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Review Article DOI: 10.17354/cr/2016/194 Fight-O-Chemicals: An Update on Applications of Phytochemicals in Health and Disease Aarathi Shenoy, Neha Sukhthankar, Bhavya Amin, Nithin Bhat Oral and Maxillofacial Radiologiest, Goa University, Goa, India, Consultant Orthodontist, Goa University, Goa, India, Consultant Prosthodontist, Goa University, Goa, India, Dental Surgeon, Dental Rendezvous Multispeciality Dental Clinic, Goa, India Since time immemorial, plants have been used as a source of medicine to treat various human diseases all over the world. Since ancient times, traditional methods and techniques have been practiced in India, for the maintenance of oral health and prevention of oral diseases. Unfortunately, this valuable knowledge is at the verge of extinction as it is not being documented adequately. This article is an attempt in creating ecological awareness about the unexplored benefits of useful chemicals present in plants. Increased knowledge of phytochemicals coupled with technological advancements will lead to an explosion in the field of research aimed at phytopharmaceuticals and in turn, the development of new organic drugs with minimal side effects. Keywords: Herbs, Phytochemicals, Phytodentistry, Phytopharmaceutics, Traditional medicine INTRODUCTION Studies carried out by eminent scientists; dietary consultants and pharmacists have proved that a diet rich in fruits, vegetables, legumes, whole grains, and nuts is helpful in maintaining the healthy state of the body.1 Organic diet helps to prevent many chronic diseases like diabetes, coronary heart disease, and cancer. This happens by virtue of certain chemicals present in the plants which according to Greek terminology are called as phytochemicals (PhtyoGreek wordMeaning plant).2 Phytochemicals by definition are biologically active, naturally occurring chemical compounds found in plants which provide health benefits for humans further than attributed to micronutrients and macronutrients.3 These chemicals are produced by the plant cells for self-protection against pollution, UV exposure, stress, and drought. They also help the plants preserve their aroma, color and flavor.1,3 Results of botanical studies have isolated approximately 4000 phytochemicals out of which 150 have been studied extensively and documented for their varied benefits to mankind.2,4 The history of herbal medicine dates back to early 19th century when therapeutic benefits of alkaloids such as morphine, strychnine, quinine were discovered.5 This Access this article online Month of Submission Month of Peer Review Month of Acceptance Month of Publishing : : : : 12-2015 01-2016 01-2016 02-2016 www.ijsscr.com prompted many researchers to do extensive research in this field. But unfortunately, investigations were restricted to phytochemical and chemotaxonomic properties only which resulted in the invention of synthetics drugs. Thus, the era of 20th and early 21st century was marked by chemical products and synthetic drugs. Medical prescriptions were flooded with drugs which were easy to administer. All these events overshadowed phytomedicine. 3,5 However, because of the numerous side effects of these drugs, the field of phytomedicine is regaining its glory. Increased interest of major pharmaceutical companies in herbs, increased number of phytopharmaceuticals preparations, better results and minimal side effects are main reasons for this renewal of interest. The aim of this article is the dissemination of knowledge through proper documentation of phytochemicals and their applications in dentistry. CLASSIFICATION Table 1 shows classification of phytochemicals.6 Role of phytochemicals in maintaining health • Phytochemicals stimulate the immune system • They protect the body from carcinogens • Phytochemicals scavenge free radicals and thus protect from oxidative stress4 • Stops the cell cycle of cancerous cells at G0-G1 phase2,4 • Promote apoptosis of damaged cells that may be precursors to cancer • Prevent DNA damage and help with DNA repair mechanisms7 Corresponding Author: Dr. Aarathi Shenoy, Dental Rendezvous, Shop No. 32, Kamat Plaza, St. Inez, Panaji - 403 001, Goa, India. E-mail: [email protected] IJSS Case Reports & Reviews | February 2016 | Vol 2 | Issue 9 37 Shenoy, et al.: Phytodentistry Table 1: Classification of phytochemicals6 Primary Common sugars, amino acids, proteins, purines and pyrimidines of nucleic acids, chlorophyll Secondary Alkaloids, terpenes, flavonoids, lignans, plant steroids, curcumines, saponins, phenolics and glucosides • Help to regulate hormones, such as estrogen and insulin.7 Results of research investigating phytochemicals have proved that phytochemicals may reduce the risk of coronary heart disease by preventing the oxidation of low-density lipoprotein (LDL) cholesterol, reducing the synthesis and/or absorption of cholesterol, normalizing blood pressure and clotting, and improving arterial elasticity.8,9 Phytochemicals neutralize free radicals, inhibit enzymes that activate carcinogens, and activate enzymes that detoxify carcinogens. Phytochemicals have also been promoted for the prevention and treatment of diabetes, high blood pressure, and macular degeneration.7,9 Role of Phytochemicals in Prevention and Treatment of Potentially Malignant and Malignant Disorders of Oral Cavity The oral cavity is under persistent abuse from different types of foods and drinks, deleterious substances like alcohol, tobacco and its products, microbial infections along with systemic illness. Since the oral tissues are delicate, they are more likely to experience cell damage caused by free radicals and oxidative stress. A balance between oxidative free radicals and antioxidants is maintained in the body by oxygen scavengers. In cases where there is an excess of free radical production, these scavenging systems are overwhelmed and fail to reduce the oxidative stress. This causes damage to the cell membrane phospholipids and cell organelles and is termed as oxidative damage. Pre-cancer, cancer, and other chronic diseases are mainly caused as a result of this oxidative damage.10 Phytochemicals show a synergistic function when supplemented along with other antioxidants.8 Lower than optimal levels of serum beta-carotene are seen in people who smoke cigarettes and consume alcohol which is further associated with increased risk of oral cancer. Beta-carotene is found in abundance in yellow and green colored fruits and vegetables.11 Lycopene is a bright red pigment found in tomatoes and other red fruits such as red carrots, watermelons, and papaya. It is one of the most potent antioxidants has been proved to prevent carcinogenesis and atherogenesis by protecting critical biomolecules such as lipids, lipoproteins, and DNA. It suppresses carcinogen-induced phosphorylation of regulatory proteins such as p53 and Rb antioncogenes.12 Phenolic phytochemicals form the largest category of phytochemicals. These include flavonoids, phenolic 38 acids, and polyphenols. The phenolic acid in healthy state is responsible for increased bile secretion, reducing blood cholesterol and lipid levels.9 It protects against oxidative damage and thus prevents cardiovascular diseases, inflammation, and cancer. Reports of various studies have documented its antiulcer, antiinflammatory, antimicrobial, antioxidant, antitumor, antispasmodic and antidepressant activities.13 Flavonoids are present in vegetables, fruits and beverages such as tea, coffee, and fruit drinks. These act by inhibiting xanthine oxidase and arachidonic acid metabolism. 14 Flavonoids have been reported to possess varied biological properties like antioxidant, antimicrobial, cytotoxicity, antiinflammatory, antiallergic as well as antitumor activities. Results of studies indicate that flavonoids such as luteolin and cathechins are better antioxidants than the nutrients antioxidants such as vitamin C, vitamin E, and β-carotene.14,15 The best property of flavonoids is that it offers unmatched protection against harmful effects of oxidative stress by the following mechanisms:15 • Direct radical scavenging: Some flavonoids directly s c a ve n g e s u p e r o x i d e w h i l e o t h e r s s c a ve n g e peroxynitrites • Nitric oxide: Nitric oxide produced by macrophages reacts with free radicals producing peroxynitrite which can react with LDL thereby producing irreversible injury to the cell membrane. Flavonoids scavenge nitric oxide as well as peroxynitrite thus reducing the amount of oxidative damage • Xanthine oxidase: Under ischemic conditions, xanthine dehydrogenase is changed to xanthine oxidase which during reperfusion reacts with molecular oxygen resulting in formation of superoxide free radicals. Flavonoids scavenge these superoxide molecules thus resulting in less oxidative injury16 • Leukocyte immobilization: Flavonoids cause a decrease in the number of immobilized leukocytes, degranulation of neutrophils and mast cells and provide a protective action during reperfusion by modulation of receptor-directed calcium channels in the plasma membrane.17 Results of studies conducted on elderly population in Zutphen revealed a significant inverse association between flavonoid intake and myocardial infarction.14 Similarly, findings from the Seven Countries Study (comparing the diets of men living in Finland, Italy, Greece, the former Yugoslavia, Japan, Serbia, the Netherlands, and the United States) suggested that consumption of flavonoids was responsible for 25% of the observed difference in mortality rates in the various countries studied.15,16 Tannins are classified on the basis of their structural characteristics into gallotannins, ellagitannins, complex tannins, and condensed tannins. Tannins are found commonly in fruits such as grapes, blueberry, tea, chocolate, IJSS Case Reports & Reviews | February 2016 | Vol 2 | Issue 9 Shenoy, et al.: Phytodentistry legume forages (sorghum, corn) and trees (Acacia). 18 In traditional Asian medicine, tannins have been used since ages as astringents and as diuretics. Moreover, they offer anti-inflammatory, antiseptic, antioxidant and hemostatic benefits.18,19 Alkaloids have been employed as dyes spices, drugs or poisons since centuries. These are naturally synthesized by animals, plants, bacteria and fungi. Alkaloids have many pharmacological activities including analgesic, antihypertensive, antiarrhythmic, antimalarial and anticancerous.20 Terpenoids have been available commercially as flavors and fragrances in foods and cosmetics. These have medicinal properties such as anticarcinogenic, antimalarial, antiulcer, hepaticidal, antimicrobial, and diuretic activity.21 Table 2: Summary of all Phytochemicals Phytochemical Carotenoids • Betacarotene • Lycopene • Lutein • Zeaxanthin Flavonoids • Quercetin • Narigin • Catechin • Anthocyanins Phenolic acid • Ellagic acid • Resveratrol Source Red, orange and green fruits and vegetables broccoli, carrots, tomatoes leafy greens, sweet potato, apricots, oranges and watermelon Apples, onions, broccoli, berries; citrus fruits; green/black tea, red wine; strawberries, grapes, wine tea Green tea, grapes, wine, berries, citrus fruits, apples, whole grains and peanuts Benefit • Prevents carcinogenesis • Antioxidants • Immunostimulant • Prevents atherogenesis • • • • • • • • • • • • Tannins Grapes, blueberry, tea, • • Gallotannin chocolate, legumes • • Ellagitannin • • Complex tannin • • Condensed tannin • Inositol Bran from corn, oats, • • Phytic acid rice, rye, wheat, nuts, • soybeans and soy products Isoflavones Soybeans and soy • • Daidzein products (tofu, soy • • Genistein milk, edamame) • Alkaloids Isothiocyanates Terpenes • Perillyl alcohol • Limonene • Carnosol Antioxidant Antimicrobial Anti‑inflammatory Antiallergic Antitumor Antiulcer Anti‑inflammatory Antimicrobial Antioxidant Antitumor Antispasmodic Antidepressant Anti‑inflammatory Antiseptic Antioxidant Astringent Diuretics Antioxidant Antitumour Antitumour Antioxidant Regulates level of hormones Plant, animal, bacterial • Analgesic and fungal origin • Antihypertensive • Antiarrhythmic • Antitumour • Antimalarial Cruciferous vegetables • Antitumor (broccoli, cabbage, • Antioxidant cauliflower and • Induce detoxification Brussels sprouts) of carcinogens Cherries, citrus fruit • Antitumour peel, rosemary • Antimalarial • Hepaticidal • Antimicrobial • Diuretic IJSS Case Reports & Reviews | February 2016 | Vol 2 | Issue 9 CONCLUSION There are many beneficial phytochemicals contained in the nature’s basket. Oral physicians should advise the patients to have a diet rich in green fruits and vegetables or provide dietary supplements. Though we are well versed with benefits of systemic administration of phytochemicals, their topical effects are still unknown. Future research should be directed towards analyzing the effect of topical phytochemicals on cells of the oral mucosa. REFERENCES 1. Hasler CM, Blumberg JB. Phytochemicals: biochemistry and physiology. Introduction. J Nutr 1999;129:756S-7. 2. Gibson EL, Wardle J, Watts CJ. Fruit and vegetable consumption, nutritional knowledge and beliefs in mothers and children. Appetite 1998;31:205-28. 3. Mathai K. Nutrition in the adult years. In: Mahan LK, Escott-Stump S, editors. Krause’s Food, Nutrition, and Diet Therapy. 10th ed., Vol. 271. Philadelphia: W.B. Saunders; 2000. p. 274-5. 4. Meagher E, Thomson C. Vitamin and mineral therapy. In: Morrison G, Hark L, editors. Medical Nutrition and Disease. 2nd ed. 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Kerala Dent J 2008;31:24-33. 18. Mangan JL. Nutritional effects of tannins in animal feeds. Nutr Res Rev 1988;1:209-31. 19. Serrano J, Puupponen-Pimiä R, Dauer A, Aura AM, SauraCalixto F. Tannins: Current knowledge of food sources, intake, bioavailability and biological effects. Mol Nutr Food Res 2009;53 Suppl 2:S310-29. 20. Elbein AD, Molyneux RJ. In: Barton D, Nakanishi K, editors. Comprehensive Natural Products Chemistry. Vol. 3. Amsterdam: 40 Elsevier; 1999. p. 129. 21. Harborne JB, Tomas-Barberan FA. Ecological Chemistry and Biochemistry of Plant Terpenoids. Oxford: Clarendon; 1991. p. 53. How to cite this article: Shenoy A, Sukhthankar N, Amin B, Bhat N. FightO-Chemicals: An Update on Applications of Phytochemicals in Health and Disease. IJSS Case Reports & Reviews 2016;2(9):37‑40. Source of Support: Nil, Conflict of Interest: None declared. IJSS Case Reports & Reviews | February 2016 | Vol 2 | Issue 9