Ancient Science of Life Vol. No 17(3) January 1998 Pages 158 - 168
FREE RADICALS IN AYURVEDA
YAMINI B. TRIPATHI
Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University,
Varanasi – 221 005
Received: 12 September, 1997 Accepted: 12 September, 1998
Abstract: There has been considerable interest in free radicals and their control by extracts of
medicinal herbs. This article reviews the advances made in this frontier area of research.
As we know, the genetic control, more
specially the transcriptional and the
translational regulations control the whole
physiology of a living cell. Similarly the
three body humours Vata, Pitta and Kapha
have the key of life, as per ayurvedic
concept. All the diseases are the outcome of
the imbalance of these humours or the
disturbed genetic expression of different
macromolecules. Similarly the treatment
part is also holistic in ayurveda, which
means, by treating the basic body hours, all
the diseases could be curd. Therefore, the
diseases and their treatment part is also
divided into 3 basic groups. This is the
baseline, which could be developed to
understand the scientific basis of ayurvedic
The possible correlation between these
ancient concepts and the established modern
theories of some diseases, with special
reference to the free radical mediated
diseases and vata disorders will be dicussed
Free Radical Reactions and Herbal
With the development of earth planet, living
system came into existence as the anaerobic
organism but slowly the captured transition
metal from the environment and used
sunlight as the source of energy. This
process, later named as photosynthesis,
produced oxygen which finally introduced
the existence of aerobic organisms. These
living entities acquired oxygen and iron as
the essential components for their
Although these two elements are essential
for the existence of the existence of a living
aerobic organism but they have several side
effects also. So nature has simultaneously
developed the defence mechanism against
the toxicity, created b these essential
elements. In other words the use of Fe and
o2 is a double edged weapon.
During the process of metabolism the
unwanted molecules are produced as the by
product of the aerobic processes within the
mitochondria which are now named as free
radicals, They are defined as molecules
having unpaired electrons in the outer orbit
and have ability to participate in the 1
electron transfer reactions. They are highly
reactive in nature, thus also known as
reactive in nature, thus also known as
reactive oxygen species.
If we consider the electronic configuration
of oxygen, it is thermodynamically inert but
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from electropotential point of view, it is
highly active. In the native state, it has two
unpaired electrons with parallel spin in its
outermost orbit, which restricts its reactivity.
Mitochondria is the power house of cell,
NADPH produced in TCA cycle passes
trough the electron transport chain and its
hydrogen-electron gradually reduces the
oxygen which is the ultimate electron
acceptor of this reaction leading to the
formation of water. In this redox reaction
there is addition of 4 electrons to a molecule
of oxygen for its complete reduction, but 1-
5% of oxygen leaks out of this system and
produces superoxides. This ultimately
enters to a chain reaction of free radical
generation and thereby lipid peroxidation.
Free radicals are reactive molecules and
atoms, having unpaired electrons. They
have short life and are formed by (1)
homolytic cleavage of covalent bonds where
each fragment retains one electron or (2) by
loss of single electron or (3) by addition of
single electron. For attaining the stability,
there free radicals abstract an electron from
a stable molecule, converting tit to a new
free radical. This leads to a chain reaction
which can be divided into three steps: (a)
initiation (b) propagation (c) termination. It
can be interrupted by using chain breaking
antioxidants or it can be terminated by
destroying free radicals through enzymes or
Generation of free radicals
The generation of free radicals may be
accidental or deliberate and the major source
should be the leakage from Electron
transport chain. FR generation is a chain
process. The reaction between H2O2, Fe3+
and O2 produces OH radicals and several
other radicals, In addition to this reaction,
superoxides are also converted to singlet
oxygen where one of the unpaired electron
is moved to high energy orbital and changes
its spin direction, I get paired an a also react
with the double bouds of all t
macromolecules present in the cell, the
output of the chain reaction is different types
of free radicals and proxy radicals as sown
At this moment it would be better to discuss the different species of reactive oxygen species.
O2 + e- O2 + H+ HO2 Peroxy radicals.
H2O2 is produced by 2e- reduction of oxygen.
When two superoxides dismutates then H2O2 is formed
O2- + O2- H2 O2 + O2
H2O2 is not a free radical but is produces OH radicals which are highly reactive -2 ways.
O2- + H2 O2 OH + OH-
Fe2+ + H2 O2 Fe3+ OH + OH-
Reducing agents continue the cycle of conversion of Fe3+ Fe 2+ like ascorbate.
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OH2 By protonation of superoxides. It is less polar than O2-, so easily traces the biological
membrane. It is more reactive than O2- and can directly attack on the fatty acids.
Sources of ROS
(1) Exogenous interaction- UV, X-rays,
(2) Endogenous mitochondrial leakage
Sites of free radical generation within the
cell are mitochondria, lysosomes,
peroxisomes, nuclear membrane,
endoplasmic reticulum and plasma
Free radicals mediated damages can attack
on every double bond - Brings deformity to
enzymes, nucleic acids through base
hydroxylation, cross linking and strand cession.
Collagen and hyaluronic acid are also
vulnerable o FR attack. Role of iron 1:1 –
1:7 Fe2+: Fe3+ is essential for LPO.
Pure lipid peroxides are fairly stable, but
when they react with Fe Alkoxyl radicals
RO2 peroxyl radicals RO2 are produced.
Oxygen containing free radicals are the most
critical species of radicals. When oxygen is
exposed to high energy such as radiation, or
undergoes partial reduction in the electron
transport chain, the molecular oxygen is
converted to singlet oxygen or superoxides.
Here, the two electrons have parallel spin
which make it unstable and reactive, further,
true oxygen species produce superoxide
radicals, second way of reduction of
molecular oxygen radicals, second way of
reduction of molecular oxygen is by transfer
of electrons leading to superoxides which
produce hydrogen peroxide after
These products react to form water and
hydroxyl radicals. Superoxides and
transition metals may also react with H2O2 to
generate hydroxyl radicals known as haber-
weiss and fenton’s reaction respectively.
Ferrous (Fe++) and cuprous (Cu+) ions are
much more reactive than their oxidized
O2 + H2O2 H2O2 + O2
Fe3 + O2- Fe3+ + OH + OH-
Free radicals are also produced during
respiratory burst in neutrophils and
macrophages. Is generation is enhanced b
certain exogenous sources including toxic
foreign bodies, radiations, car smoke,
hydrophobic chemicals, pathogens,
carcinogenic substances, tobacco smoke,
pesticides, hyperoxic environment,
anaesthetics and organic solvents.
Besides oxygen radicals, there are other free
radicals specially carbon centered radicals ®
They are formed by the attack of OH
radicals on lipids, nucleic acids
carbohydrates and proteins, free radicals are
also generated by auto oxidation of small
molecules such as thiols and catecholamines
and by the activity of certain oxidases such
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as cyclooxygenases, lipoxygenases,
dehydrogenases and peroxidases.
Free radical Reactions.
The free radicals damage the membranes
and thereby change the receptor’s
alignments and ion channels. These changes
finally affect the normal functioning of a
cell by affecting the process of signal
Primary target of free radicals are
unsaturated bonds in the lipids of
membranes. This leads to the loss of
membranes fluidity, receptor alignment and
cellular lysis. It also attacks he sulphur
containing enzymes resulting in the
inactivation, cross linking and denaturation.
Nucleic acids are also affected by the free
radicals, Ultimate result of these actions are
destruction of endothelial cells of blood
vessels, macrophage invasion, suppressed
immune response, inflammatory response,
destruction of lung tissue, hastening of aging
process and also impotency and infertility.
In a living system, lipid peroxidation is
induced by free radicals and reactive oxygen
species, which ultimately damage the ells,
metals also induce LPO which may be of
two types enzymatic and non-enzymatic. In
the later case reducing agents, responsible
for converting Fe+++ to Fe++ for further
reaction are of chemical nature such as
ascorbate, cysteine etc However, in the
enzymatic mechanism, the reducing agent is
an enzyme catalyzed reaction such as
NADPH – cytochrome P-450 reductase.
CCl4 induced lipid peroxidation is also an
example of enzymatic mechanism because
here CCl4 is metabolically activate to CCl30
Free Radicals and Diseases:
Free radicals are involved in more than 50
diseases. Day to day researchers are adding
more number of diseases to this list, In some
cases it interacts wit the progress of a
disease along with other theological factors
ad in other cases the diseases are primarily
due to free radicals.
Rheumatoid arthritis ischaemic and post
iscaemic conditions, malignancy,
mucocutaneous syndrome radiation effects,
immune deficiency avitaminosis, aging and
hypoxia are examples o such diseases where
free radicals are involved in the pathology of
several organs besides these disease,
Alzheimer’s disease, parkinsonism cerebral
ischaemia are conditions were central
nervous system is involved. Nephrotic
syndrome, toxicity due to nonsteroidal anti-
inflammatory drugs and metals, are diseases
where free radicals attack the renal system.
Other examples are atherosclerosis alcohol
cardiomegaly, drug hepatitis, pollutant
toxicity, tobacco toxicity cataract,
retinopathy dermatitis, diabetes mellitus,
ulcerative colitis etc.
I describes below briefly; some diseases
which are being investigated in my
laboratory for the past six years.
Free Radicals in Nervous diseases
Reactive Oxygen Intermediates, produced as
a consequence of a physiological metabolic
reactions, promote issue injury which leads
to rain trauma, ischemia, toxicity &
Free Radicals and infertility
Reactive oxygen species are produced by
living spermatozoa, its excess production n
long persistence could be a significant cause
of male infertility. They produce less motile
sperms which are ineffective for
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fertilization. The abnormal spermatozoa is a
primary source of free radicals.
Free redicals in arthritis
Rheumatoid arthritis is recognized as a
disease of oxidant stress. Infiltration of
synovium by inflammatory cells lead to the
formation of free radicals which causes
extensive disruption of synovial membrane
and promotes inflammatory tissue damage
with cartilage and bone destruction.
Free radicals in Diabetes
free radical and oxidative stress are
implicated in the pathogenesis of diabetes
mellitus and its long term complications, In
insulin dependent diabetes mellitus (IDDM),
some environmental factors may play the
role of initiator, in addition to genetic
Another etiology is immunological ere toxic
agents induce autoimmunity by causing
antigen perturbation, As a result, cytotoxic
antibodies are formed which cover the B-
cells. This complex releases the chemotactic
factors, which attract small lymphocytes,
neutrophils and some granulocytes, these
cells undergo respiratory burst and produce
reactive oxygen intermediates (ROIs) such
as O2 superoxide radical anion, hydrogen
peroxides, hydroxyl radical and singlet
oxygen etc. These free radicals finally
damage the B-cell and hamper the secretion
of insulin secretion which leads to the onset
of symptoms of Type I diabetes mellitus
Management of Diseases and Free
Concept of Health in Ayurveda:
A living organism is e union of four
components i.e Sense, Organ, Psyche and
soul. It is the combination of three body
humours, (Tridosh), seven basic tissues
(Sapta dhatus) and three excretions
(Trimalas). The five major elements of the
body are panchmahaboota which are based
on the existence in elation to nature and
The union of four components, described
above, are regulated by another three factors
named as Pran, Agni & Ojha, agni is of 13
types. The one which is responsible for
digestive power (Jathragani) is considered to
e the most important
When Pran, Agni & Ojha are weakened, the
interaction of three doshas is disturbed and it
leads to the destabilization of the
equilibrium of the body humors or disturbed
normal physiology. These changes are
manifested in the form of symptoms of a
Disease process is the resultant of all the
three factors i.e physical, psychic and
environmental which operate
simultaneously. There is a general concept
of Atiyoga (excess), Heeneyoga (Less) or
Mithyayoga (unwholesome use) of normal
requirement as the root cause of all the
diseases. The health practices can be
visualized as nutrition, exercise, massage,
rest, sleep, hygiene and follow up of daily
routine to maintain the body humous.
Nutrition is the critical determinant of
immunocompetence and risk of illness,
Undernourished individuals have impaired
immune response which leads to more
infections and immunie related disorders.
This nutritional deficiency includes protein-
energy malnutrition, vitamin deficiency and
shortage of minerals and coenzymes. All
these factors have different mechanisms for
affecting an individual and could be
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counteracted by specific supplementation,
some of these components directly affect the
system and some have indirect effect by
regulating the synthesis itself is reduced,
therefore at this stage the diet having direct
action becomes more important (direct
Regarding the management of a disease,
Ayurveda believes in the concept of natural
healing of a disease by the regression of the
causative factor (Swabhavoparamvada).
The treatment part is bersons and the other
which cures the diseases.
First group of medicines enhances the
energy of an individual, delays ageing
improves metabolism specially anabolic
path ways, prevents from diseases, improves
fertility ad sexuality upto old age.
In the modern concept, level of hormones
and enzymes go down. Signaling
mechanism is retarded and post translational
changes in protein occur. These processes
lead to the abnormal physiology resulting to
the accumulation of toxic materials,
unwanted body components, free radicals,
reduced immunity, low vitality etc.
Ubiquitous presence of free radicals have
prompted the scientists to investigate their
role in different biochemical pathways of a
living system. Now it is well establishing
that free radicals play an important role in
regulating ageing process, memory, immune
system, inflammatory disorders, diabetes,
atherosclerosis, would healing, phagocytosis
We all know Ayurveda is based on the
triboshas concept of Vata, Pitta and Kapha.
Although many vaidyas and modern
scientists have tried to explain these terms in
the scientific language but still it is not up to
If we see out past normal ethos, habits, rules
and regulations of different dharmas have
always given preaching to keep the life
health. Ayurveda has the holistic concept of
treatment i.e. to concept of treatment i.e to
consider t patient and its environment
together while diagnosis & treating a
But what is happening now. This modern
civilization has led us to no where. This
hurry, worry & curry have created several
diseases, related to the metabolism such as
diabetes, blood pressure, arthritis, Anxiety,
depression etc. If you see, in young age or
when the Oja is strong enough one can fight
with the metabolic imbalances, created by
the activities of this so called modern
civilization but when oja goes down a new
situation is created.
In Ayurveda this new situation is coined as
the accumulation of doshas and in modern
science one of the symptoms of this
unwholesome habit is the excess generation
of free radicals and the accumulation of the
lipid peroxides such as lipofusins in the
Rasayana drugs and Antioxidants
Before describing the term “Antioxidants” it
seems logical to discuss the term “Rasayana
drug” of Ayurveda.
As per ‘Maharshi Charaka’, Rasayana is a
group of medicines which basically vitalize
a cell b opening all the srotas (systems),
which are either blocked or partially open.
Because of this basic property, these
medicines are being used not only as a
curative medicine for disease but also as the
supportive medicine to almost every disease.
In other words, it can be safely said that
medicines of Rasayana group can be given
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in every disease wither alone or along with
the main drug of that disease. At one hand,
it cures a disease by itself and on the other
hand it improves the efficacy of the other
main drugs which are being given along
with Rasayana. Its use is recommended
from the adulthood with the objective to
delay the aging process and to prevent the
onset of other old age metabolic disorders.
Similar is the case with the use of
antioxidants. They are being recommended
in all types of diseases and even for general
health. Nowadays people are taking
antioxidants as the diet supplement to
prevent the process of aging and old age
What are Antioxidants?
Those agents which lower the burden of free
radicals are known as antioxidants. The
have different classifications based on their
site of action in the free radical chain
reaction. They could be divided into three
(b) Chain breakers,
(c) Chain terminators.
Based on the structural specifications, they
are divided into
(b) Non-Enzymatic (Natural or
One functional basis antioxidants could be
further grouped under two main categories.
(i) The one which prevents the
generation of free radicals and
(ii) The other, which intercepts the
free radicals, already generated.
The preventive defences include efficiency
of electron transfer and sequestration of
transition metal ions. Other form of
prevention is the removal of superoxides and
peroxides (H2O2 and lipid hydroperoxides)
that react with transition metal ions to
produce reactive free radicals, superoxides
dismutase, catalase and glutathione
peroxidase are examples of this group.
Antioxidants exist in membrane as well as in
Pharmacological antioxidants have their
specific action. For example allopurinal and
folic acid inhibit xanthine oxidase. Soybean
trypsin inhibitors phenyl methlsulfonyl
fluoride (PMSF) are protease inhibitors,
adenasarine, local anaesthetics, calcium
channel blockers etc inhibit superoxide
generation by inhibiting NADPH oxidase.
Some non- enzymatic free radical
scavengers are mannitol, DMSO, Dimethyl
thiourea (DMTU) which scavenge OH
radical. Other examples are spin traps,
bilirubin, urate, glutathione, 17-
aminosteroids and albumin. Ceruloplasmin,
transferring and desferoxamine are other
antioxidant which inhibit the iron redox
Some antioxidants act trough augmenting
the endogenous antioxidant activity such as
ebselen and acetylcysteine which act by
enhancing glutathione peroxidase activity.
Third category of natural antioxidant
defence is the repair process, which removes
damaged biomolecules before they can
accumulate and alter cell metabolism.
A great deal of efforts are being made on
finding our the effective antioxidant drugs
for the management of free radical diseases,
such as ‘Probucol’ Phytochemicals have a
significant part to play in t management of
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Mechanism of action: Various classes of
phytochemicals have been sown to have
antioxidant property. The have different
mechanisms of action and act at different
sites in the chain reaction. The activity of
natural products- antioxidants is due to the
presence of substituted groups such as
carbonyl, phenolic, phytyl side chain,
electron withdrawing group electron
donating group etc. They may be phenolic
or on phenolic.
In phenolics, the number and position of
phenolic groups decide the antioxidant
potential of a compound. Here hydroxyl
group donates hydrogen to radicals which
are converted to a stable non-radical product
and the chain propagation is terminated.
Phenolic group at para position enhances the
Non – phenolic compounds participate in the
antioxidant mechanism through electron
transfer & resonance stabilization process.
The quinine acts as electron acceptor and
prevents free radical chain reaction.
Alkaloids, such as strychnine, Engenol,
Withaperuvin E, Nonberginine,
Benzylisoquinoline; Flavonoids as sylibin,
Anthraquinones as Rubiadin, Emodin. Etc.
are a few examples. Synthetic antioxidants
include parabenzoquinone, probucol etc.
Physiological enzyme based reduction of
these quinines are caused by xanthine
oxidase, cytochrome p-450 reductase,
resulting to the formation of semiquinone
Natural products, which prossess a factor
favouring quinine formation, or the presence
of an electron withdrawing group a para
position are reported to be good
antioxidants. Vitamin E, Vitamin A (Beta
carotene) and Vitamin C are important
components of this family which interfere at
t level of propagation. Glutathione, is
another important antioxidant in the system.
It undergoes oxidation and reduction under
enzymatic control and inactivates free
With this basic similarity in Rasayana drugs
of Ayurveda and antioxidants of modern
medicine, we have investigated the effect of
several Ayurvedic medicines. Some of them
are Rubia cordifolia, strychnos nuxvomica,
Moringa oleifera, semecarpus anacardium,
Mucuna pruriens, Bacopa monnieri,
Nardostachys jatamansi etc. We have
observed that these medicinal plants have
anti-oxidant property and can be used as a
medicine to manage the free radical
mediated diseases. Of course, their active
fraction could be more effective and with
lesser side effects. These observations
support the basic theory of Ayurveda.
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2. Abstracted in International seminar on ‘Free radicals mediated diseases and Ayurveda’, Help
at Banaras Hindu University, India 1996.
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cordifolia; Comparison with Vit E and phenozoquinone. Phytotherapy Rex 9,440.
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Linn, Ind J exp Biol 31,533.
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potato lipoxygenases, Ind J.Exp. Biol 33,109.
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antioxidant from Rubia cordifolia India J of biochemistry & Biophysics 34, 600 – 604.
17. Tripathi YB, & Chaurasia S. Effect of strylcunon Nux vomica Alcohol Extract on Lipid
peroxidation in Rat Liver Int of pharmacogonosy (1997) Vol 3 (in press) USA.
18. Antixidant property of Rubia cordifolia: comparison with Vit E and p- benzoquinono.
Phytotherapy Res. 9:440-443.
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anacardium on the cell cycle of U -145 cells phytomedicine 1998 (in press).
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20. Tripathi YB. Chaurasia S, Tripathi E, Upadhyay A, & Dubey G.P Bacopa monniera Linn. As
an antioxidant: Mechanism of action Indian journal of Experimental Biology Vol 34, June 1996,
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jatamanasi Indian journal of experimental biology Vol 34, November 1996, pp. 1150-1151.
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