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Chapter 10 Medicinal and aromatic plants used in respiratory diseases 383
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Amra Alispahić✶, Emina Boškailo, Alema Dedić,
and Hurija Džudžević-Čančar
Chapter 11
Medicinal and aromatic plants with
antioxidant properties
Abstract: Reactive oxygen and nitrogen species (ROS/RNS) are two substances that are
both naturally produced in the human body. They are required for the delivery of an
oxidative burst to immune cells to kill microorganisms. However, their overproduction
leads to several detrimental processes, including aging and cancer. Substances that
eliminate the effects of free radicals are called antioxidants. Increased plant intake can
be beneficial here because plants contain numerous natural antioxidants, mostly poly
phenolics and flavonoids. These biologically active components in herbal essential oils
have been used as therapeutic agents, as they are natural sources of antioxidants. They
inactivate free radicals, reduce oxidative stress, and have been used in the pharmaceu
tical, cosmetic, and food research fields. In fact, studies have shown that there is a positive relationship between the total phenol content of medicinal plants and aromatic
plants and their antioxidant capacity. Today, reliability concerns on synthetic antioxi
dants are increasing. Therefore, the interest of the health and food industry in aromatic
plants and the natural antioxidants obtained from these plants has also increased. Aro
matic and medicinal plants have been used in many fields, such as food, medicine, cosmetics, and spices since the beginning of human history. This chapter focuses on the
antioxidant properties of medicinal and aromatic plants, as aromatic plants are widely
considered to be rich sources of antioxidants.
-
-
-
-
Keywords: aromatic plants, medicinal plants, free radicals, antioxidants
11.1 Introduction
The human body converts at least 5% of the oxygen intake by breathing into reactive
oxygen species (ROS). It has become clear in recent decades that ROS can have detri
✶
Corresponding author: Amra Alispahić, Department of Chemistry in Pharmacy, University of
Sarajevo-Faculty of Pharmacy, Sarajevo, Bosnia and Herzegovina, e-mail: amra.alispahic@ffsa.unsa.ba
Emina Boškailo, Department of Ecology and Environmental Protection, Faculty of Social Sciences
Dr. Milenko Brkić, Herzegovina University, Mostar, Bosnia and Herzegovina; International Society of
Engineering Science and Technology, Nottingham, UK
Alema Dedić, Hurija Džudžević-Čančar, Department of Chemistry in Pharmacy, University of
Sarajevo-Faculty of Pharmacy, Sarajevo, Bosnia and Herzegovina
-
386 Amra Alispahić et al.
mental impacts on human health under some circumstances. By neutralizing the impacts of free radicals, antioxidants can help the body protect itself from a variety of
harmful factors and illnesses. Recent research on antioxidants and free radicals has
opened a new era of health management against a number of illnesses [1]. Recent advancements in pharmaceuticals and functional foods derived from medicinal and
nutritional plants (fruits and vegetables) have improved all facets of life, including extending human lifespan, reducing the need for synthetic antibiotics, and alleviating
physical disorders [2]. To prevent oxidative deterioration and prolong food storage,
the food industry mostly uses synthetic antioxidants such as propyl gallates, butyl hydroxytoluene, tertiary butyl hydroxyquinone, and butyl hydroxy anisole [3]. Despite
their excellent efficacy, stability, and affordability, these synthetic antioxidants may
have mutagenic, carcinogenic, and teratogenic adverse effects [3].
Free radicals are produced by a variety of external or environmental factors during the course of regular metabolic processes in both humans and animals. ROS are
unstable and have a short lifetime. They may therefore readily interact with a wide
range of biological components found in plant, animal, and human organism, including proteins, lipids, carbohydrates, and nucleic acids. They consequently contribute to
the emergence of numerous illnesses and conditions (cancer, liver, deficiency in immune system, etc.), particularly aging in people [4].
The industry has been searching for natural sources of antioxidants due to consumer preferences and the understanding that antioxidants eliminate free radicals. As
a result, medicinal and aromatic plants have gained increasing importance. Since plants
are the primary natural source of antioxidants, plants, essential oils, and plant extracts
are regarded as significant antioxidizing agents [5]. Flavonoids, coumarins, tocopherols,
phenolic acids, cinnamic acid, and other phenolic and polyphenolic compounds are the
most prevalent types of natural antioxidants. Furthermore, flavonoids and polyphenolic
antioxidants derived from natural plants are efficient in defending against the free radicals that are produced within the human body, which is of great importance [6].
Under normal circumstances, the body’s powerful antioxidant defense system
prevents the harm that oxygen radicals inflict. According to studies, certain phenolic
antioxidants can stop or prevent oxidative stress-induced cell death. Numerous aromatic and therapeutic plants from various plant groups have been shown to contain
high levels of phenolic and flavonoid compounds [7].
Some medicinal and aromatic plants that have economic and industrial value in
some countries of the world are produced using tissue or cell techniques under controlled conditions, as an alternative method, because of limited production quantities,
challenges in obtaining products of standard quality, distance of production areas
from industrial areas, and high extraction and purification costs [8].
In artificial nutritional settings and aseptic conditions, micropropagation is the
process of creating new plants from plant parts (seed, leaf, root, stem, sprout, embryo,
callus, etc.) that have the capacity to produce a whole plant [9]. Numerous plant sources have been evaluated for antioxidants due to growing interest in finding natural
Chapter 11 Medicinal and aromatic plants with antioxidant properties 387
alternatives to synthetic antioxidants. The assessment of antioxidant activity is made
more difficult by nutraceuticals that double the effect of natural antioxidants that stabilize foods and optimize health benefits. As a result, phytomedicine is gaining popularity again, and numerous species of medicinal plants are currently being evaluated
for their pharmacological potential [9]. These plants, particularly those that contain
high levels of phenolic components such as phenolic acids, flavonoids, tannins, stilbenes, and anthocyanins, have long been employed as sustainable, safe, and effective
natural antioxidants or free radical scavengers [10]. These phenols are primarily
thought to support the antioxidant activity of food and medicinal plants, which helps
organism to fight a variety of pathological ailments like diabetes, cancer, aging, cardiovascular disease, and other degenerative diseases [10]. The food industry has been
using aromatic and medicinal herbs for a long time, which serve a variety of functions, to enhance the flavor and taste of food products. Their aromatic properties also
play a particularly important role. There are several plants that are rich in compounds, known to have antioxidant properties. Furthermore, plants also possess various antimicrobial and antiviral properties that vary, depending on the plant species,
the type of microorganisms, and the concentration of essential oil in the plant [11, 12].
11.2 Oxidative stress
Oxidative stress is a global concept in biology, medicine, biochemistry, and nutritional
science. Firstly, the term “oxidative stress” was introduced and explained in 1985, and
since then, it has received significant attention through various research, especially in
recent years [13]. The occurrence of oxidative stress is directly related to oxygen, one
of the most abundant elements on the Earth, without which there is no life, but which
can still be toxic to living beings, in certain states.
Oxidation and reduction reactions in living systems form the basis for numerous
biochemical metabolic processes. One of the most important oxidation processes is
the respiratory chain, which occurs in the mitochondria of eukaryotic cells. During
this process, carbohydrate molecules, such as glucose, are oxidized to CO
and the energy released during oxidation is used to create adenosine triphosphate
(ATP), which is then use as an energy source in cells. This is where oxygen plays a key
role in mammals, since it is the final electron acceptor in mitochondrial electron
transport. However, during this process, toxic metabolites of ROS are also produced,
which if they leave the mitochondria, cause cellular damage through the oxidation of
biological molecules in the cytoplasm [13].
Oxidation process is the loss of one or more electrons from an atom, while reduction process is the acceptance of one or more electrons in an atom. A reductant (antioxidant) is a substance that donates electrons, while an oxidant is a substance that
accepts electrons [
14]. An imbalance in cellular redox processes toward oxidation or
and water,
2
388 Amra Alispahić et al.
an excessive production of free radicals is known as oxidative stress [15]. Individual
characteristics, including genetics, gender, age, lifestyle, habits, and most importantly,
diet, affect the body’s defense mechanisms’ capacity to reduce oxidative stress and
enhance oxidative state. Many cells can withstand oxidative stress, and in certain
cases, it is essential for their function (e.g., endothelium, lung, and blood cells) [16].
A class of extremely reactive chemical entities containing one or more unpaired
electrons in the outer shell is known as free radicals [14]. In addition to interacting with
other radicals, free radicals can also interact with non-radical molecules by removing
or accepting electrons. While a chain reaction of generated radicals happens with nonradicals, resulting in oxidative stress, the first scenario involves a radical-radical reaction that ends without producing oxidative stress or cell damage. Although many chemical species include unpaired electrons, molecules, and chemical species that contain
carbon, nitrogen, and oxygen perform the most significant roles in the human body
[15]. ROS are among the most significant subgroups of extremely reactive chemical species. More than a hundred human diseases, including atherosclerosis, arthritis, ischemia, disorders of the central nervous system, gastritis, cancer, and AIDS, are proved to
be caused by free radicals [17]. Environmental pollution, radiation, chemicals, poisons,
deep-fried and very spicy foods, and physical stress all produce free radicals, which
weaken the immune system, alter gene expression, and produce aberrant proteins. Natural antioxidants may be required as free radical scavengers because of the immune
system’s fatigue in a number of diseases [18].
11.2.1 Reactive oxygen species
ROS are normally generated in essential physiological processes in biological organisms. Although ROS have an adverse effect on the organism, they also play an important role in the mechanisms of cellular repair and regeneration (e.g., in apoptosis),
and can be secondary messengers, signaling molecules, and catalysts for the modulation of protein structures. They also participate in wound healing and immune response, and in the mobilization of cellular transport systems. Whether ROS will serve
as a beneficial biological agent or as an initiator of oxidative damage depends on the
balance of ROS generation and scavenging reactions [19]. ROS include both radicals
and non-radical oxygen derivatives. The most important radicals of physiological and
pathophysiological processes in humans include superoxide radical (O
radical (OH
peroxide (H
•
), and hydroperoxyl radical (HOO•), while non-radicals include hydrogen
), singlet oxygen (1O2), and ozone (O3) (Figure 11.1) [19].
2O2
In addition to ROS, other free radicals are lipid radical (L
•
), lipid peroxyl radical
(LOO•), lipid alkyl radical (LO•), and protein radical (P•). Reactive nitrogen species (RNS)
are nitrogen dioxide (NO
•
), nitrogen oxide (NO•), and peroxynitrite (ONOO–). Non-
2
radicals include lipid hydroperoxide (LOOH), iron-oxygen complex (Fe=O), and hypochlorite (HOCl) [15].
•–
), hydroxyl
2
superoxide radical
(O
2
•-
)
hydroxyl radical
(OH•)
hydroperoxyl radical
(HOO•)
Radicals
hydrogen peroxide (H2O2)
singlet oxygen (1O2)
ozone (O3)
Non-
radicals
Figure 11.1: Reactive oxygen species (ROS).
Chapter 11 Medicinal and aromatic plants with antioxidant properties 389
Overproduction of ROS causes oxidative damage to biomolecules like DNA, protein
modification, and lipid peroxidation, which can contribute to the development of diseases because of increased apoptosis; ischemia damage to muscle tissue, necrosis, inflammation; and also lead to insulin resistance [19]. Diseases associated with oxidative
stress include cardiovascular diseases, atherosclerosis, diabetes and similar endocrine
diseases, neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases,
cancer, gastrointestinal diseases, etc. ROS significantly affect human ontogenesis, as
well as the aging process itself [
19, 20]. HO
•
is considered the most reactive ROS and is
responsible for many pathological processes. However, its half-life is very short (10
ns), which means that it reacts only with molecules that are in the immediate vicinity
of the site where it was generated. On the other hand, the half-life of
1
O2 in aqueous
solution is approximately 4 μs, which allows it to diffuse over a distance of 150–220
nm. Therefore,
affect surrounding molecules and organelles more widely than HO
1
O2 can react at various sites outside of its site of origin, allowing it to
•
. However, this distance is not sufficient for extracellularly generated 1O2 to penetrate the cell interior.
Therefore,
1
O2 generated inside the cell can damage various cellular components, in-
cluding DNA and organelles [21].
11.2.2 Sources and generation of free radicals
Free radicals can originate from both external (exogenous) and internal (endogenous)
sources. Internal sources include phagocytes, xanthine oxidase, mitochondria, arachidonic acid pathways, ischemia/reperfusion, exercise, inflammation, xanthine oxidase,
and processes involving iron and other transition metals. However, external sources
include things like cigarette smoke, toxins in the environment, radiation, UV light,
some medications, pesticides, anesthetics, industrial solvents, and ozone [22].
Oxygen is an element, whose molecule at temperatures compatible for life is in
the lowest energy state, the triplet state. In order to more easily enter into chemical
reactions, it must first pass into the singlet state by absorbing energy [19]. In the outer
π nonbonding orbital, oxygen has two unpaired electrons (biradical) with equal spins,
π
2px
π
2px*
σ
2p*
σ
2p
3
O
2
E
π
2py*
π
2py
π
2px
π
2px*
σ
2p*
σ
2p
1
O
2
π
2py*
π
2py
Figure 11.2: Triplet and singlet state of oxygen (electronic configuration).
390 Amra Alispahić et al.
which is a paramagnetic property that makes the oxygen molecule more reactive.
This is why oxygen in this state reacts very slowly with organic compounds, but reacts
extremely quickly with radicals. In contrast, singlet molecules have electrons in their
orbitals in pairs, where the electron spins are opposite, which does not cause a magnetic moment and results in a lower orbital energy (Figure 11.2) [19, 23].
Singlet oxygen therefore readily reacts with and oxidizes most organic compounds.
The state in which the electrons are paired is more energetically rich in the case of
singlet oxygen. If one electron is received, triplet oxygen can change to superoxide
radical [23].
In mammalian cells, about 95% of oxygen is metabolized to water by a tetravalent
reaction:
O
+ 4H++ 4e
2
−
! 2H2O
However, at least 5% of oxygen undergoes a gradual one-electron transfer reduction,
whereby free radicals are formed as intermediates:
�
�−
2
2O2
OH
O
2
Reaction 1: O2+ e ! O
Reaction 2: O
Reaction 3:H
Reaction 4:
�−
+ e ! H
2
+ e !
2O2
�
OH +e ! H
The given reactions explain the formation of ROS during cellular respiration, which
takes place in the mitochondria. Under normal conditions, reactive intermediates do
not leave this process until the end of the reaction, but in certain pathophysiological
conditions, ROS may leave this complex and initiate oxidative damage [14].
Chapter 11 Medicinal and aromatic plants with antioxidant properties 391
11.3 Consequences of oxidative stress
on human organism
11.3.1 Lipid peroxidation
The two most prevalent ROS that have the ability to profoundly impact lipids are hydroperoxyl and hydroxyl radicals. The smallest, most mobile, water-soluble, and chemically
most reactive kind of ROS is the hydroxyl radical. This short-lived molecule can be created from O
droxyl radicals are produced by a cell every second. Each cell produces over 4 million
hydroxyl radicals in a day, which can either attack or neutralize biomolecules [
development of atherogenesis in blood arteries, as a result of oxidative stress caused by
lipid peroxidation, raises the risk of heart attack. At the systemic level, ROS play an ac
tive role in cardiovascular contractility, hemostasis, angiogenesis, immunological and
cognitive control, blood pressure regulation, and platelet activation, in response to injury [23]. Intrinsic or dietary phospholipids reside in the circulation as stable antioxidant-conjugate lipoproteins, which are selectively oxidized through a complex series of
enzymatic and nonenzymatic pathways, resulting in unstable lipoids in serum and cell
plasma. Although these oxidized metabolites play their part in signaling and cellular
metabolism, their large amounts can cause atherogenic problems. Cells also include opposing processes to preserve redox balance, such as antioxidants and stabilizers. But in
conditions like atherosclerotic cardiovascular disease, the redox balance changes in
favor of pro-inflammatory mechanisms, which either directly or indirectly inhibits the
antioxidant activity and causes the system to produce more free radicals [25]. Three
steps make up the entire lipid peroxidation process: start, propagation, and termination. Prooxidants such hydroxyl radical abstract allylic hydrogen at the first stage of
lipid peroxidation, creating a carbon-centered lipid radical (L
(LOOH) and a freshly formed L
the lipid radical (L
which extracts hydrogen from another lipid molecule. Antioxidants like vitamin E pro
vide the LOO
vitamin E radical that then combines with another LOO
Following the initiation of lipid peroxidation, chain reactions will continue to spread
until the termination products are produced [
during cellular metabolism and under a variety of stressors. About 50 hy-
2
24]. The
•
•
•
) quickly combines with oxygen to form a lipid peroxyl radical (LOO•),
•
species a hydrogen atom in the termination reaction, creating a matching
(which restarts the chain reaction) are produced when
•
). Lipid hydroperoxide
to create non-radical products.
24].
-
-
11.3.2 Protein oxidation
The two main types of oxidative protein changes are irreversible oxidation and reversible oxidation, which can be specifically brought on by RNS and ROS. Protein car
bonyls and 3-nitrotyrosine are involved in irreversible oxidation, whereas products of
-
392 Amra Alispahić et al.
cysteine modification, including sulfonic acid, nitroso thiols, and S-glutathione, are involved in reversible oxidation. Arginine, histidine, lysine, proline, threonine, and cysteine are among the amino acid residues that generate protein carbonyls, which are
frequently employed as biomarkers to quantify protein oxidation and oxidative stress
in aging and disease states [26].
RNS and a protein’s tyrosine residue combine to generate nitrotyrosine, typically
3-nitrotyrosine. Glutathione (GSH), which, although a primary cellular antioxidant,
can also affect proteins through the creation of mixed disulfides, leading to functional
changes in target proteins. This can shield the target protein from permanent and irreversible harm, but it is also frequently linked to negative consequences on target
protein function. This implies that some protein oxidation processes can still be advantageous and reduce cellular oxidative damage [26].
11.3.3 DNA oxidation
Nucleic acids and 2-deoxyribose are also targets of ROS and other reactive chemical species, resulting in DNA damage manifested through mutagenesis and carcinogenesis. The
most frequent ROS that causes oxidation at the DNA level is the hydroxyl radical [27].
The most prevalent and well-characterized indicators for oxidative DNA and RNA lesions among the several nucleoside oxidation products are the guanosine oxidation
products 8-hydroxyguanosine (8-OHG) and 8-oxo-7,8-dihydroguanosine (8-oxoG). Despite being less deadly to cells than genetic changes, oxidative RNA damage is linked to
a number of age-related illnesses, including cancer, type 2 diabetes, and neuropsychiatric disorders. Certain studies suggest that patients suffering from schizophrenia or depression have increased concentrations of oxidatively damaged RNA in their urine. Although cells possess DNA and RNA repair mechanisms, if oxidative stress exceeds the
repair capacity, damage accumulation occurs in the form of base mismatches, abnormal cell signaling, and the synthesis of irregular protein structures [27].
11.4 Defense of the organism against ROS
The human body has several defenses against ROS, including free radicals. Because they
target distinct oxidants or act in separate areas of the cells, these systems work in concert. A system of enzymes that lower the concentration of the most harmful oxidants,
including glutathione peroxidases, superoxide dismutase, and catalase, is one of the
main processes. Since catalase breaks down hydrogen peroxide, superoxide dismutase is
especially crucial because it catalyzes the transformation of superoxide radicals into hydrogen peroxide and oxygen. Selenium-containing glutathione peroxidases are crucial
for reducing hydroperoxides, particularly those produced by lipid oxidation [28].