Xanthine promote the Belitung the beautiful place

1. Budi Riyanto Semarang 1
Welcome to Bangka Belitung
Beautiful of Indonesia

2. Free radicals and antioxidant
: functions and human disease
( Astaxanthin)
Budi Riyanto

3. Antioxidant
Antioxidant activity
oxygen
hydrogen nitrogen
Carbon
atoms
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4. Anti oxidant and free radicals
• An antioxidant is a molecule that inhibits the oxidation of other
molecules.
• Oxidation is a chemical reaction that transfers electrons or
hydrogen from a substance to an oxidizing agent.
• Oxidation reactions can produce free radicals.
• In turn, these radicals can start chain reactions. When the chain
reaction occurs in a cell, it can cause damage or death to the cell.
• Antioxidants terminate these chain reactions by removing free
radical intermediates, and inhibit other oxidation reactions.
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5. The role of antioxidants
Kumar S. Advances in Applied Science Research, 2011, 2 (1): 129-135

6. Effects of free radicals
If free radicals are not inactivated, their chemical reactivity can
damage all cellular macromolecules including proteins,
carbohydrates, lipids and nucleic acids. Their destructive effect on
protein may play a role in the causation of diseases and aging.
Kumar S. Advances in Applied Science Research, 2011, 2 (1): 129-135

7. Although oxidation reactions are crucial for life, they can also be damaging .
Plants and animals maintain complex systems of multiple types of
antioxidants, such as glutathione, vitamin C, vitamin A, and vitamin E as
well as enzymes such as catalase, superoxide dismutase and various
peroxidases.
Insufficient levels of antioxidants, or inhibition of the antioxidant enzymes,
cause oxidative stress and may damage or kill cells.
Oxidative stress is damage to cell structure and cell function by overly
reactive oxygen-containing molecules and chronic excessive inflammation.
Oxidative stress seems to play a significant role in many human diseases,
including cancers.
The use of antioxidants in pharmacology is intensively studied, particularly
as treatments for stroke and neurodegenerative diseases
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Homeostasis of cell

8. Pro Oxidants
• Pro-oxidants are chemicals that induce
oxidative stress, either by generating
reactive oxygen species or by inhibiting
antioxidant systems
• The oxidative stress produced by these
chemicals can damage cells and tissues
• Some substances can serve as either
antioxidants or pro-oxidants, depending on
conditions
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9. Oxidative stress
• Oxidative stress reflects an imbalance between the
systemic manifestation of reactive oxygen species
and a biological system's ability to readily detoxify
the reactive intermediates or to repair the resulting
damage
• Disturbances in the normal redox state of cells can
cause toxic effects through the production of peroxides
and free radicals that damage all components of the
cell, including proteins, lipids, and DNA
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10. Oxidative stress
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Pathways of ROS formation, the lipid peroxidation process and the role of glutathione
(GSH) and other antioxidants in the management of oxidative stress

13. ROS
• In general, harmful effects of reactive oxygen species on
the cell are most often:
– Damage of DNA
– Oxidations of polyunsaturated fatty acids in lipids (lipid
peroxidation)
– Oxidations of amino acids in proteins
– Oxidatively inactivate specific enzymes by oxidation of co-factors
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• Positive effects of reactive oxygen species on the cell
are :
– Induction of host defences
– Genes and mobilisation of ion transport systems.
– In hematology's system, esp. : Wound injury -recruit additional
platelets to sites of injury.
– recruitment of leukocytes adaptive immune

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ANTIOXIDANTS
Enzymatic antioxidants
Primary enzyme
SOD,catalase,glutathione
peroxidase
Secondary enzymes :
Glutathione reductase,glucose 6
phosphatasedehydroginases
Non enzymatic antioxidants
Mineral
Zinc,Selenium
Carotenoids :
ß caroten, lycopene,
Lutein, zeaxanthin
Low molecular weight
antioxidants:
Glutahione,uric acid
Polyphenols
Vitamins:
vitA,vitE,VitC,vit K
Organosulfur compounds
Antioxidants co-factors
Co-enzyme Q10

15. Carotenoids
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17. • 600 known carotenoids*
• Humans cannot
synthesise carotenoids.
• Need to obtain carotenoids
from food.
• <25 obtained from food.
• Basic carotene structure
• Xanthophyll Class
– Lutein
– Astaxanthin
Molecular Formula: C40H52O4
Molecular Weight: 596.82
CAS No: 472-61-7
O
HO
O
OH
*Parker RS.,1997
A M E M B E R O F T H E
C A R O T E N O I D F A M I L Y
Astaxanthin
Lutein
-Carotene
OH
OH

18. As tax anthin
J. Agric. Food Chem. 2000, 48, 1150−1154; J. Nat. Prod. 2006, 69, 443-449
• A red-orange carotenoid pigment
• Unique molecular structure.
• Powerful biological antioxidant that occurs naturally in a wide variety of
living organisms
• Has been associated with reduced risk of diseases such as age-related macular
degeneration and ischemic diseases, effects attributed to its potent antioxidant
activity
Lipophilic backbone
Hydrophilic
polar-end
Hydrophilic
polar-end

19. Physical Quenching
1O2 + 1Carotenoid → 3O2 + 3Carotenoid*
3Carotenoid* → 1Carotenoid + thermal energy*
↓
ASTAXANTHIN ELIMINATES FREE RADICALS
EXTREMELY FAST BY ENERGY TRANSFER**
Chemical Reaction (e.g. -Carotene)
1O2 + Carotenoid → Carotenoid RADICAL → OXIDIZED
*B.R.Nielsen, K.Jorgensen and L.H.Skibsted : Triplet-triplet extinction coefficients, rate constants of triplet decay and rate
constants of anthracene triplet sensitization by laser flash photolysis of astaxanthin, β-carotene, canthaxanthin and
zeaxanthin in deaerated toluene at 298K, J.Photochem.Photobio.A:Chem., 112, 127-133 (1998).
A N T I O X I D A N T M E C H A N I S M S
“The energy of the singlet state oxygen is quickly transferred to the carotenoid by direct contact, and the carotenoid in
the triplet state relaxes to the singlet state very quickly by the transformation of the potential energy into thermal energy
through the vibration of conjugated double bonds in the polyene chain.” (Miki, M., Biological Functions and Activities of
Animal Carotenoids. Pure Appl. Chem. 63. 141-146. 1991.)

20. e－ e－
３O2 → ・O2
－ → H2O2 → ・OH O２ LH
１O2 LH → L・ → LOO・ → LOOH
H2O L・
SOD Catalase Ascorbic Acid
Astaxanthin
↓ ↓ ↓ ↓
↓ ↓
QUENCHING
550 x Vitamin E*
40 x -carotene*
INHIBITS
PEROXIDATION
1000 x Vitamin E**
N E U T RA L I Z I N G R O S
(Superoxide radical)
(Singlet oxygen radical)
(Hydroxy radicals)
(Peroxide
radicals)
*N.Shimizu et al.: Carotenoids as singlet oxygen quenchers in marine organisms, Fisheries Science, 62, 134-137 (1996).
**Miki, W. Pure & Appl. Chem. 63(1);141-46. (ROS: Reactive Oxygen Species)
Astaxanthin
Vitamin E
(tocopherol)

21. How does
ASTAXANTHIN
work?
Kidd, P., Alternative Medicine Review Volume 16, Number 4
Capelli B. Natural Astaxanthin. 2012
The membrane systems of cells are
particularly vulnerable to free radical
or other oxidative attack. Astaxanthin
incorporates both oil and water
soluble components within a single
molecule. This enables it to protect
both parts of our cells and provide
exceptional antioxidant and anti-
inflammatory protection to the entire
cell.
Unlike other antioxidants, it can
protect the whole cell at once.
Beta - carotene
Protect the Entire
Cell and the Entire
Body

22. As tax anthin
J. Agric. Food Chem. 2000, 48, 1150−1154; J. Nat. Prod. 2006, 69, 443-449
Lipophilic backbone
Hydrophilic
polar-end
Hydrophilic
polar-end

23. T H E A S T A X A N T H I N S H I E L D
Lignell A., & Wood V., Astaxanthin: Radical Cellular Defense. May 2004 Innovations in Food Technology.

24. P R O P E R T I E S O F A S T A X A N T H I N
Antioxidant Potency
Powerful singlet oxygen
quenching and free radical
scavenging activity.
Protects against lipoperoxidation.
Solubility
Spans the membrane bi-lipid layer
– comprehensive protection and
strengthens rigidity
Protection Forms a protective shield and
defends against continuous free
radical attack at the cellular level.
Safety Defined as a pure antioxidant
unlike other well known
antioxidants that can become pro-
oxidants.

25. Natural Astaxanthin :
Powerful Antioxidant
without Pro-oxidant
effects
• 550 times stronger than vitamin E
• 6000 times stronger than vitamin C
• 800 times stronger than CoQ10
• 40 times stronger than beta carotene
Yamashita E, Functional Foods in Health and Disease 2013; 3(7):254-258 ;Capelli dan Cysewski, Cyanotech Corporation 2007

26. ASTAXANTHIN: King of the Carotenoids
Capelli B. Natural Astaxanthin. 2012
1. Cross the blood-brain barrier and bring antioxidant and anti-
inflammatory protection to the brain and central nervous system
2. Cross the blood-retinal barrier and bring antioxidant and anti-
inflammatory protection to the eyes
3. Travel throughout the body effectively to bring antioxidant and
anti-inflammatory protection at a high activity level to all the
organs and the skin
4. Span the cell membranes
5. Bond with muscle tissue
6. Work as a super-powerful antioxidant and quickly eliminate free
radicals and neutralize singlet oxygen
Some of the many things that Astaxanthin can do that beta
carotene
(and many other carotenoids) cannot:

27. Health promotional effects of astaxanthin
Numerous studies have shown that
astaxanthin has potential health-promoting
effects in the prevention and treatment of
various diseases, such as cancers, chronic
inflammatory diseases, metabolic syndrome,
diabetes, diabetic nephropathy, cardiovascular
diseases, gastrointestinal diseases, liver
diseases, neurodegenerative diseases, eye
diseases, skin diseases, exercise-induced
fatigue, male infertility.
It has been proven in over 65 clinical studies,
featured in over 300 peer-reviewed
publications.
Yamashita E. Functional Foods in Health and Disease 2013; 3(7):254-258

28. I N F L A M M A T O R Y R E S P O N S E –
I N A C T I V A T I O N OF N F – K B
Lignell A., & Wood V., Astaxanthin: Radical Cellular Defense. May 2004 Innovations in Food Technology.

29. Astaxanthin
targets reactive
oxygen species
(ROS), NF-кB
and adiponectin
to maintain
healthy
inflammatory
responses

30. Astaxanthin decreased
oxidative stress and
inflammation and enhanced
immune response in humans
Park et al. Nutrition & Metabolism 2010, 7:18

31. The effects of astaxanthin on atherosclerosis prevention and development
Astaxanthin has been
documented to have:
Cardiovascular protective
effects.
 Reduces
 Oxidative stress and
inflammation, known
contributors to the
pathophysiology of
atherosclerotic and
Cardiovascular
disease
 Astaxanthin may prove
more beneficial at
attenuating
cardiovascular disease
than vitamin E and
vitamin C
http://www.astareal.com/what-is-astaxanthin/health-benefits/cardiovascular-health Fassett RG and Coombes DS. Molecules 2012, 17, 2030-2048

32. Astaxanthin in hypertension
Hussein G, et al. J. Nat. Prod. 2006, 69,

33. Astaxanthin increases serum HDL-cholesterol and
adiponectin in subjects with mild hyperlipidemia
Yoshida H.Atherosclerosis (2009), doi:10.1016/j.atherosclerosis.2009.10.012
Subject with Lower levels of HDL and
higher levels of serum triglyserides are
more likely to develop cardiovascular
diseases

34. Astaxanthin improved blood rheology
Astaxanthin (6
mg/day)
supplementation for
10 days improves
blood flow in
humans as tested by
MC-FAN.
Miyawaki H, et al.J. Clin. Biochem. Nutr., 43, 69–74

35. Astaxanthin in prevention of dementia
Astaxanthin supplementation results in improved erythrocyte antioxidant status and
decreased PLOOH levels, which may contribute to the prevention of dementia
Changes in carotenoids, phospholipid hydroperoxides (PLOOH)
contents in
erythrocytes taken before and after the 12-week administration of
0, 6 or 12mg astaxanthin
Higher levels of phospholipid hydroperoxides
(PLOOH), the primary oxidation products of
phospholipids (PL) accumulate abnormally in the
erythrocytes of dementia patients. Such erythrocytes
with high levels of lipid hydroperoxides have been
postulated to have a decreased ability to transport
oxygen to the brain, which may impair blood rheology,
thus facilitating dementia
After 12 weeks of treatment, erythrocyte astaxanthin
concentrations were higher in both the 6 and 12mg
astaxanthin groups than in the placebo group. In
contrast, erythrocyte PLOOH concentrations were
lower in the astaxanthin groups than in the placebo
group.
Nakagawa K, et al. British Journal of Nutrition (2011), 105, 1563–1571

36. Terimakasih perhatiannya
Semoga bermanfaat untuk ilmu dan mata … hehehe
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