Continuing Medical Education (CME) 13 th September 2009 SUNDAY, AH & RC AUDITORIUM,
Arya vaidya sala,kottakkal.
1
‘ANTIOXIDANTS’ New Insight in Disease Management -an ayurvedic perspective
Dr SUDHEER AMBADI PHYSICIAN ARYA VAIDYA SALA, KOTTAKKAL. 2
History/Global review
Early 19 th- 20 th century SIES,1996 AO based formulations for prevention of 3 rd Generation / functional disease: 27% 57 % ANTIOXIDANTS used are single /multiHERBAL formulations
3
CONTENT History/Global review Free radicals Ageing & Oxidative stress Antioxidants Pro oxidants AYURVEDIC PERSPECTIVE Agni Concept of bhutagni & dhatwagni Malam Amam Vyadhikshamathwam Amayanam Rasayanam Geriatrics/Gerontology New insights in Antioxidant Research Conclusion 4
Oxygen -a paradox in metabolism
Highly reactive molecule that damages living tissue by producing ROS/RNS
5
FREE RADICALS
An atom or group of atoms possessing one or more unpaired electrons 6
How it is formed ? Human cell
Extra cellular space Metabolism
Free radicals
7
History… Free Radical Biochemistry 2 nd world war (1939-1945) 6th Aug 1945-Hiroshima 9th Aug 1945-Nagasakhi
8
Free radicalsas Molecular terrorists
9
FREE RADICALS Etiology of many human diseases/ageing Short lived with half life milli/macro/nano seconds Harman,1958. Halliwell & Gutteridge 1997 ROS(Reactive oxygen species) RNS (Reactive nitrogen species)
- byproduct of Metabolism. H2O
H+ & OH10
More with... Exposure to ionizing radiation (from industry,sun exposure,cosmic rays & x rays) Ozone and nitrous oxide (primarily from automobile exhaust) Heavy metals ( like mercury,cadmium &lead) Alchohol & Cigarette smoking (Both active & passive) Stress 11
Reactive Oxygen Species (ROS) Superoxide -O2Hydroxyl radical - OH Hydrogen peroxide - H2O2 Peroxide radical - ROO Singlet oxygen - O2 Ozones - O3
12
Reactive nitrogen species(RNS)
Nitric oxide - NO Peroxynitrite ONOOPeroxynitrous acid ONOOH Nitrogen dioxide NO2
13
FREE RADICALS
- Friends or Foes ? • Generation of ATP (oxidative phosphorylation) • Detoxification of oxidizing enzymes • Killing of micro organism and cancer cells • Generation of regulatory modulators
14
Molecular damage induced by free radicals • Lipids • Carbohydrates • DNA • Proteins
15
Lipids as lipid peroxidation Atherosclerotic angiopathy
16
Carbohydrates as oxyradicals
17
DNA
18
Protein as hydroperoxides
19
PRO OXIDANTS
20
Pro-oxidants Are chemicals that induce oxidative stress, either through creating R O S or inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues. Eg: an overdose of the acetaminophen can cause fatal damage to the liver , partly through its production of ROS
21
Pro-oxidants • Vitamin C • Uric acid • homocysteine
22
Natural antioxidant mechanism Superoxide dismutase (SOD) Glutathione peroxidase Glutathione reductase Thioredoxin
23
Superoxide Dismutase (SOD)
• is an enzyme that repairs cells and reduces the damage done to them by superoxide, the most common free radical in the body. • is found in both the dermis and the epidermis.
24
Superoxide Dismutase (SOD) •
Acts as both an antioxidant and anti-inflammatory in the body, neutralizing the free radicals that can lead to wrinkles and precancerous cell changes.
•
Act as an anti-aeging treatment, since it is now known that SOD levels drop while free radical levels increase as we age.
25
Two types of SOD
• Copper/zinc (Cu/Zn) SOD – protects the cells’ cytoplasm
• Manganese (Mn) SOD. – protects their mitochondria from free radical damage 26
What Do We Concern Frequently in Our Life?
27
What is Ageing ?
Ageing is mainly due to the cumulative results of free radical oxidation of the protein, lipid and nucleic acid of our body.
28
Concept of Oxidative stress SIES - 1986
29
Oxidative Stress The oxidative stress leads to the aging of body.
Antioxidant
ROS 30
Effects of Reactive Oxygen Species on Degenerative Diseases for Aging Gastro intestinal Hepatitis
Eye
Skin
Heart
Cataractogenesis
Age pigment
Heart attack
Teeth Periodontis
Reactive Oxygen Species
Joints Arthritis
Vessels
Multiorgan failure
Brain
Lung
Atherosclerosis
Cancer
Stroke
Asthma 31
MRI Brain-Study. C. thrombosis
Alzheimer’s
32
Age related Macular degeneration in human eye Fundus-comparision
33
Can We Slow Down the Clock of Aging?
34
ANTIOXIDANTS
35
ANTIOXIDANTS Substances that neutralizes free radicals or their actions ( SIES 1996 ) It is a molecule capable of slowing or preventing the oxidation of other molecules. (Oxidation reactions can produce free radicals which start chain reactions that damage cells.)
36
Characteristics of antioxidants
Mono hydroxy or polyhydroxy phenol compounds having low activation energy to donate hydrogen.
37
Classification
• Hydrophilic-water soluble
• Hydrophobic-lipid soluble
38
Types of antioxidants Preventive AO Prevention of free alkyl radical formation in initiation Singlet oxygen quenchers Antioxidant enzymes
Radical Scavenging AO Prevention of peroxy radical chain reaction in propagation Hydrogen donating antioxidants 39
Kinds of antioxidants
Natural antioxidants Tocopherol(delta>gamma>beta>alpha) Sesamol,Gossypol
Synthetic antioxidants Butylated hydroxy anisole(BHA) Propyl gallate(PG) Tertiary butyly hydroquinone(TBHQ) 40
ANTIOXIDANTS D- alpha tocopherol ( Vit E ) Ascorbic acid ( Vit C ) Beta -Carotene ( Precursor of Vit A ) Lutein Lycopene Zinc & Selenium
41
Uric acid - C5H4N4O3 50% of antioxidant capacity of Blood plasma comes from uric acid.
PURINE METABOLISM Xanthine oxidase XANTHINE
HYPOXANTHINE
42
Dietary antioxidants
A substance in food that significantly decrease the adverse effects of reactive oxygen species and nitrogen species on normal physiological function
43
Diversity in Dietary antioxidants Essential Vit E (Tocopherol) Vit C (Ascorbic acid) Vit A (Retinol&Caroteniods) Minerals like Cu,Mn,Zn,Se,Fe.
Non essential Glutathione, small peptides etc 44
What are they ? • Beta carotene:-Orange colour – sweet potato,carrot,apricot,pumpkin,sweet mango. etc. • Lutein:- Green colour – leafy vegetables,spinach,greens etc. • Lycopene:-Red colour – tomato,water melon,guava,pappaya,pink grapes.etc..
45
.
Others.. Vit E Vit A Vit C Selenium Glutathione melatonin
46
Antioxidant v/s
Pro oxidants
47
Antioxidants- Recap
48
Free radical -Antioxidant -intra cellular view.
49
Assays• Lipid peroxidation assay. • Reduced glutathione assay. • Superoxide dismutase assay
50
DPPH ASSAY (1,1-Diphenyl-2-picryl hydrazil) • is a stable free radical with red color. • If free radicals have been scavenged, DPPH will generate its color to yellow
51
Q C LABORATORY
Quality Assurance Department
Accredited by Dept of AYUSH Recognised as SIRO by DSIR Recognised by PCB
52
Antioxidant activity of chyavanaprasam DPPH (1,1-diphenyl picryl hydrazil)Assay,2008 Effective concentration for reducing the absorbance by 50%( EC 50 value) which is inversely proportional to the antioxidant activity. EC 50 value of leham : 40 microgram 53
EC 50 values
Dasamoolakatuthryadi kashayam: 40 microgram Patolakatukurohinyadi kashayam: 60 microgram
54
Ayurvedic perspective:-
55
METABOLISM Anabolism - Biosynthesis cÉÏrÉiÉå A³ÉÉÌSÍpÉ: Catabolism - Degradative zÉÏrÉïliÉå AlÉålÉ CÌiÉ zÉUÏUqÉ mÉëÌiɤÉhÉÇ ¤ÉÏrÉqÉÉhÉÉå SåWûÉ:
56
Cellular metabolism & THRIDOSHA • Vatha:
Communication/Transport/ kinetics
• Pitha:
Digestion/Transformation/ Biochemical energy production and regulation
• Kapha : Basic reserve/Cohesion/Lubrication 57
A³ÉuÉWûxÉëÉåiÉxÉç • • • • • •
mÉëÉhÉlÉç xÉqÉÉlÉlÉç AmÉÉlÉlÉç urÉÉlÉlÉç mÉÉcÉMüÌmɨÉÇ
• YsÉåSMü
: : : : : :
A³ÉmÉëuÉåzÉlÉÇ aÉëWûhÉÇ ,mÉcÉlÉÇ ,ÌuÉuÉåcÉrÉlÉÇ ,qÉÑgeÉlÉÇ ÌlÉw¢üqÉhÉÇ A³ÉÉxuÉÉSlÉÇ, xÉÉUÌMüûÌuÉpÉeÉlÉÇ, kÉÉiÉÑ iÉmÉïhÉÇ rÉÉålÉÉæ zÉÑYsÉmÉëÌiÉmÉÉSlÉ: (A S ) mÉcÉlÉÇ ,ÌuÉpÉeÉlÉÇ
: A³ÉxÉÇbÉÉiÉÇ, A³ÉYsÉåSlÉÇ
58
Concept of AÎalÉ AÉrÉÑuÉïhÉÉåï oÉsÉÇ xuÉÉxjrÉqÉÑixÉÉWûÉåmÉcÉrÉÉæ mÉëpÉÉ •
AÉåeÉxiÉåeÉÉåÅalÉrÉ: mÉëÉhÉɶÉÉå£üÉ SåWûÉÎalÉWåûiÉÑMüÉ: Charaka chikitsa 15/1
zÉÉliÉåÅalÉÉæ ÍqÉërÉiÉå rÉÑY¨Éå ÍcÉUÇ eÉÏuÉirÉlÉÉqÉrÉ: Charaka chikitsa 15/2
59
AÎalÉ • ‘””mÉÉMüÉÌSMüqÉïhÉÉÅlÉsÉzÉÎoSiÉqÉç • A H SU • • • •
eÉPûUÉÎalÉ irÉY¨ÉSìuÉiuÉqÉç ¤ÉÌmÉiÉxÉÉåqÉaÉÑhÉÇ -
AH CHARAKA
kÉÉiuÉÎalÉ pÉÔiÉÉÎalÉ
60
xuÉxjÉ:
• xÉqÉSÉåwÉ: xÉqÉÉÎalÉxcÉ xÉqÉkÉÉiÉÑ qÉsÉÌ¢ürÉ: mÉëxɳÉÉiqÉåÎlSìrÉqÉlÉÉ: xuÉxjÉÌrÉirÉÍpÉkÉÏrÉiÉå Su Su 15
Well balanced state of Dosha ,Agni ,Dhatu and Malam
61
Concept of Bhoothagni & Dhathwagni Amam -Contemporary perspective .2005 Dr Muraleedharan & Dr Reena Ramesh varier
* Selective discrimination, * Biochemical individuality
62
kÉÉiuÉÎalÉqÉÉl±Ç in DM • AÉqÉÇ • • • •
xÉÉqÉkÉÉiÉÑ qÉÉÇxÉkÉÉiuÉÎalÉ qÉåSÉåkÉÉiuÉÎalÉ DIABETIC KETOSIS 63
•
zÉUÏUaÉÑhÉÉ:
• qÉsÉpÉÔiÉÉ:
- zÉUÏUxrÉÉoÉÉkÉMüU:
• mÉëxÉÉSpÉÔiÉÉ
- mÉëxÉÉSlÉÇ
• zÉUÏUaÉÑhÉÉ: mÉÑlÉ̲ïÌuÉkÉÉ: xÉlaÉëWåûhÉ - qÉsÉpÉÔiÉÉ: mÉëxÉÉSpÉÔiÉÉ¶É . iÉ§É qÉsÉpÉÔiÉÉxiÉå rÉå zÉUÏxrÉÉoÉÉkÉMüUÉ: xrÉÑ: iɱjÉÉ- zÉUÏUÎcNûSìåwÉÔmÉSåWûÉ: mÉ×jÉaeÉlqÉÉlÉÉå oÉÌWûqÉÑïZÉÉ: mÉËUmÉYuÉÉ¶É kÉÉiÉuÉ: mÉëMÑüÌmÉiÉÉ¶É uÉÉiÉÌmɨÉzsÉåwqÉÉhÉ: rÉå cÉÉlrÉåÅÌmÉ MåüÍcÉcNûUÏUå ÌiɸliÉÉå pÉÉuÉÉ: zÉUÏUxrÉÉåmÉbÉÉiÉÉrÉÉåmÉmɱliÉå xÉuÉÉïÇxiÉÉlqÉsÉå xÉÇcɤqÉWåû Charakasamhita saareeram6/17
64
qÉsÉÇ xÉÉqÉlrÉ qÉsÉÇ • Normal cellular level metabolic wastage
• ÌuÉzÉåwÉ qÉsÉÇ • Undesirable ( pathological? ) cellular level wastage.
65
AÉqÉÇ MåüÍcÉiÉç iÉÑ qÉsÉxÉlcÉrÉqÉç Madhavanidanam 25/5
Eg:Uric acid /Urea in CKD
AÌuÉmÉYuÉqÉxÉÇrÉÑ£Çü SÒaÉïlkÉÇ oÉWÒûÌmÉÎcNûsÉqÉç xÉSlÉÇ xÉuÉïaÉɧÉÉhÉÉÇ AÉqÉ: CirÉÍpÉkÉÏrÉiÉå Madhavanidanam 25/5
66
AÉqÉÇ ÌMül¨ÉÑ kÉÉiuÉÎalÉÍpÉUmÉÉMüÉiÉç AÉqÉ: CirÉÑcrÉiÉå Su Su 15-32
FwqÉhÉÉåÅsmÉoÉsÉiuÉålÉ kÉÉiÉÑqÉɱqÉmÉÉÍcÉiÉqÉç SÒ¹qÉÉqÉÉzÉrÉaÉiÉÇ UxÉqÉÉqÉÇ mÉëcɤÉiÉå A H Su 13/25
67
AÉqÉÇ as TOXIN
– AlrÉå SÉåwÉåprÉ LuÉÉÌiÉSÒ¹åprÉÉåÅlrÉÉålrÉqÉÔcNïûlÉÉiÉç – MüÉåSìuÉåprÉÉå ÌuÉwÉxrÉåuÉ uÉSlirÉÉqÉxrÉ xÉqpÉuÉqÉç A H Su 13/26
68
CONCEPT OF
urÉÉÍkɤÉqɨuÉqÉç
ç
• urÉÉÍkɤÉqɨuÉqÉç against urÉÉÍkÉ • urÉÉÍkɤÉqɨuÉqÉç against kÉÉiÉÑuÉæwÉqrÉqÉ to preserve and promote kÉÉiÉÑxÉÉqrÉÇ
69
urÉÉÍkɤÉqɨuÉqÉç
Comprehensive concept IMMUNITY interwoven with
NUTRITION & DHATU PARINAMA
70
How to go about it ? Conditional ? ÍcÉÌMüixÉÉrÉÉqÉç ÌWû mÉëSÉlÉqÉuÉxjÉÉlÉÑÌuÉkÉÉlÉqÉç Rasavaiseshikam
71
Only option ? zÉÉÎliÉUÉqÉÌuÉMüÉUÉhÉÉÇ pÉuÉÌiÉiuÉÅmÉiÉmÉïhÉÉiÉç A H Su 8/20
CAUTION -
• AÎalÉoÉsÉqÉç • urÉÉkrÉuÉxjÉÉ oÉsÉxÉÇU¤ÉhÉqÉç
72
It must be…
• • • •
AÉqÉmÉÉcÉlÉÇ AÎalÉuÉkÉïlÉÇ xÉÇzÉÉåkÉlÉÇ UxÉÉrÉlÉÇ
73
xÉqrÉMçü zÉÉåkÉlÉqÉç oÉÑήmÉëxÉÉSÇ oÉsÉÍqÉÎlSìrÉÉhÉÉÇ kÉÉiÉÑÎxjÉUiuÉÇ euÉsÉlÉxrÉ SÏÎmiÉqÉç ÍcÉUÉŠ mÉÉMÇü uÉrÉxÉ: MüUÉåÌiÉ xÉÇzÉÉåkÉlÉÇ xÉqrÉaÉÑmÉÉxrÉqÉÉlÉqÉç. A H Su 18/59
74
CCRAS study on Samsodhanam Sir sundar lal hospital & BHU 1993 •
Vamanam – Total Mucopolysaccharides content.
•
Virechanam – Total sercobilinogen content
•
Cleansing effect-Sroto visodhanam – D-xylose excretion rate
75
Intestinal profile-before & after Samsodhanam (CCRAS/ BHU.1993) 50 45 40 35 30 25 20 15 10 5 0
Intestinal Flora profile Enzymatic activity D xylose excretion rate
Before
After 76
AqÉÉrÉlÉÇ v/s UxÉÉrÉlÉÇ
77
Rasayanam for healthful longevity mÉzrÉåqÉ zÉUS:zÉiÉqÉç eÉÏuÉåqÉ zÉUS:zÉiÉqÉç Atharva veda
mÉÔuÉåï uÉrÉÍxÉ qÉkrÉå uÉÉ AH/SU
78
UxÉÉrÉlÉÇ sÉÉpÉÉåmÉÉrÉÉå ÌWû zÉxiÉÉlÉÉÇ UxÉÉSÏlÉÉÇ UxÉÉrÉlÉqÉç Charakasamhita chikitsa 1.
rÉ‹UÉurÉÉÍkÉÌuÉkuÉÇÍxÉ pÉåwÉeÉÇ iÉiÉç UxÉÉrÉlÉÇ
79
UxÉÉrÉlÉÇ SÏbÉïqÉÉrÉÑ:xqÉ×ÌiÉ qÉåkrÉqÉÉUÉåarÉÇ iÉÂhÉÇ uÉrÉ: mÉëpÉÉuÉhÉïxuÉÉåUÉæSÉrÉïÇ SåWåûÎlSìrÉoÉsÉÇ mÉUqÉç uÉÉÎYxÉ먂 mÉëhÉÌiÉÇ MüÉÎliÉÇ sÉpÉiÉå cÉ UxÉÉrÉlÉÉiÉç A H 39/1 Healthful longevity Maintenance of positive health Improvement of mental faculties of intelligence( dhi ),perseverance(dhriti ), & memory( smriti). Resistance against disease. 80
Vayasthapana gana (charaka samhita)
Guloochi Hareetaki Amalaki Rasna Aparajitha
Jeevanthi Satavari Mandookaparni Saliparni Punarnava 81
Rasayana in Susruta – uÉrÉxjÉÉmÉlÉÇ – AÉrÉÑoÉïsÉMüUÇ – qÉåkÉÉoÉsÉMüUÇ – UÉåaÉÉmÉWûUhÉÇ
82
Drug selection ???? Chithraka Tippali Ardrakam Hareetaki ……etc
83
UxÉÉrÉlÉÇ
v/s
Geriatrics/Gerontology
84
Gerontology
• the study of the social,psychological and biological aspects of aging • it is distinguished from geriatrics, which is the branch of medicine that studies the diseases of the elderly.
85
New insights in Antioxidant research !!!!
86
Cambridge Heart antioxidant study (C HAOS Study) Cambridge Heart foundation.UK.
2002 patients
Poor ejection fraction ( E F )below 30 % were treated with heavy Vit E &Vit C for 3 years-improved to 57 %. 87
Invitro studies on antioxidants in THRIPHALA
88
Antioxidant potential of ksheerapaka over srita kashayam JSS college of pharmacy,Ootacamund.
Milk decoction Coriander Ginger Pepper. Tulasi. Turmeric.
89
90
Antihyperglycemic&Antioxidant potential of Nishakathakadi choornam C H Jithendra &P Muraleedharan Dept of pharmacology C L Baidmetha college of pharmacy,Chennai,TN
1 gm/1 kg body weight (after 4 hrs) equals to the drug Glibenclamide
91
Evaluation of antioxidant potential of kaempferia rotunda (Changazhineer kizhangu) Himalayan pharmacy institute,Rangpo,Sikkim Indian journal of pharmaceutical sciences,june 2008
Crotepoxide - useful for the inhibition of tumors
92
Red Cabbage (Brassica oleracea) prevents Diabetic Nephropathy
. Hazem A. H. Kataya and AlaaEldin A. Hamza
(Department of Biology, Faculty of Science, UAE University, Al-Ain, PO Box: 17555, UAE)
93
Cold-Storage Affects Antioxidant Properties of Apples
Andrea Tarozzi, Alessandra Marchesi, Giorgio Cantelli-Forti and Patrizia Hrelia2 (Department of Pharmacology, University of Bologna, 40126 Bologna, Italy .May 2004) 94
Protective activity of glycyrrhiza glabra (Irrattimadhuram) on Carbon tetrachloride induced peroxidative damage School of Biosciences MG university,kottayam FEB,2004 Glabridin, Hisplaglabridin A,& B.
A potential antioxidant and attenuates the hepatotoxicity of CCl4
95
Green tea (Camellia sinensis)
96
What is Our Choice ?
97
Whether Nutraceuticals help ?
98
Importance of
* xÉSèuÉëרÉÇ
* ÌSlÉcÉrÉÉï * GiÉÑcÉrÉÉï
99
Updates.. AqÉ×iÉqÉåWûÉËU cÉÔhÉïqÉç AqÉ×iÉÉkÉȨ́ÉUɧÉÏhÉÉÇ xÉqÉÇ qÉåWûÉËUqÉÔsÉMüqÉç • • • •
Tinospora cordifolia Phyllanthus emblica Curcuma longa Salacia reticulata 100
Updates.. Spl case of clinical interest UK citizen, 50/male, C/o Pain knees. Not DM/HTN/Dyslipidemia
Moderate OA -Both knees Rx Swarna bhasma capsule (1) -3 months at bedtime followed by one glass of diluted milk.
101
Updates..
102
Conclusion
103
Submitted for discussion
Thank you drsudheer@mbadi
104
