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Chapter 11 Medicinal and aromatic plants with antioxidant properties 393
Maintaining enzymatic defense against free radicals is mostly dependent on nutrition. The structure and function of the aforementioned enzymes depend on minerals
like zinc, copper, manganese, and selenium. Enzymatic defenses may be less efficient if
certain minerals are deficient [28]. Small molecules that function as antioxidants, reacting with oxidizing chemicals to reduce their harmfulness, are the second line of defense. Normal metabolism produces some of these antioxidants, including ubiquinol,
glutathione, and uric acid. The only known fat-soluble antioxidant made by animal cells
is ubiquinol, which is crucial for shielding cells from oxidative damage. Vitamins E and
C are examples of antioxidants that are present in diet. Plant pigments also include cer
tain antioxidants. One example of a carotenoids is vitamin A, which is a vital component of the receptors for eyesight and crucial for healthy embryonic development, making it an essential nutrient in the human body. Antioxidants have no caloric value in
the diet [29].
11.4.1 Free radicals and antioxidants
ROS and RNS are the two main components of free radicals, which are byproducts of
many biological activities. ROS are produced in the human body as a result of a variety of environmental factors, xenobiotics, and human-caused causes that change an
organism’s biological activity [30, 31]. ROS (hydroxyl, superoxide, peroxyl, and hydrogen peroxide) can cause damage to biomolecules (lipids, proteins, enzymes, and nucleic acids) and can cause a variety of disorders if they are produced in excess of normal physiological levels [32]. Naturally occurring in people, animals, and plants,
antioxidants shield cells from the damaging effects of free radicals [33]. Antioxidants
scavenge free radicals and prevent organisms from producing them in excess [34].
There are two main classes of antioxidants [35]:
– Natural antioxidants
– Synthetic antioxidants
-
Fruits and vegetables typically include natural antioxidants such as vitamin C (ascorbic
acid), vitamin E (tocopherols and tocotrienols), carotenoids, and polyphenols. Among
the tocopherols and tocotrienols found in vitamin E, α-tocopherol has been the subject
of the most research. Functionally, α-tocopherol is more active, acting against peroxyl
radicals and quenching singlet oxygen (Figure 11.3) [36]. Because it contains the enediol
group [37], vitamin C is a well-known natural antioxidant that has the ability to scavenge ROS. There are around 700 known naturally occurring carotenoids from plants
that have antioxidant properties [36]. The most prevalent polyphenolics in plants include flavonoids, stilbenes, phenolic acids, and lignans [38]. On the other hand, flavonoids are strong metal chelators and scavengers of free radicals [39]. Numerous artificial antioxidants have been incorporated into a broad range of dietary items and
cosmetics. However, overuse of synthetic antioxidants may result in mutagenicities and
Antioxidants
Natural
Antioxidants
Enzymatic
Superoxide dismutase,
Gutatyon peroksidaze,
Glutathione reductaze,
Glutatyon-S-transferaze
Non-Enzymatic
Glutatyon, Vitamin A,
Vitamin C, Vitamin E,
β-karoten, Bilirubin,
Albumin, Flavanoids,
Anthocyanins,
Stibelenes, Lignans,
Terpenoids
Syntetic
Antioxidants
BHT, BHA, Troloks,
Askorbil palmitat, Propil
Gallat, tertiary butyl
hydroquinone , 2,4,5-
trihydroxybutyrophenon
e, di-tertbutyl-4-
hydroxymethylphenol,
octylgalate,
nordihydroguaiaretic
acid, 4-hexylresorcinol
Figure 11.3: Classification of antioxidants.
394 Amra Alispahić et al.
toxicities, which could be detrimental to health [40]. Nonetheless, a large range of natural antioxidants have distinct characteristics, such as their components, modes of action,
and target locations [41]. The ability of plants and animals to naturally produce proteins,
enzymes, and secondary metabolites is one of the primary characteristics of natural antioxidant enzymes. Antioxidative enzymes, such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and others, biocatalysis metabolic pathways by
converting ROS and RNS into stable compounds [42]. High-molecular-weight substances
that prevent metal production, catalyzed by free radicals, include albumin, transferrin,
and ceruloplasmin [43]. Water-soluble antioxidants and lipid-soluble antioxidants are
the two subcategories of low-molecular-weight molecules. Ascorbic acid, uric acid, and
certain polyphenols are water-soluble antioxidants, while tocopherol, quinines, carotenoids, bilirubin, and certain polyphenols are lipid-soluble antioxidants [44]. The antioxidative qualities of minerals and micronutrients such as manganese, copper, zinc, and
selenium, among others, have been extensively established [45]. Well-known stable antioxidants, vitamins A, C, and E are crucial in reducing the possibility of peroxidationinduced damage to the biological system. Vitamin C removes various types of radicals,
such as OH
(ascorbyl radical anion) or loses an electron to form its oxidized form, DHA (dehydroas-
•−
, H2O2 and O
•−
. Vitamin C donates one electron to O
2
•−
to produce ASC
2
•−
Chapter 11 Medicinal and aromatic plants with antioxidant properties 395
corbic acid) [46, 47]. Natural antioxidants are mostly found in fruits, vegetables, and medicinal plants. Consumers have recently become quite interested in new spices and
herbs as natural antioxidant sources, and some of these have been discussed here [48].
11.4.2 Antioxidants action mechanism
Antioxidants have varying mechanisms of action. The reactivity of substances with
free radicals produced during the lipid oxidation process, which results in the formation of inert molecules, is the most significant mechanism of antioxidant activity. As
real antioxidants, these substances typically react with alkoxyl or peroxyl free radicals that are produced during the breakdown of lipid hydroperoxides [49]. Lipid peroxides are stabilized by other antioxidants, which stop them from breaking down into
free radicals. For antioxidants, two primary mechanisms of action have been proposed. The major antioxidant neutralizes free radicals by donating an electron
through the first method, known as chain breaking. The second preventative mechanism eliminates ROS/RNS initiators by quenching the chain initiation step through the
action of secondary antioxidants (Table 11.1) [49].
Table 11.1: Mechanism of antioxidant activity [49, 50].
Antioxidant class Mechanism of action Examples of antioxidants
Real antioxidants Inactivation of free lipid radicals Phenolic compounds
Hydroperoxide stabilizers Preventing the decomposition of
hydroperoxide into free radicals
Synergists Strengthening the activity of real
antioxidants
Metal chelators Binding of heavy metals into inactive
components
“Quenchers” or singlet oxygen
extinguishers
Substances that reduce
hydroperoxides
Transfer of singlet oxygen to triplet
oxygen
Reduction of hydroperoxide in a
non-radical way
Phenolic compounds
Citric acid and ascorbic acid
Phosphoric, ascorbic and citric acid
Carotenoids (beta-carotene,
lycopene, and lutein)
Proteins and amino acids
Antioxidants, capable of neutralizing free radicals, act at different levels of defense
such as prevention, radical scavenging, repair and adaptation. The first line of defense
consists of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, selenoprotein, transferrin, lactoferrin, ferritin, some minerals Mn, Zn, Cu, and Se,
and non-enzymatic proteins, which are considered preventive antioxidants and limit
the formation of free radicals. Superoxide dismutase converts superoxide radical (O
–
2
)
396 Amra Alispahić et al.
into hydrogen peroxide (H2O2). Catalase catalyzes the decomposition of hydrogen peroxide (H
) into water (H2O) and molecular oxygen (O2). Glutathione peroxidase is a sele-
2O2
nium-dependent enzyme that detoxifies lipid hydroperoxides to alcohols. Cytosolic superoxide dismutase is a Cu-containing enzyme that removes superoxide radicals from
the cytosol. Selenium is an essential element for the removal of peroxides from the cytosol and cell membranes. Zinc is a component of several enzymes such as alcohol dehydrogenase, carbonic anhydrase, alkaline phosphatase, and cytosolic superoxide dismutase, and also plays an important role in growth and reproduction [38].
The second line of defense includes glutathione (GSH), vitamin E, vitamin C, uric
acid, bilirubin, albumin, carotenoids, and flavonoids, which have radical scavenging activity. Glutathione scavenges ROS such as lipid peroxyl radical, peroxynitrite, and hydrogen peroxide. It also helps in detoxification of inhaled oxidizing air pollutants. Vitamin E protects polyunsaturated fatty acid and low-density lipoproteins by scavenging
peroxyl radical intermediates generated in lipid peroxidation reactions. It prevents coronary heart disease and atherosclerosis. Vitamin C quenches radicals such as singlet
oxygen, superoxide radical, and hydroxyl radical. β-carotene helps in scavenging singlet
oxygen. Flavonoids inhibit lipoxygenase and lipid peroxidation. The third line of defense includes a group of enzymes required for the repair mechanism of damaged
DNA, proteins, and lipids. These enzymes are capable of stopping the chain propagation
of the lipid peroxyl radical, for example, DNA repair enzymes, proteases, lipases, transferases, and methionine sulfoxide reductase. The fourth line of defense is an adaptation
in which immunology plays an important role in the production and reaction of free
radicals with appropriate antioxidants [38, 50]. Flavonoids and polyphenols achieve
their antioxidant effect in several ways, including direct scavenging and scavenging of
free radicals, reduction of leukocyte immobilization, and regulation of nitric oxide and
xanthine oxidase activities. Several flavonoids, including quercetin, reduce ischemiareperfusion injury by interfering with the inducible activity of nitric oxide synthase.
Nitric oxide itself can be considered as a radical that is directly scavenged by flavonoids. Therefore, it is assumed that the scavenging of nitric oxide plays a role in the
therapeutic effects of flavonoids. The significant effects of polyphenols are the result of
radical scavenging, but another possible mechanism of action is the interaction with
various enzyme systems such as superoxide dismutase, catalase, and glutathione peroxidase [38]. Furthermore, in vitro studies have shown antiproliferative activity of polyphenols through inhibition of polyamine biosynthesis and signal transduction enzymes
such as protein tyrosine kinase, protein kinase C and phosphoinositide 3-kinase, induction of apoptosis and cell cycle arrest in the G1/G2 phase, differentiation of transformed
cells, and rehabilitation of cellular homeostasis [51].
Chapter 11 Medicinal and aromatic plants with antioxidant properties 397
11.5 Methods for determination of antioxidative activity
Methods for measuring antioxidant activity in plant extracts, food, and biological systems can be divided into several ways according to:
1. test system (in vivo and in vitro),
2. detection method (spectrophotometric, fluorimetric, and chemiluminescent),
3. directness of determination (direct and indirect),
4. presence of lipids in the system (the degree of inhibition of lipid substrate oxida-
tion and measurement of the antioxidant capacity of free radicals in systems that
do not contain lipids), and
5. reaction mechanism (methods based on hydrogen atom transfer (HAT) reactions
and methods based on electron transfer reactions that take place between antioxidant compounds and free radicals) [51].
11.5.1 Methods based on hydrogen atom transfer
Methods based on HAT are based on a reaction in which the antioxidant and the substrate compete for peroxyl radicals created by the terminal decomposition of the azo
component, and the result is obtained on the basis of a kinetic curve. The methods are
composed of synthetically produced free radicals, antioxidants, and oxidants. In these
methods, the hydrogen atom donating capacity of the antioxidant is measured [
This group of methods includes:
– IOU method (English inhibited oxygen uptake method)
– Inhibition of induced lipid autooxidation
– TRAP method (total radical trapping antioxidant parameter)
– ORAC method (oxygen radical absorbance capacity assay)
– CBA method (crocin bleaching assay)
– Fluo-lip
– HORAC method (hydroxyl radical antioxidant capacity assay)
52].
11.5.2 Methods based on electron transfer
Methods based on the transfer of one electron are based on a redox reaction with an
antioxidant as an indicator of the end point of the reaction. This method includes two
components in its reaction mixture: oxidant and antioxidant [
the following electron transfer reaction:
oxidant + e–(from antioxidant) → reduced oxidant + oxidized antioxidant
52]. They are based on
398 Amra Alispahić et al.
The oxidant receives an electron from the antioxidant, which results in a color change
of the oxidant. The intensity of the color change is proportional to the concentration
of the antioxidant. The end point of the reaction is reached when the color change
ceases. After that, the direction of the change in absorbance as a function of the antioxidant concentration is plotted.
This group of methods includes:
– FCR method (total phenols assay by Folin-Ciocalteu reagent)
– FRAP method (ferric reducing antioxidant potential)
– DPPH method
– TEAC method (Trolox equivalent antioxidant capacity)
– Determination of antioxidant potential by reduction with copper [52].
11.5.3 Other methods for determination of antioxidant potential
– TBARS method (thiobarbituric acid reactive substance): In the process of lipid
peroxidation, lipid peroxides are formed with the subsequent formation of per-
oxyl radicals, and the entire process is followed by a decomposition phase in
which aldehydes such as hexanal, malondialdehyde, and 4-hydroxynonenal are
formed. This method is based on the detection of a stable pink-colored product
formed in the reaction between aldehyde and thiobarbituric acid in the aqueous
phase. The concentration of the reaction product is monitored spectrophotometri-
cally and provides data on the strength of lipid peroxidation.
– CBT method (β-carotene bleaching test): This method is based on the loss of the β-
carotene yellow color during the reaction with free radicals, which are formed by
the oxidation process of linoleic acid. The presence of antioxidants slows down
the process of β-carotene decolorization. The reaction is monitored spectrophoto-
metrically [53].
– TOSC method (total oxidant scavenging capacity): This method enables determina-
tion of the antioxidant potential, specifically according to three oxidants: hydroxyl
radical, peroxyl radical, and peroxynitrite. As a substrate that is oxidized, α-keto-γ-
methylbutyric acid is used, which forms ethylene. The time of ethylene formation
is monitored by the gas chromatography method, and the antioxidant potential is
determined based on the antioxidant’s ability to inhibit ethylene formation.
– PLC method (photo-chemiluminescence method): PLC is based on a thousand-fold
acceleration of the oxidation reaction in vitro compared to normal conditions.
This effect is achieved by optical excitation of a suitable photosensitizer, which
results in the formation of superoxide radicals. The radical is detected with the
chemiluminescent reagent luminol. Luminol acts as a photosensitizer, but it also
participates in the reaction with radicals. The light emission is measured with the
help of a luminometer. Light emission occurs as a result of the oxidation of lumi-
nol with the catalytic action of peroxidase. In the presence of antioxidants, the
Chapter 11 Medicinal and aromatic plants with antioxidant properties 399
oxidation of luminol is prevented and light emission is also inhibited. The duration of inhibition indicates the quantity of antioxidants present [54].
– Biosensor methods: These methods use the most common enzymatic electrodes
based on superoxide dismutase, an enzyme used as a biosensor for the determination of superoxide radicals in aqueous and nonaqueous solutions for the determination of antioxidant potential [55].
11.6 Medicinal and aromatic plants as natural antioxidants
Aromatic and medicinal plants (AMPs) are plants with taste and smell qualities that are
also utilized as medications because of their therapeutic properties. Since ancient
times, people have utilized plants and their essential oils to treat certain medical conditions and enhance the flavor of food and drink. Their cultural and economic significance is demonstrated by their use to cover up offensive odors, draw attention from
others, treat certain medical conditions, and benefit humans. The phenolic chemicals in
AMPs’ structure are linked to their antioxidant activity [56]. Flavonoids, phenolic acids,
and phenolic terpenes are the most prevalent of these substances. By scavenging free
radicals, forming compounds with metal ions (metal chelation), and preventing or lowering the generation of ROS, phenolic substances have an antioxidant effect [57, 58]. In
order to stop free radicals from oxidizing lipids and other biological components, the
compounds can supply hydrogen through hydroxyl groups in their aromatic rings.
Plants’ leaves, flowers, and woody parts are the primary sources of flavonoids and other
phenolic chemicals. As a result, AMPs are frequently employed as essential oils or extracts made by extraction and distillation processes, or as medications made by drying
sections of leaves and flowers. Since the chemical composition of aromatic plants varies,
depending on many factors, their antioxidant effects will also vary (Figure 11.4) [59, 60].
Essential oils, which are made up of many chemical compounds, are volatile, aromatic, oily liquids that are extracted from plant materials such as leaves, roots, flowers, peels, bark, seeds, and twigs. These substances, which are secondary produced to
shield plants from insects and microorganisms, have a potent odor. In addition to creating distinctive fragrances to draw pollinating insects, plants also create essential
oils to protect themselves from unavoidable elements like sunshine, pollution, and
hunger [61]. Medicinal plants continue to be a significant source of bioactive chemicals for drug development, many of which have served as the foundation for novel
chemical structures in the food and pharmaceutical industries. The World Health Organization estimates that 80% of people worldwide still depend on herbal drugs, and
few drugs are derived from medicinal plants.
Recently, there has been increasing interest in the therapeutic potential of medicinal plants as antioxidants in reducing tissue damage caused by free radicals. In addition
Medicinal and aromatic
plants (MAPS)
Extracts
Antioxidant
Antimicrobial
Antiinflammatory
Neuroprotective
Cardiovascular
Pharmaceutics
Nanotechnology
Biomedical
Essential oils
Antioxidant
Antimicrobial
Antiproliferative
Natural aromas
Aromatherapy
Natural fragrances
Isolated
phytoconstituents
Antioxidant
Antimicrobial
Natural aromas
Natural dyes
Food colorants
Figure 11.4: Few potential applications of medicinal and aromatic plants.
400 Amra Alispahić et al.
to the well-known and traditionally used natural antioxidants from tea, wine, fruits,
vegetables, and spices, some natural antioxidants (e.g., rosemary and sage) are already
commercially used either as antioxidant additives or as food supplements [62]. Many
other plant species have been investigated for new antioxidants [63–65], but in general,
there is a demand for more information on the antioxidant potential of different plant
species. It is assumed that plants possess an antioxidant effect due to their phenolic
compounds content [18]. In particular, despite the widespread use of wild plants as
medicines, the literature contains few reports on the antioxidant activity and chemical
composition of plants from different parts of the world. The relationship between total
flavonoid content and total phenolic content and antioxidant activity is usually determined. In the long term, plant species (or their active ingredients) that have been found
to have high levels of antioxidant activity in vitro may be valuable in the design of further studies to discover new treatment strategies for radical-induced disorders [66].
Spices as aromatic plants are very rich in antioxidants. Various metabolic products
and their derivatives obtained from spices and aromatic plants have been identified as
important antioxidants (Figure 11.5) [67]. A spice can be defined as a plant, the specific
parts of which provide color and flavor, along with a stimulating odor, which is used in
culinary and seasoning, as well as in cosmetics, fragrances, and medicines. These specific properties of herbs and spices have supported their application in functional foods
for nutrients, bioactive compounds, disease prevention, and health promotion. The different parts of plants used as spices are rhizomes, leaves, buds, flowers, fruits, seeds,
excretory products, and even tree bark [68]. Since a long time, plants have been used
for almost all medical therapies until the development of synthetic drugs. Aromatic
plants affect various systems of the body such as the cardiovascular, gastrointestinal,
reproductive, and nervous systems [69]. All plant groups include common antioxidants,
Plant-derived antioxidants
Vitamins
Vitamin A
Vitamin E
Vitamin C
Polyphenols
Flavonoides
Flavonones
Flavonols
Isoflavanoids
Anthocyanidins
Non-flavonoides
Ferulic acid
Gallic acid
Ellagic acid
Small molecules
Glutathione
Ubiquinone
Trace elements
Selenium
Zink
Iodine
Copper
Figure 11.5: Examples of natural plant-derived antioxidants.
Chapter 11 Medicinal and aromatic plants with antioxidant properties 401
with a few exceptions. Spice and aromatic plants have been found to have some unique
antioxidant chemicals. Rosmarinic acid is the dominant compound in some plants of
the Lamiaceae family with four hydroxyl groups (catechol structures) in the structure,
which is responsible for its antioxidant properties. Caffeic and gallic acids are also pres
ent in these plants and possess antioxidant activity due to the catechol structure [70].
Eugenol and its derivatives contain a phenolic group in the structure and have relatively lower antioxidant activity than other phenols with multiple hydroxyl groups. The
phenolic group plays an important role in the free radical scavenging activity of euge
nol. Eugenol, cumin aldehyde, curcumin, piperine, zingerone, and linalool have been
reported as effective antioxidants. These compounds inhibit lipid peroxidation [
71].
Recently, much attention has been focused on the development of less-toxic ethnomedicines and their potential application in the prophylaxis and treatment of various
diseases. There is a lot of data on the antioxidant activity of essential oils extracted
from plants of different species, and harvested in different places and different stages
of plant development. Volatile essential oils and nonvolatile secondary metabolites
-
-
402 Amra Alispahić et al.
from plants have wide applications in food additives, flavorings and food preservation,
folk medicine, and the fragrance industry [52]. Several reports have confirmed the antioxidant efficacy of plant-based essential oils in vitro and in vivo [72].
Chemical composition of these oils depends on several factors (age of the plant, part
of the plant, developmental stage, growing site, harvest period, and chemotype), but the
correlation between the biological activity (i.e., antioxidant activity) of essential oils and
their chemical composition is often very complicated. Furthermore, due to the many different methods for in vitro assessment of antioxidant activity based on completely different mechanisms, the interpretation of the data is not straightforward. Consequently, the
results on the antioxidant activity of essential oils from the same plant, reported in numerous studies, showed many variations [73, 74]. It is necessary to emphasize that there
is no perfect system to assess the antioxidant activity of a single compound or a complex
mixture. Differences in the analytical methods used and the measurement conditions
may be responsible for such variations in the same samples [75].
Terpenes are the main constituents of essential oils extracted from medicinal plants,
which are considered natural antioxidants. Essential oils of basil, cinnamon, cloves, nutmeg, oregano, and thyme possess antioxidant properties due to the presence of terpenes.
Thymol and carvacrol are responsible for the antioxidant activity of the essential oils of
Thymus spathulifolius and Origanum vulgare ssp., and Melissa officinalis essential oil
shows free radical scavenging activity, too. In addition, isomenthone, 1,8-cineole, and
menthone present in the essential oils of the Mentha species show antioxidant activity.
The antioxidant capacity of the essential oil of Melaleuca alternifolia (tea tree) is a result
of the compounds α-terpinene, γ-terpinene, and α-terpinolene [37, 76–78].
In addition, AMP extracts are widely used in most cultures to improve the taste and
preserve food, beverages, cosmetics, and perfumes. Many MAP extracts (anise, fennel,
basil, mint, tarragon, marjoram, rosemary, thyme, parsley, juniper, and bay leaf) serve as
a rich source of polyphenolic compounds with strong antioxidant activity. Apart from
their beneficial effects on human health, these plants also serve as natural food preservatives because they prevent oxidation, one of the main causes of chemical spoilage and
deterioration of nutritional quality, color, flavor, and texture of various products [76].
11.7 MAPs with antioxidant activity
Angelica: Angelica sinensis is a member of the Apiaceae plant family. This hairy plant,
which has fern-like leaves and white blooming umbels, was considered an “Angel’s
Herb”. Chinese medicine has been using the plant’s well-known yellowish-brown root
for thousands of years. Angelica possesses antioxidant, cytoprotective, antimutagenic,
antiproliferative, and antiseizure properties. Numerous studies have demonstrated the
extremely strong antioxidant capacity of angelica root extracts. The antioxidant benefits
of Angelica root extracts may generally be attributed to the presence of phenolic com-