The term nutraceutical is well-defined as “a food or a part of food that provides medical or health benefits including the prevention and treatment of a disease”. However, the term does not represent the perfect terminology in the market and may refer not only to a supplement in the diet, but also to its role in the prevention and treatment of a disease or a disorder. The term nutraceutical was defined by Stephen DeFelice from the combination of the terms nutrition and pharmaceutical in 1989 (DeFelice 1995; Baragi et al. 2008). Herbal nutraceuticals are powerful tools for maintaining health and they act against nutritionally induced acute and chronic diseases, by promoting optimal health, longevity and quality of life (Khan et al. 2014).

Nutraceuticals in Ayurveda

Medicinal plants contain several secondary metabolites that have medicinal properties against diseases (Padmavathi 2013). In ayurvedic pharmaceutics there are some dosage forms like ghrta, taila, avaliha, asavarista and ksirapaka that can be equated with nutraceuticals (Khamkar and Dubewar 2019). One of the techniques of Ayurveda, Ajasrk Rasayana, applies to the use of food products that can be consumed on a daily basis. These have the ability to improve the status of health by offering protection against stress factors. The nutraceuticals that can be commonly employed on a daily basis include Cyavanprasa for overall health and prevention of respiratory disease, Phala Ghrta for reproductive health, Brahma Rasayana to protect from mental stress, Arjuna Ksirapaka and Rasona Ksirapaka for cardioprotective functions and Satavari Ghrta in women’s health (Rani and Sharma 2005). Thus, herbal formulations that can protect general health have gained worldwide importance on account of their diverse benefits (Kumar and Sharma 2020).

Chronic Diseases

The term chronic condition is a state of physical or mental health that can last for more than a year with functional restrictions or the condition requiring ongoing management (Basu et al. 2016). It affects health and quality of life globally, leading to death and disability (Raghupathi and Raghupathi 2018). Chronic diseases which are also known as non-communicable diseases include a range of disorders such as arthritis, Alzheimer’s disease, Parkinson’s disease, cancer, cardiovascular disease and diabetes (Kunnumakkara et al. 2018a; Khwairakpam et al. 2018). The general risk factors that are related to these chronic diseases include unhealthy lifestyles with physical inactivity, poor routine in diet, exposure of the body to radiation, stress, excessive consumption of tobacco or alcohol and infection to pathogenic microorganisms (Kunnumakkara et al. 2018a). Three essential components such as research, performance measurement and quality improvement are required for continued management of chronic diseases (Davis et al. 2000).

Role of Nutraceuticals in Chronic Diseases

Nutraceuticals may vary from dietary supplements, specific nutrients, herbal products, processed food such as cereals and beverages containing bioactive components (Prakash et al. 2012; Khamkar and Dubewar 2019). In terms of chemical origin, nutraceuticals can be isoprenoids, phenolic compounds, carbohydrate derivatives, fatty acids, structural lipids, amino acids, microbes and minerals (Prakash and Sharma 2014). On the basis of natural sources, they are termed nutrients, herbals, dietary supplements, dietary fiber and so on, out of which dietary supplements (with 19.5% annually) and natural/herbal products (with 11.6% annually) are the most rapidly growing segments in the sector. Nutraceuticals have an overall global market estimate of US$117 billion (Chauhan et al.

2013). The properties of nutraceuticals are important in terms of their effectiveness against several chronic ailments like cardiovascular disease, diabetes, metabolic syndrome, obesity, cancer and neurodegenerative disease (Chauhan et al. 2013; Islam et al. 2020).

Nutraceuticals in Diabetes

Diabetes mellitus is one of the most important metabolic disorders. The major cause of mortality and morbidity of the disease is due to its associated complications that are related to increased glucose levels (Prabhakar et al. 2014). It is characterized by abnormally high blood glucose levels which may be either due to insufficient insulin production or lowered effectiveness of insulin. The general forms of this disease are diabetes type 1, representing 5%, which is an autoimmune disorder and type 2 diabetes, representing 95%, which is linked with obesity. One rare type is gestational diabetes which occurs during pregnancy (Rajasekaran et al. 2008). The disease can give rise to many short-term complications like hypoglycemia, ketoacidosis or non-ketonic hyperosmolar coma, if it is not properly managed. It can also give rise to long-term problems that include cardiovascular disease, diabetic nephropathy or chronic renal failure, retinal damage that can cause blindness and severe nerve damage (Baldi et al. 2013).

In a clinical study, human subjects were provided with the composition of nutraceuticals that contained epicatechin added to an equivalent quantity of gymnemic acid and others in smaller quantities, such as Cinnamomum tamala, Syzygium cumini, Azardichta indica, Trigonella foenum graceum, Tinospora cordifolia and Ficus racemose for four and 12 months. The subjects were administered one to two grams of composition thrice daily before meals. The treatment caused regeneration of the pancreatic cells resulting in insulin production (Dhaliwal 1999). Another study evaluated the outcome of aqueous extract of Pterocarpus marsupium bark that decreased the levels of blood sugar from 2 hours after the extract was orally administered in alloxan-induced diabetic rats. A similar effect was observed from the alcohol extract of Trigonella foenum-graecum seeds and the leaves of Ocimum sanctum both in normal and alloxan-induced diabetic rats. The extracts also showed its effect on glucose disposition in hyperglycemic rats fed with glucose (Vats et al. 2002). Further, various extracts of Momordica charantia reduced fasting blood glucose by 48% w'ith no association of nephrotoxicity and hepatotoxicity complications, suggesting it as a safe alternative in managing glucose levels (Virdi et al. 2003). Similar results were observed in another clinical study which reported that daily dose of 1 to 6 grams of cinnamon powder resulted in decreasing about 20% of fasting glucose and improving the levels of serum lipid by reducing triglyceride, L.D.L. cholesterol and total cholesterol levels (Khan et al. 2003). The ethanol extract of the rhizomes of wild ginger (Zingiber zerumbet) was also found to have the property of reducing blood sugar levels in a diabetes-induced rat model (Muhtadi et al. 2018).

Nutraceuticals in Cardiovascular Diseases

Cardiovascular diseases are the leading causes of death (Di Girolamo et al. 2020). This disease involves a number of disorders that affect the heart and blood vessels. Nearly one out of three suffers from this disease, with many complications that can result in ischemic heart attack or stroke (Park et al. 2020). Cardiovascular diseases can be mainly grouped into ischemic heart disease and cerebrovascular disease, which account for nearly 2 million and 1 million mortality rates respectively (Di Girolamo et al. 2020). Many psychological factors have been known to increase the risk of cardiovascular diseases (Larkin and Chantler 2020). Undeniably, this disease commonly affects adults above 60 years of age and factors like obesity, hyperlipidemia, diabetes mellitus, hypertension, metabolic syndrome and lifestyle risk factors that include unhealthy diet routine, smoking and less physical activity are associated with this disease (Sosnowska et al. 2017).

It has been reported that greater consumption of plant sterols could lower the total serum L.D.L., non-H.D.L. cholesterol and carotid intima-media thickness in humans (Wang et al. 2012). Additionally, grape extracts rich in polyphenol at a 700 mg dose on healthy subjects with risk of cardiovascular disease, reduced total plasma cholesterol and L.D.L.-C. concentrations (Yubero et al. 2013). The dietary intervention of grape nutraceutical containing 8 mg of resveratrol markedly improved the inflammatory condition and fibrinolytic status in patients, who were under primary prevention of cardiovascular disease. The outcome was due to suppression of h.s.-C.R.P. expression after a one-year regimen that could be related to decreased level of the pro-inflammatory cytokine T.N.F.-a and thrombogenic P.A.I.-l (Tome-Carneiro et al. 2012).

In humans, berberine has the property of lowering lipids and the insulin-resistance status, as observed in numerous randomized clinical trials. Moreover, berberine possesses the ability to decrease endothelial inflammation and improve the vascular health condition in patients affected by cardiovascular diseases (Cicero and Baggioni 2016). Fenugreek has been showed to lower blood glucose and cholesterol levels in animals. It decreases plasma cholesterol in chickens and rabbits, reducing risk for heart disease. Polyphenols from fenugreek seed extract protect from ethanol-induced damage in human liver cells and the effect is comparable to hepatoprotective drug silymarin (Thomas et al. 2011).

Nutraceuticals in Neurodegenerative Diseases

Neurodegenerative diseases represent advanced disorders of the neurons that could cause destruction or abolish the function of the neurons (Kannappan et al. 2011). Neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease are known to have general features in cellular and molecular mechanisms that include protein aggregation and inclusion body formation (Ross and Poirier 2004). A wide range of these disorders are characterized by damage in neurons which might be a result of toxic and aggregate-prone proteins (Taylor et al. 2002). They pose a great threat to human health and have increasingly affected the elderly population in recent years (Heemels 2016).

These diseases are well-known for their signs related to memory and cognition, affecting the ability of the person to move, speak and even breathe appropriately (Wyss-Coray 2016). The main feature of neurodegenerative diseases like Alzheimer’s disease is brain inflammation, characterized by increased activation of microglia and astrocytes that increases during aging (Sawikr et al. 2017). Several nutraceuticals were shown to be neuroprotective in experimental models and serve as an alternative to other synthetic drugs like L-Dopa that are identified to cause many adverse side- effects (Hang et al. 2016). Nutraceuticals affect several neurodegenerative diseases through modulation of various signaling pathways. A nutraceutical like curcumin was shown to inhibit fAbeta (fAp) formation from fresh Abeta (Ap) and then destabilize the preformed fAp in vitro where the fAP destabilized by N.D.G.A. show less toxicity than the intact fAP (Ono et al. 2004). The binding of AP to a neurotrophin receptor (p75N.T.R.) could activate N.F.-кВ (nuclear factor kappa-B), and induce brain cell death, and curcumin could inhibit this process of N.F.-кВ activation to prevent the AP-induced cell death in a human neuroblastoma cell line, which signifies a possible option for Alzheimer’s disease treatment (Kannappan et al. 2011).

In an animal model study in rats, resveratrol was observed to inhibit the reuptake of noradrenaline and 5-HT with dose-dependent increase in hippocampal serotonin. Further, it reduced neuronal inflammation and cell death in oxidation-induced neuronal toxicity animal models. It also protected the slices of organotypic hippocampus from the hydroperoxide damage (Mecocci et al. 2014). The other possible mechanisms of neuroprotection by resveratrol are related to its antioxidant properties and the ability to modulate Ap processing and upregulation of sirtuin 1 expression (Pocernich et al. 2011; Mecocci et al. 2014).

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