*2.1.1 Glutathione peroxidase*

The oxidation of the glutathione directed as hydroperoxide which can be considered as hydrogen peroxide or others for example lipid hydroperoxide.

$$\text{ROOH} + 2\text{GSH} \rightarrow \text{GSSG} + \text{H}\_2\text{O} + \text{ROH} \tag{1}$$

Selenium dependent that is GPx, EC 1.11.1.19 and independent on selenium for example glutathione S transferase, GST, EC 2.5.1.18 are considered as the two different forms. In the humans, reported are four types of se-dependent glutathione peroxidases which are mentioned as addition of two electrons to carry out reduction of peroxides through formation of selenole (SeOH) and these antioxidant properties of the selenoenzymes carries elimination of peroxides as important substrate for the reaction termed as Fenton reaction. Along with the tripeptide glutathione that is GSH, selenium dependent glutathione peroxides will be acting, and it exists in comparatively higher concentrations present in the cells and also catalyses the formation of hydrogen peroxide or the organic peroxide into water or alcohol, while causing oxidation of GSH simultaneously. It is able to compete with that of catalase and hydrogen peroxide as a substrate so, considered as an important source of giving protection against oxidative or the nitrosative stress which at very low levels [4].

*Antioxidant Potential of Phytoconstituents with Special Emphasis on Curcumin DOI: http://dx.doi.org/10.5772/intechopen.103982*

#### *2.1.2 Catalase*

The first antioxidant enzyme was considered as the Catalase that is EC 1.11.1.6 and it was reported to carry out the conversion of hydrogen peroxide into the water and oxygen as indicated:

$$\rm H\_2O\_2 \rightarrow 2H\_2O + O\_2 \tag{2}$$

Amongst all the enzymes, catalase was reported to have the highest rate of turnover, one molecule of the catalase is having capacity to converting around 6 millions of hydrogen peroxides to water and oxygen, each of minute. Some from this catalase is found in all the tissues, majorly activity of catalase is found in liver and erythrocytes [5].

## *2.1.3 Superoxide dismutase*

One from the enzymatic antioxidants that is superoxide dismutase called as EC 1.15.1.1, can reported to be an intracellular enzymatic antioxidant and is responsible to convert superoxide dismutase anions in dioxygen and ions of hydrogen peroxide as:

$$\text{O}\_2\text{}^- + \text{O}\_2\text{}^- + 2\text{H} + \rightarrow \text{H}\_2\text{O}\_2 + \text{O}\_2\tag{3}$$

This superoxide dismutase, is existing in the form of various isoforms, which majorly different in the natures of the active metal centre, composition of the amino acids, cofactors and other related features. Three different froms related to SOD are available in the human beings for example cytosolic, Zinc- SOD, mitochondrial Mn-SOD, and extracellular SOD. By undergoing successive oxidative and reductive pathways related to transition metal ions at their sites of activity, neutralization of superoxide ions by superoxide dismutase is carried out [6].

#### **2.2 Nonenzymatic antioxidants**

#### *2.2.1 Vitamin E*

Vitamin E majorly available as fat soluble and it can be found in eight different varieties [7]. A chromanol ring along with the phytyl tail and difference in numbers and position related to methyl groups in these rings are observed in the tocopherols including α, β, γ, and δ. These substances are reported to be lipid soluble with a prominent antioxidant potential. According to the literature, these are found to be more active than that of polyunsaturated fatty acids which are having peroxyl radicals and thus show their action by breaking the lipid peroxidation [8].

The important role of this vitamin is to give protection from the lipid peroxidation and also literature is available to support this, there is synergestic effect of ɑ tocopherol and ascorbic acid, involved in cyclic type reactions. Due to the donation of the hydrogen from ɑ tocopherol to the lipid radical or lipid peroxide radical and it gets converted to ɑ tocopherol radical. Further, this ɑ tocopherol radical can get reduced in the form of ɑ tocopherol due to the ascorbic acid [9].

#### *2.2.2 Vitamin C-ascorbic acid*

This considered as one of the antioxidants reported to work in an aqueous medium of the body. In the presence of metal ions it is oxidized into dehydroascorbic acid in an extracellular environment of the body, which is further carried into the cells with help of glucose transporters. It works alone with the antioxidant enzymes and also Vitamin E and carotenoids are termed as its primary partners. From the ɑ tocopherol radicals it forms ɑ tocopherol in the membranes and lipoproteins, vitamin C plays an important role along with vitamin E, ultimately it increases the levels in glutathione in cells, thus protecting the protein thiol groups against oxidative damage. It is present in the reduced form in the cells, due to reaction with glutathione, thus catalyzing protein disulfide isomerase and glutaredoxins. Ascorbic acid is reported as the best potential reducing agent that effectively causes neutralization of ROS for example hydrogen peroxide [10].

#### *2.2.3 Thiol antioxidants*

This is a very important intracellular thiol antioxidant which is present in intracellular region is tripeptideglutathione which is also known as GSH. Acoording to the literature, it is considered as a redox buffer of the cell. It is found to be present in the cytosol, mitochondria and nuclei and present in the soluble form of antioxidants in these compartments. The levels of glutathione are important for inducing the postmititic phenotype, which are confirmed based upon the studies on the human fibroblasts, and hence it is reported that the implementation of the depletion of glutathione has very important role during the control in aging at cellular level from human skin.

As this glutathione acts as cofactor for various enzymes which cause detoxifying actions, its participation in the amino acid transport through the plasma membrane, scavenging of hyrdroxyl radical and direct scavenging of the singlet oxygen, regeneration of the active forms of vitamin C and E, has a very potential role for protective action against oxidative or nitrosative stress [11].

Decrease in the glutathione levels are the signals of the oxidative stress which is increased in the ischemic brain disorders, cancer, cardiovascular disorders and decreased concentrations of glutathione are also indicative of both that is type 1 and type 2 diabetes mellitus [12–16].

#### *2.2.4 Thioredoxin*

Another potential example of the thiol antioxidants is thioredoxin which is also known as TRX system, which are the types of proteins available both in the mammalian and prokaryotic cells and capable of oxidoreductase activity. It is consisting of disulphide and two cysteins which are redox active with conserved active sites as Cys-Gly-Pro-Cys. This antioxidants consists of two –SH groups which are adjacent forms which are present in the reduction form, then are converted into disulphide units in the oxidized form as TRX after it undergoes redox reactions including multiple proteins in it. The levels of thioredoxin is comparatively lesser than that of GSH, but these may be having functions which are overlapping and in similar compartments related to the stimulation and regulation of various transcription factors. Many of the normal and neoplastic cells, secrets this thioredoxin in the oxidative or nitrosative stress and also in the inflammatory conditions [17, 18].

*Antioxidant Potential of Phytoconstituents with Special Emphasis on Curcumin DOI: http://dx.doi.org/10.5772/intechopen.103982*

#### *2.2.5 α-Lipoic acid—1, 2-dithione-3-pentanoic acid*

Metal chelating and antiglycation potentials are associated with this third thiol antioxidant which is present as natural substance called as α-Lipoic acid called as ALA. Different than other antioxidants which are either lipid soluble or soluble in aqueous medium, lipoic acid can be considered as active in the aqueous as well as lipid phases. In most of the tissues, lipoic acid is transferred to dihydrolipoic acid that is DHLA through the action of NADH or NADPH, and then it can be readily digested and absorbed too. There are various actions which are related to lipoic acid such as direct termination of the free radicals, chelation of transition metal ions for example copper and iron, glutathione levels observe to be increased, vitamin C levels and prevention of the toxicities which are associated with their loss [19].

Lipoic acid is also capable of crossing the blood brain barrier and thus it can be covered by all central and peripheral regions of nervous system. For the free radicals associated with the oxidative stress, lipid peroxides that is LPO is considered as the biomarker. A sequence of the reactions is initiated after the action of free radicals on the polyunsaturated fatty acids called as PUFA in the biological systems, which ultimately results in the production of the conjugated dienes and lipid peroxidases [20].

#### *2.2.6 N-acetylcysteine*

To decrease the conditions related oxidative or nitrosative stress, one of the thiol antioxidant is N-acetylcysteine. It prevents from liver damage related to paracetamol caused in the human beings, causes attenuation in liver damage and also reported to prevent the GSH depletion in the mice [21].

N-acetylcysteine also possesses properties such as metachelation, and is implemented in several clinical conditions. Due to the thio groups present in this N-acetylcysteine, it decreases the free radicals and supplies chelation sites to that for metals. Hence, in the metal poisoning conditions and various diseased conditions, N-acetylcysteine is found to have a potential role as is effective in renovating inbalanced prooxidant and antioxidant conditions.

#### *2.2.7 Melatonin*

The melatonin shows its free radical scavenging potential due to donation of electron so as it can release variety of ROS or RNS, containing majorly toxic hydroxyl radicals. Along with that melatonin also increases an enzymes which are considered as antioxidative such as superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase etc [22].

This efficiency related to electron transport chain is reported to be increased and as a result decreased electron leakage and production of the free radicals. Due these highly potential actions of melatonin, it is considered as a very important entity used in treating variety of neurological diseases which are having oxidative damage as a part of the etiology concerned [23].

#### *2.2.8 Carotenoids*

One of the potential antioxidants, which are reported to be lipid soluble and containing isoprenoid carbok skeleton is the carotenoids. These are reported to be present in the membranes along with the lipoproteins and a very useful example is


#### **Table 1.**

*Various reactive oxygen species and their neutralizing antioxidants.*

ɑ- carotene. The efficiency of these antioxidants is considered to be as equivalent as that of ɑ tocopherol as they effectively scavenge singlet oxygen and also result in trapping of the peroxyl radicals at low levels of oxygen pressures (**Table 1**). Those caratenoids show brings are distinguished with the pro-vitamin A activity. As in β- carotene, it indicates presence of two brings on the both the ends related to carbon chain, it possesses highest activity. Vitamin A is also reported to show highly potential antioxidant activity which is independent on that of the oxygen concentration [24].
