinin, neurotensis, and angiotensins .
Important biological functions in organs such as the brain and have been implicated to play a role in the development of neurodegenerative conditions such as AD.
Furthermore, specific inhibitors of PEP have anti-amnesic effects, and some of them have been synthesized as anti-amnesic drugs.
Figure 2: PEP inhibitory activities presented as percentage inhibition values for the trout myofibrillar protein thermolysin hydrolysates, 10-kDa and 3-kDa filtrates.
Catalase AAQKPDVLTTGGGNPVGDKLNS 20-41 2139.104 (2+) 10-kDa-UFH Full hydrolysate
Catalase LVQDVVFTDEMAH 51-63 1503.714 (2+) 10-kDa-UFH Full hydrolysate
Fatty acid-binding protein
VGMPDDIIQKGKD 22-34 1415.719 (2+) 10-kDa-UFH Full hydrolysate
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**Mora & Hayes, 2012, Identification of Peptide Sequences and Bioactive Characterization of Rainbow Trout Thermolysin Hydrolyzate Fractions with in vitro Inhibitory activities against Enzymes Important in Heart and Brain Health (Accepted in the Journal of Agriculture and Food Chem)
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Olmix Algae Symposium - Sept. 10th, 2012
EPA (20:5 n-3)
Linolenic acid (18:3 n-3)
Palmitic acid (16:0) Palmitoleic acid (16:1 n-7)
Fatty acids Reduce risk of cardiovascular diseases
Possible health effects
Oleic acid (18:1 n-9) Antioxidant activity
Antioxidant activity
Antimicrobial activity Reduce risk of cardiovascular diseases
DHA (22:6 n-3) Improve childhood cognitive development
Reduce risk of old-age diseases such as Alzheimer Cancer prevention
Antiviral, antitumoral, antihyperlipidemia and anticoagulant
Flush with fresh solventFlush with fresh solventFlush with fresh solventFlush with fresh solventFlush with fresh solvent(0.5 min.)(0.5 min.)(0.5 min.)(0.5 min.)
Flush with fresh solventFlush with fresh solvent(0.5 min.)(0.5 min.)
Extract readyExtract readyExtract readyExtract readyExtract ready(total time, 12(total time, 12(total time, 12(total time, 12
Extract readyExtract ready(total time, 12(total time, 12--14 min14 min.)
Heat and pressuriseHeat and pressurise(5 min.)(5 min.)
Purge with nitrogenPurge with nitrogen(1(1--2 min.)2 min.)
Founded on pioneering spirit and internationally oriented, Globe Export has specialised in the sale and transformation of nutritional marine plants for more than 25 years.
Used for ages, these plants are to expand their role in human nutrition over the next 15 years, thanks to their natural nutritional properties.
We develop healthy, nutritional, and tasty products which exceed expectations in terms of taste and nutrition.
High in protein, trace-elements and omega 3, combined with a low fat content, seaweed is a food source which can’t be beaten.
We cultivate and promote innovation & originality, thereby driving our development.
Algae: A “new” nutrient resource for human food
Globe Export, a vision for a future based on nutritional marine plants
Based in Brittany, in an unspoiled setting including one of the largest natural seaweed fields in the world, providing extremely high-quality raw materials, Globe Export covers all aspects of the food production process
Small-scale production / trade: Algues de Bretagne®
Research and development / innovation: Creativ'Concept®
With Algues de Bretagne, you can go beyond traditional nutrition.
Algae: A “new” nutrient resource for human food
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Algues de Bretagne is the specialist in edible seaweed, with a wide range of products providing a plethora of tastes and ensuring high nutritional value.
With its three separate ranges, Algues de Bretagne brings its specialist’s expertise to the table.
1. Seaweed range : Raw material for niche products: Seaweed tartare, marine spices, glasswort and sea ”beans”, fish rillettes with seaweed, seaweed chutney, fresh salted seaweed, fish soup and seaweed toast
Flavour Pearls range (solid on the outside with a liquid centre which bursts in your mouth). Available in ambiant T° with a shelf life of one year or in frozen form(IQF) with a shelf life of 12 months at -18°C.
Flavour Clouds range (dried arometized oils melt in the mouth), and Emulsions range (vinaigrette, citrus bergamot, Tomato Coriander base).
Design, produce and distribute products & services that improve soils vital functions and that stimulates plants, allowing an optimized use of natural resources.
Origin of elicitors and stimulants? What is their impact
Traditionnals use « re-discovery » -> recent insite Technology transfert from food, healh or cosmetical domains to Agronomy Recent structured screening (physiology, proteomics) -> since the1980’s
Frequent common point with elicitors : they are inducing plant defense mechanism that are expressed at high level in the resistant varieties. A few secondary metabolites do have biocide, biostatic or direct inhibition properties on some pathogens organisms. Frequent point for stimulants : They can counteract some nutrion limitations from the soil or from the leaves.
Allowed for food use : most consummed seaweed in Europe Tradionnaly harvested on the Britany costs Consummed fresh, finely chopped together with vegetables, cooked or dried High content in proteins (18 %) and polysaccharides High content in sulfur Vitamines A, B1, C Minerals (30 %) including :
– I, Ca, Cu, Si – Fe (12x lentils, = 2x wheat germ contents ), – Mg (up to 2 - 3 %)
Seaweeds flowed on the sand by the tide: -> legal status = waste – Decomposition is started, – High microbial load, – Hich sand load, – High variability, -> heavy and costly processes. Weak and variable quality.
Sea harvested seaweeds: -> legal status = natural ressource – Fresh and well preserved – Less microbial load – Low sand pollution -> better characterized raw-material with higher quality, simple
E.U. regulations (2012) • Fertilizers : Yes • Amendments : No (only national) -> E.C. in 2014 • Pesticides : Yes • Elicitors & phytostimulants : No, 3 exceptions (DE,IT,ES) + « PNP » in France
Paradoxal situation • Some farmers do have their own experimental basis + some good practices • Intentions (ex : ECOPHYTO-2018 in France) • Social opinion heavy tendency towards sustainability • Scientific litterature & patents on elicitors • Large and increasing number of R&D projects
Regulation is a limiting point for players together with the registration cost
This situation favors chemical groups (already structured + critical size)
Effects are not fully understood. Interactions are not known. Which one to chose? Price/value ratio ? Which association and /or formulations are the best ?
What are industrials approaches for having a biological active solution?
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Integrator : buying and formulate an already existing molecule -> Short-term (R&D is already done outside). -> Proportional cost. -> Exclusivity is diffcult to have or on short-term and limited area.
Screening available raw-material witch are not qualified for « agriculture » -> Midle term; -> Intermediate investment (R&D, formulation, agronomy), applicative IP possible; -> Risk on raw-material sourcing, variability (sometime).
Specific development of an active -> ex : ULVANS collaborative project -> Midle-long term -> significant investment -> Sourcing & quality are easier -> Exclusive, IP, homologation is possible.
Seed coating Solid Fertilizers Ferti-irrigation Foliar spraying -> need for formulations design for each application -> need further segmentation for crop species
Classical fertilizers positive list (N, P, K, Ca, Mg, K, Na, S, B, Co, Cu, Fe, Mn, Mo, Zn). Seaweed brings some more rare and “free” elements linked to natural molecules
– Directs nutrition effects Stimulants molecules (Improve efficiency of fertilizer
elements, improve photosynthesis and major element capture from soil by rhizospheric microflora,…).
– Both directs or indirects effects Elicitors of plant defense mechanisms
– Efficiency = f (Stress type and intensity) ? – Efficiency = f (patho-system) ? – Witch mechanisms & witch messagers ? – Robustness towards genetic variability of the crop
plants and of the pathogens too ? – Is it robust towards pedo-climatic conditions in the field?
* Soil : silt-clay type with no limitation (1 kg soil/ pot, no stress) ** Earthwoms: Nicodrilus giardi or Allolobophora terrestris or Aporrectodea terrestris, anecis specie (6 g/kg dry soil) *** Plant : Ray Grass (1 gramme / pot)
2 treatments / ecosystem: Control – PRP SOL
Microcosme where followed for 45 days at 20 – 23 °C, 3 pots / object
Advantages • Supposed to be safer than conventional pesticides due to the
indirect mode of action
• Risk of developing resistant strains is limited
• Broader spectrum of action
Limits • Treatments are preventive
• Efficiency sometimes weak and unsteady, especially under conditions of production in the field (possibly linked to formulation problems, interferences with cultural conditions such as the variety, the abiotic and biotic stresses, plant nutrition , …)
Fig 1. Schematic representation of physiological effects elicited by seaweed extracts and possible mechanism(s) of bioactivity, From Khan et al., 2009 (Journal of Applied Phycology) 24