Dietary Antioxidants and Good Health

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Vishal.R.Tandon

The role of oxidative stress is well recognized now in numerous pathological states, where antioxidants can play very important role. Recent studies provide evidences that low levels of antioxidants are associated with increased risk for many pathological states and that increased intake appears to be protective. However, there are conflicting studies also, that question the rationale for synthetic antioxidant supplementation in these conditions by suggesting detrimental effects to the health. Suicidal oxidative stress produced by some of the antioxidants under certain circumstances remains the major cause of concern, as many antioxidants can act as pro-oxidants in certain conditions.

Moreover, at present there are number of unanswered questions associated with practical application of synthetic antioxidant therapy like appropriate timing of administration, dose & duration of therapy, which still need to be determined. Thus, under the shadow of these concerns, the supplementation of natural dietary antioxidant resources seems to be a safe and effective approach currently. In recent times many dietary factors have been recognized to possess antioxidant action and are useful in many pathological conditions because of their antioxidant actions.1The therapeutic potentials of these antioxidant dietary factors have been reviewed in this review article.

1. Indian antioxidant dietary constituents

Cancer chemoprevention:

The major food items of Indian include rice, wheat, diary products, and abundant fruits and vegetables. Beside these, there are several kinds of herbs and spices as important ingredients, containing many photochemical with medicinal properties, adding taste to Indian cuisine. These vital ingredients used in Indian cooking include turmeric, cloves, ginger, aniseed, mustard, saffron, cardamom and garlic. An impressive body of data exists in support of the concept that Indian food ingredients can be used in preventive strategies aimed at reducing the incidence and mortality of different types of cancers because of their antioxidative, antimutagenic and anticarcinogenic properties2, 3.

In recent years, extensive research has focused on the anticarcinogenic potential of commonly used allium vegetables like garlic, onion, leeks, chives, scallions and their constituents, viz., allylsulfides and flavonoids. Epidemiological studies have shown that higher intake of allium products is associated with reduced risk of several types of cancers. These epidemiological findings are well correlated with laboratory investigations2.Organosulfur compounds present in Allium vegetables, are considered to be responsible for the beneficial effects of these herbs. Several mechanisms have been proposed to explain the cancer-preventive effects of Allium vegetables and related organosulfur compounds. These include inhibition of mutagenesis, modulation of enzyme activities, inhibition of DNA adduct formation, free-radical scavenging, and effects on cell proliferation and tumor growth.4

Similarly, among the spices, saffron (Crocus sativus, L) a member of the large family Iridaceae, has drawn attention because apart from its use as a flavouring agent, pharmacological studies have demonstrated many health promoting properties including radical scavenging, anti- mutagenic and immuno-modulating effects.5 Although there are sufficient evidences from preclinical data that dietary antioxidants can help in prevention of carcinogenesis but their role from clinical data is still unclear. As, many present studies suggest that antioxidant dietary factors based on cereals, pulses, spices, dark green leafy vegetables such as kale and spinach, citrus fruits, crude palm oil, soybean oil, cod liver oil, sprouts, peppers, whole grain, honey, walnuts and black tea can significantly increase the hepatic antioxidant enzymes and their supplementation reduces the risk of cancers effectively and safely6-8. Even in one of the recent expert review on cancer care has suggested that high doses of multiple dietary antioxidants as an adjunct to standard therapy improves tumor response, decrease toxicity as well as reduce the risk of recurrence of original tumor.9

Where as, on the other side a recently published meta-analysis based on seven case control studies and three cohort studies did not reveal increased risk for bladder cancer with diet low in retinol or β-carotene.10 In agreement to this meta-analysis, prospective studies published recently also found no association between dietary vitamin antioxidant supplementation and bladder cancer11 or colorectal cancer risk12.Hence, still larger trials are required to establish clear role of dietary antioxidants in cancer chemoprevention.

Cardiovascular health

Indian antioxidant dietary constituent’s supplementation reduces the risk of coronary heart disease effectively and safely particularly phenotic compounds like flavionoids present in fruits and vegetables. They improve endothelial function and inhibit platelet aggregation in humans, Therefore helpful in maintaining Vascular homeostasis, endothelial function and helpful in conditions like acute coronary syndrome, including Myocardial infarction and unstable angina. Moreover pharmacological synthetic antioxidants and the fact that dietary antioxidants supplementation is effective and safe it is recommended that al good sources of natural antioxidants should be increased of natural antioxidants should be increased in the diet for the prevention and treatment of various cardiovascular conditions. The best reconnected action is to increase the intake of natural dietary antioxidant vitamins by consuming cereals, pulses, nuts, fruits, vegetables CVS health. 13-15

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2. Bilberry16-17: Edible berry anthocyanins possess a broad spectrum of therapeutic properties. Berries are rich in anthocyanins, compounds that provide pigmentation to fruits and serve as natural antioxidants. Anthocyanins repair and protect genomic DNA integrity. Earlier studies have shown that berry anthocyanins are beneficial in reducing age-associated oxidative stress, as well as in improving neuronal and cognitive brain function. Six berry extracts (wild blueberry, bilberry, cranberry, elderberry, raspberry seeds, and strawberry) have been suggested to posses antioxidant efficacy, cytotoxic potential, cellular uptake, and anti-angiogenic (the ability to reduce unwanted growth of blood vessels, which can lead to varicose veins and tumor formation) properties.

It is also one of the Worlds famous herbs recognized for healthy vision. It is presumed that in world war- II, prior to flying in low light areas the pilots of Jet fighters were served Bilberry Jam in the Breakfast. The active principle of Bilberry (anthrocyanidins) is an antioxidant & eye friendly as it helps in clear vision & light adjustment. Cataracts and macular degeneration remain the major cause of blindness and acuity of vision deterioration in the elderly. Both pathologies have been attributed to damage by free radicals. Bilberry's flavonoids are known as potent antioxidants, scavenging free radicals and used for multiple age-related ocular disorders.

3. Garlic: Endothelium-dependent vasodilatation is impaired and predicts the risk of a coronary event in patients with coronary artery disease (CAD). Oxidant stress and increased systemic inflammation may contribute to this endothelial dysfunction. Aged garlic extract (AGE) contains antioxidant compounds that increases nitric oxide production and decreases the output of inflammatory cytokines. Thus, short-term treatment with AGE may improve impaired endothelial function in men with CAD treated with aspirin and a statin 18.

Reactive oxygen species (ROS) has been implicated in the pathogenesis of many diseases including hypertension. Therefore, certain compounds with antioxidative capacity are believed to be protective against such diseases. Some components of garlic are known to possess antioxidative properties. Therefore, dietary supplementation of garlic may be beneficial in reducing blood pressure and oxidative stress in hypertensive individuals19. The use of these organosulfur agents derived from garlic could also protect partially oxidized and glycated LDL or plasma against further oxidative and glycative deterioration, which might benefit patients with diabetic-related vascular diseases.20

4. Green Tea: Exogenous administration of green tea leaf extract and ascorbic acid as natural antioxidants have been shown to protect separately increased lipid peroxidation caused by phenylhydrazine, and the degree of protection is more in case of green tea leaf extract than ascorbic acid. Thereby, suggesting that oxidative damage in vivo due to haemolytic disease may be checked to some extent by using natural antioxidants21.

Even in a randomized, double blinded, and placebo controlled phase IIa chemoprevention trial, green tea polyphenols (GTP) in 124 individuals in daily doses of 500-mg and 1,000-mg for 3 months have been suggested to provides effective chemoprevention by diminishing oxidative DNA damage in high-risk individuals of liver cancer22.

Tea consumption is varying its status from a mere ancient beverage and a lifestyle habit, to a nutrient endowed with possible prospective neurobiological-pharmacological actions beneficial to human health. Accumulating evidence suggests that oxidative stress resulting in reactive oxygen species generation and inflammation play a pivotal role in neurodegenerative diseases. As a consequence, green tea polyphenols are now being considered as therapeutic agents in well controlled epidemiological studies, aimed to alter brain aging processes and to serve as possible neuroprotective agents in progressive neurodegenerative disorders such as Parkinson's and Alzheimer's diseases.23 In addition antidiabetic, skin protection, oral health and cardiovascular properties mediated by its antioxidant constituents have been proposed.

5. Soya Protein (SP) rich diet: SP diet increases eNOS and antioxidant gene expression in the vasculature and other tissues, resulting in reduced oxidative stress and increased NO bioavailability. The improvement in endothelial function, increased gene expression, and reduced blood pressure by soy isoflavones have implications for alternative therapy for postmenopausal women and patients at risk of coronary heart. It long-term supplementation during gestation and adult life results in decreased oxidative stress, improved endothelial function, and reduced blood pressure24.

6. Grapes: that grape seed polyphenols decrease arterial pressure in spontaneously hypertensive rats SHR, probably via an antioxidant mechanism. 25

7. Apple: At individual compound level, epicatechin and procyanidin B2 are the major contributors to the antioxidant activity of apple. Hydroxycinnamic acids may have a significant role in the flesh.26 The high content of phenolic compounds, antioxidant activity, and antiproliferative activity of apple peels indicate that they may impart health benefits when consumed and should be regarded as a valuable source of antioxidants.27

8. Strawberries: Because strawberries are known to contain higher concentrations of phytochemicals and have higher antioxidant capacity among common fruits, their neuroprotective activity has been tested in vitro on PC12 cells treated with H2O2. The strawberry phenolics significantly reduce oxidative stress-induced neurotoxicity. Strawberry show the highest cell protective effects among the samples. The protective effects appear to be due to the higher phenolic contents including anthocyanins, and anthocyanins in strawberries seemed to be the major contributors.28

{mospagebreak title=Carrot, Red wine, Spinach}

9. Carrot: Several lines of evidence indicate that diet rich in fruit and vegetable can protect against cardiovascular diseases by acting on cholesterol metabolism and on oxidative stress. Ingestion of carrot decreases lipemia and improves antioxidant status, suggesting that carrot intake may exert a protective impact against CVD linked to atherosclerosis. It is likely that these effects could be due to the synergistic effect of fiber and associated antioxidants.29

10. Red wine: moderate red wine consumption improves endothelial function and decreases oxidative stress in patients with an acute coronary syndrome by its antioxidant activity.30However larger dose of wine can be detrimental to health.

11. Spinach or spirulina: Chronic treatment with spinach or spirulina reduces ischemia/reperfusion-induced apoptosis and cerebral infarction and can reduce the free radicals which are involved in neurodegenerative disorders, such as ischemia and aging. 31

12. Unsaturated fatty acids: are important constituents of neuronal cell membranes and have neuroprotective, antioxidant, and anti-inflammatory properties. Therefore their consumption in diet is recommended.32

13. Dietary vitamin E vitamin C and beta carotene: Antioxidant nutrients rich in these antioxidants can protect against environmental toxic insult to the vascular endothelium by down-regulation of signaling pathways involved in inflammatory responses and atherosclerosis. Dietary vitamin E vitamin C and beta carotene also have been suggested to possess neuroprotective effect attenuating the risk of PD. 33-35

14. Flavonoids exist extensively in plants, fruits, vegitables and many herbs, and several biological effects of flavonoids have been demonstrated. The anti-tumor effects in colorectal carcinoma cells (HT29, COLO205, and COLO320HSR) of eight flavanones have been demonstrated. Antitumor activities demonstrated in vitro, ex vivo, and in vivo are due to of 2'-OH flavanone via apoptosis induction and by its antioxidant action. Thus 2'-OH flavanone is an active compound worthy of development for cancer chemotherapy in future. 36

Apigenin is another natural dietary flavonoid. It has recently been shown to have anti-cancer effects on prostate and ovarian cancer cells. However, the molecular basis of apigenin on cancer cells still remains to be elucidated. In one study, it is found that apigenin inhibit A549 lung cancer cell proliferation and vascular endothelial growth factor (VEGF) transcriptional activation in a dose-dependent manner.37

Consumption of fruits and berries has been associated with decreased risk of developing cancer. The most abundant flavonoid constituents of fruits and berries are anthocyans (i.e. anthocyanins, glycosides, and their aglycons, anthocyanidins) that cause intense colouration. Anthocyanidins have been shown to inhibit malignant cell survival and confound many oncogenic signalling events in the 10(-6)-10(-4) M concentration range38.

15. Lupeol, a triterpene: is a principal constituent of common fruit plants such as olive, mango, fig and medicinal herbs that have been used to treat skin aliments. Lupeol has been reported to possess a wide range of medicinal properties that include strong antioxidant, antimutagenic, anti-inflammatory and antiarthritic effects. Lupeol possesses antiskin tumor-promoting effects in CD-1 mouse and inhibits conventional as well as novel biomarkers of tumor promotion. Thus, lupeol is an attractive antitumor-promoting agent that must be evaluated in tumor models beside skin carcinogenesis. 39

16. Others: Curcumin in turmeric, corilagin, ellagic acid &gallotanins in amla, piperine in black pepper, capaisin in green &red chili peppers are the antioxidant constituents which have been suggested to decrease oxidative stress in neurodegenerative diseases40.

In conclusion many dietary factors have been recognized to possess antioxidant action and are useful in many pathological conditions like carcinogenesis, cardiovascular diseases, inflammatory diseases, neurodegenerative disorders, diabetic-related vascular diseases, age-related ocular disorders, haemolytic disease and so many other diseases where oxidative stress is known to plays a role. Keeping such therapeutic potentials of diet in mind the present recommended approach is to increase the consumption of such dietary antioxidant factors for good health.

References

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About Authors

Kiran Kapoor, Vishal. R. Tandon, B. Kapoor

Post Graduate Department of Pharmacology & Therapeutics, Govt Medical College, Jammu (J&K) India – 180001.

First Author

Dr Kiran Kapoor

Post Graduate student, Post Graduate Department of Pharmacology & Therapeutics, GMC, Jammu (J&K) India - 180001

Dr Kiran Kapoor is currently working as postgraduate student in the Post graduate Department of Pharmacology and Therapeutics, GMC, Jammu (J&K)-India, with a very bright academic future ahead in the field of Pharmacology.

Corresponding Author

Dr Vishal. R. Tandon(Senior Demonstrator) (MD)

Post Graduate Department of Pharmacology & Therapeutics,GMC, Jammu (J&K) India - 180001.

E-mail: dr_vishaltandon@yahoo.com ,Phone: 9419195126

Dr Vishal R.Tandon has received his doctorate in Pharmacology from Nagpur University, Maharashtra (India) in Dec, 2002.He has authored and/or coauthored over 55 publications in many national and international journals. Two chapters in different national books are also to his credit. His research interests include herbal drug screening, especially working on plant Vitex negundo. He is Expertise in designing and conducting clinical trials. He is currently working as Senior Demonstrator Post graduate department of pharmacology and therapeutics, GMC, Jammu (J&K)-India. His current job responsibilities include teaching UG/PG classes as well as supervising research. He bears following post, a) Editorial Secretary JK-SCIENCE, Journal of Medical Education & Research. This Journal is indexed in Excerpta Medica/EMBASE, Ulrich periodical Dictionary& Indian Science Abstract. b) Secretary-Indian Rheumatology Association-J&K CHAPTER. c) Pear reviewer World Journal of Medical Science. He is also life Member of Indian Pharmacological society, Association of Physiologist and Pharmacologist of India, Indian Rheumatology Association and Indian Menopause Society.

Co-Author:

Dr B. Kapoor (Professor& Head), Post graduate Department of Pharmacology and Therapeutics, GMC, Jammu (J&K)-India is a well known personality in

field of Pharmacology in India.

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