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dants in combating it [2]. Antioxidants are badged as bona
de warriors of the defense mechanism against free radicals
which are achieved by maintenance of balance between antioxidants and oxidants [3]. Recent studies have proved that
food supplements and foods with antioxidant property play a
major role in maintaining the health and compensate with the
required supplements for anabolic and catabolic processes of
the body which ensure immunity in the body to withstand
ailments. There is a huge cornucopia of antioxidant vitamins
and minerals from herbal sources which promotes normal
functioning of the body whose usage in day-to-day life not
only normalizes the metabolism but also prevents the disease
by boosting the immune system of the body and also keeping
the body away from lifestyle diseases [4]. Many plants having compounds as secondary metabolites which are proved
clinically having several properties like antioxidizing, analgesic, anti-inammatory, diuretic, antipyretic, carminative,
and also help in releasing stress and blood pressure as well as
asthma [5]. This review is a summarization of the causes of
lifestyle diseases and its management by using antioxidant
vitamins and minerals from plant sources which helps in
maintaining a healthy and disease-free life.
2 Role ofOxidative Stress inLifestyle
Diseases
Oxidative stress is caused by the harmful reactive oxygen
species (ROS) which are produced during different metabolic activities of the cell which include processes of transcription, signal transduction, and responses of immune
system [6]. Some common reactive oxygen species of the
cells are hydroxyl radical (OH−), superoxides (O
hydrogen peroxide (H2O2) [7, 8]. These reactive oxygen species cause oxidative damage to different biomolecules when
produced in excess and harm structural skeletons of the cell
like lipids, amino acids, and DNA which gradually lead to
the development of diseases like cancer, cardiovascular,
respiratory, neurodegenerative, digestive, hypertension, diabetes, and aging [6]. Oxidative stress, as described is caused
by the reactive oxygen species which eventually lead to
apoptosis [9]. Antioxidants are patented to have free radical
scavenging potential and as the reactive oxygen species are
nothing but free radicals, it scavenges the ROS and reduces
the oxidative stress faced by the cell [6]. Increase in oxidative stress causes several chronic diseases due to low supply
or production of antioxidants in the body which becomes a
ag bearer of ailments like hypertension, obesity, atherosclerosis, chronic heart failure, risk of stroke, cardiovascular diseases, cancer, and neurological disorders [3]. The intake of
antioxidant-rich foods and beverages helps in neutralizing
the oxidative stress produced by the harmful reactive oxygen
−
), and
2
species. Hence, malnutrition and deciency of vitamins and
minerals rich in antioxidants are directly correlated to the
chronic diseases due to lifestyle disorder like diabetes,
hypertension, cardiovascular, and respiratory diseases [6]. A
distorted oxidation reduction balance and nutritional deciency are noticed in the patients suffering from oxidative
damage. The deciency of antioxidants promotes the risk of
disease occurrence which is due to the malnutrition [10–12].
In this review, we have tried to put collective information
regarding the antioxidant vitamins and minerals which can
help to regulate, cure, and keep immuned from diseases
related to reactive oxygen species-mediated oxidative stress
diseases.
3 Some Lifestyle Diseases Suered by
Humans
The world has been undergoing through a massive paradigm
shift of technology, advancement, and urbanization which
have contributed to induction of several chronic diseases
caused by a lacuna in lifestyle management. Pattern of
chronic diseases circles around the lifestyle disorders which
are generally noncommunicable diseases like respiratory,
cardiovascular, neurodegenerative, polycystic ovarian disease, cancer, digestive diseases, aging, diabetes, and hypertension (Fig. 1). The risk and detriments of these chronic
diseases are a collective form of malnutritive diet, unhealthy
lifestyle, smoking and drinking habits, obesity, exposure to
pollutants, lack of exercise, and stress [13] and are mainly
affected in the middle-aged people [14].
3.1 Respiratory Diseases
From recent studies, it is revealed that respiratory diseases
like chronic obstructive pulmonary disease and asthma are
major chronic health issues which are increasing the rate of
mortality all over the globe [15, 16]. Exposure to environmental pollutants in the air and smoking of cigarettes promotes these diseases among urban humans. The drastic
noxiousness of the reactive oxygen species damages the
lungs by affecting the alveoli and connective tissues which
thereby paves a pathway to chronic obstructive pulmonary
disease [17]. The pathophysiology of asthma also indicates
increased oxidative stress [18] which can cause inammation and leads to progression of asthma [19]. The transcription factors like activator protein-1 (AP-1), mitogen-activated
protein kinase (MAPK), nuclear factor-kappa B (NF-κB),
and proinammatory mediators get activated and cause
inammation in the airways due to increased oxidative stress
during bronchial asthma [6] and promote secretion of mucin
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Fig. 1 Diagrammatic
representation of some
noncommunicable diseases
suffered by humans
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related to asthma [19–21]. The heavy formation of oxidative
stress destroys the respiratory system which also increases
the production of reactive oxygen species due to dismantled
defense mechanism of antioxidant [22]. Malnutrition and
stumpy body mass index are correlated to the austerity of
chronic obstructive pulmonary disease [23]. The chronic
obstructive pulmonary disease patients those who are underweight are more familiar to pulmonary impairment, intolerant to exercise, and have high rates of mortality than people
with standard weights [23, 24]. Deciency in dietary antioxidants like vitamin E, vitamin C, polyphenols, carotenoids,
etc. deteriorates the antioxidant defense mechanism and
aggravates the development of the disease [23, 25]. The diet
rich in fruits, green vegetables, whole grains, and sh has
been found to be related to enhancement in the function of
pulmonary tissues which lowers the risk of chronic obstructive pulmonary disease [26]. The supplements has proved to
improve the function of respiratory tissues in patients with
poor diet plans in patients suffering from chronic obstructive
pulmonary disease [6]. Vitamin D supplements help to
strengthen the muscles responsible for respiratory function
and increase their capacity to perform exercise in individuals
suffering from chronic obstructive pulmonary disease [27].
Vitamin C helps in reduction of oxidative stress and pulmonary inammation not only by scavenging the reactive oxygen species but also activating the NF-κB pathway [28].
Melatonin is another antioxidant which regulates the circadian biological clock and also diminishes lung damage
related to oxidative stress [29]. A study has proved that intake
of vitamin A and vitamin C is inversely proportional to the
occurrence of asthma in an individual [30]. The juxtaposition
of Vitamin C along with Vitamin E helps in stimulating the
process of regeneration of α-tocopherol from its state of oxidization [31]. The carotenoids which are rich sources of antioxidants have shown promising outcomes in asthma and
healthy functioning of lungs [32]. The natural antioxidant
plays an important role between oxidative stress and incidence of respiratory disorders [33]. Though intake of antioxidants helps in attenuating the respiratory disorders, but
these supplements when consumed above the recommended
dose can act as oxidative stress promoters and prooxidants
[34]. These studies help in supporting the fact that natural
antioxidants have the potential to alleviate respiratory diseases like chronic obstructive pulmonary disease and asthma.
3.2 Cardiovascular Diseases
In USA, cardiovascular diseases are responsible for nearly
more than a million of deaths every year [6]. In majority of
the cases of cardiovascular disorder, development of atherosclerosis caused by oxidative stress plays a pivotal role [35].
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In a vascular cell, excess amount of reactive oxygen species
can be produced from NAD(P) H oxidase, uncoupling of
nitric oxide synthases, plus mitochondria, which are responsible for modication in lipoprotein of low density by oxidation [35–37]. These oxidized form of low-density lipoproteins
are transported by the arterial lumens and persuade the process of apoptosis in the cells of endothelium and smooth
muscles. After phagocytosis of oxidized low-density
lipoproteins, the macrophages get transformed into foam
cells which discharge some growth mediators for attracting
the smooth muscle cells inside the intima. The extracellular
matrix secreted from the smooth muscle cells forms a cap
which is thin and brous and surrounds the fatty streak [6,
35–37]. The fatty streaks get converted to brous plaque of
advanced level by constant proliferation of monocytes,
smooth muscles cells, and macrophages which thereby paves
a pathway to occlusion of vessels [35]. Oxidative stress has
also been reported to subsidize cardiac failure by development of cardian hypertrophy, apoptosis of myocytes, and
ischemic-reperfusion injuries [35, 38]. Several studies have
been focused of evaluation of natural antioxidants in cardiovascular diseases implicated by reactive oxygen species [6].
The intake of green vegetables and fruits has found to elevate
the antioxidant levels in the blood which include vitamin C
and carotene and also helps to reduce oxidation of cholesterol [6]. In a study where meta-analysis was done, about 16
reported cases showed the inverse ratio of cardiovascular diseases and consumption of green vegetables and fruits [39].
Natural α-tocopherol has been reported to reduce
cardiovascular- related mortality in patients with coronary
atherosclerosis [6]. Antioxidants like polyphenolic compounds and lycopene can play a major role in protecting cardiovascular diseases [40]. RRR-AT which is the natural form
of antioxidant vitamin E has shown positive response against
this disease [35, 41]. The prooxidant activity of vitamin C at
elevated doses may cause production of reactive oxygen species which hinders the protective nature of the antioxidant
supplements. Lycopene that is present in tomatoes is a source
of natural antioxidants which was found to reduce the cardiovascular diseases in a study [6, 42, 43]. Lycopene inhibits
the synthesis of cholesterol by hindering the oxidation of
low-density lipoproteins and further degrades it [40]. In
another study, it was revealed that lycopene has substantial
shielding role in patients of myocardial infarction. So, it
likely supported the intake of vegetables rich in lycopene
[44]. Almost all fruits, green vegetables, beverages, and cereals contain ample amount of polyphenolic compounds which
signicantly reduce the threat for cardiovascular diseases
[45]. Flavonoids are found to mend better functioning of
endothelium which plays a prominent role in cardiovascular
diseases [6]. The polyphenols have intrinsic antiinammatory potential which helps in vasodilation regulation and endothelial cell apoptosis [46].
3.3 Neurodegenerative Diseases
Neurons contain high amount of polyunsaturated fatty
acids containing cell membranes and have elevated mandate for consuming oxygen which makes them vulnerable
to oxidative stress-associated destruction [47]. Several
studies revealed that the reactive oxygen species triggers
the incidence of neurodegenerative disorders like
Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and spinocerebellar
ataxia [8, 48–52]. Huntington’s disease is caused by expansion of CAG repeat after mutation in exon 1 of the gene and
produces a mutated protein “huntingtin” (mHtt). It is an
autosomal dominant disease. The oxidative stress is a characteristic of Huntington’s disease which increases the oxidation on DNA in the patient’s brain. The dysfunctional
pattern of mitochondria is induced by oxidative stress
which intensies the formation of reactive oxygen species.
An enzyme of Kreb’s cycle, mitochondrial aconitase, is
damaged in this disease by reactive oxygen species-induced
oxidation of Fe-S cluster present in the enzyme [53]. The
expression of glucose transporter (GLUT)-3 decreases due
to oxidative stress which leads to glucose uptake restrictions and excessive lactate accumulation [52]. Alzheimer’s
causes dementia in old-aged people as aging triggers the
production of oxidative stress which thereby leads to lesion
formation in Alzheimer’s disease [54, 55]. Before the
occurrence of plaque pathology and accumulation of
amyloid-β (Aβ), the events of oxidation initiates which
paves a pathway for oxidative stress-induced damages in
Alzheimer’s disease [56, 57]. The JNK/p38 MAPK pathways get modulated by oxidative stress which leads to Aβ
accumulation and tau proteins hyper-phosphorylation [50].
Excessive production of reactive oxygen species plays a
major role in the mechanism related to progression of
Parkinson’s disease. The antioxidant defense mechanism is
damaged and presence of glutathione is noted at the initial
stages of the disease. The proteins, lipids, and DNA get
oxidized at an alarming rate which produces toxic end
products and causes death of the cell [58]. The complex I of
the mitochondria responsible for respiration show retarded
activity which induces the production of reactive oxygen
species responsible for dopaminergic neuron apoptosis [6].
Mutation of superoxide dismutase (SOD) 1 and degeneration of mitochondria are the two major reasons responsible
for amyotrophic lateral sclerosis [59]. A substantial degeneration of the vacuoles in mitochondria were noticed in the
neurons of SOD1 mutant mice which depicts that malfunctioning of mitochondria is the initiation point for amyotrophic lateral sclerosis. The abnormal interaction between
mitochondria and mutant SOD1 leads to release of cytochrome C and apoptosis activation [56]. The SOD1 mutation causes damage in the antioxidant mechanism which
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leads to degeneration of motor neurons [8]. The excessive
amount of oxidative stress inhibits the neuroprotective
IGF-I/AKT pathway which results in dysfunctional neuron
cells [48]. Again, alterations in the mitochondria instigated
by oxidative stress are found to be responsible for spinocerebellar ataxia development [60]. The optimization of reactive oxygen species is considered to be a prospective
method for treating and mitigating neurodegenerative diseases [61]. There are several clinical evidences which indicate that proper consumption of natural antioxidants in the
diet can ameliorate neurodegenerative disorders [62].
Vitamin D is a potent antioxidant which helps to regulate
the excite-toxicity of the neurons which is calcium-mediated and induces the neurotransmitters and structural proteins of the synapse. Its deciency can become a major
subsidizing aspect which leads to neurological aberration
[63, 64]. Deciency of Vitamin D in blood serum is corre-
lated to dopaminergic neurons loss in the brains of patient
suffering from Parkinson’s disease [64]. Vitamin B is
another major antioxidant which when decient causes
impairment of neurons related to Parkinson’s disease and
Alzheimer’s disease [65]. In both invitro and invivo studies, it is revealed that resveratrol, rutin, and vitamin E,
improve the neurodegenerative conditions caused by reactive oxygen species associated cascades like NF-κB and
JNK [8]. Vitamin E works more actively in modulation of
oxidative stress than Vitamin A and Vitamin C in rodent
brains [66]. In a cohort study, it was found that vitamin E
administration at a dose of 2000IU per day showed positive response in Alzheimer’s disease [67]. The amalgamation of coenzyme Q10 and Vitamin E helps to improve
generation of energy in Friedreich ataxia by mitigating oxidative stress and functional restoration of mitochondria
[68]. Several phytochemicals, phenolic components, and
avonoids present in green vegetables and fruits have
higher antioxidizing potential which can be effective in
Parkinson’s disease [69]. Strawberries contain anthocyanins which have antioxidant, antiapoptotic, and anti-inammatory properties. They help in amelioration of astrogliosis
and preservation of neuromuscular junctions and functions
of muscles in amyotrophic lateral sclerosis [70]. Resveratrol
protects the neurons from Aβ and oxidative stress-induced
toxicity in Alzheimer’s disease [71, 72]. Lipoic acid
enhances the generation of glutathione and helps in depletion of lipid peroxide which protects the proper functioning
of mitochondria in the neurons from oxidative stress [73,
74]. MitoQ is another antioxidant which resorts the func-
tion of mitochondria in Purkinje cells and helps to alleviate
motor incoordination in spinocerebellar ataxia [60].
Neurodegenerative disorders target the antioxidant defense
system as a whole, so consumption of single antioxidant
would not enough to revive the cellular damages [75].
3.4 Cancer
The initiations, promotion, and proliferation are the three
stages of cancer growth which involves association of reactive oxygen species [76–78]. Firstly, during the stages of initiation, accumulation of mutated DNA occurs in the
cancerous cells which are induced by reactive oxygen species [79]. The over production of reactive oxygen species
leads to oncogenic DNA mutation which contributes to cancer development [80]. Due to alteration in the metabolic system and high demand of energy, excess synthesis of reactive
oxygen species is a characteristic feature of every cancer cell
when compared to normal cells [81]. The reactive oxygen
species triggers cell proliferation by enhancing cellular signaling, resistance of tumors during therapies, supply of blood
to tumors, and accelerating metastasis [82]. They also promote cellular expansion by modication of genes relation to
transcription factors, apoptosis, and cell proliferation [83]. It
causes an upregulation of antiapoptotic genes and downregulation of proapoptotic proteins by PI3K/AKT and ERK/
MEK pathways [84]. It upregulates the metalloproteinases of
the matrix, inhibits the antiproteases action and angiogenesis
which leads to metastasis [85–87]. The endogenous antioxidants get depleted which disrupts the redox equilibrium
which triggers development of cancer. Several studies proved
that modication in the diet helps to prevent cancer by 35%
[88]. The green vegetables and fruits containing antioxidants
help to protect from the risk of cancer development [89, 90].
The polyphenolic components from plant sources have
proved to show antioxidant activity [91–94]. These antioxidants have anticancerous potential which helps them to combat against breast, lung, larynx, tongue, gastric, prostate, and
colon cancers [95, 96]. Fruits which possess elevated amount
of phenolic compounds have the potency to substitute OH−
group in their aromatic ring [97, 98]. They can persuade cancer cell apoptosis, inhibition of mutated cell proliferation,
reduction of cyclooxygenase-2 (COX-2) production, and
downregulation of gene expression related to cancer [99–
102]. Vitamins and minerals show antioxidizing potency
which inhibits cell proliferation, maintains methylation of
DNA, and promotes arresting of cell cycle [88, 103].
Consumption of antioxidant-rich diets modies the biological markers related to progression of cancer [104]. Food
from natural plant sources reduces the risk of breast cancer
[105, 106], neck and head cancer [107], and colorectal cancer [108]. Oral cancer can be inhibited by Vitamin A and E
[109]. Vitamin D and some minerals like selenium and carnitine show promising results in cancer treatment [110, 111].
Effective consumption of green vegetables, fruits, and whole
grains with lower intake of red meat and alcohol helps to
maintain a healthy lifestyle and decreases the probability of
cancer threat [112].
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3.5 Digestive Diseases
Several studies have established that the oxidative stress
related to inammation in the intestine plays a pivotal role
in gastrointestinal diseases and inammatory bowel syndrome [113]. The pathological symptoms showing the etiology of inammatory bowel disease clearly signify reactive
oxygen species to be responsible [114, 115]. Imbalance in
the intestinal microora, presence of pathogens, and food
particles in the gastrointestinal tract trigger the excessive
production of reactive oxygen species and hamper the
endogenous mechanism of antioxidant defense [116].
Epithelium barrier of the intestine gets disrupted by oxidative stress which elevates the permeability of the intestine
thereby causing inammation. Inammatory bowel disease
comprises of ulcerative colitis which is dened by chronic
inammation related to oxidative stress in the gastrointestinal tract [113]. The patients diagnosed by inammatory
bowel syndrome show increased level of proinammatory
mediators like leukotriene B4 (LTB4) and platelet-activating factor in the mucous sample which triggers the reactive
oxygen species by excessive stimulation of phagocytes and
these reactive oxygen species are cytotoxic in nature [117–
119]. Throughout the massive inltration of neutrophils
which are polymorphonuclear and macrophages, myeloperoxidases get secreted which produce hypochlorous acid by
hydrogen peroxide metabolism. Different enzymes like
5-lipoxygenase, cyclooxygenase, and xanthine oxidase are
the foundation of reactive oxygen species in the intestinal
mucosa. Some deciency in antioxidants in diet also subsidizes oxidative stress development [120]. In patients with
Crohn’s disease shows deciency of antioxidant vitamins
and minerals which is due to poor nutritional diet [120,
121]. Vitamin A concentration is greatly inuenced in mal-
nourished patients of inammatory bowel syndrome due to
lower consumption of green vegetable and fruits [113]. The
mucosal linings are protected and repaired by Vitamin C
which is deteriorated in gastritis and peptic ulcers [122].
Deciency of Vitamin D causes morbidity of the skeletons
in patients of Crohn’s disease [123, 124]. Excessive oxidative stress damages the permeability of epithelium in gastrointestinal tracts through lipid peroxidation and distortion of
tight junction. This hampers the microora of the gastrointestinal tract and inhibits its colonization which promotes
the occurrence of pathogenic bacteria [123, 124]. These
pathogenic bacteria cause infections and trigger the synthesis of reactive oxygen species and lead to inammation
which increases the threat of inammatory bowel syndrome
[114]. The consumption of antioxidants from natural sources
help to maintain the redox potential which helps to mitigate
the damages caused to the intestine by reactive oxygen species and leads to healthy gastrointestinal tract [115].
Consumption of antioxidants showed fruitful results in
Crohn’s disease with upliftment in serum antioxidants. It
also attenuated inammation in Crohn’s disease when consumed in combination of n−3 fatty acids [125]. Intake of
over dose of antioxidant supplements has detrimental effect
by removing reactive oxygen species from biological
metabolism. So it is highly recommended to consume antioxidants from natural sources [126, 127]. α-tocopherol,
which is a component of vitamin E and some minerals has
the potential to alleviate reactive oxygen species like selenium interacts with GPx and zinc interacts with superoxide
dismutase to ght the oxidative stress. Selenium and Vitamin
E in combination protect the colon from oxidative damage
in rats [128].
3.6 Aging
During the process of aging, accretion of oxidative destruction inside the cells is unalterable and advanced [129]. The
redox balance gets shifted toward oxidized state in the aging
cells which is designated by low GSH/GSSG ratio. This distorts the capacity of the cell to duffer reactive oxygen species
in normal physiological conditions and during exterior stress
[130]. The accumulation of reactive oxygen species damages
the proteins, DNA, lipids which dismantle the normal function of the cell [8]. Mitochondrial DNA gets mutated easily
due to oxidative stress and hence triggers the process of
aging which was supported by the study done in mice which
showed signs of aging like loss of hair, osteoporosis, short
life span with mutated mitochondrial DNA [131]. Elevated
levels of reactive oxygen species cause shortening of telomere which accelerates senescence of cells [130]. The oxidative stress-associated aging causes inammation by activating
the NF-κB, which are regulatory factors for interleukin
(IL)-1β, IL-6, and tumor necrosis (TNF-α). The NF-κB signaling has short span which is induced by oxidative stress
and triggers aging. A continuous and slight inammation can
become the reason for age-related diseases like cancer,
dementia, and atherosclerosis [132]. The malnutrition
becomes a reason for deteriorated rate of metabolism and
digestion in aged person [133]. Deciency of Vitamin D
results in loss of bone density, prone to fracture, and hyperparathyroidism. Natural sources of antioxidants can reduce
these threats of elderly patients [134]. The antioxidants suppress the production of free radicals which retard the process
of aging [135]. Studies show that consumption of green leafy
vegetable of the family Brassicaceae shows decline in the
cognitive function [136]. Increase in life span was seen in
Caenorhabditiselegans and fruit ies where blueberry
extract which is diet-rich antioxidants were provided [137,
138]. The activity of catalase and superoxide dismutase was
increased which showed the fruitful effects of blueberry
extract by booting the antioxidant system of the body.
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Polyphenols from apple, anthocyanin from black rice,
theaavins from black tea showed elevated antioxidant
potential in different animal models [138].
3.7 Hypertension
Hypertension is the major reason for cardiovascular diseases.
Several studies has established the fact that excess production of reactive oxygen species causes oxidative stress which
plays a pivotal role in hypertension pathogenesis. The vasomotor system gets modulated by reactive oxygen species
which inuences endothelin-1, angiotensin II, and urotensin II leading to vasoconstriction. The redox system also regulates the nitric oxide which is a vasodilator. During excessive
presence of reactive oxygen species, oxidative damage is
caused which contributes to vascular dysfunction. The
hydrogen peroxide and superoxide anions increase during
pathophysiological hypertension which decreases the bioavailability of nitric oxide and antioxidant system gets damaged. In this scenario, the consumption of antioxidants
neutralizes the system as they are reducing agents. The intake
of Vitamin C and Vitamin E has been proved to show promising results as its helps to protect the vascular epithelial injury
[139]. The hypertension caused by the reactive oxygen species triggers renal disorders by altering glomerulus by mediating glomerular lesions which has inammations and also
glomerulopathy [140]. Not only the kidney, the central nervous system is also affected by pathogenesis of hypertension
which increases the central sympathetic outow which is
caused by the reactive oxygen species generated in the brainstem cells due to hypertension [141–143]. Some endogenous
antioxidants of the cells are catalase, superoxide dismutase,
and glutathione peroxidase which neutralize the oxidative
stress. Some exogenous antioxidants have proved to sow
wonders in this condition like, Vitamin C, Vitamin E, polyphenols, selenium, and N-acetylcysteine. Vitamin C upregulates the eNOS and declines the level of NADPH oxidase.
The plasma ascorbate thus has proved to have inversely proportional to blood pressure. The consumption of antioxidants
reduces blood pressure and stimulates vascular functioning
vigorously. It acts on nitric oxide and promotes vascular dilation [139]. Increased consumption of Vitamin E regulates the
generation of hydrogen peroxide and superoxides of the
mitochondria via its antioxidizing potential thereby reducing
the threat of cardiovascular diseases [144]. Vitamin C and
Vitamin E in combination regulate the α-tocopheroxyl radical which has an antihypertensive effect [145].
3.8 Diabetes
The complication of diabetes is also triggered by the oxidative stress in both microvascular and cardiovascular diseases.
The superoxides of the mitochondria are produced in excess
in the endothelial cells of the vessels and myocardium during
the diabetes abnormality in the metabolism. The overproduction of superoxides promotes ve important pathways like
elevated synthesis of advanced glycation end products,
polyol pathway ux, overexpression of the advanced glycation end products receptor and its ligands activation, protein
kinase C (PKC) isoforms activation, and excess activity of
the hexosamine pathway. It also nullies the activity of the
enzymes, namely, eNOS and prostacyclin synthase which
are antiatherosclerotic enzymes. The elevated intracellular
reactive oxygen species harms the ischemia and causes
defective angiogenesis. It also turns on several proinammatory pathways and leads to enduring epigenetical changes
thereby continuing the proinammatory gene expression
when diabetes becomes normal. In type 2 diabetes, cardiomyopathy and atherosclerosis are seen which lead to resistance of insulin thereby elevating the mitochondrial reactive
oxygen species from fatty acids which causes antiatherosclerosis enzymes inactivation. Superoxide dismutase is the savior for cardiomyopathy, nephropathy, and diabetic
retinopathy [146]. Consumption of Vitamin C and α-lipoic
acid (ALA) from natural sources helps to prevent diabetes.
α-lipoic acid reduces blood glucose by reducing oxidative
stress which leads to lowering the insulin resistance.
Antioxidant minerals like zinc and magnesium also help in
triggering the glucose metabolism which leads to lowering
the threat of diabetes. Vitamin A (retinol) is an antioxidant
which helps to improve the function of pancreatic cells by
regulating stress leading to normal synthesis of insulin [147].
3.9 Polycystic Ovarian Disease
Polycystic ovarian disease is caused in women during the
reproductive stage which results in anovulation and infertility. This disease is mainly caused due to lifestyle disorder by
intake of junk food and fast foods which triggers excess
amount of reactive oxygen species in the body thereby leading to oxidative stress. The oxidative stress is the main reason for polycystic ovarian disease where the symptoms are
obesity, hirsutism, acne, and irregular menstrual cycle. This
chronic disorder leads to hypothyroidism, insulin resistance,
hyperandrogenemia, and inammation. The reactive oxygen
species attacks the DNA and mutates them leading to gene
aberration and mutation which suppress the tumor suppressor genes and trigger the cell proliferation which contributes
to incidence of gynecological cancers in patients suffering
from polycystic ovarian disease. About 45% of women suffering polycystic ovarian disease face the problem of obesity
as it creates a metabolic disorder which leads to elevated levels of malondialdehyde, oxidized low-density lipoprotein,
thiobarbituric reactive substances, advanced oxidation protein products, body mass index, and oxidative stress. Insulin
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resistance is another factor which is triggered by the high
concentration of oxidative stress due to high levels of free
fatty acid and low glucose metabolism [148]. Antioxidants
have a promising effect in patients suffering from polycystic
ovarian disease. Both enzymatic antioxidants like catalase,
superoxide dismutase, glutathione reductase (GR), and glutathione peroxidase (GPx), and nonenzymatic antioxidants
like α-tocopherol (vitamin E), glutathione (GSH), β-carotene
and ascorbate (vitamin C), alpha lipoic acid, coenzyme Q,
N-acetylcysteine, resveratrol, melatonin, and carnitine show
positive results in polycystic ovarian disease [149, 150]. The
antioxidants improve the environment of the ovary, reduce
the level of androgen, and promote maturation of follicles. It
also improves vascular epithelial function and triggers lipid
metabolism which prevents deposition of lipids in obese
patients [151]. Some minerals like selenium [152], magnesium, zinc [153], and chromium [154] also have antioxidant
activity which helps in polycystic ovary.
4 Antioxidant Vitamins fromHerbal
Sources toCombat Lifestyle Diseases
Antioxidant vitamins play a major role in combating the oxidative stress caused by reactive oxygen species which are
generated in different metabolism of the body leading to
dreadful life-threatening diseases and are mainly caused by
lifestyle disorder. Consumption of sufcient amount of vitamins helps to neutralize the oxidative condition of the cells
which leads to healthy disease-free life. Each of the antioxidant vitamins, its mechanism of regulating oxidative stress,
and natural sources are elaborated in the sections below.
density lipoproteins are the major carriers of triglycerides
and cholesterol and also inlter arteries. This when oxidized,
it causes activation of adhesion factors in the endothelial
cells which lead to adherence of monocytes and macrophages are differentiated. These macrophages accumulate
the low-density lipoproteins which are oxidized and stay in
vascular wall forming foam cells which develop lesions in
atherosclerosis. Ascorbate decreases the process of oxidation
of low-density lipoproteins and reduces the initiation of oxidants [157–159]. Again oxidation of protein occurs when
oxidants cleave the chain of peptides of single amino acid.
Methionine and cysteine are two oxidant prone amino acids.
By reducing the induction of oxidants, ascorbate helps to
reduce the oxidation of proteins and amino acids. It also
acted as a substrate for several end products of glycation
[155]. DNA can also be attacked by the oxidative stress
which includes oxidation of protein where alteration of DNA
repair genes and DNA polymerases occurred. Again when
lipids were attacked by oxidants, it caused lipid peroxidation
which triggered mutation of DNA [160]. In DNA, guanine is
more susceptible to oxidant attacks 8 hydroxyguanine and
8-hydroxy-2-deoxyguanosine [161]. When the attackers are
nitrogen species, nitrosamines are produced as derivatives
[155]. There are several natural sources which are rich in
Vitamin C like fruits and green vegetables. The fruits include
kiwi, grapefruit, honeydew, cantaloupe, orange, mango,
strawberries, papaya, tangerine, tangelo, and watermelon.
The vegetables include brussels sprouts, broccoli, asparagus,
cauliower, cabbage, mustard greens, kale, pepper (red or
green), potatoes, plantains, sweet potatoes, tomatoes, and
snow peas [155] (Table1).
4.1 Vitamin C
Vitamin C is a strong antioxidant as it is an electron donor
and is also known as ascorbic acid. Being a donor of electron, it is hydrophilic in nature. It is an electron donor and
donates two electrons from the double bond which is between
third and second carbon of six carbon structure which prevents oxidization of other compounds. After donation of
electron-free radical, ascorbyl is formed which is stable in
nature; therefore, ascorbate is used as a strong antioxidant
which reacts with harmful free radicals and for a lesser harmful ascorbyl radical which is less reactive which proves its
radical scavenging potential [155]. Vitamin C acts on lipid,
proteins, and DNA which are found in different envelopes of
cell. In lipids, the membrane lipids when interact with reactive oxygen species undergo lipid peroxidation which produces free radicals which will lead to oxidative stress.
Vitamin C helps to combat the free radicals thus produced by
inhibiting the process of lipid peroxidation [156]. Low-
4.2 Vitamin E
The basic component of Vitamin E is α-tocopherol which is
actually responsible for its antioxidant potential. They scavenge the oxidative species and nitrogen species and also
restrict the 5-lipoxygenase-catalyzed eicosanoids and cyclooxygenase and suppress the signaling of inammation like
STAT3/6 and NF-κB.The eight stereoisomers of Vitamin E
are α, β, γ, δ tocopherol and α, β, γ, δ tocotrienol. Dextrorotary
d-α-tocopherol is hyperactive [162]. As is it fat soluble in
nature, it protects the cell membranes from oxidative damage
[34]. The unsubstituted fth position γT attacks electrophiles
and hence nitrogen species are trapped. The tocotrienol and
tocopherol from δT have radical scavenging potential as
compared to αT [163]. Vitamin E helps to maintain the
homeostasis of skeletal muscles and promotes the repairing
of plasma membrane. It also prevents aggregation of platelets by inhibiting protein kinase C (PKC). It also helps to
inhibit the process of cholesterol biosynthesis by suppression of suppressing 3-hydroxy-3-methylglutaryl-CoA
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Table 1 Showing the herbal sources of antioxidant vitamins and minerals to alleviate lifestyle diseases
Sl.
no. Name of sources
1 Cereals Vitamin E, zinc [194–199]
2 Oil seeds Vitamin E, zinc [163, 199,
3 Nuts Vitamin E, selenium, zinc [199–202]
4 Broccoli Vitamin E, iodine [197, 200]
5 Cooking oil Vitamin E [163, 200]
6 Brussels
sprouts
7 Cauliower Vitamin E, vitamin C,
8 Citrus fruits Vitamin C [204]
9 Guava Vitamin C, vitamin A [205]
10 Tomatoes Vitamin C, vitamin E,
11 Goose berry Vitamin C [204]
12 Sprouted
pulses
13 Green leafy
vegetables
14 Papaya Vitamin A [206]
15 Musk melon Vitamin A [207]
16 Mango Vitamin A [204]
17 Pumpkin Vitamin A, zinc [199]
18 Carrots Vitamin A, vitamin C,
19 Mushrooms Vitamin B, vitamin E,
20 Whole grains Selenium, zinc, iodine [201, 202]
21 Seafood Vitamin E, selenium [201,
22 Asparagus Vitamin C [211]
23 Pink grape
fruit
24 Beet root Vitamin C [203, 213,
25 Avocado Vitamin E, vitamin C,
26 Pears Vitamin C, vitamin A [216]
27 Pomegranate Vitamin C [217]
28 Peas Vitamin A, vitamin C,
29 Spinach Vitamin A, vitamin C,
30 White onion Vitamin A, vitamin C,
31 Green tea Vitamin C, vitamin E,
32 Oatmeal Selenium, zinc, manganese [199, 219]
33 Banana Selenium, iodine [220]
34 Peach Selenium [221]
35 Lettuce Selenium [202]
36 Potatoes Selenium [208, 209]
37 Soybean Zinc, vitamin E, iodine [163, 199]
38 Flax seed Zinc [199]
Antioxidants vitamins and
minerals References
200]
Vitamin E, zinc [199]
vitamin A, iodine
vitamin A
Vitamin C, zinc [199]
Vitamin A, zinc [199]
vitamin E, selenium
vitamin C, copper, selenium
Vitamin C [212]
vitamin A, magnesium
vitamin E, selenium, iodine
vitamin E, selenium
vitamin E
vitamin A, vitamin B,
manganese, zinc, copper
[203]
[203]
[203, 208,
209]
[206]
208–210]
214]
[215]
[203, 204,
208, 209]
[200,
202–204]
[203, 204]
[199, 204,
218]
Table 1 (continued)
Sl.
no. Name of sources
39 Pepper Vitamin C [204]
40 Cabbage Vitamins C, vitamin E,
41 Kiwi Vitamin E [200]
42 Aloe Vitamin E, vitamin C,
43 Apple Vitamin C, vitamin E, zinc [223]
44 Parsley Vitamin A, vitamin C,
45 Peppermint Vitamin E, vitamin C,
46 Lavender Vitamin C [4, 226]
47 Drumstick Vitamin C, vitamin A [227]
48 Red pepper Vitamin A, vitamin E [206]
49 Squash Vitamin A [228]
50 Chia seed Selenium [183]
51 Pineapples Manganese, iodine [189]
52 Strawberries Iodine [229]
53 Cranberries Iodine [229]
54 Green beans Iodine [229]
55 Cassava Iodine [230]
Antioxidants vitamins and
minerals References
[203]
vitamin A, iodine
[222]
vitamin A
[4, 224]
magnesium
[4, 225]
vitamin A, magnesium
(HMGCoA) reductase in liver cells. Vitamin E also stimulates wild-type p53 tumor suppressor gene, downregulates
p53 proteins, upregulates heat shock proteins which help to
prevent cancer. Γ-tocopherol prevents cell proliferation in
cancer by scavenging the free radicals which causes mutation of DNA and promotes malignancy in the cells. It also
arrests cell cycle by suppressing Cyclin D and promotes the
process of apoptosis. The γ and δ tocopherol inhibits the
sphingolipids in prostate cancer cells and induces apoptosis.
It actually promotes cytochrome c synthesis, caspase-9 and
caspase-3 are activated and polyadenosine diphosphate
(ADP)-ribose polymerase (PARP) cleaving. The process of
cytotoxicity due to production of hydrogen peroxide by oxidation of protein and peroxidation of lipids in Alzheimer’s
diseases are blocked by Vitamin E [164]. The consumption
of food containing Vitamin E can be helpful in alleviating the
diseases related to lifestyle disorders. The diet rich in Vitamin
E containing herbal sources like cereals, oil seeds including
sunower seed, pumpkin seed, cooking oils including coconut oil, palm oil, corn oil, olive oil, peanut oil, soybean oil,
wheatgerm oil, safower oil, and sunower oil, almonds,
hazelnut, peanut, spinach, broccoli, kiwi, mango, tomato,
brussel sprouts, carrots, mushrooms, peas, white onion,
green tea, cabbage, and aloe can reduce the lifestyle diseases
by promoting the radical scavenging property of Vitamin E
containing foods (Table 1). Vitamin E is predominantly
dependent on Vitamin C, selenium, and glutathione. A combination of Vitamin E with Vitamin C works as a more potent
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S. Ganguly and J. Kumar
antioxidizing agent by enhancing the antioxidant defense
system of the cell [164].
4.3 Vitamin A
Vitamin A is the transcriptional regulator which regulates the
expression of hundreds of genes. It has an indirect antioxidant potential by regulation of various transcriptional genes
in response to which the free radicals are scavenged. The
antioxidant potential of Vitamin A convenes to polyene
chains which are hydrophobic in nature and has the capacity
to scavenge free radicals of oxygen and neutralizes thiyl radicals which lead to stabilization of peroxyl radical. It has
auto-oxidation capacity which helps to decrease the oxygen
tension during physiological process in a cell. Food rich in
antioxidant Vitamin A helps to reduce coronary heart failure
and diabetic cardiomyopathy by reduction of oxidative stress
[165]. β-carotene is the precursor of Vitamin A, and is fat
soluble in nature. This gets converted to retinol which has
prominent antioxidizing potential [34]. The consumption of
foods rich in Vitamin A are cauliower, guava, tomatoes,
papaya, musk melon, mango, pumpkin, carrots, pears peas,
spinach, white onion, green tea, cabbage, ale, parsley, peppermint, avocado, and drumstick (Table1) which can reduce
the risk of cardiovascular diseases, cancer, and cellular function of the pancreas thereby preventing diabetes [166].
consumed by humans. The selenoproteins reduce the synthesis of oxidized low-density lipoprotein which lowers the
risk of cardiac disorders [167]. TrxR is an essential selenoenzyme which reduces oxidative stress by increasing the
bioavailability of nitric oxide which leads to prevention of
atherosclerosis [168, 169]. The consumption of seleniumrich diet reduces reperfusion and in deciency can cause
intrinsic myocardial tolerance to ischemic insult [170–172].
Ebselen is another organoselenium compound which has
activity like glutathione peroxidase which provides protection from myocardial ischemia-reperfusion injury. This
compound induces stress protein HSP27 and preserves glutathione [173]. It also has neuroprotective role when administered with thrombolytic tissue plasminogen activator
[174]. Selenium also has evidence to reduce the progress of
cancer in men [175]. Selenium in combination with Vitamin
E shows inverse relation with incidence of prostate cancer
[176, 177]. The mineral reduces oxidative stress and prevents damage of DNA [88, 178–181]. It promotes the arrest
of cell cycle, triggers the process of apoptosis, and inhibits
cell proliferation and protein kinase C activity [178, 181–
183]. The consumption of selenium-rich diet helps to
reduce the risk of lifestyle diseases. The foods from herbal
sources are Brazilian nuts, brown rice, chia seed, ax seed,
whole wheat breads, baked beans, oatmeal, lentils, spinach,
cashew nuts, green peas, bananas, potato, peach, carrot,
and lettuce [184].
5 Antioxidant Minerals fromHerbal
Sources toCombat Lifestyle Diseases
Minerals are required in negligible amount in the body and
its deciency can cause several lifestyle diseases. They help
in scavenging the free radicals from the biological system
due to normal activity of the cell. There are some minerals
required in large amount known and macronutrients and
some are required in trace amount known as micronutrients.
The antioxidant minerals and its herbal sources are discussed
in the following section.
5.1 Selenium
Selenium is one of the most essential antioxidant microminerals which has tremendous power of antioxidant in the
form of selenoprotein which has the potential to scavenge
the free radicals in oxidative stress. This selenoprotein is
synthesized by incorporation of selenocysteine into protein
which is directed by a termination codon UGA.In selenoproteins, selenium can be present in both organic and inorganic forms. Out of all the forms, organic form of selenium
as selenomethionine is predominantly present in the foods
5.2 Zinc
Zinc has a prominent antioxidizing potential and is maximum found as cofactors in enzymes involved in antioxidant
defense system. It acts as a membrane stabilizer and NADPHOxidase inhibitor. During diabetes, cancer, and obesity, the
harmful reactive oxygen species are scavenged by metallothionein proteins whose synthesis is triggered by zinc. It
regulates glutathione peroxidase and forms the structural
component of superoxide dismutase of cellular cytoplasm. It
regulates the glutamate-cysteine ligase which is responsible
for de novo synthesis of glutathione. It regulates transcription of NF-κB by protein A20 which is anti-inammatory
and also regulates the receptor signaling pathways [185].
Deciency of zinc creates dysfunctioning of epithelium
which induces responses of inammation mediated by a process related to elevated production of oxidative stress. It also
protects the vascular system by regulating a transcription
factor Nrf2, which promotes encoding of gene related to
antioxidant enzymes and metallothionein [186–188]. The
foods from herbal sources which are rich in zinc are cereal,
oil seed, nuts, brussel sprouts, sprouted pulses, leafy vegetables, pumpkin, whole grain, green tea, oatmeal, soybean, ax
seed, and apple (Table1).
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5.3 Manganese
Manganese is required in trace amount and found in livers,
bones, pancreas, and kidneys. It helps in formation of connective tissues, blood clotting factor, hormones, and bones. It
regulates the metabolism of carbohydrates, fats, and blood
sugar. It also helps normal functioning of nerve and brain. It
as an important component of superoxide dismutase enzyme
which has free radical scavenging property. The free radical
damages the DNA and cell membranes. It also has role in the
process of aging, cardiovascular diseases, and cancer. The
superoxide dismutase neutralizes the reactive oxygen species and prevents in cellular damage. Deciency of this
micronutrient causes infertility, malformation of bone, and
weakness. The diet rich in nuts, seeds, and whole grains promotes the concentration of manganese in the system [189].
5.4 Iodine
Iodine is another micronutrient which is responsible for
healthy functioning of thyroid. It has free radical scavenging
potential. It depolarizes the hyaluronic acids, increases the
antioxidant potential of human blood, promotes enzyme
activities, and decreases peroxidases and malondialdehydes.
It protects from the risk of cardiac diseases, and respiratory
diseases which produce oxidative stress. The iodide ion
attacks the lipid peroxidases and hydrogen peroxidases. A
therapy known as balneotherapy is being used in patients
with high oxidative stress. It is proven to have antiproliferative effect in mastalgia [190]. Its been used in therapy of
prostate and breast cancer [191]. In cardiovascular diseases,
the increased level of thyroid hormones is favorable. It
decreases the triglyceride and cholesterol levels. It also helps
in ischemia reperfusion injuries [192]. Reactive oxygen species produced by respiratory disorders can be alleviated by
iodide by augmenting antiviral innate immunity [193]. Food
rich in iodine like Broccoli, cauliower, whole grain, peas,
banana, soybean, cabbage, pineapples, strawberries, cranberries, green bean, and cassava should be consumed in daily
diet to keep away the risk of cardiovascular and thyroidrelated diseases (Table1).
6 Summarizing Remarks andProspects
A balanced lifestyle with healthy diet can show positive
results by reducing oxidative stress. Consumption of antioxidants is the best source to alleviate oxidative stress as it
damages the DNA and causes cellular damage and plays a
key role in incidence of several dreadful diseases.
Chromosomal aberrations and structural deformity are
promoted by oxidative stress. In spite of the production of
reactive oxygen species in several biological metabolism, it
can be concluded that consumption of antioxidant-rich diet
and maintaining a healthy lifestyle plays a pivotal role in
oxidative stress control. In the recent year, herbal natural
antioxidants have gained popularity due to its lesser side
effect and cheaper price which has shown promising results
in having therapeutic potential in not only treating the disease but also preventing it [231]. Regular consumption of
these herbal sources also shows chemoprotective activity.
The plant-based antioxidant vitamins and minerals are also
effective against cardiac problems, neurodegenerative disorders, cancer, polycystic ovarian disease, diabetes, aging,
respiratory disease, hypertension, and digestive disorders.
Further, isolation of chemical compound with antioxidant
potency can be achieved in future for safer and wider
acceptability of these herbal sources. It can be concluded
that oxidative stress is directly linked to lifestyle disorder
and can be managed by consumption of antioxidant-rich
diet which will help to keep away from the risk of disease
development and maintain a healthy life.
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