RESEARCH PLAN PROPOSAL ANTIOXIDANT AND CANCER PREVENTIVE PROPERTIES OF PHALSA (Grewia asiatica) FRUIT AND ITS LEAVES For registration to the degree of Doctor of Philosophy IN THE FACULTY OF SCIENCE THE IIS UNIVERSITY, JAIPUR Submitted by KULDEEP KAUR IISU/2011/7120 Under the Supervision of Supervisor Co- Supervisor Dr. Ila Joshi Dr. Sreemoyee Chatterjee Professor and Head Sr. Asstt. Professor Department of Home Science Head, Department of Biotechnology Department of Home Science May, 2014 1. INTRODUCTION Nutrition may be defined as the science of food and its relationship to health. It is concerned primarily with the part played by nutrients in body growth, development and maintenance. Through centuries, food has been recognized as important for human beings in health and diseases. More recently a great deal of interest has been focused on the role of dietary factors in the pathogenesis of non-communicable diseases such as coronary heart diseases, diabetes and cancer (Park, 2011). Many compounds have been isolated from plant foods, mainly fruits, green leaves and vegetables, which have been identified to play a protective role in the human system (Dorothy et al., 2013). Natural phenolic phytochemicals in plants have been receiving increased interest from consumers and researchers for their antioxidant activity (Nataraj et al., 2013). 1.1 Antioxidants And Their Benefits Antioxidants are substances that may protect cells from free radical (Shereen, 2014). Antioxidants are molecules which can safely interact with free radicals and terminate the chain reaction before vital molecules are damaged. Although there are several enzyme systems within the body that disarm free radicals, the principal antioxidants are vitamin E, beta- carotene, vitamin C , and selenium. When these antioxidants neutralize free radicals by donating an electron particle, they are left with a small problem. The antioxidants are now missing an electron and have become free radicals themselves. The body cannot manufacture these antioxidants, thus it is important to include a major amount of antioxidants in daily diet (Brown, 2013). 1.1.1 Antioxidants and their role in healthy living Antioxidant compounds like phenolic acids, polyphenols and flavonoids (anthocyanins), scavenge free radicals such as peroxide, hydroperoxide or lipideroxyl and thus inhibit the oxidative mechanisms that lead to degenerative diseases (Scartezzini and Speroni, 2000 and Timberlake and Bridle, 1982). Free radicals are molecules with one or two unpaired electrons. These reactive radicals are important at physiological level to maintain homeostasis in signal transduction and defense against infections (De laminrande et al., 1997). The role of free radicals and active oxygen is becoming increasingly recognized in the pathogenesis of many human diseases including cancer, aging and atherosclerosis (Chen et al., 2005). Humans have evolved a highly sophisticated and complex antioxidant protection system, to neutralize free radicals. These components includes 1.1.1.i Nutrient-derived antioxidants e.g. vitamin C, tocopherols and tocotrienols (vitamin E), carotenoids and aother low molecular weight compounds such as glutathione and lipoic acid. 1.1.1.ii Antioxidant enzymes superoxide, dismutase, glutathione peroxide and glutathione reductase, which catalyze free radicals quenching reactions. 1.1.1.iii Metal binding proteins such as ferritin, lactoferritin, albumin and ceruloplasmin that isolate free iron and copper ions that are capable of catalyzing oxidative reaction. 1.1.2 Role of antioxidants in maintaining food quality Antioxidants are used in lipid containing foods to minimize rancidity, preventing off flavour, delay the formation of oxidative products, maintain nutritional quality and prolong the shelf life of foods products (Maisuthisakul et al., 2007). The antioxidants play an important role in the manufacturing, packaging and storage of fats and fatty foods and have been proven to retard oxidation (Lin et al., 1981). There is some evidence that antioxidants in plant foods may become especially important as age increases and body produce free radicals. Plants produce hundreds of antioxidants for their own protection. Some that may also be useful to human body are present in vegetables, fruits, herbs and spices, nuts and whole grains. Tea, coffee, extra virgin olive oil, red wine and dark bitter chocolate is also rich in antioxidants. Antioxidants produce the bright colours in fruits and vegetables and the flavor of extra virgin olive oil, tea or coffee. The variety and combination of antioxidants in their natural food sources may also be important as isolated antioxidants may not function in the same beneficial way (Stanton, 2012). 1.2 Antioxidants and Their Major Dietary Supplements Changing lifestyle and environment is led to a great change in the health profile of human population. Higher stress levels among individuals, sedentary lifestyle and deficient diets have increased the onset of degenerative diseases like cancer, diabetes mellitus and cardio vascular diseases. One of the common pathways by which the causative factors initiate or promote the diseases in the human system is through the generation of free radicals. Phenols, polyphenols, flavonoids, terpenes in fruits and vegetables and specific components e.g. lycopene in tomatoes and its products and green tea polyphenols prevent degenerative diseases, offer chemo protection and reduce oxidative stress (Jaganathan et al., 2013). In fruit vitamin A, vitamin C, B-complex group, selenium, phosphorus, etc present in major amount they are rich in antioxidant properties because ample amount of vitamin A, vitamin E, vitamin C, zinc, selenium etc present in fruit and these known as antioxidants in nature. Antioxidants are found in many foods, including fruits and vegetables. Eating a diet with lots of vegetables and fruits is healthy and lowers risks of certain diseases such as heart disease, blood pressure, Alzheimer’s disease, cancer, etc. experiments showed that antioxidants interacted with free radicals and stabilized them, thus preventing the free radicals from causing cell damage. The three major antioxidant vitamins are beta-carotene, vitamin C, and vitamin E. 1.2.1 Beta-Carotene Beta-carotene is converted to vitamin A, an essential nutrient. It has antioxidant activity, which helps to protect cells from damage. Beta-carotene is the main safe dietary source of vitamin A, essential for normal growth and development, immune system function and vision (Nutri facts, 2011). The richest sources of beta-carotene are yellow, orange and green leafy fruits and vegetables such as carrots, spinach, lettuce, tomatoes, sweet potatoes, broccoli and winter squash. In general, the more intense the colour of the fruit or vegetable, the more beta-carotene is present (Bayrel, 2008). The recommended dietary allowance for beta-carotene are, for age 1 to 4, the daily dose is 60-90 mg, age 5 to 8 years, 90-120 mg, age 9 to 12 years, 120-150 mg, age 13 to 16 years, 150-180 mg; and age 16 and older, 180 mg. For more sensitive people to sun the dose of beta-carotene can be increased by 30-60 mg per day for children under 16 years old, and up to a total of 300 mg per day for people older than age 16 (Webmd, 2005). 1.2.2 Vitamin E Vitamin E is an important vitamin required for the proper function of many organs in the body. It is also an antioxidant; it helps to slow down processes that damage cells. Vitamin E is a vitamin that dissolves in fat. It is found in many foods including vegetable oils, cereals, meat, poultry, eggs, fruits, vegetables, and wheat germ oil. It is also available as a supplement. Vitamin E is also used for cataracts, asthma, and respiratory infections, skin disorders, aging skin, sunburns, cystic fibrosis, infertility, impotence, chronic fatigue syndrome (CFS), peptic ulcers, for certain inherited diseases and to prevent allergies (Webmd, 2005). Vitamin E also protect against the skin effects of chemicals used for cancer therapy (chemotherapy). The Food and Nutrition Board at the Institute of Medicine Recommended Intakes for Individuals for vitamin E. for infants 0 to 6 months: 4 mg/day, for 7 to 12 months: 5 mg/day For children upto 1-3 years: 6 mg/day, 4 to 8 years: 7 mg/day, 9 to 13 years: 11 mg/day. For Adolescents and Adults it is recommended 15 mg/day for 14 and older. For pregnant teens and women it is 15 mg/day and for Breastfeeding teens and women, 19 mg/day. The highest safe level of vitamin E supplements for adults is 1,500 IU/day for natural forms of vitamin E, and 1,000 IU/day for the man-made (synthetic) form (Institute of Medicine, Food and Nutrition Board, 2000) 1.2.3 Vitamin C Vitamin C plays a huge role in maintaining a healthy lifestyle, and preventing disease. Vitamin C influences the body in a variety of ways. The four most noted functions those vitamins C affect are: antioxidant activity, collagen synthesis. Furthermore, vitamin C is vital for the cardiovascular system. When the body's arteries become clogged, there isn't enough blood flow to the heart which results in a heart attack. Vitamin C's antioxidant properties are absorbed into the blood stream, and repress the accumulation of arterial plaque. Vitamin C can be thought of as a type of "Drain-o" for arteries. It cleans the arteries, and enables a healthy flow of blood to the heart. Vitamin C is extremely important in immune system function because it is involved with T-cells and white blood cells. Vitamin C boosts the white blood cell count; by consuming a high dose of vitamin C had a less likely chance of contracting diseases. The daily recommended dietary allowances (RDAs) are: Infants 0 to 12 months, human milk content (older recommendations specified 30-35 mg); Children 1 to 3 years, 15 mg; Children 4 to 8 years, 25 mg; Children 9 to 13 years, 45 mg; Adolescents 14 to 18 years, 75 mg for boys and 65 mg for girls; Adults age 19 and greater, 90 mg for men and 75 mg for women; Pregnancy and Lactation: age 18 or younger, 115 mg; ages 19 to 50 years 120 mg.