INTRODUCTION:

In simple words the term “Nutraceutical” is called as a fortified food or dietary supplement which supplies health boundaries in conjunction with its basic nutritional value. Any harmless food element which provides scientifically recognized health aids with treatment and inhibition. It can be a naturally nutrient- rich food or a definite component of a food. Dietary supplements, nutritional supplements and medical foods this are some alternative expressions for nutraceuticals. They are obtained from foods which are used in various pharmaceutical form such as pills, capsules or liquids and again provide condensed physiological benefits.

Nutraceuticals fundamentally ranges from dietary supplements, herbal products, genetically engineered “designer” foods, isolated nutrients. They are nourishing food or food component having medicinal standards. Principal focus of such products is to progress or preserve health and used to recover general health. The medicinal plants are significant fields of traditional medicine all over the world as they hold phytochemicals which have been used in ancient systems of medicines like Ayurveda, Homeopathic, Siddha, and Unani. They have great interest because of safety, therapeutic effects and potential nutritional purpose^.1,2,3 Health Canada defines nutraceutical as: a product isolated or purified from foods, and generally sold in medicinal forms not generally related to food and demonstrated to possess a physiological use or deliver protection against chronic disease⁴. The utilization of nutraceuticals gets widely held around the world in the twenty-first century. Nutraceutical industries earns billons of $ annually.

Eating habits as well as trends in food production in addition to consumption have health, environmental and social impacts. Nutraceutical helps in anticancer, anti-inflammatory, antioxidant, immunomodulatory, adaptogenic, and in numerous other health benefits. They are used for the prevention and treatment of chronic diseases such as cancer, arthritis, cardiovascular, diabetes and respiratory disorders. Recently, Dr. Margaret Chan, Director-General at the World Health Organization (WHO), stated that traditional medicine holds great potential to improve people’s health and wellness in every part of the world.^[5] Foods and nutrients have important role in normal functioning of the body as well as they are not only helpful in maintaining the health but also in reducing the risk of different diseases.⁴Role of nutraceuticals in human nutrition is one of the most important areas of investigation, with wide- powerful implications for clientele, health-care providers, food supplement producers.^[12] Regulations in the area of such products vary from country to country and many products have been launched in market^6,7A clear understanding of nutraceuticals in a regulatory system will decrease the misperception in establishing the policy for nutraceuticals. However, in current scenario the regulatory position of nutraceuticals is different depending on the country’s regulatory framework.^7,8.

History:^9,57

The fundamental idea for the concept of “Nutraceuticals” emerged 3000 years ago. The father of modern medicine, Hippocrates developed relationship between food for health and their therapeutic benefits. Foods have the ability to prevent the disease or treatment of disease. About 2,500 years ago, Hippocrates delineated the principle truth by his statement “Let food be your medicine and medicine be your food". Ancient writing and artwork of Egyptians, Roman and Greek civilization revealed the medicinal and spiritual use of plants. During the past few centuries, many crewmen on long journey were died of scurvy, when their body was examined actuality highlighted the absence of vitamin B and C in diet. In such like manner, Goiter turns out as a common problem due to deficiency of Iodine in salt. Around the beginning of 1900s, food manufacturers in US initiated addition of Iodine to salt to prevent Goiter which symbolise the first attempt at creating a functional component through fortification. Dr. Stephen DeFelice officially invented the term “Nutraceuticals” 1^st time in 1989 from two words i.e. nutrition and pharmaceuticals. DeFelice originally defined nutraceuticals as ‘a food (or part of the food) that provides medical or health benefits, including the prevention and/or treatment of a disease^3,10. In 1994, watershed legislation was passed in USA to regulate the manufacture and marketing of nutraceuticals. This law is known as The Dietary Supplement Health and Education Act. This law passed the definition of Nutraceuticals expanded by adding vitamins, minerals, herbs and other botanicals, amino acids and the dietary substances. Nutraceuticals has evolved considerably over the years but the idea of nutraceuticals is not entirely new.

· Pharmaceuticals {drugs}

The FD and C Act defines drugs as "articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and articles (other than food) intended to affect the structure or any function of the body of man or other animals"^12,20. Any substance or combination of substances which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis²⁰.

· Ntraceuticals:^2,11,12,13

Nutraceuticals are the food product. They provide health in addition to medical benefits as well as they help in the prevention and treatment of numerous diseases. They are mostly defined by dietary supplement industry as, “any nontoxic food component that has scientifically proven health benefits, including disease treatment and prevention. Nutraceuticals have been consumed in the format of capsules or syrups. They generally act as a counter measure to protect body from harmful agents. anti-arthritic, cold and cough, sleeping disorders, digestion and prevention of certain cancers, osteoporosis, blood pressure, cholesterol control, pain killers, depression and diabetes are some therapeutics areas which covered by nutraceuticals.¹⁴All the nutraceuticals are the resources of nature.

Benefits of Nutraceuticals:

Nutraceuticals have been used to:¹⁵

· Increase the health value of our diet.

· Help us live longer.

· Help us to avoid particular medical conditions.

· Give a psychological benefit from doing something for one self.

· Show action on immune system, respiratory system and digestive system.

· Provide the right amount of nutrition for our body.

· Prevent the signs of ageing as well as chronic diseases.

· Protect your body against chronic diseases.

· Increase life expectancy and improve Immunity.

· Reduce the effects of stress and improve mental clarity as well as to relieve anxiety.

· Enhance sleep quality and quantity.

· Provide sense of well-being.

· Nutraceuticals have no known side effect.

Veterinary Nutraceutical^{9,46,47,48,49}

As defined by the newly created North American Veterinarian Nutraceutical Council, Inc. (NAVNC), “a substance which produced in a purified or extracted form and administered orally to patients to provide agents required for normal body structure and function and administered with the intent of improving the health and wellbeing of animals.” The American Veterinary Medical Association defined Veterinary nutraceutical medicine as ‘the use of micronutrients, macronutrients and other nutritional supplements as therapeutic agents’. Veterinary nutraceuticals provide an additional health benefit in addition to your animal’s normal diet. Not only humans but also species of animals such as reptiles, birds, horses, cats, dogs, and marine mammals, etc. are treated by nutraceuticals. Nearly all Veterinarians suggest the use of nutraceuticals to prevent diseases in animals or to combat the current disease condition. Vitamins, minerals and fatty acids often have additive effect and promote optimum health, immune status, vitality, fertility, growth and muscle and tendon strength and recovery. For convalescing animals, such supplements help to improve healing, promotion of weight gain and to increase appetite.

In dogs and cats the supplements are majorly to improve digestive health and for the shiny coat/skin. In dogs and cats the nutraceuticals may be used for the good health of the heart. Similarly in horses the supplement for the mobility of the joint and improved performance is widely used.

In the treatment of the Osteoarthritis of cats and dogs the nutaceuticals like Chondroprotectants have become an alternative therapy. The term chondroprotectant is applied to various compounds that have a positive effect on the health and metabolism of chondrocytes and synoviocytes. Chondroprotectants have three primary effects:

1. They support or enhance metabolism of chondrocyte and synoviocyte (anabolic)

2. They inhibit degradative enzymes within synovial fluid and cartilage matrix (catabolic)

3. They inhibit formation of thrombi in small blood vessels supplying the joint (antithrombotic).

Commonly used Veterinary Nutraceuticals:

1. Glucosamine

2. MSM (Methyl-Sulphonyl-Methane)

3. Anti-Oxidants or Free Radical Scavengers

a. Vitamin C (Ascorbic Acid)

b. Vitamin E

c. SAMe (sadenosylmethionine)

d. Proanthocyanidins/Bioflavonols

e. Co-enzyme Q10

4. Essential Fatty Acids (EFA’s)

5. Omega 3 Fatty Acids

6. Vitamin-B Complex

7. Glutamine

8. Milk Thistle

9. Curcumin

10. Colostrum

Safety of Veterinary Nutraceuticals:

In 2018 a survey showed that 87% of dairy products of animals that fed on the nutraceuticals were safe. 45%of the horse owners feel safe to administer nutraceuticals to the horse in order to improve performance. Despite that 84% owners gave supplements to at least their one horse. Many herbs that are in small doses safe for the humans have shown toxic effects in the cats, dogs and horses. Although the FDA-CVM requests reporting of adverse effects from the feeding of pet supplements, but it should be noted that lack of reporting of adverse effects does not mean that a product is safe, especially with long-term use. If there is concern about any nutraceutical product the consumers can request the analysis of supplement or consulting to the veterinary expert.

Classification of Nutraceuticals:¹⁶

· Classification Based on Food Availability:

1) Traditional Nutraceuticals:

Nutraceuticals is categorised in some categories. Traditional nutraceuticals is one of the categories of nutraceuticals. Under this category unchanged food are made. It is totally natural. In this category food have new information about their potential health qualities. Actual food does not changed but other than the way of consumption which perceived by consumer. Numerous fruits, vegetables, grains, fish; dairy and meat products contain several natural components. Traditional nutraceuticals are generally obtained directly from nature. Their natural form maintained as it is. Constituents such as lycopene, omega-3 fatty acids, or saponins are available and consumed for health beneﬁts. Various types of traditional nutraceuticals are as follows:

a. Chemical constituents:

i. Nutrients:

Nutrients are the substances like vitamins, minerals, amino acids and fatty acids with established nutritional functions. Plant and animal products which contains vitamin have many health beneﬁts. They help in curing diseases related to heart, kidney, lungs, etc. Primary metabolites like amino acids, vitamins, and fatty acids had well-deﬁned functions in various metabolic pathways. Natural products which are gained from plants are beneﬁcial in treating various disorders, and they provide strength to bones and muscles. They also help in neurotransmission, and maintain rhythm of heart muscles. Fatty acids, omega-3 PUFAs had inﬂuenced the inﬂammatory response, brain function and reduced cholesterol in the arteries. Vegetables, wholegrain cereals, dairy products, fruits contain vitamins which are helpful in curing heart diseases, stroke, cataracts, osteoporosis, diabetes and cancer. Not only the plant products but also animal products like meat, poultry, had widely used to cure various disorders.²² Minerals which is mainly found in plant, animal and dairy products are useful in various conditions like osteoporosis, anaemia, build strong bones, teeth, muscles, improve nerve impulses and heart rhythm²³. Antioxidant, water and fat-soluble vitamins are most commonly known nutrients. Antioxidants have many potential benefits in the form of supplementation or dietary intake. Cancer and cerebrovascular disease may be prevented by antioxidants. Greater dietary intake of vitamin E may prevent Parkinson’s disease. Supplementation with selenium in genetically predisposed patients may help to prevent this condition in which pancreatic cancer have low serum level of selenium. Zinc is one of the essential components in hundred enzymes which involve digestion, metabolism and wound healing.

ii. Herbals:

Herbals are as old as human civilization. They have provided a huge storehouse of almost all remedies to cure acute and chronic diseases. Information of herbals has stored over thousands of years so that today we possess many effective means of ensuring health care. Nutraceuticals takes a great promise to improve health as well as prevent chronic diseases with the help of herbals. Some examples are willow bark which is anti-inflammatory, analgesic, antipyretic, astringent and anti-arthritic. Parsley (Petroselinum cripsum) contains flavnoids and has diuretic, carminative and anti-pyretic properties. Peppermint contains menthol as an active constituent and helps to cures cold and flu. Lavender contains tannin and helps to cure depression, hypertension, stress, cold, cough and asthma like conditions. Cranberries contain proanthocyanadin and useful in cancer, ulcers and urinary tract infections. Herbals have been used for prevention and treatment of various disorders from ancient time.

iii. Phytochemicals:

Phytochemicals are classified on the basis of chemical name given according to their phytochemical properties. Carotenoids are present in vegetable and they improve the immune system, mainly killer cells numbering for an anticancer response. Carotenes which hepls remove cholesterol are not present in legumes, palm oil and grains. A class of secondary metabolites which is occurs in various plants i.e. flavonoid and it have more than 4000 clinically proven varieties which used to prevent diseases like cancer, diabetes, heart diseases, and kidney problem. Flavonoid polyphenolics are found in berries, fruits, vegetables, and legumes. Non-flavonoid polyphenolics are derived from dark grapes, raisins, berries, turmeric roots and they are strong anti-inflammatory, anti-oxidants, and effective anti-clotting agents. Phenolic acids which are found in blueberries, tomatoes and bell peppers like citrus fruits, red wine have antioxidant activity. Phenolic acids are the largest class of secondary metabolites. They also show anticancer and antitumor activity.

b. Probiotic microorganisms:^3,19,20,21

The term was coined by Metchnikoff. It has ability of making the intestine friendlier for processes like absorption as well as metabolism. Probiotics remove the toxic flora of intestine for making life smoother and maintain friendly environment. Presently numerous probiotic products are available in the market with adequate nutrients to counter various pathogens. The work of Metchnikoff to convert the toxic micro flora of the large intestine to a host-friendly colony of Bacillus bulgaricus was found by Hord has boosted the scientific interest in probiotics. ‘Probiotics’ mean ‘for life’ and are defined as live microorganisms, which when consumed in adequate amounts, confer a health effect on the host. They are beneficial bacteria that elevate healthy digestion also absorption of some nutrients. They act to force out pathogens, like yeasts, other bacteria as well as viruses which may otherwise cause disease and develop symbiotic relationship with the human gastrointestinal tract. They have an antimicrobial effect. They compete with pathogenic microorganisms and prevent adhesion of pathogens to the intestinal epithelium, also producing an antitoxin effect and reversing some of the consequences of infection on the intestinal epithelium, like secretory changes and neutrophil migration. Moreover, probiotics are terribly helpful in lactose intolerance by the production of related enzymes (ß-galactosidase) and hydrolyzing lactose into its sugar components.

c. Nutraceutical enzymes:^3,16

Enzymes are biocatalyst which are produced by the cell and proteinous in structure. The GIT related medical problems such as GERD (gastroesophageal reﬂux disease) or constipation or diarrhea or ulcerative colitis could be cured with enzyme supplements. Enzymes could be a choice for diabetic patients. Nowadays, the several rare diseases like Gaucher disease, Hunter syndrome, Fabry disease, and Pompe disease could be treated with enzyme therapies. Enzymes are important factor of life, without enzyme our body terminate to function. The people suffering from medical conditions like hypoglycemia, blood sugar disorders, digestive problems and obesity, eliminate the symptoms by enzyme supplements to their diet. These enzymes are sourced from microbial, plant and animal sources

2) Non-traditional Nutraceuticals:¹⁷

They are foods upgraded with supplements or biotechnologically designed crops to elevate the nutrients; as an example, rice and broccoli are rich in β-carotene and vitamins, respectively. Food samples contain bioactive component which are engineered to produce products for human wellness. They are arranged as follows:

a. Fortiﬁed Nutraceuticals:¹⁸

It establishes fortified food from agricultural breeding. E.g. orange juice fortified with calcium, cereals with added vitamins or minerals and flour with added folic acid. Some examples are milk fortified with cholecalciferol used in vitamin D deficiency. Prebiotic and probiotic fortified milk with Bifidobacterium lactis HN019 used in diarrhea, respiratory infections and severe illnesses, in children. Banana fortified using soybean ferritin gene in iron deficiency was discovered by Kumar. These types of nutraceuticals include breeding at the agriculture level or addition of compatible nutrients to the main ingredients such as minerals added to cereals, ﬂour fortiﬁed with calcium, iron, and folic acid, and milk fortiﬁed with cholecalciferol commonly used for vitamin D decency.

b. Recombinant Nutraceuticals:

For the extraction of the enzyme which is helpful for supplying essential nutrients at optimum, biotechnology tools applied for a fermentation process in variety of food materials like cheese and bread. Biotechnology is widely employed for the production of Energy-providing foods, like bread, alcohol, fermented starch, yogurt, cheese, vinegar, and others. Biotechnology is employed tool for the production of probiotics and the extraction of bioactive components by enzyme/fermentation technologies and genetic engineering technology.

· Classiﬁcation Based on Mechanism of Action:

Nutraceuticals also classified on their specific therapeutic activities which shows antimicrobial, anti-inﬂammatory, and antioxidant properties.

· Classiﬁcation Based on Chemical Nature:

This class of nutraceuticals is mainly depending upon their primary and secondary metabolite sources such as isoprenoid derivatives, phenolic substances, fatty acids, carbohydrates, and amino acid-based substances.

Food Sources:

The food sources used as nutraceuticals are all natural and can be categorized as:^2,14

1. Dietary fiber:

Dietary fiber (DF) composed of non-digestible carbohydrates and lignin that are intrinsic and intact in plants. Functional fibre (FF) contains isolated, nondigestible carbohydrates which have advantageous physiological effects in humans. Total fiber is made of dietary and functional fiber. These definitions expand the category and permit resistant starches, oligosaccharides and other non-digestible carbohydrates to be categorised as functional fibres. The Dietary Reference Intake (DRI) explained the adequate intake for fibres as 38 grams/day for adult men and 25 grams/day for adult women. There was inadequate evidence to decide a tolerable upper intake level for dietary or functional fibre. Probiotics are "good" or "helpful" bacteria as they keep gut healthy. Probiotics are found naturally in your body and can also in some foods and supplements. It's only been since about the mid-1990s that people have wanted to know more about probiotics and their health benefits. Dietary fibre is not hydrolysed by enzymes secreted by the digestive tract, but digested by microflora in the gut. It includes non-starch polysaccharides (NSP) like celluloses, hemicelluloses, gums and pectin, lignin, resistant dextrin and resistant starches. Foods loaded with soluble fibre include fruits, oats, barley and beans. Chemically dietary fibre is defined as carbohydrate polymers with a degree of polymerization not lower than 3, which are not digested as well as not absorbed in the small intestine.

2. Probiotics:

A probiotic is live microbial feed supplement, which gives good affects the host animal by boosting its intestinal microbial balance, when administered in sufficient amount. Generally, the following classes of bacteria included in probiotics:

A. Lactobacilli such as L. acidophilus, L.cellobiosus, L.delbrueckii sub sp. bulgaricus, L.casei, L.brevis.

B. Gram-positive cocci such as Lactococcus lactis, Streptococcus salivarius subsp. thermophilus, Enterococcus faecium.

C. Bifidobacteria such as B. bifidun, B.infantis, B.adolescentis, B.longum, B. thermophilum.

Probiotics are available in various forms such as:

1 Powder form,

2 Liquid form,

3 Gel or paste

4 Granule forms,

5 Capsule forms etc.

Probiotics are generally used in treatment of gastrointestinal (GI) conditions such as acute diarrhea, lactose intolerance, and antibiotic associated GI side effects. Probiotic agents are non-pathogenic and non-toxic. They have resistance to gastric acid. They adhere to antibacterial substance producing gut epithelial tissues. There are evidences that administrating probiotics decreases the risk of systemic conditions, like allergy, asthma, cancer also various other infections of the ear, urinary tract.

3. Prebiotics:

Prebiotics are dietary ingredients which beneficially affect the host by selective modification of the composition or metabolism of the gut microbiota. These are short-chain polysaccharides having unique chemical structures which are not digested by humans; in particular fructose-based oligosaccharides that exist naturally in food or are added in the food. Generally the growth of Lactobacillus and Bifidobacterial in the gut is promoted by the prebiotic administration this helping in metabolism. Vegetables such as chicory roots, banana, tomato, alliums are loaded with fructo-oligosaccharides. Raffinose and stachyose, found in beans and peas are some other examples of these oligosaccharides. The prebiotics show improved lactose tolerance, antitumor properties, neutralization of toxins, and stimulation of intestinal immune system, reduction of constipation, blood lipids and blood cholesterol levels. The growth of bifidobacteria is elevated by a daily intake of 5– 20g of insulin and oligosachharides. Again, administration of large amounts of like oligosaccharides causes diarrhoea, abdominal distension and flatulence.

4. Polyunsaturated fatty acids:

The poly-unsaturated fatty acids (PUFAs) divided into two groups: omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA), having difference in the position where first double C-bound is present. Two PUFAs which cannot be synthesized in the human body and are vital for physiological integrity are called essential fatty acids. They must be obtained from the diet. One is linoleic acid (LA) which belongs to the n-6 family and the other one is α-linolenic acid (LNA) which belongs to the n-3 family. These essential parent compounds can be converted to longchain (LC) fatty acid in the human body but humans cannot interconvert n-3 and n-6 fatty acids. The use of omega-3 oils/long-chain ω3 PUFA is a most promising developments in human nutrition and disease risk reduction in the past three decades. Long-chain ω3 PUFA is effective in prevention as well as treatment of coronary heart disease, hypertension, diabetes, arthritis and other inflammations, autoimmune disorders mental health and neural function as in depression and schizophrenia and cancers and are essential for maintenance and development of normal growth, especially for the brain and retina. Polyunsaturated fatty acids (PUFAs) and phytochemicals are also important as healthy dietary bioactive compounds. A balanced PUFA composition of food influences diverse aspects of immunity and metabolism. The interactions between PUFAs and components of the gut microbiota may influence their biological roles. Omega-3 polyunsaturated fatty acids (PUFAs) decreases the production of inflammatory eicosanoids, cytokines and reactive oxygen species, possess immunomodulatory effects and attenuate inflammatory diseases. Fatty acids of the omega-3 series (n-3 fatty acids) present in fish are well established dietary components. It affects plasma lipids and the major cardiovascular disorders, like arrhythmias. The fish oil have health-promoting effect is now known to be because of the omega-fatty acids, especially omega-3 and omega6. In fish oil the main omega-3 fatty acids are docosahexaenoic (DHA) and eicosapentaenoic acids (EPA). DHA is important structural component of the brain also contributes to improved memory functions. Recently, enhancement of brain memory development has been promoted by increase in incorporation of DHA into margarines and baby food and a role in reducing the severity of Alzheimer's disease has been suggested for DHA.

5. Antioxidant:

Body uses oxygen for metabolic reactions. During oxidation oxygen reacts with body compounds and form unstable molecules called “free radicals.” Free radicals are able to attack the healthy cells of the body and causes in lose their structure and function. Free radicals at a molecular level damage everything that comes in contact. If free radical damage becomes extensive, health problems can develop. Oxidative stress has been identified as a causative factor in:

· Cognitive performance:

· Aging process

· Development of diseases such as cancer, arthritis, cataracts, and heart disease.

Antioxidants are able to neutralize or deactivating, free radicals before they attack cells and reduce oxidative damage. Antioxidants have the potential to inhibit the oxidants chain reactions and ultimately reconstitute the damaged membranes. Antioxidants prevent against free radical damage, and are critical for maintaining optimum health and wellbeing. Humans have developed a highly sophisticated and complex antioxidant protection system. It involves various endogenous as well as exogenous components, that function interactively and synergistically to neutralize free radicals. These components include:

· Nutrient-derived antioxidants

· Antioxidant enzymes

· Metal binding proteins

· Numerous other antioxidant phytonutrients

a) Endogenous Antioxidants

b) Dietary Antioxidants

c) Metal Binding Proteins

Antioxidants are known to deactivate or prevent free radicals causing limited risk of Oxidative Stress (OS) and associated disorders. They inactivate Reactive Oxygen Species (ROS) at cellular and molecular level and under specific low concentration inhibit or delay oxidative processes by interrupting the radical chain reaction of lipid peroxidation. Carotenoids, tocopherols, ascorbates, lipoic acids and polyphenols are strong natural antioxidants with free radical scavenging activity. Endogenous antioxidant enzymes such as super oxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase, minerals like Se, Mn, Cu, Zn, vitamins A, C and E, carotenoids, limonoids and polyphenols gives synergistic actions in scavenging free radicals. During the last few years researches has confirmed that many common disease (CVS, diabetes, cataracts, high blood pressure, infertility, respiratory infection and rheumatoid arthritis) are associated with tissue deficiency and/or low dietary levels of compounds called antioxidants which make them an essential part of the nutraceutical market. Dietary antioxidants and some accessory molecules, such as zinc and certain vitamins maintains free radical scavenging systems, biosynthetic capacity, membranes, enzymes and DNA. Antioxidants are present in the vegetable oils e.g., Soybean oil, canola oil, corn oil, oat oil, wheat germ oil, palm oil, evening prime rose oil. Antioxidants are much important in the treatment of almost all diseases because most chronic diseases possess with them a great pact of oxidative stress. Oxidative stress plays a main role in neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington’s disease (HD). The ageing process elevates oxidative stress along with lack of dietary antioxidants. Researchers recommended that avoiding AD is actually not that complex.

6. Polyphenols²

Polyphenols which are produced by plants as secondary metabolites form a large group of phytochemicals, to protect them from photosynthetic stress, reactive oxygen species. There are approximately 8,000 different classes of polyphenols, the most important being flavonols, flavones, flavan-3-ols, flavanones and anthocyanin. The majority of polyphenols synthesized by branched phenylpropanoid pathway. The flavonoids and phenolic acids are the most commonly occurring polyphenols in food. These apart, polyphenols also have antioxidant, anti-inflammatory, anti-microbial, cardio protective activities and acts in the prevention of neurodegenerative diseases and diabetes mellitus. On the basis of their structural chemistry, the polyphenols are mostly acknowledged for their antioxidant activities. Polyphenols shows more effective antioxidants in vitro than vitamin E and C on a molar basis. For determination of their biological activity, bioavailability of polyphenols is an important factor. This depends on the chemical properties of polyphenol, conjugation and reconjugation in the intestines, intestinal absorption, and enzymes available for metabolism. An interesting aspect of polyphenols has also focused by research. It has been found that, the expression of γ-glutamylcysteine synthetic also modulated by flavonoids, an important rate-limiting enzyme involved in glutathione synthesis.

7. Spices:

Spices are complex food adjuncts that are used to enhance the sensory quality of foods. These provide characteristic flavor, aroma, or piquancy and color to foods, trigger our appetite as well as improve the texture of food. Most of the spice components are terpenes and other constituents of essential oils which have been found to be beneficial in different forms. Administration of garlic along with fish oil is effective on serum lipid and lipoprotein concentrations by supplying a combined lowering of total cholesterol, LDL cholesterol and triglyceride concentration. When Spices and herbs are used as food they found harmless, but when used as medicine, because of their relative higher dose administered, or rather due to the possibilities of their interactions with other pharmaceutical medications, they may exhibit toxicity. Again reports say those adverse effects on health such as anaemia, weight loss, heart, liver, kidney toxicity and other dermatological problems shown by excessive consumption of garlic. High doses of onion (500 mg/kg) may causes lung and tissue damage in rats. Regular intake of curcuminoids at about 0.5 g lowers blood lipid peroxide level up to about 33% because of their antioxidant activity. Table 3 depicts the effective functional aspects of various spices.

Nutraceuticals in Ailments:

Following are some ailments where nutraceuticals plays a significant role:

1. Diabetes:^2,11,31

Diabetes mellitus is occurred by abnormal high levels of blood glucose. Blood glucose is increased either due to insufficient insulin production, or due to its incompetence. Diabetes has two types. The most common forms of diabetes are type1 diabetes (5%), an autoimmune disorder which is associated with less or no insulin production by the intestines, and type 2 diabetes (95%), which is associated with obesity. Gestational diabetes is also a one of the type of diabetes, which occurs mainly during pregnancy. Treatment with Nutraceutical is helpful in diabetes. Insulin resistance is controlled by Docosahexaenoic acid. Docosahexaenoic is vital for neurovisual development. This is very important in women with gestational diabetes mellitus which encourage the recommendation for essential fatty acids during pregnancy. Lipoic acid is also very useful in treatment of diabetes neuropathy and it is a universal antioxidant. Lipoic acid may be more effective as a long-term dietary supplement which is aimed at the prophylactic protection of diabetics from complications. Dietary fibers occurred from psyllium have been used as pharmacological supplements. It is also a food ingredient, in processed food to control glucose in diabetic patients, and it also helps to reduce lipid levels in hyperlipidemia. Good magnesium status helps reduces diabetes risk and improves insulin sensitivity chromium picolinate, calcium and vitamin D which appear to promote insulin sensitivity. They improve glycaemic control in some diabetics. Various extracts of plants like bitter melon and of cinnamon have the ability to treat and prevent diabetes. Ethyl esters of n-3 fatty acids may be helpful in diabetic patients. Ginger is also used to treat diabetes. Some other neutraceuticals also have been reported to lower blood glucose level include Raphanus sativus as well as turmeric.

2. Cardiovascular diseases^25,31,40

For the prevention and treatment of CVD Anti-oxidants, Dietary fibres, Omega-3 polyunsaturated fatty acids, Vitamins, minerals are mostly used. Reports show that low consumption of fruits and vegetables is associated with a high death rate in CVD. Rice bran helps lowering serum cholesterol levels in the blood, lowers the level of (LDL) and increases the level of (HDL) in cardiovascular health. Higher the ratio more will be the risk of coronary heart diseases. Rice bran contains Lutein as well as Zeaxanthin, which improves eyesight. Important risk factors for CVD include factors like obesity, increased blood cholesterol level, increased blood pressure and type 2 diabetes. Consumption of poor diets and lifestyle habits such as smoking and alcohol intake amplifies the risk of CVD. People who take a healthy diet, do not smoke and consume less amount of alcohol tend to have a reduced risk of CVD. Diets lead to elevate serum total cholesterol, LDL-cholesterol, and triacylglycerol concentrations, while lead to reduced HDL-cholesterol concentrations and it leads to reduced risk of coronary artery disease. Treatment of hypercholesterolemia has mainly focused on increasing faecal excretion of cholesterol and bile acids. It helps to reducing hepatic cholesterol synthesis through diet modification. Blood pressure control is important in the prevention of heart disease, kidney disease and stroke. Factors like atherosclerosis, imbalances in the renin angiotensin system, and hyperinsulinemia may increase the blood pressure. The latter increasing sodium retention in the body and speeding up atherosclerosis. Accordingly, a general nutritional plan to minimize hypertension risk includes attaining as well as maintaining a healthy body weight. People with risk of CVD have to consume a diet rich in calcium, phosphorus, and magnesium. Alcoholic beverages and sodium consumption should be less in this people.

3. Cancer:^9,26,31,42

Cancer development is a dynamic and long-term process. This process involves many complex factors with stepwise progression. These factors ultimately lead to an uncontrolled spreading and growth of cancerous cells throughout the body, called metastasis. According to the Epidemiological studies, dietary factors can modify carcinogenesis. Laboratory research demonstrated that a number of bioactive dietary components or natural products have the ability to prevent cancer. Many food constituents with yet undefined nutritional benefits have been found to possess antimutagenic and anti-carcinogenic properties. Nutraceuticals also help in overcoming side effects of cancer treatment and improve general health of patient. Some research estimates that one-third of all cancers deaths are preventable by life-style changes, which include appropriate nutrition. Botanicals are widely used in the treatment of cancer. Alkaloids the Vinca species (vincristine and vinblastine) and of the Pacific yew Taxus brevifolia (Taxol) are effective in treatment of cancer disease. It is frequently found that the same plants are used in a number of cultures for the same symptoms, signifying that are probably medicinally quite effective for those types of aliments. Though there are much medical advancement still cancer is a worldwide health problem. Many plant extracts are useful in treatment as well as prevention of cancer. Nutritional modulation may be beneficial in the treatment of cancer patients. There is indication that foods, comparatively low amount in simple carbohydrates with moderate amounts of high-quality protein, fiber, and fat are beneficial for cancer patients. Nutraceuticals may also be helps to reduce the toxicity, associated with chemotherapy and radiation therapy. It may lead to better life conditions by reducing cancer. The phytochemicals have different mechanism of actions at different cellular levels. Versatile source of antioxidants affecting the signaling pathway related to redox mediated transcription factors. Moreover, they directly modulate the endocrine system, immunological cascade as well as enzymes related to inflammation. Some of them have shown direct effect on DNA repair and cleavage process.

4. Parkinson’s disease^{2,11,27,33,36}

It is a brain disorder. It is the most common neurological movement disorder worldwide. It results from nerve damage in certain regions of the brain. PD is aging-related disorder. It causes muscle rigidity, shaking, and difficult walking usually occurring in mid to late adult life. Various vitamins, such as vitamin B3, vitamin B9 or folate, vitamin B12, vitamin B6, vitamin D, vitamin E, and vitamin C, can be used in Parkinson’s disease. The anti-Parkinson drugs presently employed prevent disease development by offering symptomatic relief only. Some research shows that vitamin E in food may have a protective role against Parkinson's disease. Creatine declines the clinical signs of the Parkinson’s disease and also modifies disease state. Research study showed that glutathione has power as an antioxidant and it also has effect on the nerves. The appropriate long-term dosing, side-effects and the most effective method of administration are not yet clear. Nutritional supplements have important to remember that there is not sufficient scientific data to recommend them for Parkinson's disease at present. There is no known cure for PD, but it may prevent or delayed by nutraceuticals. The exact mechanisms of PD are not yet totally understood. Vitamin D deficiency may have a major role in the growth and progression of PD. unsaturated fatty acids may reduce the risk of developing PD. Natural products employ favourable effects in PD by reducing the different pathologic pathways inducing it, such as oxidative stress, dysfunction of mitochondria, neuro-inflammation, and apoptosis. Ginseng and its derivatives, ginsenosides, verified neuroprotective action in several studies on PD. Vincamine which is an alkaloid obtained from the vinca plant, has demonstrated anti-PD activity through different mechanisms of action. Oxidative stress as well as iron is targeted by vincamine to recover the production of DA and decline the neuronal damage produced.

5. Irritable bowel syndrome:^{2,28,35,38,43,44,45}

Irritable bowel syndrome (IBS) is a chronic functional syndrome of the gastrointestinal tract. Most recent approaches on classification of IBS approve that the diagnosis of IBS and its clinical subtype necessity depend on classifying typical symptoms. Ulcerative colitis (UC) and Crohn’s disease (CD) are collectively called as inflammatory bowel disease (IBD). Meanwhile IBD patients, particularly Crohn’s disease patients, are frequently categorized by malnutrition, altered body composition and/or mesenteric obesity, due to steroid treatment, artificial nutrition is often requested during the clinical course of the disease. Natural product therapy in IBD includes modulation of mediators involved in the inflammatory procedure. The Luminal bacteria adapt the immune response and rejuvenation of intestinal healing. Aloe Vera gel, an extract of Aloe barbadensis, is generally used in the treatment of IBD. In a small set of IBS patient curcumin at 72mg or 144mg, given daily for 8 weeks to decline the abdominal pain intensity as well as improved quality of life. Fibre may act as a bulking agent to progress intestinal transit and also to decrease constipation in a subgroup of IBS patients. Some S. cerevisiae strains are used as probiotics marking to help IBS symptoms. Additional study estimated a mixture of various herbal medicines (Boswellia carterii, Zingiber officinal, and Achillea millefolium) with helpful effects in patients with IBS.

6. Anti-inflammatory activities:^{2,30,31,35,37,38}

Curcumin (diferuloylmethane) is a polyphenol of turmeric. It has anti-oxidative, anti-carcinogenic, and anti-inflammatory properties. Spinach leaves, Cucumber fruits, and turmeric rhizomes possess anti-tumor activity. Gamma linoleic acid is used for treating problems with inflammation and auto-immune diseases. Glucosamine and chondroitin sulfate are used in contradiction of osteoarthritis and regulate gene expression and acts as a potent anti-inflammatory agent.

ACKNOWLEDGEMENT:

We would like to express our special thanks of gratitude to our principal Dr. N.H. Aloorkar who gave us the golden opportunity.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

REFERENCES:

1. Rajasekaran, A., Sivagnanam, G. and Xavier, R., Nutraceuticals as therapeutic agents: A Review. J. Pharm. Sci. Technol.2008; 1.

2. A Review on Nutraceuticals: Classification and ITS Role in Various Diseases Garima Verma; International Journal of Pharmacy and Therapeutics. 2016; 7(4): 152-160

3. Jagtar Singh; Classification, Regulatory acts and Applications OF Nutraceuticals for Health; IJPBS. 2012; 2(1): 177-187

4. Krishan Kumar. Role of nutraceuticals in health and disease prevention: A review. South Asian J. Food Technol. Environ. 2015; 1(2): 116-121.

5. Chan, M. Supporting the integration and modernization of traditional medicine. Science. 2014; 346: S2.

7. Zeisel SH. Regulation of Nutraceuticals. Science. 1999; 285:185-186.

8. Bhawna Verma and Harvinder Popli. Regulations of nutraceuticals in India and us. The Pharma Innovation Journal. 2018; 7(7): 811-816

9. Palthur MP, Palthur SS, Chitta SK. Nutraceuticals: a conceptual definition. Int. J Pharmacy Pharm Sci. 2010; 2(3): 19-27

10. Sapkale Anita P. Nutraceuticals - Global status and applications: a Review. International Journal of Pharmaceutical and Chemical Sciences. 2012; 1 (3).

11. Kalra, E. K., Nutraceutical-definition and introduction. AAPS Pharm. Sci. 2003; 5: 2-3.

12. Chintale Ashwini G. Role of Nutraceuticals in Various Diseases: A Comprehensive Review. IJRPC. 2013; 3(2).

13. http://blog.jigschemical.com/what-are-nutraceuticals/

14. https://www.curegarden.in/blogs/curegarden-team/nutraceuticals-the-new-breed

15. Lipi Das, Eshani Bhaumik, Utpal Raychaudhuri and Runu Chakraborty. Role of nutraceuticals in human health. J Food Sci Technol. 2012; 49(2):173–183. DOI 10.1007/s13197-011-0269-4 https://www.crchealth.com/types-of-therapy/nutraceutical-therapy/

16. Chanda Silpi, Tiwari Raj Kumar, Arun Singh Kuldeep. Nutraceuticals Inspiring the Current Therapy for Lifestyle Diseases. Advances in Pharmacological Sciences. 2019. 1-5. 10.1155/2019/69087

17. Klatte ET, Scharre DW, Nagaraja HN, Davis RA, Beversdorf DQ. Combination therapy of donepezil and vitamin E in Alzheimer disease. Alzheimer Dis Assoc Disord. 2003; 17: 113-116

18. Casey, C. F., Slawson, D. C. and Neal, L. R. Vitamin D supplementation in infants, children, and adolescents. Am. Fam. 2010; 81: 745-748.

19. M. Pineiro and C. Stanton. Probiotic bacteria: legislative framework-requirements to evidence basis. The Journal of Nutrition. 2007; 137(3): 850S–853S.

20. Michail, S., Sylvester, F., Fuchs, G. and Issenma, R. Clinical efficacy of probiotics: Review of the evidence with focus on children, clinical practice guideline. J Pediatr Gastroenterol Nutr. 2006; 43(4)

21. Hord, N. G. Eukaryotic microbiotic crosstalk: potential mechanisms for health benefits of prebiotics and probiotics. Annu. Rev. Nutr. 2008; 28: 215–231

22. www.cdc.gov/

23. www.netdoctor.co.uk/

24. Namdeo Shinde, Bhaskar Bangar, Sunil Deshmukh, Pratik Kumbhar. Nutraceuticals: A Review on current status. Research J. Pharm. and Tech. 2014; 7(1): 110-113.

25. Avrelija Cencic and Walter Chingwaru. The Role of Functional Foods, Nutraceuticals, and Food Supplements in Intestinal Health; Nutrients. 2010; 2: 611-625. doi:10.3390/nu2060611

26. Elia Ranzato, Simona Martinotti, Cinzia Myriam Calabrese and Giorgio Calabrese. Role of Nutraceuticals in Cancer Therapy. Journal of Food Research. 2014; 3(4).

27. Chao J, Leung Y, Wang M, Chang RC. Nutraceuticals and Their Preventive or Potential Therapeutic Value in Parkinson's disease. Nutrition Reviews. 2012; 70 (7): 373–386.

28. Piero Portincasa, Leonilde Bonfrate, Ornella de Bari, Anthony Lembo, and Sarah Ballou. Irritable bowel syndrome and diet. Gastroenterology Report. 217; 5(1): 11–19.

29. Rathod S, Mali S, Shinde N, Aloorkar N. Cosmeceuticals and Beauty Care Products: Current trends with future prospects. Research Journal of Topical and Cosmetic Sciences. 2020;11(1): 45-51.

30. Al-Okbi, Sahar. Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis. Toxicology and industrial health. 2012; 30. 10.1177/0748233712462468.

31. Tewari S, Ramkrishna KS. A Review on Nutraceutical: The combination of Nutrition and Pharmaceutical. J Nutraceuticals Food Sci. 2020; 3:4

32. Howes, Melanie-Jayne. Phytochemicals as Anti-inflammatory Nutraceuticals and Phytopharmaceuticals. 2018; 10.1016/B978-0-12-805417-8.00028-7.

33. Lama, Adriano Pirozzi, Claudio Avagliano, Carmen Annunziata, Chiara Mollica, Maria Calignano, Antonio Meli, Rosaria Mattace Raso, Giuseppina. Nutraceuticals: An integrative approach to starve Parkinson’s disease. Brain, Behavior, and Immunity - Health. 2020; 2. 100037. 10.1016/j.bbih.2020.100037.

34. Hang, Liting Basil, Adeline Lim, Kah-Leong. Nutraceuticals in Parkinson’s Disease. NeuroMolecular Medicine. 2016; 18. 10.1007/s12017-016-8398-6.

35. Gao, Xiang Liu, Jingwen Li, Li Liu, Wei Sun, Meiyan. A Brief Review of Nutraceutical Ingredients in Gastrointestinal Disorders: Evidence and Suggestions. International Journal of Molecular Sciences. 2020; 21. 1822. 10.3390/ijms21051822.

36. Makkar, Rashita Behl, Tapan Bungau, Simona Zengin, Gokhan Mehta, Vineet Kumar, Arun Uddin, Md. Sahab Ashraf, Ghulam Abdel Daim, Mohamed Arora, Sandeep Oancea, Roxana. Nutraceuticals in Neurological Disorders. International Journal of Molecular Sciences. 2020; 21: 4424. 10.3390/ijms21124424.

37. Huang, M.T, Ghai, G. Ho, Chi-Tang. Inflammatory Process and Molecular Targets for Antiinflammatory Nutraceuticals. Comprehensive Reviews in Food Science and Food Safety. 2006; 3: 127 - 139. 10.1111/j.1541-4337.2004.tb00063.x.

38. Cencic, Avrelija Chingwaru, Walter. The Role of Functional Foods, Nutraceuticals, and Food Supplements in Intestinal Health. Nutrients. 2010; 2: 611-25. 10.3390/nu2060611.

39. Parian, Alyssa Limketkai, Berkeley Shah, Neha Mullin, Gerard. (). Nutraceutical Supplements for Inflammatory Bowel Disease. Nutrition in clinical practice: official publication of the American Society for Parenteral and Enteral Nutrition. 2015; 30: 10.1177/0884533615586598.

40. Zoltani, Csaba. Nutraceuticals in Cardiovascular Diseases. 2019; 10.1007/978-3-030-04624-8_28.

41. Gupta, Bhanushree Kumar, Bhupesh Sharma, Anshuman Sori, Deeksha Sharma, Rahul Mehta, Saumya. Nutraceuticals for Antiaging. 2019. 10.1007/978-3-030-04624-8_25.

42. Roudebush, Philip Davenport, Deborah Novotny, Bruce. The use of nutraceuticals in cancer therapy. The Veterinary clinics of North America. Small Animal Practice. 2004; 34: 249-69 viii. 10.1016/j.cvsm.2003.09.001.

43. Taus, Marina Busni, Debora Petrelli, Massimiliano Nicolai, Albano. New nutritional approach to inflammatory bowel disease: The nutraceuticals. Mediterranean Journal of Nutrition and Metabolism. 2009; 145-148. 10.1007/s12349-008-0022-3.

44. Uranga, José Lopez-Miranda, Visitacion Lombó, Felipe Abalo, Raquel. Food, nutrients and nutraceuticals affecting the course of inflammatory bowel disease. Pharmacological Reports. 2016; 68. 10.1016/j.pharep.2016.05.002.

45. Larussa, Tiziana Imeneo, Maria Luzza, Francesco. Potential role of nutraceutical compounds in inflammatory bowel disease. World Journal of Gastroenterology. 2017; 23. 2483-2492. 10.3748/wjg.v23.i14.2483.

46. Joshi, Vivek Alam, Shahjahan and Dimri, U. and Vinodhkumar, Obli. Veterinary Nutraceuticals: An Alternative Medicine. Indian Dairyman. 2016; 68. 90-93.

47. Taillon, C and Andreasen, A. Veterinary nutraceutical medicine. The Canadian veterinary journal. La Revue Vétérinaire Canadienne. 2000; 41. 231-4.

48. Beale, Brian. Use of nutraceuticals and chondroprotectants in osteoarthritic dogs and cats. The Veterinary clinics of North America. Small animal practice. 2004; 34. 271-89, viii. 10.1016/j.cvsm.2003.09.008.

49. Dzanis, DA. Nutraceuticals in veterinary medicine. Australian Veterinary Journal. 1999; 77. 238-9. 10.1111/j.1751-0813.1999.tb11709.x.

50. A. S. Suresh, Bhavna Pawar. A Study of Factors of Lifestyle and its impact on Nutraceutical Consumption: India Perspective. Asian Journal of Management. 2018; 9(1):203-211.

51. Sarika S. Lokhande. Role of Nutraceuticals in Various Diseases: A Comprehensive Review. Asian J. Pharm. Res. 2018; 8(4): 236-240.

52. Seema Thakur, Neha Srivastava. Nutraceuticals: A Review. Asian J. Res. Pharm. Sci. 2016; 6(2): 85-94.

53. Vipul Singh, Sangeeta Mahaur, Sanjay Kumar Kushwaha. Nutraceuticals: A New Golden Era in Health and Disease. Asian J. Research Chem. 2018; 11(3):652-658.

54. G. Sreeramya, C.N. Nalini, Ramalakshmi.N, Kondaviti Sahini, Amudha Lakshmi.S. A new Era in Medicine – Neutraceuticals. Research J. Pharm. and Tech 2018; 11(8): 3572-3576.

55. R. Arivuchudar, Tamilchudar R. An Overview on the Sway of Nutritional Supplements on Dry Eye Disease. Research J. Pharm. and Tech. 2020; 13(10):5004-5008.

56. A Rajasekaran, G Sivagnanam, R Xavier. Nutraceuticals as therapeutic agents: A Review. Research J. Pharm. and Tech. 2008; 1(4): 171-174.

57. Kavitha PG, M Umadevi. Medicinal Properties and Pests and Diseases of Noni - A Review. Res. J. Pharmacognosy and Phytochem. 2016; 8(1): 41-48.

58. The Pharmaceutical Journal, PJ, July 2000;()::DOI:10.1211/PJ.2021.1.71102

59. Divyadharsini V. Genetically Modified Foods – A Review. Research J. Pharm. and Tech. 2014; 7(3): 392-395.

60. S. Subasree, Karthikeyan Murthykumar, Dr. Dhanraj. Effect of Aloe Vera in Oral Health – A Review. Research J. Pharm. and Tech. 2016; 9(5): 609-612.

61. M. Vaishali. Antioxidants in Health and Diseases. Research J. Pharm. and Tech. 2014; 7(4): 489-493.

62. Sripradha S., Karthikeyan Murthykumar, Subasree Soundarajan, Niha Naveed. Garlic, its Role in Oral Health-A Review. Research J. Pharm. and Tech. 2014; 7(6): 727-729.

63. Tandra Das.T. Role of Antioxidants in Health and Diseases-A Review. Research J. Pharm. and Tech. 2015; 8(8): 1033-1037.

64. Amina Mehrin Bano, Vishnupriya. V, Gayathri. R. Nutritional awareness among Adolescents. Research J. Pharm. and Tech. 2016; 9(7): 898-902.

65. K.V. Swathi. Probiotics –A Human Friendly Bacteria. Research J. Pharm. and Tech. 2016; 9(8):1260-1262.

66. Pal Neha, Joshi M. D. Piper nigrum: An Overview of effects on Human Health. Research J. Science and Tech. 2020; 12(4):331-337.

67. Ponnambily Chandy Jobin. The Nutritional Status, Dietary Pattern and Health Outcomes among the Adolescent Girls in the Suburban areas of Chennai. Int. J. Nur. Edu. and Research. 2019; 7(2): 165-169.

68. Suby Elizabeth Oommen. Health Care System of India–A Comparison with health indicators. Res. J. Humanities and Social Sciences. 2018; 9(3): 575-579.

69. Archana A. Bele, Anubha Khale. An approach to a Nutraceutical. Research J. Pharm. and Tech. 2013; 6(10): 1161-1164.

Received on 18.04.2021 Modified on 22.09.2021

Asian J. Pharm. Res. 2022; 12(1):61-70.

DOI: 10.52711/2231-5691.2022.00010