Natural Antioxidants to the Rescue?

*Cenk Aydin and Nilay Seyidoglu*

## **Abstract**

Natural antioxidant compounds have different mechanisms of treatment and prevention against various diseases due to their richest ingredients. There are several antioxidants used today, such as phytogenic ingredients, flavonoids, capsaicin, spirulina, beta-glucan, polyphenol etc. Besides the outbreak of diseases, the ability to scavenge oxidative conditions of the natural antioxidants have been notably important. Thereby, therapeutic strategies of diseases have been interested by researchers. Try to seek a kind of effects of natural antioxidants to various diseases, especially viral or pandemic diseases are being important nowadays. This chapter we'll mention about how to viral or pandemic disease's effects on oxidative status in both animals and humans, and what kind of phytochemical ingredients would be a positive effect on. At the same time, the latest advances about these natural antioxidant compounds and pharmaceuticals will be critically highlighted and discussed with newest literatures.

**Keywords:** natural antioxidants, phytogenic ingredients, essential oils, pandemic, vitamins

## **1. Introduction**

Antioxidants either endogenous or exogenous are essential substances to regulate the oxidative process. The endogenous antioxidants known as glutathione, glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), have an inhibition role on free radicals during oxidation [1]. Nevertheless, either these antioxidant mechanisms are inadequate or for a better healthy life, exogenous antioxidants should be preferred [2]. The exogenous antioxidants which are especially called natural antioxidants such as vitamins, flavonoids, polyphenols, minerals, plants and phytochemicals, are derived from foods and medicinal plants. Over the years, the relationship between natural antioxidants and health has been discussed due to their important efficiencies. Generally, natural antioxidants have a wide range of effects especially antioxidant, antimicrobial, anticancer, immunomodulatory, and antiviral [3–5]. Belong these, natural antioxidants have been drawing great attention for scientific studies.

There are several multidisciplinary studies with natural antioxidants that have focused on human and animal experiments. The researchers have examined to understand the mechanisms of antioxidants on oxidative stress. They have been widely documented the knowledge of free radicals with antioxidants by identifying the oxidative stress pathway, cellular efficiencies and general health impact [6, 7].

Besides, although higher clinical complications have been observed in diseases, the mechanisms for the use of natural antioxidants are still not fully understood.

Since the past century, there have been essential diseases needed to determine how diseases progress and how the world could control them. Environmental factors, insufficient water, climate changes or new viruses influence the spread of contagious disease, and thereby cause epidemics. Nevertheless, The World Health Organization (WHO) has been still working on epidemiological studies to identify the possible sources of outbreaks, and to observe the pathogens spread from one region to different regions of the world [8]. Throughout history, there have been many significant pandemics recorded in human history. Some examples of the most up to date are Influenza virus (H1N1), Severe Acute Respiratory Syndrome (SARS), the Middle East Respiratory Syndrome (MERS), Ebola, Zika, Yellow Fever, Cholera, Malaria, and Tuberculosis [9].

Today, in response to pandemics, people have been transformed into plants and phytochemicals to protect their health. Also, researchers have advocated that these natural foods could meet antioxidant protection. However, studies are still ongoing. This chapter aims to summarize the essential natural antioxidants, their mechanism, and their effects on pandemic diseases.

## **2. The reality of diseases in the 21st century**

In recent years, climate change, lack of safe drinking water, poor living conditions and food insecurity have been the main causes of illness, epidemics and pandemics. Besides, there are also many chemicals or toxins, which can contaminate food, drink, and medicines that cause death, injury or harm to organs. The WHO reported that besides environmental changes, many diseases can occur in animals and can be transmitted if animals and people come into close contact, for example, animal husbandry, wildlife trade, etc. Also, urbanization and air travel are essential factors for outbreaks nowadays. First and foremost, flights across the world can cause illness in other countries. This means that the pathogen has a new home, and a pandemic is realized within hours [8].

The WHO indexed the 21st century's serious diseases, which threaten public health and have no therapeutic strategies, especially vaccines or new medicines, in 2018. Some important as follows: Influenza virus (H1N1), Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), Ebola, Zika, Yellow Fever, Cholera, Malaria, Tuberculosis. It was also reported that in the 21st century, epidemics can spread faster and farther than ever. Besides that, the last announced one, coronavirus-disease 2019 (COVID-19), was accepted as a pandemic disease by the WHO.

The global strategy is to eliminate and eradicate these illnesses through vaccines or medical investments. The WHO also recommends fresh foods and healthy nutrition during pandemics, which positively affect immunity [10]. The key vision of the relationship between nutrition, their role in immunity, and stress management was highlighted. Recent advances are also being critically demonstrated in antioxidant compounds, herbal ingredients, and pharmaceutical products with literature. The coronavirus diseases such as MERS, SARS, and COVID-19, it was reviewed that vitamin C, D and E, have an important role in the regulation of T cell differentiation in immunity [11]. Also, Leite Diniz et al. [12] reviewed that several natural antioxidants can have antiviral properties on metabolic modulation, and can treat the clinical symptoms in SARS, MERS, and COVID-19.

Nevertheless, it was reviewed that some herbal remedies such as geranium, green tea, pomegranate or Echinacea may be safer than drugs against influenza

**133**

*Natural Antioxidants to the Rescue?*

study [15].

*DOI: http://dx.doi.org/10.5772/intechopen.96132*

infections due to the anti-inflammatory, antibacterial and antioxidant activities of herbs and their extracts [13]. Also, it was showed that all these herbs and extracts have potential effects on respiratory complications and pro-inflammatory cytokines. Kaihatsu et al. [14] reported that natural phenolic compounds and coffee ingredients can inhibit the influenza virus by possessing radical scavenging activity. Moreover, flavonoids in citrus fruits have anti-inflammatory and antioxidant activities on the pulmonary system which showed by a bronchial epithelium model

The effect of thyme and its volatile oils may affect the penetration of the virus into the host cell or block viral proteins that are necessary for the virus to enter the host cells. Thyme may also act as an antiviral against intracellular viruses. In the meantime, evidence shows that natural compounds have plays a key role in alternative treatments to fight SARS-CoV-2. Recently determined that SARS-CoV-2 has spike glycoprotein consisted of two units. The first unit initiating virus attachment to the host cell surface and the second unit responsible for the virus-host membrane. Subunits are of great clinical importance as inhibition of the receptor binding domain which is the first step to hinder viral infections. Studies have shown that carvacrol, anethole, cinnamaldehyde, thymol, camphene, pulegone, ocimene and menthol showed good binding affinities and those natural compounds may

Furthermore, the potential effects of marine algal antioxidants on viral diseases has been reported [18]. Besides, some researchers reported that natural foods and natural compounds can have antibacterial and antiviral effects on cellular and molecular pathways, and thereby immunity is improved in several outbreaks such

Pandemics are old as humanity as well as natural antioxidants. Several natural foods and antioxidants have been used for healthy nutrition. However, the impact of several pandemics in the last century, there has been a growing interest between healthy food, nutrition, natural antioxidants and disease. Researchers studied the

A healthy life is associated with the oxidative status of the organism. In a cellular mechanism, the oxidative process starts with oxygen generation to energy. Thereby, free radicals occur as a consequence of energy in mitochondria. The rest products are reactive oxygen species (ROS) and reactive nitrogen species (RNS) which have a role in toxicological and pathological conditions. On the contrary, both ROS and RNS positively affect the cellular mechanism and immune system when they are at low levels, which means a normal metabolic process. Free radicals produce against stress conditions and antioxidants during the normal healthy condition, which is also called homeostasis. So, the body tries to maintain the oxidant and antioxidant balance. Oxidative stress markers, ROS and RNS, produce homeostasis through enzymatic and non-enzymatic reactions. Enzymatic reactions include cellular oxidase system like peroxidase, NADPH oxidase, hydrogen peroxidase. On the other side, the non-enzymatic process is based on organic compounds of the organism; for example, oxidative phosphorylation in mitochondria [22, 23]. ROS and RNS are formed from endogenous and exogenous sources that belong to several physiological and psychological mechanisms. Endogenous sources are generally occurring by immune cell activation, infection, excessive exercise, aging, or mental stress. However, environmental pollutants, drugs, heavy metals or radiation are exogenous

new therapeutic possibilities of the natural antioxidant for this purpose.

**3. Life related to free radicals, oxidative stress and antioxidants**

sources, and are metabolized in free radical processes [22, 24].

contribute to the stability of the complex protein ligand [16, 17].

as Ebola, Cholera, Malaria and Tuberculosis [19–21].

#### *Natural Antioxidants to the Rescue? DOI: http://dx.doi.org/10.5772/intechopen.96132*

*Antioxidants - Benefits, Sources, Mechanisms of Action*

Malaria, and Tuberculosis [9].

and their effects on pandemic diseases.

pandemic is realized within hours [8].

the clinical symptoms in SARS, MERS, and COVID-19.

**2. The reality of diseases in the 21st century**

Besides, although higher clinical complications have been observed in diseases, the mechanisms for the use of natural antioxidants are still not fully understood.

Since the past century, there have been essential diseases needed to determine how diseases progress and how the world could control them. Environmental factors, insufficient water, climate changes or new viruses influence the spread of contagious disease, and thereby cause epidemics. Nevertheless, The World Health Organization (WHO) has been still working on epidemiological studies to identify the possible sources of outbreaks, and to observe the pathogens spread from one region to different regions of the world [8]. Throughout history, there have been many significant pandemics recorded in human history. Some examples of the most up to date are Influenza virus (H1N1), Severe Acute Respiratory Syndrome (SARS), the Middle East Respiratory Syndrome (MERS), Ebola, Zika, Yellow Fever, Cholera,

Today, in response to pandemics, people have been transformed into plants and phytochemicals to protect their health. Also, researchers have advocated that these natural foods could meet antioxidant protection. However, studies are still ongoing. This chapter aims to summarize the essential natural antioxidants, their mechanism,

In recent years, climate change, lack of safe drinking water, poor living conditions and food insecurity have been the main causes of illness, epidemics and pandemics. Besides, there are also many chemicals or toxins, which can contaminate food, drink, and medicines that cause death, injury or harm to organs. The WHO reported that besides environmental changes, many diseases can occur in animals and can be transmitted if animals and people come into close contact, for example, animal husbandry, wildlife trade, etc. Also, urbanization and air travel are essential factors for outbreaks nowadays. First and foremost, flights across the world can cause illness in other countries. This means that the pathogen has a new home, and a

The WHO indexed the 21st century's serious diseases, which threaten public health and have no therapeutic strategies, especially vaccines or new medicines, in 2018. Some important as follows: Influenza virus (H1N1), Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), Ebola, Zika, Yellow Fever, Cholera, Malaria, Tuberculosis. It was also reported that in the 21st century, epidemics can spread faster and farther than ever. Besides that, the last announced one, coronavirus-disease 2019 (COVID-19), was accepted as a pandemic disease by

The global strategy is to eliminate and eradicate these illnesses through vaccines or medical investments. The WHO also recommends fresh foods and healthy nutrition during pandemics, which positively affect immunity [10]. The key vision of the relationship between nutrition, their role in immunity, and stress management was highlighted. Recent advances are also being critically demonstrated in antioxidant compounds, herbal ingredients, and pharmaceutical products with literature. The coronavirus diseases such as MERS, SARS, and COVID-19, it was reviewed that vitamin C, D and E, have an important role in the regulation of T cell differentiation in immunity [11]. Also, Leite Diniz et al. [12] reviewed that several natural antioxidants can have antiviral properties on metabolic modulation, and can treat

Nevertheless, it was reviewed that some herbal remedies such as geranium, green tea, pomegranate or Echinacea may be safer than drugs against influenza

**132**

the WHO.

infections due to the anti-inflammatory, antibacterial and antioxidant activities of herbs and their extracts [13]. Also, it was showed that all these herbs and extracts have potential effects on respiratory complications and pro-inflammatory cytokines. Kaihatsu et al. [14] reported that natural phenolic compounds and coffee ingredients can inhibit the influenza virus by possessing radical scavenging activity. Moreover, flavonoids in citrus fruits have anti-inflammatory and antioxidant activities on the pulmonary system which showed by a bronchial epithelium model study [15].

The effect of thyme and its volatile oils may affect the penetration of the virus into the host cell or block viral proteins that are necessary for the virus to enter the host cells. Thyme may also act as an antiviral against intracellular viruses. In the meantime, evidence shows that natural compounds have plays a key role in alternative treatments to fight SARS-CoV-2. Recently determined that SARS-CoV-2 has spike glycoprotein consisted of two units. The first unit initiating virus attachment to the host cell surface and the second unit responsible for the virus-host membrane. Subunits are of great clinical importance as inhibition of the receptor binding domain which is the first step to hinder viral infections. Studies have shown that carvacrol, anethole, cinnamaldehyde, thymol, camphene, pulegone, ocimene and menthol showed good binding affinities and those natural compounds may contribute to the stability of the complex protein ligand [16, 17].

Furthermore, the potential effects of marine algal antioxidants on viral diseases has been reported [18]. Besides, some researchers reported that natural foods and natural compounds can have antibacterial and antiviral effects on cellular and molecular pathways, and thereby immunity is improved in several outbreaks such as Ebola, Cholera, Malaria and Tuberculosis [19–21].

Pandemics are old as humanity as well as natural antioxidants. Several natural foods and antioxidants have been used for healthy nutrition. However, the impact of several pandemics in the last century, there has been a growing interest between healthy food, nutrition, natural antioxidants and disease. Researchers studied the new therapeutic possibilities of the natural antioxidant for this purpose.

## **3. Life related to free radicals, oxidative stress and antioxidants**

A healthy life is associated with the oxidative status of the organism. In a cellular mechanism, the oxidative process starts with oxygen generation to energy. Thereby, free radicals occur as a consequence of energy in mitochondria. The rest products are reactive oxygen species (ROS) and reactive nitrogen species (RNS) which have a role in toxicological and pathological conditions. On the contrary, both ROS and RNS positively affect the cellular mechanism and immune system when they are at low levels, which means a normal metabolic process. Free radicals produce against stress conditions and antioxidants during the normal healthy condition, which is also called homeostasis. So, the body tries to maintain the oxidant and antioxidant balance.

Oxidative stress markers, ROS and RNS, produce homeostasis through enzymatic and non-enzymatic reactions. Enzymatic reactions include cellular oxidase system like peroxidase, NADPH oxidase, hydrogen peroxidase. On the other side, the non-enzymatic process is based on organic compounds of the organism; for example, oxidative phosphorylation in mitochondria [22, 23]. ROS and RNS are formed from endogenous and exogenous sources that belong to several physiological and psychological mechanisms. Endogenous sources are generally occurring by immune cell activation, infection, excessive exercise, aging, or mental stress. However, environmental pollutants, drugs, heavy metals or radiation are exogenous sources, and are metabolized in free radical processes [22, 24].

The oxidative mechanism interacts with the antioxidant, endogenous, or exogenous mechanism. Both antioxidant mechanisms are capable of neutralizing free radicals and protecting the body. Endogenous antioxidant activity is the organism's first defensive system against free radicals. SOD, GPx, glutathione reductase, and CAT are the most important endogenous antioxidant in a healthy organism. Exogenous antioxidants are nutrients produced from foods and supplements, particularly vitamins E and C, flavonoids, phytochemicals, and certain essential plant-based antioxidants. These compounds can inactivate oxidizing agents and also inhibit inflammatory activation. They can modulate the enzymatic process and inflammatory mediators, including cytokines and peptides [25].

### **4. Oxidative stress in diseases**

Oxidative stress, which includes significant bodily activities, is an imbalance between the oxidizing and antioxidant processes. If the oxidative stress cannot be regulated, several damages occur in an organism. While free radicals and oxidants are in excess production, antioxidant reactions are limited, thereby oxidative stress is generated. Several membranes or cellular structures and systems are also adversely affected by this status. Cellular proteins, lipids, lipoproteins, DNA or RNA, and oxidizing compounds, and also critical systems such as cardiovascular, neurological, or immunity, are damaged. For instance, the chains of free radicals react, and the peroxidation of lipids exists. Besides, protein damage affects the structure of the cell membrane as well as the lower antibody output. Also, enzyme activity is reduced due to proteins and occurs in several molecular and cellular mutations. These changes reflect body systems, and diseases can be occur [25].

There are several significant diseases reviewed for oxidative stress in both humans and animals (**Figure 1**). Cancer is one of the most important one, creates complex changes in an organism such as chromosomal defects or induced free radicals activation. Another critical disease is cardiovascular disease related to stress, hypertension, hypercholesterolemia, diabetes, etc. Studies showed that cardiac structure changes, especially heart failure, hypertrophy, ischemia, or atherosclerosis, generate oxidative stress [26, 27]. Nevertheless, oxidative status and its generation have been described for neurological, pulmonary, and other diseases. It was reported that loss of neuron production and progression stimulates the oxidative process, thereby neurological diseases are presented [28]. The pulmonary diseases

**135**

*Natural Antioxidants to the Rescue?*

mation and diseases is inevitable.

inhibition role of viral genes [37].

**5. The truth regarding antioxidants**

exogenous antioxidants.

the oxidant process.

*DOI: http://dx.doi.org/10.5772/intechopen.96132*

are qualified by inflammation and activation of redox transcript factors [29]. Also, researchers have been studied the generation of ROS and RNS in autoimmune and renal diseases, or several other diseases [30–32]. The importance of the immune system is interested in low antibody production and low protein which concluded in increasing the risks of diseases. Besides that, macrophages' infiltration of activated immune cells causes inflammation and oxidative damage [30]. Nevertheless, some drugs, heavy metals, or lipid peroxidation molecules are accepted as strong free radicals inducers [33]. The fact that oxidative stress has a large place during inflam-

Oxidative stress has a crucial role in disease onset and development. During viral infections, there may be an increase in the production of oxidizing species not neutralized by the antioxidant system, causing oxidative stress that promotes cell damage [34–36]. However, it was reviewed that in viral diseases, viruses can control oxidative stress on their benefits in cellular replication [37]. Viruses especially can change the activation of the immune system signaling pathway in oxidative status [38, 39]. ROS and RNS production are triggered by cytokines, and thereby, cell death occurs due to the imbalance between the production of reactive species and the host's anti-oxidative status. Also, RNA viruses bring about changes in the body's antioxidant defense system. Viruses are responsible for this by affecting enzymes like SOD and CAT, as well as lowering ascorbic acid, carotenoids and reduced glutathione [40–42]. Recently, in a pandemic disease COVID-19, lung damage occurs due to the release of pro-inflammatory cytokines, which alter the oxidative stress [43]. Zhao [44] also determined that another immune response of pro-inflammatory cytokines against oxidative stress is activated phagocytes cells in COVID-19. Nevertheless, generated oxidative stress is also associated with nucleic acid damage in viral mutations. It was reported that human coronavirus disease (HCoVs) and SARS are identified by genetic mutations, and also mutations in spike protein [45]. Nevertheless, influenza viruses have been demonstrated with induced oxidative stress with the activation of the Nrf2 pathway in nuclear translocation, and expression in alveolar epithelial cells [46]. Similarly, the hepatitis C virus (HCV) has been linked with genes and phosphorylation of Nrf2 [47]. It was reviewed that the Nrf2 pathway has a critical

Management of pathogenic effects of viral diseases can be described by the mutual interaction between oxidant and antioxidant status control. Therefore this interaction is also associated with a healthy environment, balanced nutrition, and

The antioxidant process begins with oxidation when it damages a free radical compound, and then it follows by attempting to restore the body. An antioxidant may act as a pro-oxidant, which has generated ROS and RNS into two ways; breaking the chain and preventing it [48]. A chain breaking antioxidant may stabilize the formation of free radicals in the oxidative state, e.g., lipid peroxidation. Vitamins C and E, or carrots may be accepted in these anti-oxidants that break the chain. On the other hand, endogenous antioxidant enzymes such as glutathione, GPx, CAT, and SOD, may inhibit the initiation and propagation steps, consequently delaying

Along with current literature, there have been several natural antioxidants reviewed for diseases or pandemic diseases [12, 49]. Each of these antioxidant

properties is the neutralization capability of oxidative stress (**Table 1**).

**Figure 1.** *Oxidative stress related diseases.*

#### *Natural Antioxidants to the Rescue? DOI: http://dx.doi.org/10.5772/intechopen.96132*

*Antioxidants - Benefits, Sources, Mechanisms of Action*

peptides [25].

**4. Oxidative stress in diseases**

The oxidative mechanism interacts with the antioxidant, endogenous, or exogenous mechanism. Both antioxidant mechanisms are capable of neutralizing free radicals and protecting the body. Endogenous antioxidant activity is the organism's first defensive system against free radicals. SOD, GPx, glutathione reductase, and CAT are the most important endogenous antioxidant in a healthy organism. Exogenous antioxidants are nutrients produced from foods and supplements, particularly vitamins E and C, flavonoids, phytochemicals, and certain essential plant-based antioxidants. These compounds can inactivate oxidizing agents and also inhibit inflammatory activation. They can modulate the enzymatic process and inflammatory mediators, including cytokines and

Oxidative stress, which includes significant bodily activities, is an imbalance between the oxidizing and antioxidant processes. If the oxidative stress cannot be regulated, several damages occur in an organism. While free radicals and oxidants are in excess production, antioxidant reactions are limited, thereby oxidative stress is generated. Several membranes or cellular structures and systems are also adversely affected by this status. Cellular proteins, lipids, lipoproteins, DNA or RNA, and oxidizing compounds, and also critical systems such as cardiovascular, neurological, or immunity, are damaged. For instance, the chains of free radicals react, and the peroxidation of lipids exists. Besides, protein damage affects the structure of the cell membrane as well as the lower antibody output. Also, enzyme activity is reduced due to proteins and occurs in several molecular and cellular mutations. These changes reflect body systems, and diseases can be occur [25]. There are several significant diseases reviewed for oxidative stress in both humans and animals (**Figure 1**). Cancer is one of the most important one, creates complex changes in an organism such as chromosomal defects or induced free radicals activation. Another critical disease is cardiovascular disease related to stress, hypertension, hypercholesterolemia, diabetes, etc. Studies showed that cardiac structure changes, especially heart failure, hypertrophy, ischemia, or atherosclerosis, generate oxidative stress [26, 27]. Nevertheless, oxidative status and its generation have been described for neurological, pulmonary, and other diseases. It was reported that loss of neuron production and progression stimulates the oxidative process, thereby neurological diseases are presented [28]. The pulmonary diseases

**134**

**Figure 1.**

*Oxidative stress related diseases.*

are qualified by inflammation and activation of redox transcript factors [29]. Also, researchers have been studied the generation of ROS and RNS in autoimmune and renal diseases, or several other diseases [30–32]. The importance of the immune system is interested in low antibody production and low protein which concluded in increasing the risks of diseases. Besides that, macrophages' infiltration of activated immune cells causes inflammation and oxidative damage [30]. Nevertheless, some drugs, heavy metals, or lipid peroxidation molecules are accepted as strong free radicals inducers [33]. The fact that oxidative stress has a large place during inflammation and diseases is inevitable.

Oxidative stress has a crucial role in disease onset and development. During viral infections, there may be an increase in the production of oxidizing species not neutralized by the antioxidant system, causing oxidative stress that promotes cell damage [34–36]. However, it was reviewed that in viral diseases, viruses can control oxidative stress on their benefits in cellular replication [37]. Viruses especially can change the activation of the immune system signaling pathway in oxidative status [38, 39]. ROS and RNS production are triggered by cytokines, and thereby, cell death occurs due to the imbalance between the production of reactive species and the host's anti-oxidative status. Also, RNA viruses bring about changes in the body's antioxidant defense system. Viruses are responsible for this by affecting enzymes like SOD and CAT, as well as lowering ascorbic acid, carotenoids and reduced glutathione [40–42]. Recently, in a pandemic disease COVID-19, lung damage occurs due to the release of pro-inflammatory cytokines, which alter the oxidative stress [43]. Zhao [44] also determined that another immune response of pro-inflammatory cytokines against oxidative stress is activated phagocytes cells in COVID-19. Nevertheless, generated oxidative stress is also associated with nucleic acid damage in viral mutations. It was reported that human coronavirus disease (HCoVs) and SARS are identified by genetic mutations, and also mutations in spike protein [45]. Nevertheless, influenza viruses have been demonstrated with induced oxidative stress with the activation of the Nrf2 pathway in nuclear translocation, and expression in alveolar epithelial cells [46]. Similarly, the hepatitis C virus (HCV) has been linked with genes and phosphorylation of Nrf2 [47]. It was reviewed that the Nrf2 pathway has a critical inhibition role of viral genes [37].

Management of pathogenic effects of viral diseases can be described by the mutual interaction between oxidant and antioxidant status control. Therefore this interaction is also associated with a healthy environment, balanced nutrition, and exogenous antioxidants.

## **5. The truth regarding antioxidants**

The antioxidant process begins with oxidation when it damages a free radical compound, and then it follows by attempting to restore the body. An antioxidant may act as a pro-oxidant, which has generated ROS and RNS into two ways; breaking the chain and preventing it [48]. A chain breaking antioxidant may stabilize the formation of free radicals in the oxidative state, e.g., lipid peroxidation. Vitamins C and E, or carrots may be accepted in these anti-oxidants that break the chain. On the other hand, endogenous antioxidant enzymes such as glutathione, GPx, CAT, and SOD, may inhibit the initiation and propagation steps, consequently delaying the oxidant process.

Along with current literature, there have been several natural antioxidants reviewed for diseases or pandemic diseases [12, 49]. Each of these antioxidant properties is the neutralization capability of oxidative stress (**Table 1**).


**Table 1.** *Natural antioxidants.*

### **5.1 Vitamins**

Vitamins, C, E and beta-carotene, which also called as primary antioxidants, have the beneficial effect either in health or diseases. Nevertheless, excessive doses of vitamins can be harmful rather than safe. So there has been ongoing research on nutritional antioxidants. WHO recommends antioxidants for malnutrition, disease, and pandemic-related needs [10]. Besides, nutritionists have endorsed antioxidant foods for humans first, while they have also pointed out that supplements may help.

Vitamins E and C have a higher antioxidative capacity among vitamins. Vitamin E (also known as tocopherol or alpha-tocopherol) has been reported to protect cellular membranes from lipid peroxide. Studies have suggested that vitamin E may be used in breast cancer, arthritis, some cardiovascular and neurological diseases. Besides, it was determined that the long-term use of vitamin E is acceptable as being available. Sources of vitamin E include vegetable oils, walnuts, cereals, eggs, poultry, and meat [50].

Nonetheless, vitamin C, called ascorbic acid, is essential for carnitine, neurotransmitter biosynthesis, and collagen. This vitamin has antioxidant, anti-carcinogenic, and immunomodulatory effects, which has also reduced the incidence of cancers. Also, vitamin C acts alongside vitamin E to quench free radicals. Vitamin C is found throughout natural sources such as fruits, vegetables, and tomatoes [51].

Beta-carotene, which is an active ingredient of pro-vitamin A, is a powerful antioxidant. Beta-carotene has the potential to quench oxygen during oxidative stress. This pro-vitamin has an antioxidant effect on cardiovascular diseases and cancer in particular. Beta-carotene comprises many foods, mainly green plants, spinach, carrots, oils, mangoes, apricots, and a watermelon [52, 53]. Another essential carotenoid, lycopene, is a vegetable nutrient that has protective effects on pulmonary cells and cancer. Lycopene was shown to be capable of balancing free radicals. The best source of lycopene is cooked tomato, juice, and sauce [54]. What are more, more red and pink fruits have this vitamin, like watermelon, grapefruit.

High doses of vitamins are recommended for using safely during pandemics. It was reported that especially Vitamin C has used for the treatment of cardiovascular, pulmonary disease as well as sepsis or nephropathy. It was evaluated that vitamin C can improve the mechanical ventilation of patients [55].

#### **5.2 Minerals**

There are several antioxidant minerals, in particular, selenium, zinc, copper, and iron. Selenium is an essential mineral in several vegetables, mushrooms, meat, and

**137**

against COVID-19 [72].

*Natural Antioxidants to the Rescue?*

*DOI: http://dx.doi.org/10.5772/intechopen.96132*

Zn inhibits replicating the virus in SARS.

hydrogen peroxide and transforms it into water.

taken in sufficient doses for the biological mechanism [61].

intake including especially vitamins and minerals.

diseases as potential phyto antiviral agents [62].

**5.3 Plants and phytochemicals**

seafood, with anticarcinogenic and immunomodulatory effects. Selenium also plays a crucial role in thyroid function, gastrointestinal, cardiovascular, and pulmonary diseases [48]. Selenium contains about 35 antioxidant proteins, which reduce free radicals and allow cytoprotective antioxidant genes [56]. The mineral targets

The other minerals Mn, Cu, Zn, and Fe, can maintain the endogenous antioxidants. Fe and Cu can suppress free radicals' formation by keeping bound to transport proteins. A high dose of Fe may negatively affect Zn′s absorption to damage the immune system. It was reported that the increase of Zn in the cell has an antiviral effect in COVID-19 [57]. Also, Te Velthuis et al. [58] determined that a low dose of

Nevertheless, Cu is an essential mineral for cellular respiration, iron metabolism, and reducing oxidative stress. It was observed that Cu has an antiviral effect in some diseases such as COVID-19, human immunodeficiency virus (HIV), or bronchitis [59, 60]. On the other hand, according to some kinds of literature, Fe and Cu may be toxic due to an increase of viral replication and mortality in diseases, for example, HIV or COVID-19 [60]. Therefore, it was accepted that Cu and Fe must be

As the pandemic diseases continuing, humans should boost their immune system

by taking sufficient minerals. Optimal nutrition can exist with dietary nutrient

Earlier scientific studies have shown that commonly used wild edible plants, spices and herbal teas have high antiviral activity against a variety of viruses. There is also evidence that some of these drugs are used for various types of coronavirus

Natural antioxidants can alternate the multiple pathological processes in oxidative stress, primarily oxidative damage, inflammation, genetic changes, growth factors, etc. It was reviewed that natural antioxidants, mostly plants, and phytochemicals, can improve either oxidant status or antioxidant capacity [12]. Several plants are alternative medicines, such as ginger, garlic, curcumin, thyme, licorice, *Echinacea purpurea* or Spirulina, etc. These plants are recommended to strengthen immunity and reduce oxidative status. It was reported that these medicinal plants have essential

Garlic, which is the most crucial spice worldwide, has a remarkably enhanced immune system booster. It may boost the activity of natural killer cells during immune deficiency. This medicinal herb has been approved as a therapeutic agent for homeostasis [65]. Furthermore, garlic has been used against cancer and cardiovascular disease [66]. This interesting spice, which has been used as a seasoning herb and traditional medicine in immunity and viral diseases, has several compounds such as saponin, cardio glycoside, and flavonoids [67–69]. Antiviral effects in garlic depend on inhibition of viral replication effects, viral protein synthesis, and viral DNA polymerization [70]. Also, garlic and its extracts have been shown to improve CAT and GPx enzymes and act as a collector of hydroxyl radicals [71]. It was reviewed that garlic and its extracts may be an alternative medicinal herbs

Ginger is a well-known herb with several effects such as treating sickness, colic, and appetite, controlling gastrointestinal problems, and respiratory infections. It is also accepted as a neuroprotectant, antidiabetic, anti-inflammatory, antioxidant, antiviral, and anticancer [73, 74]. This herb can maintain homeostasis by cooling the body, and reduce high fever. It was also reported that ginger shows its effect by

roles in pandemic diseases, especially HIV, SARS and, COVID-19 [62–64].

#### *Natural Antioxidants to the Rescue? DOI: http://dx.doi.org/10.5772/intechopen.96132*

*Antioxidants - Benefits, Sources, Mechanisms of Action*

Lycopene Iron Echinacea

Vitamins, C, E and beta-carotene, which also called as primary antioxidants, have the beneficial effect either in health or diseases. Nevertheless, excessive doses of vitamins can be harmful rather than safe. So there has been ongoing research on nutritional antioxidants. WHO recommends antioxidants for malnutrition, disease, and pandemic-related needs [10]. Besides, nutritionists have endorsed antioxidant foods for humans first, while they have also pointed out that supple-

Spirulina Liquorice

**Vitamins Minerals Plants Phtyochemicals** Vitamin E Selenium Garclic Polyphenols Vitamin C Zinc Ginger Flavonoids Beta carotene Copper Thyme Carotenoids

Vitamins E and C have a higher antioxidative capacity among vitamins. Vitamin

E (also known as tocopherol or alpha-tocopherol) has been reported to protect cellular membranes from lipid peroxide. Studies have suggested that vitamin E may be used in breast cancer, arthritis, some cardiovascular and neurological diseases. Besides, it was determined that the long-term use of vitamin E is acceptable as being available. Sources of vitamin E include vegetable oils, walnuts, cereals, eggs,

Nonetheless, vitamin C, called ascorbic acid, is essential for carnitine, neurotransmitter biosynthesis, and collagen. This vitamin has antioxidant, anti-carcinogenic, and immunomodulatory effects, which has also reduced the incidence of cancers. Also, vitamin C acts alongside vitamin E to quench free radicals. Vitamin C is found throughout natural sources such as fruits, vegetables, and tomatoes [51]. Beta-carotene, which is an active ingredient of pro-vitamin A, is a powerful antioxidant. Beta-carotene has the potential to quench oxygen during oxidative stress. This pro-vitamin has an antioxidant effect on cardiovascular diseases and cancer in particular. Beta-carotene comprises many foods, mainly green plants, spinach, carrots, oils, mangoes, apricots, and a watermelon [52, 53]. Another essential carotenoid, lycopene, is a vegetable nutrient that has protective effects on pulmonary cells and cancer. Lycopene was shown to be capable of balancing free radicals. The best source of lycopene is cooked tomato, juice, and sauce [54]. What are more,

more red and pink fruits have this vitamin, like watermelon, grapefruit.

can improve the mechanical ventilation of patients [55].

High doses of vitamins are recommended for using safely during pandemics. It was reported that especially Vitamin C has used for the treatment of cardiovascular, pulmonary disease as well as sepsis or nephropathy. It was evaluated that vitamin C

There are several antioxidant minerals, in particular, selenium, zinc, copper, and iron. Selenium is an essential mineral in several vegetables, mushrooms, meat, and

**5.1 Vitamins**

*Natural antioxidants.*

**Table 1.**

**Natural Antioxidants**

ments may help.

poultry, and meat [50].

**136**

**5.2 Minerals**

seafood, with anticarcinogenic and immunomodulatory effects. Selenium also plays a crucial role in thyroid function, gastrointestinal, cardiovascular, and pulmonary diseases [48]. Selenium contains about 35 antioxidant proteins, which reduce free radicals and allow cytoprotective antioxidant genes [56]. The mineral targets hydrogen peroxide and transforms it into water.

The other minerals Mn, Cu, Zn, and Fe, can maintain the endogenous antioxidants. Fe and Cu can suppress free radicals' formation by keeping bound to transport proteins. A high dose of Fe may negatively affect Zn′s absorption to damage the immune system. It was reported that the increase of Zn in the cell has an antiviral effect in COVID-19 [57]. Also, Te Velthuis et al. [58] determined that a low dose of Zn inhibits replicating the virus in SARS.

Nevertheless, Cu is an essential mineral for cellular respiration, iron metabolism, and reducing oxidative stress. It was observed that Cu has an antiviral effect in some diseases such as COVID-19, human immunodeficiency virus (HIV), or bronchitis [59, 60]. On the other hand, according to some kinds of literature, Fe and Cu may be toxic due to an increase of viral replication and mortality in diseases, for example, HIV or COVID-19 [60]. Therefore, it was accepted that Cu and Fe must be taken in sufficient doses for the biological mechanism [61].

As the pandemic diseases continuing, humans should boost their immune system by taking sufficient minerals. Optimal nutrition can exist with dietary nutrient intake including especially vitamins and minerals.

## **5.3 Plants and phytochemicals**

Earlier scientific studies have shown that commonly used wild edible plants, spices and herbal teas have high antiviral activity against a variety of viruses. There is also evidence that some of these drugs are used for various types of coronavirus diseases as potential phyto antiviral agents [62].

Natural antioxidants can alternate the multiple pathological processes in oxidative stress, primarily oxidative damage, inflammation, genetic changes, growth factors, etc. It was reviewed that natural antioxidants, mostly plants, and phytochemicals, can improve either oxidant status or antioxidant capacity [12]. Several plants are alternative medicines, such as ginger, garlic, curcumin, thyme, licorice, *Echinacea purpurea* or Spirulina, etc. These plants are recommended to strengthen immunity and reduce oxidative status. It was reported that these medicinal plants have essential roles in pandemic diseases, especially HIV, SARS and, COVID-19 [62–64].

Garlic, which is the most crucial spice worldwide, has a remarkably enhanced immune system booster. It may boost the activity of natural killer cells during immune deficiency. This medicinal herb has been approved as a therapeutic agent for homeostasis [65]. Furthermore, garlic has been used against cancer and cardiovascular disease [66]. This interesting spice, which has been used as a seasoning herb and traditional medicine in immunity and viral diseases, has several compounds such as saponin, cardio glycoside, and flavonoids [67–69]. Antiviral effects in garlic depend on inhibition of viral replication effects, viral protein synthesis, and viral DNA polymerization [70]. Also, garlic and its extracts have been shown to improve CAT and GPx enzymes and act as a collector of hydroxyl radicals [71]. It was reviewed that garlic and its extracts may be an alternative medicinal herbs against COVID-19 [72].

Ginger is a well-known herb with several effects such as treating sickness, colic, and appetite, controlling gastrointestinal problems, and respiratory infections. It is also accepted as a neuroprotectant, antidiabetic, anti-inflammatory, antioxidant, antiviral, and anticancer [73, 74]. This herb can maintain homeostasis by cooling the body, and reduce high fever. It was also reported that ginger shows its effect by

inhibiting productions of nitric oxide and superoxide [75, 76]. Chang et al. [77] reported that ginger can block the viral attachment in respiratory epithelium, and is effective in human respiratory syncytial virus.

A blue-green microalga named Spirulina is a popular superfood with several beneficial effects such as antioxidant, antiviral, immunomodulatory, etc. [5]. It was reported that Spirulina could inhibit viral replication by blocking replication [78]. Hernández-Corona et al. [79] found that Spirulina inhibited the viral cell penetration and replication in a virus disease named herpes simplex virus type-1 (HSV-1). It was reviewed that the antiviral features of Spirulina are belonged to acidic polysaccharides extract such as calcium spirulina. Moreover, studies suggested that Spirulina may be safe for managing influenza outbreaks, however, additional investigations are needed [80–82].

Essential oils are aromatic oily liquids derived from plant material. These natural products have been widely used, in particular fragrances, cosmetics, aromatherapy, and herbal medicine, spices, nutrition, and agriculture. Essential oils have a known biological activity, including antibacterial, antiviral, anti-fungal, and anti-inflammatory effects [83].

*Echinacea purpurea*, a popular natural food worldwide, includes essential oils, flavonoids, tannin, saponin, betain, etc. According to studies, this herbal medicine can reduce the symptoms of respiratory diseases. Antiviral and immunomodulatory effects in SARS and COVID-19 have been reported [84, 85].

Thyme, curcumin, and licorice have been used for decades safely for both therapeutic and treatments. The ingredients of the essential oils of the origanum species were linalol, γ terpinene, p-cymenon, thymol and myrcene. Thymus's essential oil consists primarily of thymol. Other components found other than thymol are carvacrol, linalyl acetate, linalool, γ-terpinene, p-cymene and geraniol. Numerous studies have been carried out over the application of detected phenolic compounds as an antioxidant and antiviral activities have been tested, and it shows the antiviral effects against respiratory syncytial virus, Coxsackie virus, and herpes simplex virus type 1 [86]. Zhang et al. [86] reported that a significant ingredient of thyme has antiviral and antioxidant features. Curcumin is an active supplement to inhibit the activation of cytokines and neutrophils in the lungs. Many clinical studies have evaluated its effect on inflammation, immunity, microbial, and viral conditions [87]. It was also reported that curcumin could induce the glutathione level as a scavenger of free radicals [37]. On the other hand, an exciting herb named licorice can grow in many geographical structures worldwide. It was reported that licorice could reduce hepatocellular damage in hepatitis B and C. Nevertheless, it has an antiviral effect on HIV and SARS virus [88]. Also, licorice has an immunomodulatory effect, and it can induce respiratory activity [89]. It was determined that licorice shows these activities by its extracts named triterpene, saponins, and flavonoids [90].

Scientific studies on different species of cistus have shown that different species of the plant contain useful phytochemical products. Plant-derived polyphenols have been shown to be strong antioxidant, antibacterial, antifungal, anti-inflammatory, anti-viral, cytotoxic and anti-cancer properties with potential health benefits [91]. *Cistus creticus* is a naturally occurring plant native to Turkey with phenolic substances and flavonoids. Plant-derived polyphenols are strong antioxidants, and have protective effects on DNA. Various reports have appeared on the antiviral and antibacterial potential, including several reports describing the antiviral activity of polyphenols against the parainfluenza 3 virus [92].

Begun to be remembered with the existence of human beings, the olive was the symbol of peace and healthy life in every period of life from antiquity. Olive leaf traditionally used against hypertension, diuretic, antipyretic, appetizing and against constipation [93]. The olive leaf contains much more oleuropein than other

**139**

*Natural Antioxidants to the Rescue?*

*DOI: http://dx.doi.org/10.5772/intechopen.96132*

parts. It has demonstrated that it is a phytochemical active against numerous diseases. Principal active constituents of the olive leaf are oleanolic acid and calcium elenolate compounds. These compounds have been shown to have anti-viral activity against many viruses such as parainfluenza, herpes simplex, pseudorabies, polioviruses (type-1, −2, and − 3), rhinoviruses, mycoviruses, coxsackievirus [94]. Phytochemicals are produced in plants, which are also referred to as naturally occurring plant chemicals. Several studies have demonstrated that flavonoids or phytochemicals may block these diseases' enzymatic activities [12, 95]. The most significant phytochemical compounds, polyphenols, flavonoids, and carotenoids, have been identified as antioxidants [96]. Polyphenols referred to as resveratrol and ellagic acid, are natural compounds in green tea, red wine, whole grains, grapes, and berries. They have potent antioxidants, metabolic, and cardiovascular effects. They can inhibit the proliferation of lung cancer cells by increasing autophagy [97, 98]. Resveratrol and ellagic acid may also help protect DNA and balance cell cycles. Also, it was reported that there is insufficient information on side effects and efficacy. Hence, traditional treatments need to be discussed before treatment. Nevertheless, it was reported that flavonoids have an inhibition role in macrophages against inflammatory cytokines production in viral diseases [99]. There are some crucial plants included flavonoids, such as green tea, grapes, apples, and *Ginkgo biloba*. Also, the richest flavonoids, catechin and quercetin, are found in green tea. Catechin in green tea has anti-inflammatory features, which increases the glucocorticoids in pulmonary diseases, especially in the lung [100]. Quercetin is extracted from some plants such as *Rubus fruticosus*, *Passiflora subpeltata*, *Hypericum perforatum*, or Lagerstroemia. It was reported that quercetin could inhibit oxidative stress by increased endogenous antioxidants SOD, CAT, and GPx, and decreased lipid peroxidation. This flavonoid can also improve the function of non-enzymatic antioxidants such as vitamin C and E, and glutathione [101–103]. It was reported that another green tea metabolite named gallocatechin could reduce nitric oxide synthesis and oxidative status, and increase antioxidant capacity, especially catalase level [104, 105]. *Ginkgo biloba*, another popular herb, is a bioflavonoid compound, and also its extract named amentoflavone has a high antioxidant capacity, especially for lung diseases due to its improvement effect on SOD and glutathione [106]. Besides, some foods such as carrots, cabbage, and apple, which has luteolin, causes an increase in glutathione, SOD, and CAT. Luteolin also can improve lipid peroxida-

tion during oxidative status in cancer and lung diseases [107].

tomatoes, carrots and watermelon.

**6. Future perspectives**

Plant carotenoids were considered in terms of their role as mediators of free radicals through oxidation or oxygenation [108]. Furthermore, carotenoids act as chemical quench, which is necessary for the antioxidant function. They may reduce the risk of disease, in particular cancer and cardiovascular disease. The most important carotenoids are lycopene, lutein, zeaxanthine, beta-carotene found in

Traditional medicinal herbs are rich compounds used in the development of medicines. They have centuries of experience with the use of herbal remedies for prevention and treatment. There are many medicinal herbs scattered geographically throughout the world. As such, further investigations are necessary to identify differences.

Several clinical approaches have been agreed upon to deal with oxidative stress. Lately, for healthy living, the use of antioxidant supplements has been targeted to provide adequate homeostasis for humans and animals in many diseases or pandemics. Besides the prevention strategies such as isolation, hygiene, and control,

#### *Natural Antioxidants to the Rescue? DOI: http://dx.doi.org/10.5772/intechopen.96132*

*Antioxidants - Benefits, Sources, Mechanisms of Action*

effective in human respiratory syncytial virus.

investigations are needed [80–82].

matory effects [83].

inhibiting productions of nitric oxide and superoxide [75, 76]. Chang et al. [77] reported that ginger can block the viral attachment in respiratory epithelium, and is

A blue-green microalga named Spirulina is a popular superfood with several beneficial effects such as antioxidant, antiviral, immunomodulatory, etc. [5]. It was reported that Spirulina could inhibit viral replication by blocking replication [78]. Hernández-Corona et al. [79] found that Spirulina inhibited the viral cell penetration and replication in a virus disease named herpes simplex virus type-1 (HSV-1). It was reviewed that the antiviral features of Spirulina are belonged to acidic polysaccharides extract such as calcium spirulina. Moreover, studies suggested that Spirulina may be safe for managing influenza outbreaks, however, additional

Essential oils are aromatic oily liquids derived from plant material. These natural products have been widely used, in particular fragrances, cosmetics, aromatherapy, and herbal medicine, spices, nutrition, and agriculture. Essential oils have a known biological activity, including antibacterial, antiviral, anti-fungal, and anti-inflam-

*Echinacea purpurea*, a popular natural food worldwide, includes essential oils, flavonoids, tannin, saponin, betain, etc. According to studies, this herbal medicine can reduce the symptoms of respiratory diseases. Antiviral and immunomodulatory

Thyme, curcumin, and licorice have been used for decades safely for both therapeutic and treatments. The ingredients of the essential oils of the origanum species were linalol, γ terpinene, p-cymenon, thymol and myrcene. Thymus's essential oil consists primarily of thymol. Other components found other than thymol are carvacrol, linalyl acetate, linalool, γ-terpinene, p-cymene and geraniol. Numerous studies have been carried out over the application of detected phenolic compounds as an antioxidant and antiviral activities have been tested, and it shows the antiviral effects against respiratory syncytial virus, Coxsackie virus, and herpes simplex virus type 1 [86]. Zhang et al. [86] reported that a significant ingredient of thyme has antiviral and antioxidant features. Curcumin is an active supplement to inhibit the activation of cytokines and neutrophils in the lungs. Many clinical studies have evaluated its effect on inflammation, immunity, microbial, and viral conditions [87]. It was also reported that curcumin could induce the glutathione level as a scavenger of free radicals [37]. On the other hand, an exciting herb named licorice can grow in many geographical structures worldwide. It was reported that licorice could reduce hepatocellular damage in hepatitis B and C. Nevertheless, it has an antiviral effect on HIV and SARS virus [88]. Also, licorice has an immunomodulatory effect, and it can induce respiratory activity [89]. It was determined that licorice shows these activities by its extracts named triterpene, saponins, and flavonoids [90].

Scientific studies on different species of cistus have shown that different species of the plant contain useful phytochemical products. Plant-derived polyphenols have been shown to be strong antioxidant, antibacterial, antifungal, anti-inflammatory, anti-viral, cytotoxic and anti-cancer properties with potential health benefits [91]. *Cistus creticus* is a naturally occurring plant native to Turkey with phenolic substances and flavonoids. Plant-derived polyphenols are strong antioxidants, and have protective effects on DNA. Various reports have appeared on the antiviral and antibacterial potential, including several reports describing the antiviral activity of

Begun to be remembered with the existence of human beings, the olive was the symbol of peace and healthy life in every period of life from antiquity. Olive leaf traditionally used against hypertension, diuretic, antipyretic, appetizing and against constipation [93]. The olive leaf contains much more oleuropein than other

effects in SARS and COVID-19 have been reported [84, 85].

polyphenols against the parainfluenza 3 virus [92].

**138**

parts. It has demonstrated that it is a phytochemical active against numerous diseases. Principal active constituents of the olive leaf are oleanolic acid and calcium elenolate compounds. These compounds have been shown to have anti-viral activity against many viruses such as parainfluenza, herpes simplex, pseudorabies, polioviruses (type-1, −2, and − 3), rhinoviruses, mycoviruses, coxsackievirus [94].

Phytochemicals are produced in plants, which are also referred to as naturally occurring plant chemicals. Several studies have demonstrated that flavonoids or phytochemicals may block these diseases' enzymatic activities [12, 95]. The most significant phytochemical compounds, polyphenols, flavonoids, and carotenoids, have been identified as antioxidants [96]. Polyphenols referred to as resveratrol and ellagic acid, are natural compounds in green tea, red wine, whole grains, grapes, and berries. They have potent antioxidants, metabolic, and cardiovascular effects. They can inhibit the proliferation of lung cancer cells by increasing autophagy [97, 98]. Resveratrol and ellagic acid may also help protect DNA and balance cell cycles. Also, it was reported that there is insufficient information on side effects and efficacy. Hence, traditional treatments need to be discussed before treatment.

Nevertheless, it was reported that flavonoids have an inhibition role in macrophages against inflammatory cytokines production in viral diseases [99]. There are some crucial plants included flavonoids, such as green tea, grapes, apples, and *Ginkgo biloba*. Also, the richest flavonoids, catechin and quercetin, are found in green tea. Catechin in green tea has anti-inflammatory features, which increases the glucocorticoids in pulmonary diseases, especially in the lung [100]. Quercetin is extracted from some plants such as *Rubus fruticosus*, *Passiflora subpeltata*, *Hypericum perforatum*, or Lagerstroemia. It was reported that quercetin could inhibit oxidative stress by increased endogenous antioxidants SOD, CAT, and GPx, and decreased lipid peroxidation. This flavonoid can also improve the function of non-enzymatic antioxidants such as vitamin C and E, and glutathione [101–103]. It was reported that another green tea metabolite named gallocatechin could reduce nitric oxide synthesis and oxidative status, and increase antioxidant capacity, especially catalase level [104, 105]. *Ginkgo biloba*, another popular herb, is a bioflavonoid compound, and also its extract named amentoflavone has a high antioxidant capacity, especially for lung diseases due to its improvement effect on SOD and glutathione [106]. Besides, some foods such as carrots, cabbage, and apple, which has luteolin, causes an increase in glutathione, SOD, and CAT. Luteolin also can improve lipid peroxidation during oxidative status in cancer and lung diseases [107].

Plant carotenoids were considered in terms of their role as mediators of free radicals through oxidation or oxygenation [108]. Furthermore, carotenoids act as chemical quench, which is necessary for the antioxidant function. They may reduce the risk of disease, in particular cancer and cardiovascular disease. The most important carotenoids are lycopene, lutein, zeaxanthine, beta-carotene found in tomatoes, carrots and watermelon.

Traditional medicinal herbs are rich compounds used in the development of medicines. They have centuries of experience with the use of herbal remedies for prevention and treatment. There are many medicinal herbs scattered geographically throughout the world. As such, further investigations are necessary to identify differences.

### **6. Future perspectives**

Several clinical approaches have been agreed upon to deal with oxidative stress. Lately, for healthy living, the use of antioxidant supplements has been targeted to provide adequate homeostasis for humans and animals in many diseases or pandemics. Besides the prevention strategies such as isolation, hygiene, and control,

nutrition, mostly natural antioxidants, is essential for improving antiviral activity against viral and pandemic diseases such as SARS, COVID-19 and, HIV etc.

Natural antioxidants have been used in many therapeutic practices because of their enzyme inhibition and their inhibitory effect on viral protein receptors. In addition, natural antioxidants may enhance immunity during diseases. As well, they have been the subject of multidisciplinary studies [109]. The WHO also acknowledged that there was insufficient evidence of herbal medicines for the treatment or treatment of viral diseases in humans, especially COVID-19 [110].

## **7. Conclusion**

Throughout history, there have been significant pandemic diseases such as the 1918 influenza pandemic (H1N1 virus), HIV and COVID-19. During pandemics, nutrition is as important as health, hygiene, or self-isolation standards. To that end, predominantly natural antioxidants have been used in therapeutic practices. Many herbal medicines, plants, and their extracts have inhibitory effects on pandemic diseases or their symptoms. These nutrients have been investigating their immunemodulating, antiviral, and antioxidant effects for decades. However, all these effects of natural antioxidants are not equal. Research into the health performance of these nutrients is therefore necessary.

## **Conflict of interest**

The authors declare no conflict of interest.

## **Acronyms and abbreviations**


**141**

**Author details**

University, Bursa, Turkey

Kemal University, Tekirdag, Turkey

provided the original work is properly cited.

\* and Nilay Seyidoglu<sup>2</sup>

\*Address all correspondence to: caydin@uludag.edu.tr

1 Department of Physiology, Faculty of Veterinary Medicine, Bursa Uludag

2 Department of Physiology, Faculty of Veterinary Medicine, Tekirdag Namik

© 2021 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,

Cenk Aydin1

*Natural Antioxidants to the Rescue?*

*DOI: http://dx.doi.org/10.5772/intechopen.96132*

Beta carotene provitamin A Blue-green algae Spirulina Thymus Thymol

Green tea Gallocatechin

*Cistus creticus* Polyphenols

Flavonoids Catechin, quercetin

*Ginkgo biloba* Bioflavonoid compound

Phytochemical compounds Polyphenols, flavonoids, carotenoids

Olive leaf Oleanolic acid and calcium elenolate compounds

Essential oils Linalol, γ terpinene, p-cymenon, thymol, myrcene Endogenous antioxidant Superoxide dismutase, glutathione peroxidase,

glutathione reductase, catalase

## **Appendices and nomenclature**


*Natural Antioxidants to the Rescue? DOI: http://dx.doi.org/10.5772/intechopen.96132*

*Antioxidants - Benefits, Sources, Mechanisms of Action*

**7. Conclusion**

nutrients is therefore necessary.

**Acronyms and abbreviations**

The authors declare no conflict of interest.

H1N1 Influenza virus

CAT Catalase

Cu Copper Fe Ferrous Zn Zinc

Ascorbic acid Vitamin C Tocopherol Vitamin E

**Appendices and nomenclature**

WHO The World Health Organization

HIV Human immunodeficiency virus

COVID-2019 Coronavirus-disease 2019 hCoVs Human coronavirus disease

ROS Reactive oxygen species RNS Reactive nitrogen species GPx Glutathione peroxidase

SOD Superoxide dismutase HCV Hepatitis C Virus

SARS Severe Acute Respiratory Syndrome

Mers-Cov Middle East Respiratory Syndrome Coronavirus

SARS-CoV-2 Severe acute respiratory syndrome coronavirus

**Conflict of interest**

nutrition, mostly natural antioxidants, is essential for improving antiviral activity against viral and pandemic diseases such as SARS, COVID-19 and, HIV etc.

Natural antioxidants have been used in many therapeutic practices because of their enzyme inhibition and their inhibitory effect on viral protein receptors. In addition, natural antioxidants may enhance immunity during diseases. As well, they have been the subject of multidisciplinary studies [109]. The WHO also acknowledged that there was insufficient evidence of herbal medicines for the treatment or treatment of viral diseases in humans, especially COVID-19 [110].

Throughout history, there have been significant pandemic diseases such as the 1918 influenza pandemic (H1N1 virus), HIV and COVID-19. During pandemics, nutrition is as important as health, hygiene, or self-isolation standards. To that end, predominantly natural antioxidants have been used in therapeutic practices. Many herbal medicines, plants, and their extracts have inhibitory effects on pandemic diseases or their symptoms. These nutrients have been investigating their immunemodulating, antiviral, and antioxidant effects for decades. However, all these effects of natural antioxidants are not equal. Research into the health performance of these

**140**


## **Author details**

Cenk Aydin1 \* and Nilay Seyidoglu<sup>2</sup>

1 Department of Physiology, Faculty of Veterinary Medicine, Bursa Uludag University, Bursa, Turkey

2 Department of Physiology, Faculty of Veterinary Medicine, Tekirdag Namik Kemal University, Tekirdag, Turkey

\*Address all correspondence to: caydin@uludag.edu.tr

© 2021 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.

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ptr.2295

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**151**

characteristics.

**Chapter 8**

**Abstract**

by oxidative stress.

**1. Introduction**

redox-potential, transposition

Oxidative Stress

*Chanjae Lee, Min K. Bae and Sung-Jae Lee*

An Antioxidant Defense System

*Deinococcus geothermalis* against

in Radiation-Resistant Bacterium

A radiation-resistant bacterium, *Deinococcus geothermalis* has various stress response mechanisms, including antioxidation. Features that maintain vitality at high radiation doses include the following: enzymatic scavengers of ROS such as catalase, SOD, and peroxidase; strain-specific DNA repair systems such as Deinococcal unique proteins; non-enzymatic responses such as manganese complexes, carotenoids, and DNA-binding proteins. This chapter summarizes the primary response mechanism by redox balance centered on the cystine transporter. It also reviews action characteristics of DNA-binding protein Dps and a putative LysR family protein, and effects on loss of function of the carotenoid biosynthesis genes by transposition of insertion sequences. Environmental adaptation and molecular evolution of radiation-resistant bacterium are also considered to explain the potentials of molecular behavior induced

**Keywords:** cystine ABC transporter, Dps, LysR regulator, oxidative stress,

The radiation-resistant bacterium of genus *Deinococcus* is an essential resource for research to understand responses to oxidative stress and mechanisms for recovering direct double-strand break damage to DNA caused by gamma-radiation [1–3]. High gamma-ray resistance is caused by the unique DNA-damage repair proteins and various protective mechanisms in these radiation-resistant *Deinococcus* bacteria [4–6]. Many researchers have studied the properties of their unique proteins. These studies have expanded our scientific understanding [7–9]. Technological advances have recently been made to understand life phenomena through genomics, metabolomics, and proteomics studies [10–12]. Despite the remarkable progress in recent omics studies, it is still difficult to fully understand these cell recovery characteristics from various cellular stress damages. The accumulation of various creative research results will eventually lead to a complete understanding of such

Only 20% of DNA damage is directly caused by radiation. In comparison, the remaining 80% is indirectly caused by reactive oxygen species (ROS) such as

## **Chapter 8**
