The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress

Sevda Inan

## Abstract

Nutraceuticals are defined as a food or food ingredients that prevent and treat diseases. They contain dietary supplements like proteins, vitamins and minerals, compound derived from natural sources. They have functions about delaying, preventing and treating chronic inflammatory diseases due to the presence of the phytochemicals. They have anti-inflammatory effects by inhibiting of the activation of NF-κB, blocking the overexpression of tumor necrosis factor and interleukin-1, downregulation of the overexpression of cell adhesion molecules and inhibiting phospholipase A2, COX-2, lipoxygenease, iNOS, myeloperoxidase and inhibiting reactive oxygen species (ROS) generating enzyme activity and increasing ability to scavenge ROS. They have antioxidative role that can reduce the level of ROS and free radicals. They have effects on the process of lipid oxidation that inhibit or slow the formation of free alky radicals and cut off the free radical chain reactions.

Keywords: nutraceuticals, inflammation, oxidative stress, protective functions, disease

### 1. Introduction

In recent years, the consumption of natural products or functional foods are increased and enlarged segment of food industry. At the same time, Nutraceuticals are increased using as an alternative for pharmaceutical industry especially variety of diseases and cancers in humans and animals.

Firstly, nutraceutical is a term used by Stefane De Felice Nutraceuticals is defined as a food, bioactive products or food ingredients that prevent and treat diseases [1–4]. They are not drugs but they have pharmacologically active substance [2]. They contain dietary supplements like proteins, vitamins and minerals, compounds derived from natural sources. They provide health and medical benefits that delay, prevent and treat chronic inflammatory diseases due to the presence of the phytochemicals [1–4].

They have anti-inflammatory effects by inhibiting of the activation of NF-κB, blocking the overexpression of tumor necrosis factor and interleukin-1, downregulation of the overexpression of cell adhesion molecules and inhibiting phospholipase A2, COX-2, 5-LOX, iNOS, myeloperoxidase and inhibiting ROS generating enzyme activity and increasing ability to scavenge ROS. They have antioxidative role that can reduce the level of ROS and free radicals. They have

effects on the process of lipid oxidation that inhibit or slow the formation of free alky radicals and cut off the free radical chain reactions. They have intracellular signaling pathway modular effects [2–4].

ROS are present in different cancer types and age related diseases as neurodegeneration, inflammation, diabetes, vision and sensory loss [12]. ROS and reactive nitrogen species damage significant biological molecules which are lipids, DNA, essential cellular proteins. Oxidative stress is imbalance between the forma-

Enzymatic and nonenzymatic antioxidant systems which are superoxide dismutase, catalase, glutathione peroxidase, lipid soluble vitamin E, carotenes and water soluble vitamin C arrange between ROS and antioxidants [4, 17, 18].

Oxidative stress starts the oxidation of polyunsaturated fatty acids (PUFA), proteins, DNA and sterols. The oxidative stress reduce in the body with consumption of fruits and vegetables including high amounts of anti-oxidative nutraceuticals and for this reason, incidence of cancer and cardiovascular diseases decrease [4, 6]. According to the recent studies, there is a relationship between ROS and atherosclerosis, vasospasm, cancers, trauma, stroke, asthma, hyperoxia, arthritis, heart attack, age pigments, dermatitis, cataractogenesis, retinal damage, hepatitis, liver

Vitamin E (alpha-, beta-, gamma- and delta-tocopherol, alpha-, beta-, gammaand delta-tocotrienol) is quite effective antioxidant and beneficial aspects for rheumatoid arthritis [4, 21, 22]. Also, vitamin E has anti-inflammatory effects in animal recent studies [4, 23]. Tocopherols and tocotrienols have nonpolar structures and consist in the lipid phase. Tocopherols are member of biological membranes and. Tocopherols have antioxidants property that defend polyunsaturated fatty acids into the membrane and LDL [4, 24]. The anti-inflammatory and anti-oxidant

> Effects on rheumatoid arthritis against the inflammation and oxidative stress

Inhibition of cyclooxygenase activity in

Decreases risk of cardiovascular disease, anti-cancer activity and decreases incidence of Alzheimer's disease

cell division and cell signaling pathways. Stimulates indirectly prostaglandin and cytokines, directly stimulates T cell function. Reduces incidence of infectious diseases including respiratory infections

macrophages

oxidation of LDL.

and asthma

References

Lee et al. [4], Aryaeian et al. [21], Bandt et al. [22]

Lee et al. [4], Beharka et al. [23]

Meydani [24]

Lee et al. [4]

Lewis et al. [25]

effects of Vitamin E and its derivatives are summarized in Table 1.

Vitamin E and derivatives Anti-oxidant and anti-inflammatory effects

(Review literature study) Changes the level cholesterol and blocks

(Review literature study) Alterations of cell membrane integrity,

tion of free radicals and antioxidant defense mechanism [15, 16].

The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress

injury and periodontitis [4, 19, 20].

DOI: http://dx.doi.org/10.5772/intechopen.83797

2. Nutraceuticals

(Review literature study), (randomized, double-blind placebocontrolled human study, 400 mg for 3 months), (The transgenic KRN/NOD mice, 0.268 mg for 6 weeks)

(Review literature study), (30 and 500 ppm for 30 days in old mice)

(Review literature study in elderly cardiovascular patients)

9

2.1 Vitamin E

The foods including antioxidative nutraceuticals are fruits (grape, citrus, blueberries, strawberries, blackberries and crowberries), vegetables (tomato, beans, broccoli, beet, mushroom, corn, white cabbage, kale, cauliflower, spinach, garlic, onion, cacao beans and soybean), spices (rosemary, oregano and thyme), herbs (sage) and beverages (tea, wine) [4–6].

People's interest about nutraceuticals is increasing day by day due to various diseases. According to the global market data, China will be first nutraceutical market as lifestyle. The nutraceutical sector is affected by the stringent regulations and approval process of European Union. Due to the country, there are different names of laws on nutraceuticals. Nutraceuticals are using different definitions and terms including dietary supplement in USA, Natural Health Product in Canada, complementary medicines in Australia, food supplements in European Union and foods for special dietary in India [7].

With the increasing technology in the food, health and pharmaceutical sectors, the orientation to functional foods is increasing and the competition is accelerating. The sales of global market for nutraceuticals are expected to be US\$250 billion by 2018 [8].

When nutraceuticals are evaluated by consumers, the consumption of food has undergone changes in the past three decades. The easing of access to media and internet, increasing in scientific studies and obesity related diseases are increased to sale nutraceutical products by consumers. Between 2018 and 2025 years, the growth rate of this sector is assumed to exceed 9.7%. The countries including Brazil, China, India, South Korea, Poland and Mexico are increasing to use functional foods. The global market of nutraceuticals is assumed to be \$578.23 billion by 2025 at CAGR of 8.8% [9].

Inflammation is a protective response against the initial cause of cell injury. Inflammation is classified as acute and chronic. Acute inflammation is first response mechanism against infections, trauma, physical and chemical agents, which are induced wound healing. If this mechanism occurs persistent, it takes chronic phase [3, 10]. The process of inflammation contain vascular and cellular changes including of swollen, redness, local heating and loss of function. The permeability of capillaries is increased, exudate including the fluid and other elements leak into the body cavities. The inflammatory cells, leucocytes and other phagocytic cells migrate through the affected region. The lytic enzymes release from lysosomes of cells. During the inflammation, chemical mediators are synthesized proinflammatory cytokines (histamine, 5-hydroxytryptamine, bradykinin, leukotrienes and prostaglandins), selectins, integrins and immunoglobulins are stimulated for releasing [1]. Arachidonic acid metabolites including prostaglandins and leukotrienes are stimulated by the increasing expression of phospholipase A2. ROS are released from the inflammatory cells including neutrophils and macrophages. NADPH oxidase, xanthine oxidase and myeloperoxidase are seen increasing due to the ROS. The inflammatory cytokines, cell adhesion molecules and enzymes are regulated by the activation of the transcription factor NF-κB [3, 11].

ROS generate intracellularly as natural by endogenous and exogenous sources. Endogenous ROS including superoxide, hydrogen peroxide and nitric oxide (NO) have functions in cell signaling and homeostasis [12]. ROS has functions in regulation of cell survival. At the moderate levels of ROS signaling support cell proliferation and survival. At the upper levels of ROS cause cell death [12, 13]. There is a relationship between ROS production and oxidative stress that play a role on redox signaling from the organelle to the cytosol to nucleus [12, 14].

The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress DOI: http://dx.doi.org/10.5772/intechopen.83797

ROS are present in different cancer types and age related diseases as neurodegeneration, inflammation, diabetes, vision and sensory loss [12]. ROS and reactive nitrogen species damage significant biological molecules which are lipids, DNA, essential cellular proteins. Oxidative stress is imbalance between the formation of free radicals and antioxidant defense mechanism [15, 16].

Enzymatic and nonenzymatic antioxidant systems which are superoxide dismutase, catalase, glutathione peroxidase, lipid soluble vitamin E, carotenes and water soluble vitamin C arrange between ROS and antioxidants [4, 17, 18].

Oxidative stress starts the oxidation of polyunsaturated fatty acids (PUFA), proteins, DNA and sterols. The oxidative stress reduce in the body with consumption of fruits and vegetables including high amounts of anti-oxidative nutraceuticals and for this reason, incidence of cancer and cardiovascular diseases decrease [4, 6]. According to the recent studies, there is a relationship between ROS and atherosclerosis, vasospasm, cancers, trauma, stroke, asthma, hyperoxia, arthritis, heart attack, age pigments, dermatitis, cataractogenesis, retinal damage, hepatitis, liver injury and periodontitis [4, 19, 20].

### 2. Nutraceuticals

#### 2.1 Vitamin E

effects on the process of lipid oxidation that inhibit or slow the formation of free alky radicals and cut off the free radical chain reactions. They have intracellular

The foods including antioxidative nutraceuticals are fruits (grape, citrus, blueberries, strawberries, blackberries and crowberries), vegetables (tomato, beans, broccoli, beet, mushroom, corn, white cabbage, kale, cauliflower, spinach, garlic, onion, cacao beans and soybean), spices (rosemary, oregano and thyme), herbs

People's interest about nutraceuticals is increasing day by day due to various diseases. According to the global market data, China will be first nutraceutical market as lifestyle. The nutraceutical sector is affected by the stringent regulations and approval process of European Union. Due to the country, there are different names of laws on nutraceuticals. Nutraceuticals are using different definitions and terms including dietary supplement in USA, Natural Health Product in Canada, complementary medicines in Australia, food supplements in European Union and

With the increasing technology in the food, health and pharmaceutical sectors, the orientation to functional foods is increasing and the competition is accelerating. The sales of global market for nutraceuticals are expected to be US\$250 billion by

When nutraceuticals are evaluated by consumers, the consumption of food has undergone changes in the past three decades. The easing of access to media and internet, increasing in scientific studies and obesity related diseases are increased to sale nutraceutical products by consumers. Between 2018 and 2025 years, the growth rate of this sector is assumed to exceed 9.7%. The countries including Brazil, China, India, South Korea, Poland and Mexico are increasing to use functional foods. The global market of nutraceuticals is assumed to be \$578.23 billion by 2025 at CAGR of

Inflammation is a protective response against the initial cause of cell injury. Inflammation is classified as acute and chronic. Acute inflammation is first response mechanism against infections, trauma, physical and chemical agents, which are induced wound healing. If this mechanism occurs persistent, it takes chronic phase [3, 10]. The process of inflammation contain vascular and cellular changes including of swollen, redness, local heating and loss of function. The permeability of capillaries is increased, exudate including the fluid and other elements leak into the body cavities. The inflammatory cells, leucocytes and other phagocytic cells migrate through the affected region. The lytic enzymes release from lysosomes of cells. During the inflammation, chemical mediators are synthesized proinflammatory cytokines (histamine, 5-hydroxytryptamine, bradykinin, leukotrienes and prostaglandins), selectins, integrins and immunoglobulins are stimulated for releasing [1]. Arachidonic acid metabolites including prostaglandins and leukotrienes are stimulated by the increasing expression of phospholipase A2. ROS are released from the inflammatory cells including neutrophils and macrophages. NADPH oxidase, xanthine oxidase and myeloperoxidase are seen increasing due to the ROS. The inflammatory cytokines, cell adhesion molecules and enzymes are regulated by the

ROS generate intracellularly as natural by endogenous and exogenous sources. Endogenous ROS including superoxide, hydrogen peroxide and nitric oxide (NO) have functions in cell signaling and homeostasis [12]. ROS has functions in regulation of cell survival. At the moderate levels of ROS signaling support cell proliferation and survival. At the upper levels of ROS cause cell death [12, 13]. There is a relationship between ROS production and oxidative stress that play a role on redox

signaling pathway modular effects [2–4].

Nutraceuticals - Past, Present and Future

(sage) and beverages (tea, wine) [4–6].

foods for special dietary in India [7].

activation of the transcription factor NF-κB [3, 11].

signaling from the organelle to the cytosol to nucleus [12, 14].

2018 [8].

8.8% [9].

8

Vitamin E (alpha-, beta-, gamma- and delta-tocopherol, alpha-, beta-, gammaand delta-tocotrienol) is quite effective antioxidant and beneficial aspects for rheumatoid arthritis [4, 21, 22]. Also, vitamin E has anti-inflammatory effects in animal recent studies [4, 23]. Tocopherols and tocotrienols have nonpolar structures and consist in the lipid phase. Tocopherols are member of biological membranes and. Tocopherols have antioxidants property that defend polyunsaturated fatty acids into the membrane and LDL [4, 24]. The anti-inflammatory and anti-oxidant effects of Vitamin E and its derivatives are summarized in Table 1.



Carotenoids Anti-oxidant and anti-

The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress

(The literature review study) Anti-obesity functions by modulating

(The review article study) Inhibits UV-induced cutaneous

adipose tissue

(25 and 50 mg/kg of body sweight in

DOI: http://dx.doi.org/10.5772/intechopen.83797

(Daily oral dose 10 mg/kg body weight and intraperitoneally 25 mg/kg body weight in female Wistar rats)

(Lycopene complex including 6% lycopene, 1.5% tocopherols, 1% phytoene and phytofluene, 0.2% betacarotene for 10 days in rats at 6 mg/kg

(The prospective randomized study in 159 primigravidas at the gestational time with the consumption of 2 mg oral lycopene daily for 77 women, placebo daily for 82 women)

(375 men and 576 women with hip fracture and nonvertebral fracture in elderly ages at different amounts of consumption of carotenoid and

(In vitro research of 25 male Holstein calves in ages of 6–10 weeks and 3 Angus Heifers in ages of 8–30 weeks with doses of etinoic acid (1 μM) or

(The review article study including animal and human in vitro researches)

(The intake of AIN-93G or AIN-93G + 10% Tangerine or red tomato powder

(The different amount of carotenoid content in commercial tomato hybrid

(The randomized double-blinded clinical trial study in 51 patients with beta- carotene fortified symbiotic food including 0.05 g beta carotene)

for 35 weeks in mice)

Zebrino)

11

β-carotene (8.3 μg/mL)

mice for 3 days)

body weight)

lycopene)

inflammatory effects

References

Gammone [42]

Duquette et al. [43]

Kaulmann [44]

Imokawa [45]

Cooperstone et al. [46]

Del-Giudice et al. [47]

Asemi et al. [48]

Antimutagenic effect Polivkova et al. [37]

Neuroprotective activity Sandhir et al. [38]

Nephroprotective activity Sahin et al. [39]

Prevents preclampsia Banerjee et al. [40]

Decreases risk of hip fracture Sahni et al. [41]

insulin resistance and reducing blood glucose levels by regulation of cytokine expression from white

Promotes leukocyte apoptosis in bronchoalveolar lavage fluid and improves efferocytosis in macrophages

Modulates intracellular signaling cascades, gene expression, and protein

translation and blocks the translocation of nuclear factor κB to the nucleus. Inhibits Interleukin-8, prostaglandin E2 and oxidative strees damage by activating phase II and glutathione-S-transferases.

inflammation, pathologic keratinization, pigmentation and

Decreases levels of insulin,

oxide and glutathione

Protects against the UVB-induced keratinocyte carcinoma.

Cytoprotective functions by mitigating ROS production and protects against the glutatione depletion and lipid

triglycerides, VLDL-cholesterol, total/ HDL cholesterol ratio, plasma nitric

wrinkling

proxidation

#### Table 1.

The effects of Vitamin E and its derivatives, relevant to anti-inflammatory and anti-oxidant activity.

#### 2.2 Carotenoids

They are classified as xanthophylls and carotenes. The carotenes have hydrocarbon and xanthophylls have oxygen [2, 4]. Carotenoids including alpha- carotene, lycopene, lutein, zeaxanthin, beta-carotene and beta-cryptoxanthin have antioxidant effects [1, 4]. The anti-inflammatory and anti-oxidant effects of carotenoids are summarized in Table 2.



2.2 Carotenoids

Table 1.

are summarized in Table 2.

(The literature review study), (The prospective study of older women between 55-69 ages)

cases and exposure, the epidemiological review study), (The prospective cohort study between 1986 and 1992, in cases of 812 prostate cancer ), (The review study related with the consumption of foods including different amounts of

carotenoids)

10

(The ranging numbers and amounts of

Carotenoids Anti-oxidant and anti-

(The literature review study) Functions on cell growth, embryonic

(The literature review study) Blocks the formation of oxidized

receptor

multiple sclerosis

(Different doses, review literature

Nutraceuticals - Past, Present and Future

(The randomized clinical trials, ranging

(The consumption of different doses, review of literature study in human)

(The ranging doses between 500 IU/kg for 4 weeks in rats, 600 mg/kg in rats,

45 and 60 mg/kg in rats)

study)

doses 33-800 IU)

They are classified as xanthophylls and carotenes. The carotenes have hydrocarbon and xanthophylls have oxygen [2, 4]. Carotenoids including alpha- carotene, lycopene, lutein, zeaxanthin, beta-carotene and beta-cryptoxanthin have antioxidant effects [1, 4]. The anti-inflammatory and anti-oxidant effects of carotenoids

inflammatory effects

development, vision property and immune system. Modulates activity of intracellular communication by interaction with nuclear receptors like pregnant X- receptor or retinoic acid

Protective roles against rheumatoid arthritis, atherosclerosis, cataracts, age-related muscular degeneration and

Decreases the expansion of cervical, colon, prostate, rectal, stomach and other different of cancer types

products of LDL cholesterol in coronary heart disease

The effects of Vitamin E and its derivatives, relevant to anti-inflammatory and anti-oxidant activity.

Prevents and treats a multitude of age related diseases. Ameliorates of lipid profile and modulates suppression of the senescence- associated secretory

Effects lonely cardiovascular diseases by reducing myocardial infarction

Prevents various types of cancer, heart disease and chronic ailments

Anti-oxidant roles by decreasing the distribution of free radicals and modulating plasmatic lipoproteins in traumatic brain injury related dementia

Vitamin E and derivatives Anti-oxidant and anti-inflammatory effects

(The clinical review literature study) Preventive and therapeutic functions in

phenotype

cardiovascular diseases.

References

Malavolta et al. [26]

Loffredo et al. [27]

Jain et al. [28]

Shahidi [29]

Dobrovolny et al. [30]

References

Lushchak [2], Ruhl [31]

Al-Okbi [1], Lee et al. [4], Cerhan et al. [32]

Giovannucci [33], Giovannucci et al. [34], Giovannucci

Weisburger [36]

[35]


Polyphenols Anti-oxidant and anti-inflammatory

The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress

(The review article study) Anti-angiogenic functions. Contributes

(The review article study) Anti-mutagenic and free radical

(The serial review article study) Modulates of intracellular

(The review article study) (the commercial apple skin powder including 995.3 mg chlorogenic acid/100 g and 14.4 mg

this review article study)

(The interval of different age, dietary source of polyphenols and contents in

DOI: http://dx.doi.org/10.5772/intechopen.83797

(The rat kidney study with the different phenolic contents and amounts in foods)

(The review article study), (The 17 hypercholesterolemic male patients with the consumption of 40-90 g/day macadamia nuts for 4 weeks)

(The review article study with different phenolic compounds activities and

(The randomized, controlled, double blind cross over human study, Olive oil including 80 mg phenolic compounds/ kg, Olive oil including 500 mg phenolic

compounds for 3 weeks)

amounts)

Table 3.

13

Trolox/g)

effects

(The review article study) Anti-inflammatory effects Lushchak et al.

(The review article study) Anti-cancer functions Lushchak et al.

References

[2], Biesalski [55]

[2], Fresco et al.

[2], Du et al. [57]

[2], Rimbach et al. [58]

Lushchak et al. [2], Corradini et al. [59]

Lee et al. [4]

Lushchak et al. [2], Williams et al. [60]

Lushchak et al. [2], Actis-Goretta et al. [61]

Al-Okbi [1], Lee et al. [4], Garg et al. [62]

Diniz et al. [64]

Martin-Pelaez et al. [65]

Yahfoufi et al. [66]

[63]

[56]

Anti-bacterial functions Lushchak et al.

Anti-atherogenic functions Lushchak et al.

formation of ROS by inhibiting enzymes

communications in the phosphoinositide 3-kinase, Akt- protein kinase B, tyrosine kinase and protein kinase C signaling

Inhibits the angiotensin converting enzyme in cardiovascular system

Decreases influence of inflammation, alters the gene expression of antioxidant enzymes and reduces the risk of cardiovascular disease and certain type of

Neuroprotective and anticonvulsive effects on brain tissue against the oxidative stress by binding to the benzodiazepine site on GABAA receptor

Improves the proportions of IgA coated bacteria and plasma levels of C-reactive

cyclooxygenase, phospholipase A2 and anti-oxidant enzymes including xanthine

or chelating trace elements

scavenging properties

cascade

cancer

protein

oxidase

The effects of phenolic compounds, relevant to anti-inflammatory and anti-oxidant activity.

(The review article study) Regulates toll like receptor, inhibits

(The review article study) Anti-inflammatory functions Chatterjee et al.

Table 2.

The effects of Carotenoids, relevant to anti-inflammatory and anti-oxidant activity.

#### 2.3 Phenolic compounds, polyphenols

The polyphenols are phenolic compounds that are defined as a benzene ring bearing one or more hydroxyl groups attached to the ring. They are including plants, vegetables, fruit, vines, tea, coffee and microalgae [2]. The phenolic compounds are classified as simple phenols, benzoquinoes, phenoic acids, acetophenones, phenylacetic acids, hydroxycinnamic acids, phenylpropens, coumarins, chromones, anthraquinones and flavonoids [4]. According to the recent articles, polyphenols have antioxidant [2, 4], anti-inflammatory [2, 55], anticancer [2, 56], antibacterial [2, 57], antiatherogenic [2, 58], antiangiogenic [2, 59], antimutagenic and free radical scavenging properties [4].

Flavonoids, which are water-soluble [3], are popular group of polyphenols and classified as flavones, flavonols, catechin or flavanols, anthocyanins and isoflavones. Flavonoids consist as free aglycones or with sugars connected the chemical structures to generate glycosides. Flavonoids have anti-inflammatory functions by inhibiting the enzymes responsible for production of phospholipase A2, cyclooxygenase and lipoxygenase [2, 3, 63]. The beneficial effects to health of phenolic compounds are listed below in Table 3.

#### 2.3.1 Flavones

They are including apigenin, chrysin, baicalein, scutellarein and wogonin [2]. The anti-inflammatory and anti-oxidant effects of flavones are summarized in Table 4.

The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress DOI: http://dx.doi.org/10.5772/intechopen.83797


#### Table 3.

The effects of phenolic compounds, relevant to anti-inflammatory and anti-oxidant activity.

2.3 Phenolic compounds, polyphenols

The polyphenols are phenolic compounds that are defined as a benzene ring bearing one or more hydroxyl groups attached to the ring. They are including plants, vegetables, fruit, vines, tea, coffee and microalgae [2]. The phenolic com-

acetophenones, phenylacetic acids, hydroxycinnamic acids, phenylpropens, coumarins, chromones, anthraquinones and flavonoids [4]. According to the recent articles, polyphenols have antioxidant [2, 4], anti-inflammatory [2, 55], anticancer

Flavonoids, which are water-soluble [3], are popular group of polyphenols and

They are including apigenin, chrysin, baicalein, scutellarein and wogonin [2]. The anti-inflammatory and anti-oxidant effects of flavones are summarized in Table 4.

[2, 56], antibacterial [2, 57], antiatherogenic [2, 58], antiangiogenic [2, 59],

classified as flavones, flavonols, catechin or flavanols, anthocyanins and isoflavones. Flavonoids consist as free aglycones or with sugars connected the chemical structures to generate glycosides. Flavonoids have anti-inflammatory functions by inhibiting the enzymes responsible for production of phospholipase A2, cyclooxygenase and lipoxygenase [2, 3, 63]. The beneficial effects to health of

pounds are classified as simple phenols, benzoquinoes, phenoic acids,

antimutagenic and free radical scavenging properties [4].

Carotenoids Anti-oxidant and anti-

(The doses of 20 and 40 mg/kg xanthophylls in hens and chicks)

Nutraceuticals - Past, Present and Future

(59 young participants with the supplementation of 13 and 27 mg/day

(The carotenoid derivatives and crystalline lycopene from tomato

(The different amounts of intake carotenoid in this review article study)

macular carotenoids)

extract)

Table 2.

inflammatory effects

jejenum

mediator

regions.

The effects of Carotenoids, relevant to anti-inflammatory and anti-oxidant activity.

(The review article study) Modulates macrophage polarization

(The review article study) Neuroprotective functions against the

Decreases inflammatory mediators and apoptosis in chick tissues including liver, duodenum and

and stops the progression of nonalcoholic fatty liver disease and provides liver homeostasis

Alzherimer's disease that prevents progression this disease and modulates of Aβ peptide production and accumulation, oxidative stress and secretion of pro-inflammatory

Reduces stress, cortisol and symptoms of emotional and physical health.

Prevents cancer and protects bone health by inhibiting of the nuclear

Reduces variety types of cancer including oral cavity and laryngeal

factor kappa B activity.

References

Gao et al. [49]

Ni et al. [50]

Mohammadzade h Honarvar [51]

Stringham et al. [52]

Linnewiel-Hermoni et al. [53]

Leoncini et al. [54]

phenolic compounds are listed below in Table 3.

2.3.1 Flavones

12


#### Table 4.

The effects of flavones, relevant to anti-inflammatory and anti-oxidant activity.

#### 2.3.2 Flavonols

They are protective functions from UV radiation [2]. They are including kaempferol, quercetin, myricetin, galangin and morin [2]. They have beneficial effects on different conditions and diseases related oxidative stress and inflammation. These effects are summarized in Table 5.

2.3.3 Flavanones

Table 5.

15

2.3.4 Catechin or flavanols

They have important effects that regulate on the inflammatory process and

inflammation

They are found in variety of fruits (apples, apricots, blackberries and grapes), red wine, black tea and cocoa [2]. For example; the long-term consumption of tea

oxidative stress. These beneficial effects are summarized in Table 6.

The effects of flavones, relevant to anti-inflammatory and anti-oxidant activity.

Flavonols Anti-oxidant and anti-inflammatory

The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress

(At flavonoid concentrations of

and Jurkat cells)

in vitro)

10–70 μmol/L were applied in HL-60, U937

DOI: http://dx.doi.org/10.5772/intechopen.83797

(The ranging content amounts of oolong tea leaves including 54 polyphenols were evaluated on the pancreatic lipase activity

(At the concentrations of 0, 50, 100 and 250 μM of quercetin for 24–72 hours were added cell culture medium including mouse embryo 3T3-L1 cells)

(The oral treatment doses at 2.8 g/kg in male Wistar rats, aged 8–10 weeks)

(At the dose of 5 μM kaempferol was added cell culture medium including rat osteoblast-like UMR106 cells)

(The extracts of Ficus carica Linn. (Moraceae) leaves and fruits and Morus alba Linn. root barks (Moraceae) were given 50 and 150 mg/kg in adult female

(At the doses of 50 and 100 mg/kg kaempferol were given orally in animal

(The review article study), (The doubleblind study was given orally 4 x 500 mg quercetin in non-smoking, un-treated

(The mice were fed Western diet including

(At the doses of 10 and 50 mg/kg quercetin were given intraperitoneally to the male

(At the doses of 0 and 210 μM quercetin or taraxasterol were added cell culture medium including human umbilical vein

Swiss albino rats)

model study)

sarcoidosis individuals)

Sprague Dawley rats)

endothelial cells)

0.05% quercetin for 18 weeks)

effects

ascorbic acid

with diabetes mellitus

Inhibits intracellular accumulation of

Inhibitory functions on pancreatic lipase

Anti-oxidant and renoprotective effects in

Hepatoptotective effects on tetrachloriderelated oxidative stress and injury in rat

streptozotocin-diabetic rats

Regulates bone sialoprotein gene transcription and new bone formation

Regulates cyclooxygenase, inhibits production of nitric oxide

Decreases of oxidative stress and inflammation in sarcoidosis, colonic damage and allergic airway conditions

Modulates on accumulation and activation of immune cells and increases expression of mitochondrial gene in adipose tissue.

Neuroprotective and anti-oxidant effects in subarachnoid hemorrhage, inhibits

Anti-atherosclerotic and cardioprotective effects against the oxidative stress and

brain damage and edema.

liver tissue

Anti-oxidant activity on cell apoptosis Hsu et al. [81]

References

Park et al. [79]

Nakai et al. [80]

Liu et al. [82]

Singab et al. [83]

Yang et al. [84]

Mahat et al. [85]

Chatterjee et al. [63], Boots et al. [86]

Kobori et al. [87]

Dong et al. [88]

Yang et al. [89]

The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress DOI: http://dx.doi.org/10.5772/intechopen.83797


#### Table 5.

The effects of flavones, relevant to anti-inflammatory and anti-oxidant activity.

#### 2.3.3 Flavanones

They have important effects that regulate on the inflammatory process and oxidative stress. These beneficial effects are summarized in Table 6.

#### 2.3.4 Catechin or flavanols

They are found in variety of fruits (apples, apricots, blackberries and grapes), red wine, black tea and cocoa [2]. For example; the long-term consumption of tea

2.3.2 Flavonols

Table 4.

14

They are protective functions from UV radiation [2]. They are including kaempferol, quercetin, myricetin, galangin and morin [2]. They have beneficial effects on different conditions and diseases related oxidative stress and inflamma-

The effects of flavones, relevant to anti-inflammatory and anti-oxidant activity.

Flavones Anti-oxidant and anti-inflammatory

(The review article study) Cyclooxygenase inhibitory ability in

(The review article study), (250 μM quercetin (specific activity, 52.9 mCi/ mM) for 10 min by injecting of Xenopus

Nutraceuticals - Past, Present and Future

(The treatment with 2.5–20 μM apigenin in cell culture including human prostate

(The study including phosphorylating five flavones and showing pancreatic cholesterol esterase inhibitory functions

(The review article study), (Apigenin which is isolated from Cordia dichotoma bark, is received 5 mg/kg, p.o. in Male

(The review article study in vitro and

(The review article study about antioxidant, anti-cancer, anti-tumoral activity, anti-inflammatory and hepatoprotective functions of dietary

(50 mg/kg of body weight doses of apigenin was injected intraperitoneally in

concentrations of flavonoids were added Murine C2C12 cell culture medium)

laevis oocytes)

by IC50)

Swiss mice)

in vivo)

flavonoids)

Male C57BL/6J mice)

(1, 10, 25, 50, 75 and 100 μM

cancer PC-3 and 22Rv1)

effects

cancer

inhibitor

(The review article study) Reduces neurodegeneration Lee et al. [4],

enzymes

macrophages cells

(The review article study) Anti-arthritic functions Laev et al. [74]

expression

leukocyte infiltration

related muscle atrophy

(The review article studies) Decreases the expression of tumor

Beneficial effects including as GLUT

Anti-tumoral activity that inhibits of the p-IKKα, NF-ĸB/p65, cell proliferation, invasion of prostat cancer cells

Acts as pancreatic cholesterol esterase

Treats colitis and reduces inflammatory

necrosis factor alpha and interleukin-6 in

Inhibits thromboxane synthesis in animal model and decreases iNOS and COX-2

Immunomodulatory effects that reduces NF-κB activity in the lungs and inhibits

Protective effects on lipopolysaccharide

Anti-inflammatory functions for neurodegenerative disease

inhibitors in diabetes

References

Lee et al. [4], Kwon et al. [67]

Lee et al. [4], Kinghorn et al. [68]

Shukla et al. [69]

Lee et al. [4], Peng et al. [70]

Gasiorowski et al. [71]

Lee et al. [4], Ganjare et al. [72]

Chatterjee et al. [63], Wu and Schauss [73]

Nabavi et al. [75]

Xiao et al. [76]

Cardenas et al. [77]

Shiota et al. [78]

tion. These effects are summarized in Table 5.


3. Conclusion

Table 7.

28 male smokers)

19 healthy men)

sumer's demand has increased in recent years.

lems are directed people to benefit better choices.

There is no conflict of interest for this chapter.

stress and inflammation related diseases.

Conflict of interest

17

long-term multidisciplinary studies.

(At the double-blind randomized study was applied daily 200 mg flavanols for

DOI: http://dx.doi.org/10.5772/intechopen.83797

(At the randomized, placebo-controlled, double blind, crossover study was applied capsules including 1 g total catechin for

(The consumption of high flavanols chocolate for 4 weeks was applied to the overweight men between 45 and 70 ages)

Nutraceuticals are alternative or functional foods or ingredients that prevent or treatment of inflammatory and oxidative stress induced diseases. Nutraceuticals are cheaper and easier availability than prescription drugs. For this reason, con-

The effects of catechin or flavanols, relevant to anti-inflammatory and anti-oxidant activity.

Catechin Anti-oxidant and anti-inflammatory

(The review article of clinical studies) Prevents vascular problems related

The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress

effects

diabetes mellitus

Anti-inflammatory effects by decreasing expression of inflammatory genes in leukocytes and increases vascular health

Cardioprotective effects by decreasing oxidation of low density lipoprotein and

incidence of atherosclerosis

Effects on endothelium related vasodilation. Increases leukocyte adhesion factors and vascular function References

Howes and Simmonds [103]

Weseler et al. [104]

Suzuki-Sugihara et al. [105]

Esser et al. [106]

The effecting on pathogenesis and activity of diseases are also essential scientific subject for animal and human health. When the effects of nutraceuticals on oxidative stress and inflammatory related disease are discovered, usages of nutraceuticals in Pharmacology and scientific studies are seen huge growth. The relation between beneficial effects of nutraceuticals and diseases are required to research

People are searching minimally processed food and want to benefit nutritional values and live healthy. For this reason nutraceutical market is growing day by day. The aging, fast rising population, changing lifestyle and lifestyle induced diseases, healthcare research, increasing cases of cancer, economic and public prob-

As a conclusion, nutraceuticals are important for nutrition of human and animal. The consumption of nutraceuticals is necessary to reduce effects of the oxidative

#### Table 6.

The effects of flavanones, relevant to anti-inflammatory and anti-oxidant activity.

inhibits low grade inflammation [73]. The chronic consumption of dark chocolate reduces serum C-reactive protein concentrations in blood circulation [63, 73]. The other effects on inflammatory and oxidative stress are summarized in Table 7.


The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress DOI: http://dx.doi.org/10.5772/intechopen.83797


#### Table 7.

The effects of catechin or flavanols, relevant to anti-inflammatory and anti-oxidant activity.

### 3. Conclusion

Nutraceuticals are alternative or functional foods or ingredients that prevent or treatment of inflammatory and oxidative stress induced diseases. Nutraceuticals are cheaper and easier availability than prescription drugs. For this reason, consumer's demand has increased in recent years.

The effecting on pathogenesis and activity of diseases are also essential scientific subject for animal and human health. When the effects of nutraceuticals on oxidative stress and inflammatory related disease are discovered, usages of nutraceuticals in Pharmacology and scientific studies are seen huge growth. The relation between beneficial effects of nutraceuticals and diseases are required to research long-term multidisciplinary studies.

People are searching minimally processed food and want to benefit nutritional values and live healthy. For this reason nutraceutical market is growing day by day.

The aging, fast rising population, changing lifestyle and lifestyle induced diseases, healthcare research, increasing cases of cancer, economic and public problems are directed people to benefit better choices.

As a conclusion, nutraceuticals are important for nutrition of human and animal. The consumption of nutraceuticals is necessary to reduce effects of the oxidative stress and inflammation related diseases.

#### Conflict of interest

There is no conflict of interest for this chapter.

inhibits low grade inflammation [73]. The chronic consumption of dark chocolate reduces serum C-reactive protein concentrations in blood circulation [63, 73]. The other effects on inflammatory and oxidative stress are summarized in Table 7.

The effects of flavanones, relevant to anti-inflammatory and anti-oxidant activity.

Catechin Anti-oxidant and anti-inflammatory

effects

functions

hepatectomy

and adhesion molecule

Flavanones Anti-oxidant and anti-inflammatory

(The review article study) Have functions in anti-malarial

(At the concentrations of 5 and 25 μM of chalcones and flavanones were given in the

Nutraceuticals - Past, Present and Future

(At the treatment daily doses of 100 mg/kg naringenin were applied to the female BALB/

(At the dose of 50 mg/kg naringenin was applied to the adult male albino rats)

(At the concentration of 0.25 mmol of naringin derivatives was applied by agar dilution technique and direct contact

(At the doses of 50 mg/kg of quercetin and naringenin were applied to mice

(At the doses of 30–200 μmol/L were treated into the cell culture including macrophage cell line RAW 274.6 and BV2 microglia)

(The review article including clinical and

(The review article study) (at the mixture of cathechin, caffeic acid and resveratrol doses of 40 and 160 mg/kg body weight/ day were given to the apoE KO mice for 8

(The dentifrice including 1.0% green tea catechin was applied to the male Wistar

(After the massive hepatectomy, green tea extract catechins were applied to the

experimantal studies)

weeks)

rats)

16

male Wistar rats)

vitro study)

c mice)

assaying)

Table 6.

intraperitoneally)

effects

Regulate LDL oxidation in

Decrease lung metastases in a breast

Anti-oxidative stress related hepatic

Anti-bacterial roles in pathogenic

Protect DNA in alloxan-induced

Inhibit synthesis of nitric oxide and expression of cyclooxygenase-2 in macrophages and microglia

Cardioprotective effects by inhibiting the NF-κB initiated production of cytokines

Anti-inflammatory and anti-atherogenic

Reduces gingival oxidative stress and

Anti-oxidative and anti-inflammatory effects on liver dysfunction with massive

periodontal inflammation

atherosclerosis

chemotherapy

cancer model

damage in rats

diabetic mice

strains

(The review article study) Anti-inflammatory effects Kontogiorgis

(The review article study) Anti-angiogenic effects Mojzis et al.

(The review article study) Inhibitory effects on carcinogenesis Kinghorn

References

et al. [68]

Miranda et al. [90]

Kumar et al. [91]

et al. [92]

Qin et al. [94]

Prabu et al. [95]

Celiz et al. [96]

Orsolic et al. [97]

Chao et al. [98]

References

Wu and Schauss [73], Norata et al. [100]

Maruyama et al. [101]

Saito et al. [102]

Bhardwaj et al. [99]

[93]

Nutraceuticals - Past, Present and Future

## Author details

Sevda Inan

Department of Pathology, Faculty of Veterinary Medicine, Tekirdag Namik Kemal University, Tekirdag, Turkey

References

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DOI: http://dx.doi.org/10.5772/intechopen.83797

The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress

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[8] Stirling C, Kruh W. Nutraceuticals: The future of intelligent food. Where food and pharmaceuticals converge. KPMG: Cutting Through Complexity. 2015. Available from: https://home. kpmg.com/content/dam/kpmg/pdf/ 2015/05/neutraceuticals-the-futureof-intelligent-food.pdf [Accessed:

[9] Jajodia S, Rawat DS, Sharma R. Indıan Nutraceuticals Market. Current Scenario & Future Trends. Assocham Indıa; 2018. Available from: https:// mrssindia.com/wp-content/uploads/ 2018/07/Nutraceuticals-Report-Final.

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Elsevier; 2018. pp. 57-59 ISBN:

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10(8):1343-1374. DOI: 10.1089/

Ogasawara MA, Del Valle NR, Huang P. Redox regulation of cell survival. Antioxidants & Redox Signaling. 2008;

nutraceutical antioxidant formulation reduces ocular oxidative stress. Functional Foods in Health & Disease. 2017;7(1):17-35. DOI: 10.31989/ffhd.

nutraceuticals. Comprehensive Reviews in Food Science and Food Safety. 2004;3:127-139. DOI: 10.1111/ j.1541-4337.2004.tb00063.x

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[3] Watson RR, Preedy VR. Fruits, Vegetables, and Herbs. Bioactive foods in health promotion. In: Barve KH, Kulkarni YA, Gaikwad AB, editors. Nutraceuticals as Therapeutic Agents for Inflammation. 1st ed. Academic Press, Elsevier; 2016. pp. 121-147. DOI: 10.1016/B978-0-12-802972-5.00007-X

[4] Lee J, Koo N, Min DB. Reactive oxygen species, aging, and antioxidative nutraceuticals. Comprehensive Reviews in Food Science and Food Safety. 2004; 3:21-33. DOI: 10.1111/j.1541-4337.2004.

[5] Bravo L. Polyhenols: Chemistry, dietary sources, metabolism, and nutrional significance. Nutrition

j.1753-4887.1998.tb01670.x

Reviews. 1998;56:317-333. DOI: 10.1111/

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[7] Ganesh GNK, Ramachandran A, Suresh KR, Senthil V, Baviya Priyadharshini R. Nutraceuticals—A regulatory review. International

nutraceuticals reducing oxidative stress intensity and cellular damage. In: Vanessa BV, Rocio OB, Ruth RS, Paola TM, Adelaida HG, Egdar CE, editors. Oxidative Stress and Diseases, Intech Open; 2012. pp. 581-610. DOI: 10.5772/

inflammatory activity as

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2535

tb00058.x

2001.00513.x

19

\*Address all correspondence to: sevdainan@nku.edu.tr

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress DOI: http://dx.doi.org/10.5772/intechopen.83797

## References

[1] Al-Okbi SY. Nutraceuticals of antiinflammatory activity as complementary therapy for rheumatoid arthritis. Toxicology and Industrial Health. 2012:1-12. DOI: 10.1177/ 0748233712462468

[2] Lushchak V. Microalgae of the Chlorophyceae class: Potential nutraceuticals reducing oxidative stress intensity and cellular damage. In: Vanessa BV, Rocio OB, Ruth RS, Paola TM, Adelaida HG, Egdar CE, editors. Oxidative Stress and Diseases, Intech Open; 2012. pp. 581-610. DOI: 10.5772/ 2535

[3] Watson RR, Preedy VR. Fruits, Vegetables, and Herbs. Bioactive foods in health promotion. In: Barve KH, Kulkarni YA, Gaikwad AB, editors. Nutraceuticals as Therapeutic Agents for Inflammation. 1st ed. Academic Press, Elsevier; 2016. pp. 121-147. DOI: 10.1016/B978-0-12-802972-5.00007-X

[4] Lee J, Koo N, Min DB. Reactive oxygen species, aging, and antioxidative nutraceuticals. Comprehensive Reviews in Food Science and Food Safety. 2004; 3:21-33. DOI: 10.1111/j.1541-4337.2004. tb00058.x

[5] Bravo L. Polyhenols: Chemistry, dietary sources, metabolism, and nutrional significance. Nutrition Reviews. 1998;56:317-333. DOI: 10.1111/ j.1753-4887.1998.tb01670.x

[6] Kaur C, Kapoor HC. Antioxidants in fruits and vegetables—The millennium's health. International Journal of Food Science and Technology. 2001;36: 703-725. DOI: 10.1046/j.1365-2621. 2001.00513.x

[7] Ganesh GNK, Ramachandran A, Suresh KR, Senthil V, Baviya Priyadharshini R. Nutraceuticals—A regulatory review. International

Journal of Drug Regulatory Affairs. 2015;3(2):22-29. DOI: 10.22270/ijdra. v3i2.165

[8] Stirling C, Kruh W. Nutraceuticals: The future of intelligent food. Where food and pharmaceuticals converge. KPMG: Cutting Through Complexity. 2015. Available from: https://home. kpmg.com/content/dam/kpmg/pdf/ 2015/05/neutraceuticals-the-futureof-intelligent-food.pdf [Accessed: 2018-12-09]

[9] Jajodia S, Rawat DS, Sharma R. Indıan Nutraceuticals Market. Current Scenario & Future Trends. Assocham Indıa; 2018. Available from: https:// mrssindia.com/wp-content/uploads/ 2018/07/Nutraceuticals-Report-Final. pdf [Accessed: 2018-12-09]

[10] Kumar V, Abbas AK, Aster JC. Inflammation and Repair Robbins Basic Pathology. 10th ed. Philadelphia: Elsevier; 2018. pp. 57-59 ISBN: 978-0-323-35317-5

[11] Huang MT, Ghai G, Ho CT. Inflammatory process and molecular targets for anti-inflammatory nutraceuticals. Comprehensive Reviews in Food Science and Food Safety. 2004;3:127-139. DOI: 10.1111/ j.1541-4337.2004.tb00063.x

[12] Kador PF. Topical applied nutraceutical antioxidant formulation reduces ocular oxidative stress. Functional Foods in Health & Disease. 2017;7(1):17-35. DOI: 10.31989/ffhd. v7i1.297

[13] Trachootham D, Weigin L, Ogasawara MA, Del Valle NR, Huang P. Redox regulation of cell survival. Antioxidants & Redox Signaling. 2008; 10(8):1343-1374. DOI: 10.1089/ ars.2007.1957

Author details

University, Tekirdag, Turkey

Nutraceuticals - Past, Present and Future

provided the original work is properly cited.

\*Address all correspondence to: sevdainan@nku.edu.tr

Department of Pathology, Faculty of Veterinary Medicine, Tekirdag Namik Kemal

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Sevda Inan

18

[14] Murphy MP. How mitochondria produce reactive oxygen species. The Biochemical Journal. 2009;417(1):1-13. DOI: 10.1042/BJ20081386

[15] Gupta RC. Nutraceuticals. In: Milatovic D, Zaja-Milatovic S, Gupta RC, editors. Oxidative Stress and Excitotoxicity: Antioxidants from Nutraceuticals. Academic Press; 2016. pp. 401-413. DOI: 10.1016/B978-0- 12-802147-7.00029-2

[16] Houston M. The role of nutrition and nutraceutical supplements in the treatment of hypertension. World Journal of Cardiology. 2014;6(2):38-66. DOI: 10.4330/wjc.v6.i2.38

[17] Thomas MJ. The role of free radicals and antioxidants: How do we know that they are working? Critical Reviews in Food Science and Nutrition. 1995;2-35 (1–2):21-39. DOI: 10.1080/ 10408399509527683

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[20] Packer L, Weber SU. The role of vitamin E in the emerging field of nutraceuticals. In: Kramer K, Hoppe PP, Packer L, editors. Nutraceuticals in Health and Disease Prevention. New York: Marcel Dekker; 2001. pp. 27-43. DOI: 10.1093/ajcn/75.4.783

[21] Aryaeian N, Shahram F, Djalali M, Eshragian MR, Djazayeri A, Sarrafnejad A, et al. Effect of conjugated linoleic acids, vitamin E and their combination on the clinical outcome of Iranian adults with active rheumatoid arthritis. International Journal of Rheumatic Diseases. 2009;12(1):20-28. DOI: 10.1111/j.1756-185X.2009.01374.x

[22] Bandt MD, Grossin M, Driss F, Pincemail J, Babin-Chevaye C, Pasquier C. Vitamin E uncouples joint destruction and clinical inflammation in a transgenic mouse model of rheumatoid arthritis. Artritis & Rheumatology. 2002;46(2):522-532. DOI: 10.1002/art.10085

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[23] Beharka AA, Wu D, Serafini M, Meydani SN. Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: Role of peroxynitrite. Free Radical Biology and Medicine. 2002;32(6):503-511. DOI: 10.1016/S0891-5849(01)00817-6

[24] Meydani M. Effect of functional food ingredients: Vitamin E modulation of cardiovascular diseases and immune status in the elderly. American Journal of Clinical Nutrition. 2000;71(6): 1665S-1668S. DOI: 10.1093/ajcn/ 71.6.1665

[25] Lewis ED, Meydani SN, Wu D. Regulatory role of vitamin E in the immune system and inflammation. IUBMB Life. 2018:1-8. DOI: 10.1002/ iub.1976

[26] Malavolta M, Pierpaoli E, Giacconi R, Basso A, Cardelli M, Piacenza F, et al. Anti-inflammatory activity of tocotrienols in age-related pathologies: A SASPected involvement of cellular senescence. Biological Procedures Online. 2018;20:22. DOI: 10.1186/ s12575-018-0087-4

[27] Loffredo L, Perri L, Di Castelnuovo A, Iacoviello L, De Gaetano G, Violi F. Supplementation with vitamin E alone is associated with reduced myocardial infarction: A meta-analysis. Nutrition, Metabolism, and Cardiovascular Diseases. 2015;25(4):354-363. DOI: 10.1016/j.numecd.2015.01.008

[28] Jain AK, Mehra NK, Swarnakar NK. Role of antioxidants for the treatment of Nutraceuticals - Past, Present and Future cardiovascular diseases: Challenges and opportunities. Current

The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress DOI: http://dx.doi.org/10.5772/intechopen.83797

Pharmaceutical Design. 2015;21(30): 4441-4455. DOI: 10.2174/1381612821 666150803151758

[14] Murphy MP. How mitochondria produce reactive oxygen species. The Biochemical Journal. 2009;417(1):1-13.

Nutraceuticals - Past, Present and Future

[22] Bandt MD, Grossin M, Driss F, Pincemail J, Babin-Chevaye C, Pasquier

[23] Beharka AA, Wu D, Serafini M, Meydani SN. Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: Role of peroxynitrite. Free Radical Biology and Medicine. 2002;32(6):503-511. DOI: 10.1016/S0891-5849(01)00817-6

[24] Meydani M. Effect of functional food ingredients: Vitamin E modulation of cardiovascular diseases and immune status in the elderly. American Journal of Clinical Nutrition. 2000;71(6): 1665S-1668S. DOI: 10.1093/ajcn/

[25] Lewis ED, Meydani SN, Wu D. Regulatory role of vitamin E in the immune system and inflammation. IUBMB Life. 2018:1-8. DOI: 10.1002/

[26] Malavolta M, Pierpaoli E, Giacconi R, Basso A, Cardelli M, Piacenza F, et al.

tocotrienols in age-related pathologies: A SASPected involvement of cellular senescence. Biological Procedures Online. 2018;20:22. DOI: 10.1186/

[27] Loffredo L, Perri L, Di Castelnuovo A, Iacoviello L, De Gaetano G, Violi F. Supplementation with vitamin E alone is associated with reduced myocardial infarction: A meta-analysis. Nutrition, Metabolism, and Cardiovascular Diseases. 2015;25(4):354-363. DOI: 10.1016/j.numecd.2015.01.008

[28] Jain AK, Mehra NK, Swarnakar NK. Role of antioxidants for the treatment of Nutraceuticals - Past, Present and Future cardiovascular diseases: Challenges and opportunities. Current

Anti-inflammatory activity of

s12575-018-0087-4

destruction and clinical inflammation in

C. Vitamin E uncouples joint

a transgenic mouse model of rheumatoid arthritis. Artritis & Rheumatology. 2002;46(2):522-532.

DOI: 10.1002/art.10085

71.6.1665

iub.1976

[15] Gupta RC. Nutraceuticals. In: Milatovic D, Zaja-Milatovic S, Gupta RC, editors. Oxidative Stress and Excitotoxicity: Antioxidants from Nutraceuticals. Academic Press; 2016. pp. 401-413. DOI: 10.1016/B978-0-

[16] Houston M. The role of nutrition and nutraceutical supplements in the treatment of hypertension. World Journal of Cardiology. 2014;6(2):38-66.

[17] Thomas MJ. The role of free radicals and antioxidants: How do we know that they are working? Critical Reviews in Food Science and Nutrition. 1995;2-35

[18] Wickens AP. Ageing and the free radical theory. Respiration Physiology. 2001;128(3):379-391. DOI: 10.1016/

[19] Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. Journal of the National Cancer Institute. 2000;92(1):61-68.

[20] Packer L, Weber SU. The role of vitamin E in the emerging field of nutraceuticals. In: Kramer K, Hoppe PP, Packer L, editors. Nutraceuticals in Health and Disease Prevention. New York: Marcel Dekker; 2001. pp. 27-43.

[21] Aryaeian N, Shahram F, Djalali M, Eshragian MR, Djazayeri A, Sarrafnejad A, et al. Effect of conjugated linoleic acids, vitamin E and their combination on the clinical outcome of Iranian adults

with active rheumatoid arthritis. International Journal of Rheumatic Diseases. 2009;12(1):20-28. DOI: 10.1111/j.1756-185X.2009.01374.x

20

DOI: 10.1042/BJ20081386

12-802147-7.00029-2

DOI: 10.4330/wjc.v6.i2.38

(1–2):21-39. DOI: 10.1080/ 10408399509527683

S0034-5687(01)00313-9

DOI: 10.1093/jnci/92.1.61

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[106] Esser D, Mars M, Oosterink E, Stalmach A, Müller M, Afman LA. Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men. FASEB Journal. 2014;28(3):1464-1473. DOI: 10.1096/fj.13-239384

**27**

**Chapter 3**

**Abstract**

**1. Introduction**

*Shantal Windvogel*

Rooibos (*Aspalathus linearis*) and

Honeybush (*Cyclopia* spp.): From

Bush Teas to Potential Therapy for

Cardiovascular disease (CVD) is a leading cause of worldwide deaths. A number of risk factors for cardiovascular disease as well as type 2 diabetes and stroke present as the metabolic syndrome. Metabolic risk factors include hypertension, abdominal obesity, dyslipidaemia and increased blood glucose levels and may also include risk factors such as vascular dysfunction, insulin resistance, low high density lipoprotein (HDL) cholesterol levels and inflammation. Rooibos (*Aspalathus linearis*) and honeybush (*Cyclopia* spp.) are indigenous South African plants whose reported health benefits include anti-tumour, anti-inflammatory, anti-obesity, antioxidant, cardioprotective and anti-diabetic properties. The last two decades have seen worldwide interest and success for these plants, not only as health beverages but also as preservatives, flavourants and skincare products. This review will focus on the current literature supporting the function of these plants as nutraceuticals

capable of potentially reducing the risk of cardiovascular disease.

**Keywords:** honeybush, rooibos, cardiovascular disease, diabetes, polyphenols

Cardiovascular disease is the leading cause of deaths worldwide, killing 17.9 million people in 2016 [1]. While the number of cardiovascular disease related morbidity and mortality in the developed world has decreased or remained steady, the developing world has seen an increase. Limited resources, poverty, poor access to affordable healthcare, poor implementation of health policies, as well as poor education may be some of the reasons for the increase in cardiovascular diseases in low to middle income countries [2]. A number of risk factors for cardiovascular disease as well as type 2 diabetes and stroke present as metabolic syndrome. Metabolic risk factors include hypertension, abdominal obesity, dyslipidaemia, increased blood glucose levels, and may also include risk factors such as vascular dysfunction, insulin resistance, low levels of high density lipoprotein cholesterol (HDL-C) and inflammation. Natural products could play a significant role in drug discovery and development with examples including morphine, isolated from the opium poppy (*Papaver somniferum*) and artemisinin, from *Artemisia afra* [3–5]. Nutraceuticals are foods or supplements with health benefits [6]. To this end, a

Cardiovascular Disease

## **Chapter 3**

[95] Prabu SM, Shagirtha K, Renugadevi J. Naringenin in combination with vitamins C and E potentially protects oxidative stress-mediated hepatic injury in cadmium-intoxicated rats. Journal of Nutrional Science and Vitaminology (Tokyo). 2011;57(2):177-185. DOI:

Nutraceuticals - Past, Present and Future

in dentifrices suppresses gingival oxidative stress and periodontal

archoralbio.2010.08.015

inflammation. Archives of Oral Biology. 2011;56(1):48-53. DOI: 10.1016/j.

[102] Saito Y, Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, et al. Green tea catechins improve liver dysfunction following massive

hepatectomy through anti-oxidative and anti-inflammatory activities in rats. Gastroenterology. 2011;140(5):S-928. DOI: 10.1016/S0016-5085(11)63850-X

[103] Howes MJ, Simmonds MS. The role of phytochemicals as micronutrients in health and disease. Current Opinion in Clinical Nutrition and Metabolic Care. 2014;17(6):558-566. DOI: 10.1097/ MCO.0000000000000115

[104] Weseler AR, Ruijters EJ, Drittij-Reijnders MJ, Reesink KD, Haenen GR,

monomeric and oligomeric flavanols on

[105] Suzuki-Sugihara N, Kishimoto Y, Saita E, Taguchi C, Kobayashi M, Ichitani M, et al. Green tea catechins prevent low-density lipoprotein

oxidation via their accumulation in lowdensity lipoprotein particles in humans. Nutrition Research (New York, N.Y.). 2016;36(1):16-23. DOI: 10.1016/j.

[106] Esser D, Mars M, Oosterink E, Stalmach A, Müller M, Afman LA. Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men. FASEB Journal. 2014;28(3):1464-1473. DOI:

Bast A. Pleiotropic benefit of

journal.pone.0028460

nutres.2015.10.012

10.1096/fj.13-239384

vascular health—A randomized controlled clinical pilot study. PLoS One. 2011;6(12):e28460. DOI: 10.1371/

[96] Céliz G, Daz M, Audisio MC. Antibacterial activity of naringin derivatives against pathogenic strains. Journal of Applied Microbiology. 2011;

111(3):731-738. DOI: 10.1111/ j.1365-2672.2011.05070.x

mice. European Journal of

10.1016/j.nutres.2010.10.011

catechins: Defensive role in cardiovascular disorders. Chinese Journal of Natural Medicines. 2013; 11(4):345-353. DOI: 10.1016/S1875-5364

[100] Norata GD, Marchesi P, Passamonti S, Pirillo A, Violi F, Catapano AL. Anti-inflammatory and anti-atherogenic effects of catechin, caffeic acid and trans-resveratrol in apolipoprotein E deficient mice. Atherosclerosis. 2007;191(2):265-271. DOI: 10.1016/j.atherosclerosis.

(13)60051-5

2006.05.047

26

[99] Bhardwaj P, Khanna D. Green tea

[101] Maruyama T, Tomofuji T, Endo Y,

Supplementation of green tea catechins

Irie K, Azuma T, Ekuni D, et al.

[97] Oršolić N, Gajski G, Garaj-Vrhovac V, Dikić D, Prskalo ZŠ, Sirovina D. DNA-protective effects of quercetin or naringenin in alloxan-induced diabetic

Pharmacology. 2011;656(1–3):110-118. DOI: 10.1016/j.ejphar.2011.01.021

[98] Chao CL, Weng CS, Chang NC, Lin JS, Kao ST, Ho FM. Naringenin more effectively inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression in macrophages than in microglia. Nutrition Research (New York, N.Y.). 2010;30(12):858-864. DOI:

10.3177/jnsv.57.177
