INTRODUCTION:

A large population is suffering from Cancer and Diabetes in all over India and World¹.Today, non communicable diseases mainly cardiovascular diseases, cancers, diabetes and chronic respiratory diseases represent a leading threat to human health and development. These four diseases are the world's biggest killers, causing an estimated 35 million deaths each year - 60% of all deaths globally - with 80% in low- and middle income countries. WHO projects that, globally, NCD deaths will increase by 17% over the next ten years². The greatest increase will be seen in the African region (27%) and the Eastern Mediterranean region (25%)

The highest absolute number of deaths will occur in the Western Pacific and South-East Asia regions.Indian Government spent about $5,451 on the cancer treatment in year 2012 and is planning to spend about $5,446 on the cancer treatment in year 2013 and about $1,079 on the Diabetes treatment in year 2012 and while $1,078 on the diabetes treatment programme in upcoming year 2013.

Antioxidants are substances that neutralize free radical or their actions, which protect the body against free radicals–unstable molecules that cause damage to cell membranes, lipids, proteins, and DNA³. They are substances capable of counteract in the damaging effects of oxidation in body tissues. Antioxidants are divided into two classes based on mechanism of action: (1) chain-breaking antioxidants, such as Vitamin E and beta-carotene,‘‘break the chain’’ of free radical formation by donating an electron to stabilize an existing free radical; and (2) preventive antioxidants are enzymes that scavenge initiating radicals before they start an oxidation chain⁴.Superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase, thioredox in, thiols and disulfide bonding are buffering systems in every cell. Tocopherol (vitamin E) is an essential nutrient which functions as a chain-breaking antioxidant which prevents the propagation of free radical reactions in all cell membranes in the human body⁵. Ascorbic acid (vitamin C) is also part of the normal protecting mechanism⁶. Other non-enzymatic antioxidants include carotenoids, flavonoids and related polyphenols, lipoic acid, glutathione etc⁷.Lipoic acid is capable of quenching free radicals in both lipid and aqueous domains thus called as “Universal Antioxidant”.⁸

Levels of Antioxidant Action:

Antioxidants act at the levels of prevention, interception and repair. Preventive antioxidants attempt to stop the formation of Reactive Oxygen Species⁹.These include superoxide dismutase that catalyses the dismutation of superoxide to H2O2and breaks it down to water. Interception of free radicals is mainly by radical scavenging.The effectors include various antioxidants like vitamins C and E, glutathione, other thiol compounds, carotenoids, flavonoids, etc. At the repair and reconstitution level, mainly repair enzymes are involved.

Concept of Oxidative Stress¹⁰:-

Free radicals are produced when the body breaks down foods for use or storage. They are also produced when the body is exposed to tobacco smoke, radiation, and environmental contaminants. Free radicals can cause damage, known as "oxidative stress," which is thought to play a role in the development of many diseases, including Alzheimer's disease, cancer, eye disease, heart disease, Parkinson's disease, and rheumatoid arthritis.

Endogenous Antioxidants¹¹ :-

Under ideal circumstances, the skin uses a series of endogenous enzymatic and non enzymatic oxidants to protect itself from free-radical damage. Enzymatic antioxidants include glutathione peroxidase, superoxide dismutase and catalyse; non enzymatic antioxidants include vitamin C, glutathione, vitamin E, coenzyme Q10 (ubiquinone-10), and alpha lipoic acid. It is known that exposure to UV light depletes these naturally occurring antioxidants as does chronologic aging.

Exogenous / Topical Antioxidants¹²:-

Supplementing the skin with additional antioxidants has been demonstrated to give additional protection from sun-induced damage, slow down skin aging, reduce inflammation and ultimately improve skin appearance. Cosmetic treatments of the latest generation, developed against wrinkles, rely on antioxidant properties of ingredients such as Super Oxide Dismutase, Vitamins C,E and alpha lipoic acid, all and various plant extracts, such as acai berry, white and green tea, rosemary, and turmeric.. Topical antioxidants are now recognized as an integral part of a comprehensive sun protection program and as a valuable addition to any anti-aging skin care regimen¹³. As such, topical antioxidants have far-reaching benefits for protecting and improving UV-damaged and aging skin.

Significance of antioxidants in relation to disease¹⁴:-

Antioxidants may prevent and/or improve different diseased states, Zinc is an essential trace element, being a co-factor for about 200 human enzymes, including the cytoplasmic antioxidant Cu-Zn SOD, isoenzyme of SOD mainly present in cytosol¹⁵. Selenium is also an essential trace element and a co-factor for glutathione peroxidase¹⁶. Vitamin E and tocotrienols (such as those from palm oil) are efficient lipid soluble antioxidants that function as a ‘chainbreaker’ during lipid peroxidation in cell membranes and various lipid particles¹⁷. Vitamin E is considered as the ‘standard antioxidant’ to which other compounds with antioxidant activities are compared, especially in terms of its biological activity and clinical relevance.Vitamin C (ascorbic acid) is a water-soluble free radical scavenger. The daily recommended dietary allowance is 60 mg. Apart from these carotenoids such as beta-carotene, lycopene, lutein and other carotenoids function as important antioxidants¹⁸.

Classification of anti-oxidants¹⁹:-

It is of two types;

1. Based on solubility:

(a) Hydrophilic antioxidants:- They are soluble in water. Water soluble antioxidants react with oxidants react with oxidants in the cell cytoplasm and blood plasma.

(b) Hydrophobic antioxidants:- They are soluble in membranes from lipid peroxidation.

2. Based on line of defence:

(a) First line defence (preventive antioxidant)²⁰:-

These are enzymes like superoxide dismutase (SOD),catalyse (CAT), glutathione peroxidase (GTX),glutathione reductase and some minerals like Se, Mn,Cuetc.SOD mainly acts by quenching of superoxide (O2),catalyse by catalyzing the decomposition of hydrogen peroxide (H2O2) to water and oxygen.

(b) Second line defence (Radical scavenging antioxidant)²¹:-

These are glutathione, Vit C, uric acid, albumin, bilirubin, vit E, carotenoids, flavonoid etc. β carotene is an excellent scavenger of singlet oxygen.Vit C interacts directly with radicals like O2,OH.GSH is a good scavenger of many free radicals like O2,OH and various lipid hydroperoxides and may help to detoxify many inhaled oxidizing air pollutants like ozone.

(c) Third line defence (Repair and de-novo enzymes)²²:-

These are a complex group of enzymes for repair of damaged DNA, protein, oxidized lipids and peroxides and also to stop chain propagation of peroxyl lipid radical. These enzymes repair the damage to biomolecules and reconstitute the damaged cell membrane. some common herbal antioxidants found used in beverages, food, and cosmetics, herbal antioxidants have quickly become very popular among consumers for their strong rejuvenating abilities²³:

Ø Green Tea Extract is one of the most common herbal antioxidants, it has been beneficial in weight loss and to lower cholesterol and blood pressure levels. It has also been shown to stimulate the immune system and help in the fight against numerous diseases²⁴.

Ø Noni is extracted from a Southeast Asian fruit of the same name. Noni has been a popular juice supplement drink and has been shown to lower blood pressure and fight cancer²⁵.

Ø Resveratrol is a popular antioxidant supplement extracted from Japanese knotweed. It has been shown to have anti-bacterial, anti-inflammatory, anti-cancer, and anti-cholesterol benefits²⁶.

Ø White Tea Prevents the inflammation of skin as well as it helps in skin lighteining and preventing wrinkles on skin²⁷.

Ø Types of the antioxidants based on their supplementation source are as follows;

Primary or natural antioxidants:-

They are the chain breaking antioxidants which react with lipid radicals and convert them into more stable products. Antioxidants of this group are mainly phenolic in structures and include²⁸:

a)Antioxidants minerals:-These are co factor of antioxidants enzymes. Their absence will definitely affect metabolism of many macromolecules such as carbohydrates. Examples include selenium, copper, iron, zinc and manganese²⁹.

b) Antioxidants vitamins:- It is needed for most body metabolic functions. They include-vitamin C, vitamin E, vitamin B³⁰.

c) Phytochemicals -These are phenolic compounds that are neither vitamins nor minerals³¹.

Flavonoids are phenolic compounds that give vegetables fruits, grains, seeds leaves, flowers and bark their colours³². Catechins are the most active antioxidants in green and black tea and sesamol³³.

Carotenoids are fat soluble colour in fruits and vegetables³⁴.

Beta carotene which is rich in carrot and converted to vitamin A when the body lacks enough of the vitamin³⁵.

Lycopene have high in tomatoes³⁶ and

zeaxantinis high in spinach and other dark greens³⁷.

Herbal Antioxidants:-

These are real antioxidant nutrients, Eleuthro Root is an adaptogen, which means that it helps the body deal with various forms of stress and has constituents with antioxidant effects and can improve peripheral circulation³⁸.Ginger Root functions as an antioxidant and has an antiglycation effect on human body.
Ginkgo Leaf( Ginkgo Biloba linn.) contains about 40 different bioflavonoids (including proanthocyanidins and quercetin) that “act as free radical scavengers”. Cerebral insufficiency many cause anxiety and stress, memory, concentration, mood impairment, andhearingdisorders³⁹.
Milk Thistle Seed( Silybum Marianum ) contains silymarin, which is a polyphenolic antioxidant flavonoid it has been studied for its role in supporting a health liver⁴⁰.
Rosemary Leaf( Rosemarinus Officinalis Linn.) contains antioxidants and can increase detoxification of carcinogens in certain instances⁴¹.

Schisandra Fruit( Schisandra Chinensis) has pronounced liver protective effects and strong antioxidant activity⁴².

Turmeric Root( Curcuma Longa)contains curcuminoids which have antioxidant and cancer-inhibiting properties⁴³.

Diseases due to creation of free radicals in body⁴⁴:-

Free radicals are molecules or molecular fragments containing one or more unpaired electrons in its outermost orbital. The unpaired electron in the outermost orbit of free radical is unstable and highly reactive. They are represented by a superscript dot (R^.). Products of partial reduction of oxygen are highly reactive like oxygen free radicals and other oxidizing agents like hydrogen peroxide and are called REACTIVE OXYGEN SPECIES (ROS).

Cancer and oxidative stress⁴⁵:-

The development of cancer in humans is a complex process including cellular and molecular changes mediated by diverse endogenous and exogenous stimuli Cancer initiation and promotion are associated with chromosomal defects and oncogene activation induced by free radicals. A common form of damage is the formation of hydroxyled bases of DNA, which are considered an important event in chemical carcinogenesis.

Cardiovascular disease and oxidative stress⁴⁶:-

Cardiovascular disease (CVD) is of multifactorial etiology associated with a variety of risk factors for its development including hypercholesterolaemia, hypertension ,smoking, diabetes, poor diet, stress and physical inactivity amongst others. In vivo and ex vivo studies have provided precious evidence supporting the role of oxidative stress in a number of CVDs such as atherosclerosis, ischemia, hypertension, cardiomyopathy, cardiac hypertrophy etc.

Neurological disease and oxidative stress⁴⁷:-

Oxidative stress has been investigated in neurological diseases including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis(ALS), memory loss, depression.The production of ß-amyloid, a toxic peptide often found present in Alzheimer’s is due to oxidative stress and plays an important role in the neurodegenerative disorder.

Pulmonary disease and oxidative stress⁴⁸:-

There is now substantial evidence that inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by systemic and local chronic inflammation and oxidative stress.

Rheumatoid arthritis and oxidative stress⁴⁹:-

Rheumatoid arthritis is an autoimmune disease characterized by chronic inflammation of the joints and tissue around the joints with infiltration of macrophages and activated T cells . The pathogenesis of this disease is due to the generation of ROS and RNS at the site of inflammation.

Nephropathy and oxidative stress⁵⁰:-

Oxidative stress plays a role in a variety of renal diseases such as glomerulo nephritis and tubule interstitial nephritis, chronic renal failure, proteinuria, uremia.The nephrotoxicity of certain drugs such as cyclosporine, tacrolimus (FK506), gentamycin, bleomycin, vinblastine is mainly due to oxidative stress via lipid peroxidation.

Ocular disease and oxidative stress⁵¹:-

Under the action of free radicals, the crystalline proteins in the lens can cross-link and aggregate, leading to the formation of cataracts . In the retina, long-term exposure to radiation can inhibit mitosis in the retinal pigment epithelium choroids, damage the photoreceptor outer segments and has been associated with lipid peroxidation.

Fetus and oxidative stress⁵²:-

Some reports indicate that blood levels of lipid peroxidation products (F2-isoprostanes,MDA) are elevated in pre-eclamptic pregnancy and intra-uterine growth retardation and it has been suggested that ROS/RNS play a role in the etiology of these diseases.

Peridontal Therapy⁵³:-

Low levels of vitamins A and C, carotene, and b-crytoxanthin also increased the risk of gum disease significantly. Low levels of most antioxidants are a risk factor for periodontal disease and infection. Free radicals are released as a result of bacteria clearance and killing. Periodontal tissue depends on natural antioxidants to overcome this oxidative stress and maintain homeostasis. When antioxidants are depleted, the ability of gum tissue to overcome oxidative stress, maintain normal tissue and control the bacterial damage appears to be compromised.

Mechanism of action of Antioxidant⁵⁴:-

Two principle mechanisms of action have been proposed for antioxidants. The first is a chain-breaking mechanism by which the primary antioxidants donate electrons to the free radicals present in the system, example lipid radicals. The second mechanism involves removal of ROS (reactive oxygen species) and RNS (reactive nitrogen species) initiator by quenching chain initiator catalyst. Chain reactions of free radicals

Initiation stage

(1) RH R˙+ H˙

(2) R˙ R˙ + O2 ROO˙

(3) 2ROOH ROO˙ + RO˙ + H2O

Propagation stage

(1) R˙ + O2 ROO˙

(2) ROO˙ + RH ROOH + R˙

(3) RO˙ + RH ROH + R˙

Termination stage

(1) R˙ + R˙ R – R

(2) R˙ + ROO˙ ROOR

(3) ROO˙ + ROO˙ ROOR + O2

(4) Antioxidants + O2 oxidized antioxidants

Mechanism of Antioxidants that Prevent Cancer and Diabetes⁵⁵:-

Cancer Treatment:-

While all antioxidants are capable of detoxifying free radicals, those that possess strong nucleophilic properties can bind and in activate the electrophilic intermediates of antineoplastic agents that act via nucleophilic substitution reactions i.e.platinum-coordination complexes and most alkylating agents. Competition between nucleophilic antioxidants and the nucleophilic cellular targets of these anticancer agents can reduce the efficacy of the therapy.

Diabetes treatment⁵⁶:-

In persons with NIDDM, increased plasma ROS generation and a marked reduction in antioxidant defenses result in oxidative stress, which in turn can lead to many of the deleterious effects of NIDDM. Exogenous antioxidants can compensate for the lower plasma antioxidant levels often observed in NIDDM and in pre-diabetic individuals, whether their diabetes is primarily genetic in origin or due to obesity and a sedentary lifestyle. In studies of humans and rodents, dietary supplementation with antioxidants is associated with decreased risk of NIDDM and induces changes that could be beneficial in reducing insulin resistance and protecting vascular endothelium.

Atherosclerosis treatment:-⁵⁷

Prospective studies of non-diabetic individuals provide evidence that vitamin E supplementation is associated with a protective effect against coronary heart disease Several studies indicate that the decline in insulin-mediated glucose uptake observed in NIDDM is due to oxidative stress, which in turn is associated with reduced glucose transporter (GLUT4) exposure and/or impairment of insulin signaling. Lipoic acid was found to increase glucose transport in muscle cells in culture by stimulating translocation of GLUT4 from internal pools to the plasma membrane integrity. Taurine and coenzyme Q₁₀ are endogenous antioxidants that can also be obtained from the diet.

APPLICATIONS OF ANTIOXIDANTS:

1) Lanthanides as anti-cancer agents⁵⁸:-

However much attention has focused on designing new coordination compound with improved pharmacological properties and a broader range of antitumor activity. Strategies for developing new anticancer agents include the incorporation of carrier groups that can target tumor cells with high specificity.

2) Lycopene as a potential anti cancer agent⁵⁹:-

Epidemiology studies have provided evidence that high consumption of tomatoes effectively lowers the risk of reactive oxygen species (ROS)-mediated diseases such as cardiovascular diseases and cancer In addition to its antioxidants properties, lycopene shows an array of biological effects including cardio protective, anti inflammatory, anti-mutagenic and anti-carcinogenic activities.

3) Selenium derivatives as cancer preventive agents⁶⁰:-

Consequently, selenium supplementation has moved from the realm of correcting nutritional deficiencies to one of pharmacological intervention, especially in the clinical domain of cancer chemoprevention and in the control of heart failure.

4) Lipoic acid, the antioxidant’s antioxidant⁶¹:-

Lipoic acid protects against diseases of aging, this offer powerful antioxidant protection against three common afflictions (two of them potentially disastrous) association with the aging stroke, heart attack and cataracts. It does it by suppressing the action of free radicals in the cells of the brain, heart and eyes. Lipoid acid has an unusual relationship with four other important antioxidants: glutathione, coenzymeQ10, vitamin C and vitamin E.

Table No:-1 List of some typical Natural Drugs along with it’s Pharmacognostic Profile

Common Name	Biological Source	Chemical Constituents	Action	Uses
Turmeric	Curcuma domestica (Zingiberaceae)	Curcumin, Camphene, Eugenol	Antiseptic	Blood purifier, Antimalarial, Antifungal, Anti infertility agent.
Akashbel	Cuscutareflexa (Convulvulaceae)	Flavonoids, Burgerin, Dulcitoland Coumarins	Inhibits parasites	Antifertilityagent,Expectorant,Diuretic,Carminative,Anthelmentic
Carrot	Daucuscarrotalinn. (Apiaceae)	Carotenes, Carotenoids, Flavonoids, Quaternary bases.	It reduces pain in cancerous ulcers	Bronchitis, Piles, Aphrodisiac, Jaundice, Leprosy, Tumour.
Karela	Momordica Charantia Linn. (Cucurbitaceae)	Stearic acid, Terpenes, Glycosides	It acts in cancer and diabetes	Laxative,Antipyretic,Anthelmentic,Antidiabetic,Aphrodisiac,Carminative,in Rheumatism.
Bavchi	Psoralea corylifolia Linn.(Fabaceae)	Fixed oil ,Resin, Bakuchiol (monoterpene phenol)	Good for heart troubles	Leukoderma,Scabies,Oxidative stress,
ChirayiaChirella	Swertia chirayina. (Gentianaceae)	Xanthose, Mangiferin, Sweratin, Chiratin, Argirine.	Action is seen in hypoglycemia	Febrifuge,Anthelmentic,Antimalarial, Laxative.
Ashwa gandha	Withania somnifera (Solanaceae)	Steroidal Lactone, Withanolides, Witharine, Glycone.	Cardioprotective, hepatoprotective,cognitive enhancer	Analgesic, Hepatoprotective, Increases immunity.
Alfaalfa	Medigosativa (Euterpeoleracea)	Proteins,calcium,minerals,vitamins B,C,D,E,K	Causes reduced fertility in sheeps	Disorders of digestive tract and kidneys
Borage seed oil	Boragoofficinalis (Boraginaceae)	Minerals, potassium, calcium and nitrates.	Inflammatory swelling	Diuretic, demulcent, emollient
Bugle weed	Lycopus virginicus	Peculiar bitter principle, tannins, volatile oil,	Mildly narcotic	In cough and bleeding from lungs.
Catauba	Erythroxylumcatauba	alkaloids, tannins, aromatic oils and fatty resins, phytosterols, cyclolignans, sequiterpenes and flavonoids.	anti-HIV activity, increases libido.	Aphrodisiac, alzheimer, dementia.
Comfrey	Symphytum officinale (Boraginaceae)	Mucilage, 0.6 to 0.8 per cent. ofAllantoin and a little tannin,starch.	for intestinal troubles, emollient action.	Demulcent, mildly astringent and expectorant.
Cranberry	Vacciniummacrocarpon (Caprifoliaceae)	bitterglucosideViburnine, it also contains tannin, resin and valerianic acid.	all nervous complaints and debility.	convulsions, fits and lockjaw, palpitation, heart disease and rheumatism.
Ginkgo biloba	Ginkgo bilobalinn	Ginkgolides A, B, C, J, M, Bilobalide, Flavonol, glycosides,, including quercitin, kaempferol, biflavones	Platelet Activating Factor Inhibition.	antioxidant, cardiovascular tonic, Antihypoxic.
Oolong Tea	Camellasinensis	Amino, and l-theanine, caffeine, catechin, polyphenols, epigallocatechingallate oxalates, fluoride, tannin.	World's Most Powerful Fat Burner.	Heart disease, cancer
Oregon Grape root	Mahoniaaquifolium	Berberin, oxycanthin.	In impure blood-conditions.	Psoriasis, syphilis, dyspepsia.
Uncariatomentosa Dc	Uncariasurinamensis (Rubiaceae)	Allosopteropodine, Allopteropodine, isomitraphylline, isopteropodine, hirsuteine.	Boostimmune system, antimutagenic(cellular protector)	Crohn's disease, arthritis, rheumatism, diabetes.
Gale sweet	Myrica gale (linn)	poisonous volatile oil.	Emmenagoge	Abortifacient.
Prunes	Prunusdomestica (linn)	sugar, gum, albumen, malic acid, pectin, vegetable fibre, etc.	Nourishing diet	mildly laxative.

5)Significance of antioxidants in red cells⁶²:-

Erythrocytes containing abnormal haemoglobin with high affinity for red cell. The subjects have shown normal levels of reduced glutathione, increased superoxide dismutase and glutathione peroxidase activities and low catalyse activity with increased antioxidant supplementation.

6) Antioxidants therapy in acute central nervous systeminjury⁶³:-

Free radicals are highly reactive molecules generated predominantly during cellular respiration and normal metabolism imbalance between cellular production of free radicals and ability of cells to defend against them is referred to as oxidative stress. Therefore, treatment with antioxidants may theoretically act as tissue damage and improve both the survival and neurological outcome.

Different Sources of Natural Antioxidants:-

Antioxidants are Phytogeographically distributed in nature. Some common Phytomaterials and it’s biological source are given in table no1. Many marketed preparations of the following plants along with it’s extracts are available in the Indian markets at the cost affordable rates, shown in table no.2.

Table No.2:- Antioxidant products in Market with their Brand/Company names.

NAME OF THE PRODUCT/ BRAND	NAME OF COMPANY
Antioxidant ZDDP	Ganesh Benzoplast Limited, Mumbai
Mangostin	Triveni Aromatics and Perfumes Pvt.Ltd,Vapi, Gujarat
Aminic Antioxidants	KK India Petroleum Specialists,Pvt.Ltd, Mumbai
Natural Antioxidants	Biobaxy Technologies India, Mumbai
Co-enzyme Q10-30mg Softgel Capsule	Xena Bio Herbals,Pvt.Ltd,Hyderabad
Nutramin Beauty care Tablets	Aurochem Laboratories, Pvt.Ltd, Mumbai
Ayurvedic Antioxidant Medicine	Streamline Pharma,Pvt.Ltd, Ludhiana
Renugen 10+10 Capsules	VHB LifescienceLtd,Mumbai
Natural Antioxidant for Neuropathy	Medisys Biotech Pvt.Ltd, Panchkula
Hilton Tablets	Hilton Health care, Ahemadabad
Antioxidant Metroforce Capsules	Metrix Healthcare Pvt.Ltd, Ahemadabad
Ashwo Tablets	Dhanalaxmi& Co. (ayurvedic world), Madurai
Meconian Tablets	CianHealthcare,Pvt.Ltd, Pune
Antioxidants for Plastics	AdekaIndia,Pvt.Ltd, Mumbai
zNutrilite Coenzyme Q-10	Shree Balaji Pvt, Mumbai
Protosun Capsules	SunproPharma, Gurgaon
kopexil	Kumar Organic Products Ltd, Bengaluru

CONCLUSION:

The implication of oxidative stress in the etiology of several chronic and degenerative diseases suggests that antioxidant therapy represents a promising avenue for treatment. In the future, a therapeutic strategy to increase the antioxidant capacity of cells may be used to fortify the long term effective treatment. Peoples should try to consume as many green leafy vegetables as possible, things such as spinach and collard greens. They should increase the intake of fruits and yellow and vegetables. Avoid rancid and trans-fatty acids, these will always lead to increased lipid peroxidation, decrease antioxidant concentrations, and tax already loaded lipid enzymatic machinery. Older patients should supplement their diet with a broad multivitamin and mineral product that gives them adequate levels of all the B vitamins, magnesium, and the trace minerals. Patients with active oxidative damage should take immediate measures to increase the intake of as many of the ingredients reduce exposure to direct sunlight with the use of alternatives. Our survival on this planet is due to air, water, food, clothes; shelter. Food is composed of vegetative part of crop plants which provides not only food and minerals but also secondary metabolites and natural antioxidants. Daily consumption of food and dietary supplements rich of antioxidants will prevent creation of disease and disorders, better than cure needed to maintain and support optimal health and protection from free radicals. Antioxidants are believed to help address the effects of aging, support healthy brain tissue, maintain capillary integrity, restore collagen strength, support health skin, and maintain a healthy cardiovascular system.

REFERENCES:

1) International project on Innovative nuclear reactors and fuel cycles- Action plan for 2012-2013.

2) The Growing Danger of Non-Communicable Diseases: Acting Now to Reverse Course, sept2011.

3), Mitchell Kanter, Free Radicals, Exercise and antioxidant supplementation the Quaker oats company, 617 W main street, Barrington, Illinosis, 60010 USA, proceedings of the nutrition society(1998),57, 9-13.

4) Kenneth A Conklin, Jonsson, Free Radicals:- The Pros and Cons of Antioxidants; Comprehensive cancer centre, UCLA, Los Angeles, CA 90095-1778. American society for nutritional sciences. J.Nutr.134:3201-3204, 2004.

5) Ye Feng and Xiaochuan Wang, Review article on Antioxidant Therapies for Alzheimer’s Disease, Hindawi publishing corporation Oxidative medicine and cellular longevity vol-2012, article 17 pgs.

6) Gilberto Perez Trueba, Gregorio Martinez Sanchez, Atiliaguiliani. Oxygen Free Radical and Antioxidant Defense Mechanism in Cancer. Frontier in Bioscience 9, 2029-2044, September 1, 2004.

7) G.B. Kavishankar, N. Laxmidevi, S. Mahadeva Murthy, H.S. Prakash, S.R. Niranjana. A review article on Diabetes and Medicinal Plants, Int J Pharm Biomed sci 2011,2(3), 65-80

8) Lien Ai Pham-Huy, Hua He, Chuong Pham-Huy, Review article on Free Radicals, Antioxidants in Disease and Health; Faculty of Pharmacy, University of Paris 5, Paris, France.

9) Marian Valko, DieterLeibfritz, Jan Moncola, Mark T.D. Cronin, Milan Mazura, Joshua Telser, Free radicals and antioxidants in normal physiological functions and human disease, The International Journal of Biochemistry & Cell Biology 39 (2007) 44–84.

10) Rasikh Javaid, Mohd Aslam, Qudsia Nizami, Raheela Javaid, Role of Antioxidant Herbal Drugs in Renal Disorders: An Overview. Vol. 2 / Issue 1 / Jan-Mar, 2012.

11. Anil Mahajan, Vishal R Tandon , A Review on Antioxidants and Rheumatoid Arthritis. J Indian Rheumatol Assoc 2004 : 12 : 139 – 142.

12. RG Shiva Manjunath, Role of Antioxidants as an adjunct in periodontal therapy. India Journal of Academy of Advanced Dental Research, Vol 2; Issue 2: May 2011.

14. Sanjiv A, Rao A, “ Tomatoe Lycophene and its Role in Human health and Chronic diseases.”CMAJ 163: 739-744, 2000.

15. Shindo Y, Witt E, Han D, et al. Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin. J Invest Dermatol 102(1):122-4 (1994 Jan).

16. Vivek Kumar Gupta and Surendra Kumar Sharma, Plants as Natural Antioxidants. Natural product Radiance Vol.5(4) 2006,pp 326-334.

17. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group (The ATBC Study Group). 1994. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J. Med. 330:1029–1035.

18. Clark L.C., B. Dalkin, A. Krongrad, G.F. Combs Jr., B.W. Turnbull, E.H. Slate, R. Witherington, J.H. Herlong, E. Janosko, D. Carpenter, C. Borosso, S. Falk, and J. Rounder. 1998. Decreased incidence of prostate cancer with selenium supplementation: Results of a double-blind cancer prevention trial. Br. J. Urol. 81:730–734.

19. Singh RP, Sharad S, Kapur S. Free radicals and oxidative stress in neurodegenerative diseases: Relevance of Dietary Antioxidants. JIACM, 2004; 5:218-25.

20. Sies, H. et al., Antioxidant Function of Vitamins. Ann NY AcadSci 1992; 669:7-20.

21. Halliwell, B. Free Radicals, Antioxidants, and Human Disease: Curiosity, Cause, or Consequence. Lancet1994; 344:721-724.

22. Ames, B. Forward p. xix-xxv, in Natural Antioxidants in Human Health and Disease, ed. Frei,B. Academic Press: San Diego 1994.

23. Shweta K. Gediya, Rajan B. Mistry, Urvashi K. Patel, M. Blessy and Hitesh N. Jain, Herbal Plants: Used as a cosmetics. J. Nat. Prod. Plant Resour, 2011, 1 (1): 24-32.

24. Prashant L Kole, Hemant R Jadhav, Prasad Thakurdesai, Anantha Naik Naggapa , Cosmetics potential of herbal extracts, Pharmacy group, Birla institute of technology and science, Pilani- 333031, Rajasthan, India.

25 The British Herbal Pharmacopoeia, British Herbal Medicine Association, 1996.

26. Ceres A, The healing power of Herbal teas, Thorsons Publishers, London 1984.

27. Krishnamurthy K.H, Ayurvedic technical studies and herbal cosmetics of ancient india. Vedams Book (Pvt. Ltd), New Delhi 2001.

29. Michael A. Weiner, Ph.D. Herbal Antioxidants in Clinical Practice.The Journal of Orthomolecular Medicine Vol. 9, No.3, 1994.

30 Thomas JA. Oxidative stress, oxidant defense, and dietary constituents. In Modern Nutrition in Health and Disease, 8th ed. Lea & Febiger, Phil.; 1994:501-512.

31 32.33,34,35,36,37. Robert A Jacob. Phd. Diabetes Self Management Article Updated October 2011.

38. Natural Herbal Remedies & Antioxidant Vitamin Wonders On http://www.free-ebooks-canada.com .

39. Lueng AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. Second Edition. New York, NY: Wiley & Sons, 1996.

40. Blumenthal M, et. al. ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin: American Botanical Council, 1998.

41. British Herbal Pharmacopoeia (1996). Fourth Edition.British Herbal Medicine Association Scientific Committee, West Yorks, England.

42, 43.V. Kapoor, A review article on herbal cosmetics for skin and hair care National botanical research institute, Lucknow- 226001, Uttar Pradesh, India.

44. Amit Kunwar and K.I. Priyadarsini, Free radicals, oxidative stress and importance of antioxidants in human health, Radiation and photochemistry Division, Bhaba Atomic Research Centre, Trombay, Mumbai- 400085, India.

45. Das, U.N: A radical approach to cancer. Med SciMonit8, 79-92 (2002).

46. Dr. T Bahorun, MA Soobrattee, V Luximon-Ramma, OI Aruoma. Free Radicals and Antioxidants in Cardiovascular Health and Disease. Internet Journal of Medical Update, Vol. 1, No. 2, Jul-Dec 2006.

47. BayaniUttara, Ajay V. Singh, Paolo Zamboni, and R.T Mahajan. Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options.

48. Hoshino Y, Mishima M. Antioxidants & Redox signaling redox-based therapeutics for lung diseases. Antioxid Redox Signal. 2008;10:701-4.

49. Karatas F, Ozates I, Canatan H, et al. Antioxidant status and lipid peroxidation in patients with rheumatoid arthritis. Indian J Med Res 2003; 118: 178-181.

50. Singh RP, Shukla KP, Panday BL, Singh RG, Usha Singh RH. Recent approach in clinical experimental evaluation of diuretic action of punarnava (Boerhaavia diffusa) with special reference to nephriticsyndrome. Journal of Research and Education in Indian medicines. 1992;11(1):29-36.

51. The Standard – An concise update of important issues concerning natural health ingredients Vol-2, pgno.1, 1999 edited by Thomas. G. Gulliams Ph.D.

52. Ashok Agarwal, Sajal Gupta and Suresh Sikka, The role of free radicals and antioxidants in reproduction, Current Opinion in Obstetrics and Gynecology 2006, 18:325–332.

53. Chapple IL. Role of free radicals and antioxidants in the pathogenesis of the inflammatory periodontal diseases. ClinMolPathol1996;49:247-255.

54. A. A. Hamid, O. O. Aiyelaagbe, L. A. Usman, O. M. Ameenand A. Lawal, African Journal of Pure and Applied Chemistry Vol. 4(8), pp. 142-151, August 2010.

55. Conklin, K. A. (2000) Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects. Nutr. Can. 37: 1–18.

56. Wadkar KA, Magdum CS, Patil SS, Naikwade NS. Antidiabetic potential and Indian medicinal plants. J Herbal Med and Toxicol 2008, 2, 45-50.

57. Simon R. J. Maxwell & Gregory Y. H. Lip, Free radicals and antioxidants in cardiovascular disease, Br J ClinPharmacol1997; 44: 307–317.

58. Irena I Kostova, Lanthanides as anticancer agents, current medicinal chemistry anticancer agents 5(6): 591-602 (2005).

59 P. K. J. P. D. Wanasundara and F. Shahidi, Antioxidants: Science, Technology, and Applications.

60. Nabil S. Kamel, MB, BCh, Julie Gammack, MD, Oscar Cepeda, MD, Joseph H. Flaherty, MD, Antioxidants and hormones as antiaging therapies: Cleveland Clinic Journal Of Medicine Volume 73,No. 12 December 2006, 1049-1058.

61. Dr. Linda Miles L. Ac., D.O.M., Natural Skincare Expert, The Secret to Anti-Aging? Antioxidants. derma e® Natural Bodycare,4485 Runway Street, Simi Valley, CA 93063. 805.582.2710. 800.521.3342, www.dermae.com © 2008.

62. Kanti Bhooshan Pandey, Syed Ibrahim Rizvi, Biomarkers OF Oxidative Stress in Red Blood Cells. Biomed Pap Med Fac UnivPalacky Olomouc Czech Repub. 2011 Jun; 155(2):131–136. DOI 10.5507/bp.2011.027.

63. Chandrashekhar D. Kamat, SunyanaGadal, Molina Mhatre, Kelly S. Williamson, Quentin N. Pye, and Kenneth Hensley, Antioxidants in Central Nervous System Diseases: Preclinical Promise and Translational Challenges, J Alzheimers Dis. 2008 November; 15(3): 473- 493.

Received on 04.02.2013 Accepted on 15.02.2013

Asian J. Pharm. Res. 3(1): Jan.-Mar. 2013; Page 33-39