Metabolism, Bioactivity and Potential Health Benefits of Flavonoids - Admission/Application Essay Example

Introduction A number of Flavonoids have been identified to have putative beneficial actions in preventing most of the prevalent cardiovascular diseases and many cancers. Numerous studies have proven the definite prevention of damage to cardiovascular endothelium by free radicals when flavonoids were incorporated in the diet. My research aims to study some of the identified flavonoids for their beneficial effects, if any, in animal models of simulated cardiac disease. Overview Modern human lifestyle has been crippled by technology which has made life unnatural as well as artificial. The growing dependence on machines and ready made foods has taken its toll and mankind is now confronted with diseases which were unheard of in the history of human civilization. Although technology has helped man to overcome many infectious diseases the ecological balance remains the same as people are succumbing to newer perils brought forth by sedentary lifestyles and junk food. Realization has dawned now and people are looking backwards to the bounties nature so abounds in, and which possess a nourishing and healing effect on the human body. One of the natural substances present in most vegetables and fruits has been classified under the group ‘Flavonoids’ which are more aptly called as ‘Bioflavonoids’ as they are derived from nature. The role of flavonoids is currently under scrutiny for their antioxidant effects in micro-quantities which is beneficial for many physiological functions inside the body. Flavonoids are basically a large class of polyphenolic compounds which occur naturally in most plants especially in the leaves and fruits of highly pigmented plants (Erdman, et al, 2005). Phenolic compounds in plants occur because of secondary metabolism and about 8000 types of its derivatives occur naturally (Erdman, et al, 2007). They have been sub classified into Flavonols, Flavones, Flavan-3ols (Proanthocyanidins), Flavanones, Anthocyanidins and Isoflavones (Erdman, et al, 2007). So far 5000 flavonoids have been identified and many tentatively recognized in a host of commonly consumed vegetables, fruits, grains, herbs and beverages (Erdman, et al, 2007). The usual sources of flavonoids according to classification are as follows (Engler & Engler, 2006): 1. Flavonols: Chocolate, Tea, Red Wine, Beans, Apricot, Cherry, Grape, Peach, Blackberry and Apple. 2. Flavanones: Citrus Fruits and Juices. 3. Isoflavones: Soy Products. 4. Flavonols: Onions, Kale, Broccoli, Tomato, Blueberry, Apples, Tea and Red Wine. 5. Anthocyanidins: Blueberry, Black Grape, Cherry, Blackberry, Black Currant, Rhubarb, Strawberry, Red Wine, Plum and Red Cabbage. Structure Activity Relationship Basic Structure of Flavonoid (Picture Courtesy: Erdman, et al, 2007) Structurally Flavonoids consist of 2 aromatic rings (known as A-Ring and B-Ring) linked by a 3-Carbon chain which forms an oxygenated heterocyclic ring known as the C-Ring (Erdman, et al, 2007). Variations in the generic structure of the C-Ring, oxidation state and the different functional groups are responsible for imparting the particular chemical nature of the flavonoid, on the basis of which they are classified. The abovementioned peculiar structure of the flavonoids imparts them the property of free radical scavenging thereby promoting cardiovascular health (Engler & Engler, 2006). The dihydroxylated B-ring allows rapid donation of hydrogen which is responsible for neutralizing the action of free radicals. Flavonoids also inhibit key enzymes such as NAD(P)H-oxidase which is a major source of endogenous free radicals (Engler & Engler, 2006). Along with this they also inhibit Tyrosine kinase and various protein kinases involved in the pathophysiology of cardiovascular disease. An enzyme in the Arachidonic Acid cascade during inflammatory processes, Cyclooxygenase is particularly suppressed by the hydroxyl groups on the B-ring and oxo groups at the 4 position of the C-ring (Engler & Engler, 2006). Flavanols in particular have a more suppressive action on the Cyclooxygenase enzyme as compared to flavonols. The chemical structure of various flavonoids has therefore a direct action on its effects in the body. Antioxidant property is more when the two hydroxyl groups on the B-ring are at the C4 position. Antiproliferative action of flavonoids, which has a bearing on their anti-cancer effects, is attributed to the additional presence of a carbonyl group at C4 and unsaturation of the C-ring (Engler & Engler, 2006). Flavonoids also exert their beneficial actions by other mechanisms such as binding to specific receptors and modulation of cellular signalling pathways as well as by altering gene expression (Engler & Engler, 2006). Mechanisms of Action Free radicals are reactive oxygen species (ROS) and reactive nitrogen species which have a direct damaging effect on cardiac muscle (Engler & Engler, 2006). Oxidative stress due to excessive ROS production is responsible for potentiating a number of cardiovascular risk factors which occur in persons indulging in smoking, alcohol abuse and in those suffering from hypertension, diabetes and dyslipidemias (Engler & Engler, 2006). The free radicals directly act upon the cellular DNA, proteins and lipids in the cardiovascular and other tissues leading to damage of cell membranes and cell organelles (Engler & Engler, 2006).They further lead to mutagenic changes and cause vascular cellular death. This leads to endothelial dysfunction and atherosclerosis which further compromise the cardiovascular functioning of the sufferer eventually leading to death. Flavonoids, by scavenging these free radicals and due to their direct antioxidant quenching action prevent many of the above diseases by altering the pahophysiological sequelae. Past studies Previous studies have explored the role of flavonoid rich foods in disease, beneficial or otherwise as in some cases certain classes of flavonoids have been blamed to produce disease instead of preventing it. In one such study, the role of green tea, black tea and flavonols/flavones/catechins was investigated through an observational epidemiological data analysis to see whether they have any beneficial or derogatory effect on the promotion of lung cancer (Arts, 2008). Three out of a total of twelve studies reported significant lowering of lung cancer risk when the intake of flavonoids was increased while one study reported the opposite action i.e. more risk of lung cancer due to higher intake of flavonoids (Arts, 2008). However, predominant effect of prolonged intake of flavonoids through tea intake was considered beneficial for the prevention of lung cancer. Contrary results were confounded by the co-occurrence of smoking in tea drinkers (Arts, 2008). Another epidemiological study shows conclusive evidence that diets rich in fruits and vegetables definitely provide beneficial effects in reducing the onset of cardiovascular disease (Grassi, et al, 2008). According to the authors, the major intake of flavonoids among US population was through the consumption of black and green teas which were rich in flavonoids, particularly flavonols which include catechin, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate (Grassi, et al, 2008). It was proven that flavonoids delay atherosclerotic plaque development and reduce endothelial dysfunction (Grassi, et al, 2008). However the authors did not agree that conclusive evidence was there to recommend any particular kind of tea or food as the results obtained so far are still controversial. That tea is the major source of flavonoids, particularly Flavan-3-ol and Flavonol in diet taken by the majority US population was confirmed in a study by Song & Chun, 2008. As only 21.3% of the total US population takes tea in any form, it was discovered that the total flavonoid intake of the tea consumers was 20 times more as compared to the non-consumers (Song & Chun, 2008). In the Third International Symposium on the role of tea and the presence of flavonoids in diet on human health, it was agreed that tea doe exert a beneficial effect on human health, but it was not clear as yet which specific component exerts that action (Blumberg, 2003). Flavonoids were attributed to have antiangiogenic, antibacterial, anticarcinogenic, anti-inflammatory, antithrombotic, antiviral, hypocholesterolimic, hypoglycaemic and vasodilatory effects but the mechanisms cannot be limited to their antioxidant and free radical scavenging actions alone (Blumberg, 2003). Comprehensive data and research therefore needs to be collected to pin point the actual component out of the innumerable flavonoids present in vegetable foods. Aims and objectives In this study, specific flavonoids which have been isolated and are available commercially will be used and the appropriate dosage calculated to provide the minimum level of individual flavonoids depending upon class to an experimental group of animals. The control group will not be administered any flavonoids. Experimental models will be used to produce cardiovascular disorders, particularly atherosclerosis by feeding excess lipids in experimental animals. The level of development of atherosclerotic lesions will then be studied in experimental and control animals to evaluate the beneficial effects, if any, of the particular flavonoids selected for the research. Pertinent literature concurrent with the experimental design will be gathered and the methodology developed according to accepted protocols. Appropriate statistical tools will be employed for the evaluation of results. Significance of Research This kind of research will contribute towards enhancing the knowledge of the role played by particular flavonoids in deterring cardiovascular disease, which will lead to identifying the foods rich in that particular flavonoid. Such foods can then be recommended for incorporation in the diet for better health of the future generations. In terms of professional knowledge, the study design will help in enhancing the knowledge of use of research tools which can lead to stimulation of further ideas and concepts. The permission for the experimental protocol will be obtained from the pertinent ethics committee and the experiments will be designed in such a way so as to provide the least distress to the animals used in the study. As far as possible, in vivo models of evaluation will be used. Modern technology provides for the measurement and evaluation of cardiovascular parameters in a non invasive manner and the maximum use of humane method will be employed during experimentation. Toxicological data will be collected and care will be taken to minimize any incidence of administration of dosage beyond the prescribed toxicological limits. In my opinion, the actual experiments will take one and a half year to complete and another such period for the compilation and analysis of data. Before the actual experiments begin, pertinent literature will have to be collected for designing the experiments. This can take any time between 3 to 6 months. REFERENCES Arts I.C.W., 2008, A Review of the Epidemiological Evidence on Tea, Flavonoids, and Lung Cancer, The Journal of Nutrition; 138, 8 Blumberg J., 2003, Introduction to the proceedings of the Third International Scientific Symposium on Tea and Human Health: Role of Flavonoids in the Diet, The Journal of Nutrition;133, 10 Engler M.B. & Engler M.M., 2006, The Emerging Role of Flavonoid-Rich Cocoa and Chocolate in Cardiovascular Health and Disease, Nutrition Reviews; 64, 3 Erdman J.W., Balentine D., Arab L. et al, 2007, Flavonoids and Heart Health: Proceedings of the ILSI North America Flavonoids Workshop, May 31–June 1, 2005, Washington, DC, The Journal of Nutrition Grassi D., Aggio A, Onori L. et al, 2008, Tea, Flavonoids, and Nitric Oxide-Mediated Vascular Reactivity, The Journal of Nutrition; 138, 8 Song W.O & Chun O.K, 2008, Tea Is the Major Source of Flavan-3-ol and Flavonol in the U.S. Diet, Proceedings of the Fourth International Scientific Symposium on Tea and Human Health Read More