Cyanotech Corporation · OTC:CYAN
Cyanotech — Technical Presentation (2006)
41 slides from Cyanotech's technical presentation, Oct 16, 2006
Slide 1: Natural Inflammatory Response
Natural Inflammatory Response Gerald R. Cysewski, Ph.D. President and CEO Cyanotech Corporation
Slide 2: Inflammation
Inflammation • Complex physical and biochemical process • Essential for our survival – Immune response to fight infection and repair damaged tissue • Excessive and prolonged inflammation can lead to tissue damage and serious disease
Slide 3: Inflammation—An innate cascade
Inflammation—An innate cascade • Mast cells are key initiators of inflammation – Found in most tissue – Cytoplasm contains granules of inflammation mediators – Cell surface coated with variety of receptors to detect pathogenic substances – Activated receptors trigger release of inflammation mediator
Slide 4: Mast Cell
Mast Cell Receptors Ligands Nucleus Granules Hi sta m ine ,T NF -_
Slide 5: Inflammation—An innate cascade
Inflammation—An innate cascade • Mast cells release many potent inflammation mediators – Some immediately by granule discharge – Some after synthesis • Mediators either: – Actively attract white blood cells or – Activate attracted cells to produce additional mediators or – Both attract and activate
Slide 6: Inflammation Mediators
Inflammation Mediators (Some major and understood mediators) • Histamine – Vasodilation—increase blood and plasma flow • Tumor necrosis factor-alpha (TNF-_) – Positive feedback to produce more TNF-_ – Increases C-reactive protein production in liver • Reactive Oxygen Species – Nitric oxide, hydrogen
Slide 7: Inflammation—A cascade that feeds upon itself
Inflammation—A cascade that feeds upon itself Example: Production of TNF-_ is rapidly amplified TNF-_
Slide 8: Inflammation Mediators
Inflammation Mediators (Some major and understood mediators) • Interleukin-1 – Stimulates synthesis of other interleukins – Induces fever • Prostaglandins – Produced from arachidonic acid – Produced by cyclooxygenases (COX enzymes)
Slide 9: Cyclooxygenase Enzymes
Cyclooxygenase Enzymes • COX-1 is a constitutive enzyme – Produces prostaglandins to protect the GI tract, kidneys, and platelets • COX-2 is an inflammation induced enzyme – Produces prostaglandins that mediate inflammation • PGE2, PGI2, and PGF2 • Involved with fever, vasodilation, vascular permeab
Slide 10: Cyclooxygenase Enzymes
Cyclooxygenase Enzymes • Non-specific COX inhibitors – NSAIDs ( Aspirin) – Control inflammation – Can lead to GI tract problems • Specific COX-2 inhibitors ( Vioxx and Celebrex) – Control inflammation – Eliminate GI track problems – Increased heart attacks and strokes • Possible imbalance of PGI2 pl
Slide 11: Inflammation—A cascade that feeds upon itself
Inflammation—A cascade that feeds upon itself • Excessive and prolonged inflammation can lead to tissue damage and serious disease – Irritable bowel syndrome – Asthma – Rheumatoid Arthritis – Heart disease – Ulcers – Alzheimer’s
Slide 12: Sources of natural Astaxanthin
Sources of natural Astaxanthin • Phaffia yeast _ 0.2 to 0.5% astaxanthin, (free) • Krill and other crustacean oils _ O.05 to 0.12% astaxanthin, (esterified) • Haematococcus microalgae _ 1.5 to 3.0% astaxanthin, (esterified)
Slide 13: Haematococcus Cells
Haematococcus Cells Motile, green Encysted cells produce massive Haematococcus cells amounts of astaxanthin (400x magnification)
Slide 14: Astaxanthin, similar to beta-carotene, but strong functional difference
Astaxanthin, similar to beta-carotene, but strong functional difference Astaxanthin
Slide 15: Astaxanthin in nature occurs with one or more fatty acids
Astaxanthin in nature occurs with one or more fatty acids attached to the molecule (R). Astaxanthin -R’ R- Unique chemistry of natural astaxanthin allows spanning of cell membranes, crossing blood-brain barrier, and bonding directly with muscle tissue. Beta-carotene and lycopene do not have these bo
Slide 16: Haematococcus carotenoid analysis
Carotenoid analysis Thin-layer chromatography Haematococcus shows astaxanthin from Synthetic AX Phaffia Y e a s t Haematococcus is most similar Krill Oil to krill, the primary source of astaxanthin in the wild. Astaxanthin diesters Astaxanthin monoesters Free astaxanthin
Slide 17: Natural astaxanthin
Natural astaxanthin • Potent antioxidant • Can cross blood-brain barrier • Supports natural inflammatory response
Slide 18: Haematococcus Production
Haematococcus Production
Slide 19: Final Production in Reddening Ponds
Final Production in Reddening Ponds The final stage Haematococcus production is in 500,000 liter ponds where high concentrations of astaxanthin accumulate in cells.
Slide 20: Astaxanthin is exceptionally powerful in singlet-oxygen quenching
Astaxanthin is exceptionally powerful in singlet-oxygen quenching • 550 times stronger than vitamin E • 11 times more powerful than beta-carotene Relative singlet oxygen quenching rates 600 astaxanthin 500 550 zeaxanthin 475 400 lutein 300 beta carotene 200 200 50 alpha tocopherol 100 1 0 Antioxidan
Slide 21: Oxygen Free Radical Scavenging
Oxygen Free Radical Scavenging 14 12.3 12 % Inhibition per mg 10 8 6 4 2 0.19 0.86 0.69 0.23 0 Vit. E Vit. C Pyc BC AX BioAstin® From D. Bagchi, Creighton University
Slide 22: Astaxanthin anti-inflammatory actions and mechanisms
Astaxanthin anti-inflammatoroy actions and mechanisms • Two studies – Mice – In vivo and in vitro – Lipopolysaccharide (LPS) induced inflammation – Injection of both LPS and astaxanthin
Slide 23: Astaxanthin suppresses production of TNF-alpha
Astaxanthin suppresses production of Tumor necrosis factor-alpha (TNF-_) 800 792 700 600 500 TNF-_, pg/ml 400 287 300 241 223 233 200 100 0 LPS 1mg/kg 10mg/kg 100mg/kg predn. Astaxanthin Concentration From K. Ohgami et. al 2003
Slide 24: Astaxanthin suppresses production of Prostaglandin PGE2
Astaxanthin suppresses production of Prostaglandin PGE2 12 10.2 10 8 PGE2, ng/ml 6 4 2.6 2 1.2 0.8 1 0 LPS 1mg/kg 10mg/kg 100mg/kg predn. Astaxanthin Concentration From K. Ohgami et. al 2003
Slide 25: Astaxanthin suppresses production of Nitric Oxide
Astaxanthin suppresses production of Nitric Oxide 140 122 120 Nitric Oxide, mg/ml 100 80 60 49.1 40 20 10 12.1 13.3 0 LPS 1mg/kg 10mg/kg 100mg/kg predn. Astaxanthin Concentration From K. Ohgami et. al 2003
Slide 26: Astaxanthin suppresses production of Interleukin-1
Astaxanthin suppresses production of Interleukin-1 450 410 400 Interleukin-1_, ng/ml 350 300 250 180 200 150 100 50 10 0 Control LPS 40 mg/kg Astaxanthin Concentration SJ Lee et. al 2003
Slide 27: Cyclooxygenase Inhibition
Cyclooxygenase Inhibition Brunswick Laboratories, in vitro testing Item COX-1 COX-2 COX-2 IC50 IC50 COX-1 mg/ml mg/ml Inhibition Astax. 0.027 0.024 1.13 Celecoxib 0.0062 0.000079 78.48 COX-1 COX-2 Inhibition Inhibition Celecoxib 4.36 303.8 69.5 Astax.
Slide 28: Astaxanthin inflammatory support actions and mechanisms
Astaxanthin inflammatory support actions and mechanisms • K. Ohgami et al 2003 Study – Astaxanthin suppresses NO, PGE2 and TNF- _ – Blocks nitric oxide sythase enzyme • SJ Lee et al 2003 Study – Astaxanthin inhibited signaling cascade of inflammatory gene expression. – Suppressed nuclear factor-kapp
Slide 29: Inflammation related clinical studies
Inflammation related clinical studies • Carpal Tunnel Syndrome – Nir and Spiller, 2002b – 20 subjects—13 treatment, 7 placebo – Astax., 12mg ax/day, 8 weeks • Rheumatoid Arthritis – Nir and Spiller, 2002 – 21 subjects—14 treatment, 7 placebo – Astax., 12mg ax/day, 8 weeks • UV Protection – Product t
Slide 30: Inflammation related clinical studies
Inflammation related clinical studies • Joint and muscle soreness – Fry 2001 – 20 subjects—10 treatment, 10 placebo – Astax., 8mg ax/day, two weeks • C-Reactive protein – Spiller et al, 2006 – 25 subjects—17 treatment, 8 placebo – Astax., 12mg ax/day, 8 weeks • Tennis Elbow – Spiller et al, 2006b –
Slide 31: CTS daytime pain rate
CTS daytime pain rate 2 1.8 1.6 1.4 1.2 Astax. Placebo 1 0.8 0.6 0.4 0.2 0 Start 4 weeks 8 weeks Positive trend in decreased pain Nir and Spiller 2002b
Slide 32: CTS duration of daytime pain
CTS duration of daytime pain 3 2.5 2 Astax. Placebo 1.5 1 0.5 0 Start 4 weeks 8 weeks Positive trend in decreased duration of pain Nir and Spiller 2002b
Slide 33: Rheumatoid arthritis satisfaction score
Rheumatoid arthritis satisfaction score 2 3 = total dissatisfaction 1.8 1.6 1.4 1.2 Astax. Placebo 1 0.8 0.6 0.4 0.2 0 Start 4 weeks 8 weeks Statistically significant increase in satisfaction Nir and Spiller 2002
Slide 34: Rheumatoid arthritis VAS pain scale
Rheumatoid arthritis VAS pain scale 0.5 0.45 0.4 0.35 0.3 Astax. Placebo 0.25 0.2 0.15 0.1 0.05 0 Start 4 weeks 8 weeks Statistically significant decrease in pain Nir and Spiller 2002
Slide 35: Inflammation related clinical studies
Inflammation related clinical studies • UV Protection – Astax. significantly altered minimal erythemal dose – Significantly more (UV) energy required to cause erythema • Joint and muscle soreness – Placebo group experienced significant increase in knee pain immediately and for a period of 48 hours a
Slide 36: Tennis Elbow, Grip Strength
Tennis Elbow, Grip Strength 500 450 400 Grip strength,mmHg 350 300 Astax. Placebo 250 200 150 100 50 0 Start 8 weeks Statistically significant increase in grip strength w/o pain Spiller 2006b
Slide 37: C-Reactive protein (CRP)
C-Reactive protein (CRP) 1.4 1.2 1 CRP, mg/dl Astax. 0.8 Placebo 0.6 0.4 0.2 0 Start 8 weeks Statistically significant decrease in CRP Spiller 2006
Slide 38: C-Reactive Protein CRP
C-Reactive Protein CRP • Acute phase protein – Levels increase during inflammation – Produced in the liver – Part of innate immune response • CRP levels may be related to cardiovascular disease risk • CRP levels may be related to systemic or “silent inflammation” – Heart disease – Diabetes – Alzheim
Slide 39: Inflammation related clinical studies
Inflammation related clinical studies • Preliminary • Small patient groups • Further studies required • Results are very encouraging
Slide 40: Astaxanthin: natural modulation of inflammation
Astaxanthin: natural modulation of inflammation • Beginning to understand mechanisms and properties of astaxanthin – Inhibits inflammatory mediators – Scavenges ROS – Mild COX inhibitor • Astaxanthin may address inflammatory conditions – Chronic or systemic inflammation – Multiple pathways of action
Slide 41: In Summary
In Summary • Based on: – Biochemical parameters – Human clinical studies • Astaxanthin may support and maintain healthy “inflammatory system” function