ROLE OF NUTRACEUTICALS IN AILMENTS

 Introduction

Nutraceuticals are getting recognized for being valuable in coronary heart disease, obesity, 

diabetes, cancer, osteoporosis, and other chronic and degenerative diseases like Parkinson’s 

and Alzheimer’s diseases. 

 As per the evidences, the natural compounds act via various biological processes that include 

activation of antioxidant defenses, signal transduction pathways, cell survival-associated gene 

expression, proliferation and differentiation of cell, and preservation of mitochondrial integrity. 

These processes have vital roles in providing protection against the pathologies of a wide array 

of age-related or chronic diseases. The nutrients found in many foods, fruits, and vegetables 

contribute to the many well known health benefits. For example, lutein and zeaxanthin prevent 

cataracts and macular degeneration; β-carotene and lycopene protect the skin from UV light 

damage; lutein and lycopene benefit cardiovascular health; and lycopene helps preventing 

prostate cancer. 

Because of these and other health benefits of Nutraceuticals should be regularly consumed, as 

they also reduce the risk factors of high cholesterol, high blood pressure, and diabetes. 

 

In Diabetes: 

 Diet therapy is the keystone for the management of gestational diabetes mellitus. There are many 

herbal dietary supplements that are believed to benefit type 2 diabetes mellitus; however, only a few 

have been proven beneficial through properly designed randomized trials. Isoflavones are 

phytoestrogens with structural or functional similarity to human estrogen and are widely consumed by 

humans. 

Soy Isoflavones are the most studied ones. Consuming isoflavone in high amounts (20-100mg/day) 

reduces the incidence and mortality rate of type 2 diabetes, heart disease, osteoporosis, and certain 

cancers. 

 Omega-3 fatty acids 

 These reduce glucose tolerance in patients prone to diabetes. Insulin is required for synthesizing long 

chain n-3 fatty acids; thus, the heart should be susceptible to their depletion in diabetes. Ethyl esters of 

n-3 fatty acids are also potentially beneficial in diabetes. �

 Docosahexaenoic acid 

 It controls insulin resistance and is helpful in neurovascular development. It is very important in women 

with gestational diabetes mellitus as such a condition demands essential fatty acids during pregnancy. 

 Lipoic acid 

 It is an antioxidant and is used in diabetic neuropathy. It may be more effective as a long term dietary 

supplement that aims at prophylactic protection of diabetic patients. 

 Dietary fibers from psyllium 

These have been used as pharmacological supplements and as food ingredients in processed food to 

help in weight loss, to control glucose in diabetics, and to reduce lipid levels in hyperlipidaemia. 

Magnesium reduces diabetes risk and improves insulin sensitivity

Chromium picolinate, calcium and vitamin D promote insulin sensitivity and improve glycaemic 

control in diabetics 

Extracts of bitter melon and cinnamon potentially treat and prevent diabetes. 

�CVS Diseases 

 Worldwide incidences of abundance of chronic diseases, like cardiovascular diseases, cancers, diabetes, 

and obesity, are rapidly increasing. In 2001, chronic diseases contributed 59% of the 56.5 million total 

reported deaths in world. 

Cardiovascular Diseases (CVD) are a group of disorders of heart and blood vessels, that include 

hypertension (high blood pressure), coronary heart disease (heart attack), cerebrovascular disease 

(stroke), heart failure, peripheral vascular disease, etc. 

In 1999, CVD contributed to 1/3rd of global deaths and by 2010 it was the leading cause of death in 

developing countries.

 

CVD are mostly preventable and controllable. Evidences suggest that less consumption of fruits and 

vegetables is associated with a high mortality in CVD. 

 Nutraceuticals in the form of antioxidants, dietary fibres, omega-3 Polyunsaturated Fatty Acids (n-3 

PUFAs), vitamins, and minerals along with physical exercise helps in preventing and treating CVD. 

Polyphenols 

These are found in grapes and wine alter cellular metabolism and signaling, which consequently 

reduces arterial disease. 

 Flavonoids 

These are found in onion, endives, cruciferous vegetables, black grapes, red wine, grapefruits, apples, 

cherries, and berries. In plants, they are available as flavones (containing apigenin found in chamomile), �flavanones (containing hesperidins found in citrus fruits; silybin in milk thistle), and flavonols (containing 

quercetin found in tea; kaempferol and rutin in grapefruit; rutin in buckwheat; ginkgo flavones 

glycosides in ginkgo), which play a major role in curing CVD. 

 Flavonoids inhibit angiotensin-converting enzyme (that increases blood pressure) by blocking the 

suicide enzyme, i.e., cyclooxygenase, that breaks down prostaglandins; thus, preventing platelet 

aggregation. 

Flavonoids also protect the vascular system and strengthen the tiny capillaries that deliver oxygen and 

essential nutrients to all the cells. Flavonoids block the enzymes that produce estrogens, thus reduce the 

risk of cancers induced by estrogens. 

In Cancer 

Botanicals are in use in cancer treatment since a long time. Many cancer chemotherapeutic drugs are 

derived from plants, like the alkaloids of Vinca species (vincristine and vinblastine) and Taxus brevifolia 

(taxol). 

 In the ancient cultures, a wide range of techniques were used for treatment and prevention of 

diseases, and for maintaining health. One subset of these techniques is plant extracts. 

Often, a number of cultures use similar plants for the same symptoms or diseases; thus, indicating that 

they are medicinally effective for those ailments. 

 Besides these medical advances, cancer still is a worldwide health problem, and various plant extracts 

are used for its treatment and prevention. Evidences suggest that foods low in simple carbohydrates and 

moderate amounts of high quality protein, fiber, and fat (especially, fats of omega-3 fatty acid series) 

are beneficial for cancer patients. 

Nutraceuticals are also helpful in reducing toxicity associated with chemotherapy and radiotherapy, thus 

lead to better life conditions by reducing cancer cachexia. Phytochemical have shown different 

mechanism of actions at different cellular levels. Most of them are versatile source of antioxidants 

affecting the signaling pathway related to redox-mediated transcription factors. They also directly 

modulate the endocrine system immunological cascade and enzymes related to inflammation. Some of 

them show direct effect on DNA repair and cleavage process. 

Main Phytochemicals Studied for Cancer Care Dietary phytochemicals are classified on the basis of their 

chemical structures, botanical origin, biological properties, biosynthesis, etc. 

� Polyphenols �

 Polyphenols are plant secondary metabolites containing one or more hydroxyl groups attached to a 

benzene ring in their structure. More than 8000 different polyphones found in food (wine, tea, coffee, 

cocoa, vegetables, and cereals) are present in human diet. 

Polyphones are classified into different groups depending on the number of phenol rings and structure 

that links these rings. The groups of Phenolics acids, flavonoids, stilbenes, and curcuminoids are very 

important for their ability to block initiation of carcinogenic process and to suppress cancer progression. 

Epigallocatechin-3-Gallate (EGCG) 

EGCG is the major catechin found in green tea (Camellia sinensis). Frequent consumption of green tea in 

Asian countries was found to be related to several health benefits and is recognized as the most 

effective cancer-preventive beverage. 

 Its antitumor properties have been identified on multiple cancer cell lines, including less common 

tumours such as anaplastic thyroid carcinoma and malignant mesothelioma. Studies determining the 

anticancer drug properties of EGCG are mostly preclinical; so, for better understanding of specific 

effects, clinical trials should be carefully designed to evaluate EGCG effectiveness. Clinical applications of 

green tea have the limitation of low bioavailability and conversion into inactive methylated metabolites. 

Biotransformation of green tea polyphenols is different in humans than in rats and mouse; this explains 

that inter-species difference exists in anti-carcinogenic properties. 

However, the numerous antitumor effects exerted by EGCG suggest that it is a potential tool for cancer 

prevention and therapy, both alone and together with antitumor drugs or other phytochemicals. 

Resveratrol 

It is the most important stilbenes related to cancer. It exhibits a natural anti-proliferative activity due to 

its role as a phytoalexin (plant antibiotic). It also has anti-cancer, anti-carcinogenesis and anti�inflammatory bioactivities. 

The mechanisms by which resveratrol produce these effects are not clear, but the main molecular 

mechanism is believed to be the activation of sirtuin proteins. There is a considerable interest in 

developing resveratrol for cancer prevention and treatment. 

 Plasma pharmacokinetics of resveratrol in humans is now well defined, and studies show that its 

repeated daily doses are safe and well-tolerated. 

However, pharmacokinetic studies of resveratrol show poor bioavailability (only 1%) due to extensive 

glucuronidation and sulfation, and metabolism by gut bacterial enzymes. �

Quercetin 

 Quercetin (a representative member of flavonoid class) is a compound derived from various fruits and 

vegetables that can reach levels in human diet as high as 16-25mg/day. 

Effects of quercetin are related to induction of cell apoptosis through multiple mechanisms. 

 In vivo studies of the anticancer effects of quercetin indicate that its oral administration can prevent 

induced carcinogenesis in the colon, inhibit melanoma growth, invasion, and metastatic potential. 

However, just like resveratrol, quercetin also faces the problem of low bioavailability. 

Vitamins and Minerals in Cancer Management 

 In several independent studies, vitamins (A, C, and E) and trace elements (selenium) were found to 

prevent cancer. Supplementation with micronutrients as adjuvant in cancer patients may prove to be 

helpful. Vitamin C (ascorbate) is an essential nutrient in human diet, but is also a widely used medicinal 

product, and has long been held as a remedy for various diseases. 

 Studies on mechanism of ascorbate toxicity reported induction of apoptosis through cell cycle arrest, 

activation of apoptosis factors, and interference with iron uptake in cells. However, ascorbate acts as an 

electron donor in redox reactions, and evidences suggest that oxidative stress plays a major role in the 

mechanism of ascorbate toxicity in tumor cells. Other in vitro and in vivo studies include evaluating the 

real potentialities of ascorbate, by combining it with chemotherapeutic drugs. 

In Irritable Bowel Syndrome Ulcerative Colitis (UC) and Crohn’s Disease 

(CD) 

 Both are together known as Inflammatory Bowel Disease (IBD). Etiology of these conditions is not 

completely understood; however, the hypotheses for causation of these conditions include genetic 

susceptibility, environmental risk factors, inappropriate and chronic immune responses to members of 

intestinal microflora, and failed immune regulatory mechanisms. 

Pathophysiology of IBD involves continued intestinal inflammation, presence of pro-inflammatory 

cytokines, increased Reactive Oxygen Species (ROS), and tissue injury triggered by luminal bacteria. 

Natural product therapy in IBD includes modulation of mediators involved in inflammatory process 

altering luminal bacteria, modification of the immune response, and rejuvenation of intestinal healing. 

5-Aminosalicylic Acid 

 (5-ASA) is a well-established therapeutic agent in the management of UC; but, its involvement in CD is 

unclear. The NF-αβ pathway is an important target. �

 In IBD, presence of pro-inflammatory cytokines such as TNF- αβ causes phosphorylation of iқ- and 

results in activation of NF-қ, thus initiating the synthesis of more pro-inflammatory cytokines. 5-ASA 

inhibits TNF- αβ induced stimulation of i- αβ phosphorylation, thus disrupts a signal transduction 

Aloe vera gel 

(an extract of Aloe barbadensis) is used in the treatment of IBD. 

In a Randomised Controlled Trial (RCT), in which aloe vera gel was administered for four weeks to 

patients with active UC, the results showed that they had greater symptom alleviation than placebo. 

Andrographis paniculata 

 It shows a significant reduction in transcriptional activity of NF-қ and reduces secretions of pro�inflammatory cytokines, including TNF- - αβ and IL-6, both of which are elevated in IBD patients. In a 

RCT (n = 224), greater clinical response was encountered in UC patients receiving A. paniculata 

treatment than placebo. Similar results were obtained in a clinical trial in which the efficacy of A. 

paniculata was compared to conventional mesalazine therapy. 

Various Gastrointestinal Diseases 

Nutraceuticals in Gastritis 

 Gastritis, i.e., inflammation of stomach lining, is the most common disorder of stomach that occurs 

due to infection caused by Helicobacter pylori and/or the effect of NSAIDs. It can also be caused by 

irritation due to excessive alcohol, smoking, cocaine, severe illness, autoimmune problems, radiation 

therapy, and Crohn’s disease. Gastritis can be diagnosed in its acute phase, when the patients 

experience nausea, pain and discomfort in the upper abdomen due to superficial inflammation of the 

stomach. In the developed stage, gastritis is termed chronic gastritis, which causes pain in the upper 

abdomen, feeling of fullness, and loss of appetite. 

Phenolic Compounds 

Phenolics compounds (or flavonoids) are found in various drinks and edible plants such as strawberry, 

apple, tea, red wine, beer, etc. They exhibit biological properties, such as antiviral, anti-inflammatory, 

antihistaminic, antioxidant, and free-radical scavenging abilities. 

The gastro protective effect of flavonoids may be attributed to its effectiveness in increasing the 

endogenous PG, reduction in histamine secretion, scavenging oxygen-derived free radicals, and gastric 

mucous stimulation. These properties restore the gastric mucosal integrity by dynamic balance and 

homeostasis between epithelial cell renewal and cellular apoptosi�s.

Quercetin 

It is a flavonoid found in various vegetables, fruits, and beverages such as tea and red wines. It is known 

to prevent gastric injuries in rats. It prevents gastric damage from the harmful effects of activated 

neutrophil infiltration by inhibiting the MPO activity. It also increases the activity of superoxide 

dismutase (SOP) to reduce lipid peroxidation and of protein carbonyl compounds to protect gastric 

mucosa against inflammation. 

Curcumin 

It is the most active constituent of the perennial herb Curcuma longa. 

 Curcumin-based therapy was found to be associated with clinical amelioration and a statistically 

significant decrease of gastric inflammation. It also inhibits the growth of H. pylori by inhibiting the 

shikimate. 

Bilberry 

It was found to reduce the occurrence and severity of experimentally induced ulcers in animals. Roots of 

Bupleurum falcatum (species of flowering plant of Apiaceae family) showed weak anti-ulcerogenic 

activity in pylorus ligated ulcer model. The polysaccharide fraction of B. falcatum was found to possess 

potent antiulcer activity against Hcl/ethanol-induced lesions in mice. �