ADAPTOGENIC AGENTS: A REVIEW

Abstract

Adaptogens are the plant-derived biologically active substances that appear to induce a state of non-specific increase of resistance of the organism to diverse assaults that threaten internal homeostasis and improve physical endurance.¹Supplementation with various macro and micronutrients and herbal preparations has been evaluated for their adaptogenic activity during exposure to a stressful environment.² Stress research in laboratory animals has assumed an important role in understanding the biological and behavioral consequences of external or internal stressors, which threaten to perturb homeostatis and may induce a number of clinical diseases when the body fails to counteract the stress situations. A variety of stress situations have been employed to investigate the consequences of stress and to evaluate antistress agents. The pharmacological assessment of adaptogens typically includes evaluation of their stimulating, tonic and stress protective effects in different screening models in which animals are challenged to acute and chronic stress conditions. Stress mediators and biochemical markers involved in mechanism ofadaptogens may be evaluated using experimental procedures.³

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International Journal of Biomedical Research
IJBR2[5][2011]285‐304www.ijbr.ssjournals.com
ADAPTOGENIC AGENTS: A REVIEW
Nidhi Tewari, Lalita Verma, Talha Jawaid*
Hygia institute of pharmaceutical education & Research, Lucknow
*Head of department , Hygia institute of pharmaceutical education & Research, Lucknow
Corresponding author*: talhajawaid78@gmail.com
This article is available online at www.ssjournals.com
SUMMARY
Adaptogens are the plant-derived biologically active substances that appear to induce a state
of non-specific increase of resistance of the organism to diverse assaults that threaten
internal homeostasis and improve physical endurance.1Supplementation with various macro
and micronutrients and herbal preparations has been evaluated for their adaptogenic activity
during exposure to a stressful environment.2 Stress research in laboratory animals has
assumed an important role in understanding the biological and behavioral consequences of
external or internal stressors, which threaten to perturb homeostatis and may induce a
number of clinical diseases when the body fails to counteract the stress situations. A variety
of stress situations have been employed to investigate the consequences of stress and to
evaluate antistress agents. The pharmacological assessment of adaptogens typically includes
evaluation of their stimulating, tonic and stress protective effects in different screening
models in which animals are challenged to acute and chronic stress conditions. Stress
mediators and biochemical markers involved in mechanism ofadaptogens may be evaluated
using experimental procedures.3
KEY WORDS: Adaptogen, Stress, Herbs
1. INTRODUCTION
An adaptogen is a herb product that is a
plant derivative. Scientifically unproven,
yet marketed as a supplement to increase
resistance to stress, trauma, anxiety and
fatigue. The term is used mainly by
herbalist who also refer to adaptogens as
rejuvenating herbs, tonics, rasayanas, or
restoratives. One specific characteristic of
adaptogen action is that its effect is
believed to help the body return to a
balanced state. However, there is no strict
definition of the adaptogenic
characteristics of a plant product, leading
to a generalized usage of the term for
commercial or pseudoscientific
reasons.Some herbalists claim that
adaptogenic herbs are distinct from other
substances in their ability to balance
endocrine harmones and the immune
system, and that they help the body to
maintain optimal homeostasis.Adaptogens
are known to have side effects including
increased heart rate, nausea, headaches,
trouble sleeping, and restlessness.
Possible effects in women may include
swollen breasts and vaginal bleeding.

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Jawaidetal ReviewArticle
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TABLE 1: PLANTS USED IN ADAPTOGENIC ACTIVITY
S.No HERBAL PLANTS COMMON
NAME
PARTS USED Reference
no.
1.Withania somniferaAshwagandhaRoot4
2.Panax ginsengGinnsuuRoot15
3.Panax ginsengGinnsuuRoot29
4.Caesalpinia bonducNickernuts Seed5
5.Hippophae rhamnoidesSea-buckthornBerry6
6.Hippophae rhamnoidesSeabuckthornLeaf16
7.Garcinia kolaBitter kolaSeeds7
8.Trichopus zeylanicusArogya pachaLeaf8
9.Rhodiola imbricata RoserootRoot9
10.Rhodiola roseaRoserootRoot, Rhizome21
11.Bacopa monnieraBrahmiLeaf10
12.Evolvulus alsinoidesSankhapushpiLeaf11
13.Hoppea dichotomaHoppeaRoot12
14.Bergenia crassifoliaSiberian TeaLeaves13
15.Butea frondosaPalashLeaves14
16.Panax quinquefoliumRedberryRoot15
17.Zingiber officinaleZingiberRhizome17
18.Eleutherococcus senticosusTouch-me-notPlant18
19.Asparagus racemosusShatavariRoot19
20.Hypericum perforatumKlamath weedPlant20
21.Ptychopetalum olacoidesMuira puamaPlant22
22.Ocimum sanctumTulsiLeaves23
23.Schisandra chinensisBailPlant24
24.Eclipta albaTakasaburouPlant25
25.Azadirachta indicaNeemLeaves26
26.Sutherlandia frutescensBalloon peaPlant27
27.Acanthopanax senticosusTouch-me-notPlant28

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28.Curcuma longaTurmericRhizome30
29.Tinospora cordifoliaGuruchiPlant31
30.Psidium guajavaGuavaLeaf32
31.Momordica charantiaBitter MelonPlant33
32.Sida cordifoliaBalaRoot34
33.Morus albaMulberryRoot35
34.Centella asiaticaGotu KolaPlant36
35.Camellia sinensisGreen teaPlant37
36.Eugenia caryophyllusCloveBud38
37.Tribulus terristrisGokshuraPlant39
38.Raponticum carthamoidesMaral rootPlant40
39.Piper longumLong PapperPlant40
40.Terminalia chebulaMyrobalanPlant40
41.Clitoria ternateaButterfly peaPlant41
42.Ginkgo bilobaMaidenhair treeRhizome42
43.Heteropterys aphrodisiacaBrazilian plantPlant43
44.Astragalus membranaceusMilk-vetch Plant44
45.Curculigo orchioidesKali Musli Rhizome45
46.Tridax procumbensCoat buttons Flower46
47.Allium sativumGarlicRhizome47
1.1. Withania somnifera:
(WS) Dunal is classified in Ayurveda, the
ancient Hindu system of medicine, as a
rasayana, a group of plant-derived drugs
reputed to promote physical and mental
health, augment resistance of the body
against disease and diverse adverse
environmental factors, revitalise the body
in debilitated conditions and increase
longevity. These attributes are remarkably
similar to the properties ascribed to
adaptogens like Panax ginseng (PG) in
contemporary medicine. As such, the
adaptogenic activity of a standardised
extract of WS roots was investigated
against a rat model of chronic stress (CS).
The stress procedure was mild,
unpredictable footshock, administered
once daily for 21 days to adult male
Wistar rats.4
1.2. Caesalpinia bonduc:
Caesalpinia bonduc Roxb.
(Caesalpiniaceae) seed extracts were
screened for adaptogenic activity using
cold stress model and swim endurance
model,the seed coat as well as kernel
extracts showed significant antistress
activity when administered orally at a
dose of 300 mg/kg. The extracts

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significantly increased the swim
endurance time. Stress induced animals
exhibited hypoglycaemia as well as
depletion in serum cortisol level and
increased total leukocyte count, the
extracts showed a significant action in
overcoming these imbalances .It was also
found that extracts proved efficient in
controlling the hyperlipidaemic condition
due to stress.5
1.3. Hippophae rhamnoides:
The present study was carried out to
investigate mechanism of adaptogenic
activity of seabuckthorn dry leaves
aqueous lyophilized extract, administered
in rats at a dose of 100 mg/kg body
weight prior to cold (5 °C)–hypoxia
(428 mm Hg)–restraint (C–H–R) exposure
up to fall of Trec 23 °C and recovery (Trec
37 °C) from C–H–R induced
hypothermia. The effect of extract
treatment was studied on key metabolic
regulatory enzymes in blood, liver and
muscle and tissue glycogen in rats on
attaining Trec 23 °C and post stress
recovery of Trec 37 °C. In control rats
during C–H–R exposure on attaining Trec
23 °C there was significant decrease in
enzyme activities of blood hexokinase
(HK), citrate synthase (CS) and glucose-
6-phosphate dehydrogenase (G-6-PD),
liver CS, and in muscle glycogen, and CS
and G-6-PD activities. In control rats on
recovery of Trec 37 °C there was also a
significant decrease in liver and muscle
glycogen levels along with decreased
enzyme activities of blood G-6-PD, liver
CS, and liver and muscle G-6-PD. The
results suggest that seabuckthorn extract
treatment caused a trend for shifting
anaerobic metabolism to aerobic during
C–H–R exposure and post stress
recovery.6
1.4. Garcinia kola:
Garcinia kola Heckel (family,
Guttifereae) , known in commerce as
‘bitter cola’, is a highly valued ingredient
in African traditional medicine. The plant
is cultivated throughout West Africa for
its edible fruit and seeds. Seeds of G. kola
have been employed in folk medicine as
rejuvenating agents and general antidotes.
Bitter cola seeds have been shown to
contain a complex mixture of
biflavonoids, prenylated benzophenones
and xanthones. Many pharmacological
effects have been demonstrated for
Garcinia biflavonoids, among them
antiviral, anti-inflammatory, antidiabetic,
bronchodilator, and antihepatotoxic
properties. Other studies show that its
antimicrobial activity is due to
polyisoprenylated benzophenone. Some
proprietary dietary supplements
containing G. kola extractives already
exist in US and African
markets.Additionally, the proprietary
products are discussed and evaluated as
they relate to efficacy and human safety.7
1.5. Trichopus zeylanicu:
Anti-stress activity was carried out on
glyco-peptido-lipid (AF) fraction from the
alcoholic extract of Trichopus zeylanicus
Gaerten and demonstrated against a
battery of tests in rats and mice. AF
exhibited significant anti-stress activity in
dose-related manners in all the parameters
studied against different models used to
induce non-specific stress viz physical
and chemically. The major parameters
studied were immobilization induced
gastric ulceration, adjuvant-induced
trauma (Stress); humoral antibody
synthesis in normal and immuno-
suppressed mice and delayed type of
hypersensitivity (DTH) reaction,
chemically stress-induced alteration in

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hepatic function and anti-oxidant
activity.The extract of Withania somnifera
root (a commercial preparation available
locally, Dabur India ltd.) was used to
compare the results. In the safety
evaluation study the maximum tolerance
dose (MTD) and oral LD50 were found to
be more than 3000 mg/kg, with no signs
of abnormalities or any mortality
observed for 15 days period under
observation after single dose of drug
administration. Feeding behaviour and
fecal output were normal8.
1.6. Rhodiola imbricate:
To examine the dose dependent
adaptogenic activity aqueous extract of
Rhodiola imbricata root was orally
administered in rats at different doses,
30 min prior to cold (5 °C)–hypoxia
(428 mm Hg)–restraint (C–H–R)
exposure. The maximal effective
adaptogenic dose of the extract was
100 mg/kg body weight. The acute and
sub-acute toxicity of the extract was also
studied in rats. Sub-acute toxicity studies
included administration of single oral
dose of 1 g/kg and 2 g/kg of extract once
daily for 14 days and maximal effective
single oral dose of 100 mg/kg once daily
for 30 days. At the end of each treatment
period the biochemical parameters related
to liver function, kidney function, lipids
(triglycerides, cholesterol) and
hematological parameters were estimated
in serum and blood. Biochemical and
hematological analysis showed no
significant changes in any of the
parameters examined in treated group’s
animal, in comparison to control
animals9.
1.7. Bacopa monniera:
As stress is linked to many diseases,
research on an effective antistress agent
(adaptogen) from plants has gained
importance. We report the investigations
on the adaptogenic property of a
standardized extract of Bacopa monniera
against acute (AS) and chronic stress (CS)
models in rats. Panax root powder (Panax
quinquefolium) was taken as a standard.
Male SD rats, weighing 180–200 g,
exposed to immobilization stress for 150
min once only for AS and for seven
consecutive days in CS, were fed with B.
monniera or Panax root powder daily for
3 days in AS and for 7 days in CS, 45 min
prior to each exposure of stress. Rats were
sacrificed immediately after stress, the
blood was collected, and the plasma was
separated out for biochemical estimation.
Adrenals, spleen, and thymus were
dissected for organ weight and stomach
for ulcer score. AS exposure significantly
increased the ulcer index, adrenal gland
weight, plasma glucose, alanine
aminotransferase (ALT), aspartate
aminotransferase (AST), and creatine
kinase (CK) but significantly decreased
the spleen weight. Pretreatment with B.
monniera at 40 mg/kg po significantly
reduced the AS-induced increase in the
ulcer index, adrenal gland weight, plasma
glucose, AST, and CK. A dose of 80
mg/kg po significantly reversed the AS-
induced changes in adrenal gland weight,
spleen weight, plasma glucose, ALT, and
AST. On the basis of our result, it is
concluded that the standardized extract of
B. monniera possesses a potent
adaptogenic activity.10
1.8. Evolvulus alsinoides:
Evolvulus alsinoides (EA) is well known
for its memory enhancement, antiepileptic
and immunomodulatory properties in the
traditional Indian system of medicine,
Ayurveda. In view of the increasing
attention towards plants offering non-

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specific resistance (adaptogens) towards
stress, we have evaluated crude ethanolic
extract of EA for its adaptogenic and
memory enhancing properties in rodents.
Adaptogenic activity was assessed in rats
subjected to acute and chronic
unpredictable stress. In CUS, EA at a dose
of 200 mg/kg p.o. found effective in acute
studies was administered 45 min prior to
stress regimen for 7 days. EA reduced the
stress induced perturbations similar to
Panax quinquefolium (PQ) (100 mg/kg
p.o.), a well known adaptogen.The
improvement in the peripheral stress
markers and scopolamine induced
dementia by EA in the present study
indicates the adaptogenic and anti-
amnesic properties of EA.11
1.9. Hoppea dichotoma:
From the roots of Hoppea dichotoma,
collected before flowering, two new
naturally occurring glucosyloxyflavans,
dichotosin and dichotosinin, have been
isolated and characterized by means of
comprehensive spectral analyses,
chemical transformation and synthesis of
the aglucone of dichotosin. This is the
first report of dichotosinin from a natural
source. Additionally, one known
glucosyloxyflavan, diffutin, earlier
reported in another Gentianaceae species
(Canscora diffusa) also has now been
isolated from this species. The
glucosyloxyflavans, individually and in
combination, produced varying degrees of
adaptogenic (anti-stress-anti-anxiety)
activity in animal models. This
observation is consistent with the use of
the plant extract as a nerve tonic in
Ayurvedic medicine.12
1.10. Bergenia crassifolia:
The adaptogenic effect of Bergenia
crassifolia black and fermented leaves
was examined based on the forced
swimming capacity and the change of
biochemical parameters in mice. The
treatment groups were orally administered
infusions of black and fermented leaves of
3 populations of B. crassifolia, while the
control group received distilled water for
7 days. Infusions from black leaves of B.
crassifolia insignificantly enhanced the
maximum swimming capacity of mice by
increasing fat utilization, and by delaying
the accumulation of plasma lactate while
infusions from fermented leaves of B.
crassifolia significantly enhanced the
maximum swimming capacity of mice
without change of the body weight by
increasing glucose utilization and
decreasing lactate level compared to the
control group.13
1.11. Butea frondosa:
The plant Butea frondosa has been
indicated in the Indian system of medicine
as a plant augmenting memory and as a
rejuvenator. The effect of oral
administration of the aqueous and
alcoholic extracts of the leaves was
assessed on stress, cognitive function, and
anxiety in albino rats. The antistress
activity was evaluated using cold restraint
induced ulcers and leukocyte count after
subcutaneous injection of milk. The
aqueous extract provides protection
against stress-induced gastric lesions
while both the alcoholic as well as the
aqueous extract normalizes the white
blood cell count. Effect on cognitive
function was evaluated using Cook and
Weidley's pole apparatus. It is concluded
that the aqueous and alcoholic extract of
B. frondosa possesses antistress and weak
nootropic activity.14

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1.12. Panax quinquefolium:
Ginseng is the root of the perennial herbs
of Panax quinquefolium and Panax
ginseng which contain a series of
tetracyclic triterpenoid saponins
(ginsenosides) as active ingredients. It is
considered a tonic or adaptogenic that
enhances physical performance (including
sexual), promotes vitality and increases
resistance to stress and ageing. The
adaptogenic properties of ginseng are
believed to be due to its effects on
hypothalamic–pituitary–adrenal axis,
resulting in elevated plasma corticotropin
and corticosteroids levels. When used
appropriately, ginseng appears to be safe.
Nevertheless, documented side effects
include hypertension, diarrhoea,
restlessness, mastalgia and vaginal
bleeding.
1.13. Hippophae
rhamnoides:
The effects of seabuckthorn (Hippophae
rhamnoides L., Elaeagnaceae), leaf
aqueous extract were examined in rats for
its adaptogenic activity and toxicity. Dose
dependent adaptogenic study of extract
was carried out at different doses
administered orally, 30 min prior to cold
(5 °C)–hypoxia (428 mmHg)–restraint
(C–H–R) exposure. After sub-acute
toxicity studies on 10 and 20 times doses
of maximal effective dose administered
for 14 days (single oral dose of 1 g/kg and
2 g/kg once daily) and maximal effective
dose administered for 30 days (single oral
dose of 100 mg/kg once daily),
biochemical and hematological
parameters were studied in the serum and
blood. The maximal effective adaptogenic
dose of the extract was 100 mg/kg body
weight.drug treated animals in
comparison to control rats. In acute
toxicity study LD50 of the extract was
observed to be >10 g/kg when given
orally. These results indicate that
seabuckthorn leaf aqueous extract possess
potent adaptogenic activity with no
toxicity even after sub-acute (30 days)
maximal effective dose administration.16
1.14. Zingiber officinale:
Ethanolic extract of rhizomes of Zingiber
officinale was investigated on anoxia
stress tolerance test in Swiss mice. The
animals were also subjected to acute
physical stress (swimming endurance test)
to gauge the anti-stress potential of the
extract. Further to evaluate the anti-stress
activity of Z. officinale in chronic stress
condition, fresh Wistar rats were
subjected to cold restraint stress (4° for
2 h) for 10 days. Pretreatment with the
extract significantly ameliorated the
stress-induced variations in these
biochemical levels and blood cell counts
in both acute and chronic stress models.
The extract treated animals showed
increase in swimming endurance time and
increase in anoxia tolerance time in
physical and anoxia stress models,
respectively. Treatment groups also
reverted back increase in liver, adrenal
gland weights and atrophy of spleen
caused by cold chronic stress and
swimming endurance stress models. The
results indicate that ethanolic extract of Z.
officinale has significant adaptogenic
activity against a variety of biochemical
and physiological perturbations in
different stress models.17
1.15. Eleutherococcus
senticosus:
The adaptogen concept is examined from
an historical, biological, chemical,
pharmacological and medical perspective
using a wide variety of primary and
secondary literature.We attempted to

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identify critically what an adaptogen
supposedly does and to determine whether
the word embodies in and of itself any
concept(s) acceptable to western
conventional (allopathic) medicine.
Special attention was paid to the reported
pharmacological effects of the
‘adaptogen-containing plant’
Eleutherococcus senticosus (Rupr. &
Maxim.) Maxim. (Araliaceae), referred to
by some as ‘Siberian ginseng’, and to its
secondary chemical composition. We
conclude that so far as specific
pharmacological activities are concerned
there are a number of valid arguments for
equating the action of so-called
adaptogens with those of medicinal agents
that have activities as anti-oxidants,
and/or anti-cancerogenic,
immunomodulatory and
hypocholesteroletic as well as
hypoglycemic and choleretic action.
However, ‘adaptogens’ and ‘anti-
oxidants’ etc. also show significant
dissimilarities and these are discussed.18
1.16. Asparagus racemosus:
It is an Ayurvedic rasayana used as an
adaptogen. Adaptogenic drugs are those
which are useful as anti-stress agents by
promoting non-specific resistance of the
body. Although, the adaptogenic effect of
AR is well documented, its use in
psychological disorders like depression is
not scientifically evaluated. Hence, the
present investigation evaluates the
antidepressant effect of methanolic extract
of roots of AR (MAR) standardized to
saponins (62.2% w/w). Rats were given
MAR in the doses of 100, 200 and
400 mg/kg daily for 7 days and then
subjected to forced swim test (FST) and
learned helplessness test (LH). The results
show that MAR decreases immobility in
FST and increases avoidance response in
LH indicating antidepressant activity.19
1.17. Hypericum
perforatum:
It (Hypericaceae) is a perennial herb that
is commonly known as St. John's Wort.
The plant has been valued for its
important biological and chemical
perspectives and its use in the treatment of
infectious diseases has been documented
in ethnobotanical reports. Most recent
interest in H. perforatum has focused on
its antidepressant effects, and only
recently has its antimicrobial activity been
evaluated against a number of bacterial
and fungal strains. The present review
gives a comprehensive summary of the
ethnobotanical uses, chemical constituents
and biological effects (antibacterial and
antifungal) of this species. The
antibacterial activity of crude extracts can
be related to the use of the herb as a
wound healer in ancient times. Based on
the chemical and pharmacological
characteristics of H. perforatum, we
concluded that this species has beneficial
therapeutic properties and has the
potential for use as an effective
adaptogenic herbal remedy.20
1.18. Rhodiola rosea:
The aim of this review article was to
summarize accumulated information
related to chemical composition,
pharmacological activity, traditional and
official use of Rhodiola rosea L. in
medicine. In total approximately 140
compounds were isolated from roots and
rhizome - monoterpene alcohols and their
glycosides, cyanogenic glycosides, aryl
glycosides, phenylethanoids,
phenylpropanoids and their glycosides,
flavonoids, flavonlignans,
proanthocyanidins and gallic acid

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derivatives. Studies on isolated organs,
tissues, cells and enzymes have revealed
that Rhodiola preparations
exhibitadaptogenic effect including,
neuroprotective, cardioprotectiv e, anti-
fatigue, antidepressive, anxiolytic,
nootropic, life-span increasing effects and
CNS stimulating activity. A number of
clinical trials demonstrate that repeated
administration of R. rosea extract SHR-5
exerts an anti-fatigue effect that increases
mental performance (particularly the
ability to concentrate in healthy subjects),
and reduces burnout in patients with
fatigue syndrome. Encouraging results
exist for the use of Rhodiola in mild to
moderate depression, and generalized
anxiety. 21
1.19. Ptychopetalum
olacoides:
With the recognition that high levels of
sustained stress are associated with the
natural course of countless illnesses,
effective anti-stress agents have gained
importance. Improved endurance to
particularly stressful periods is one of the
medicinal claims for Marapuama
(Ptychopetalum olacoides Bentham, PO),
a popular Amazonian herbal.22
1.20. Ocimum sanctum:
A methanol extract and an aqueous
suspension of Ocimum sanctum leaves
were investigated for their
immunoregulatory profile to antigenic
challenge of Salmonella typhosa and
sheep erythrocytes by quantifying
agglutinating antibodies employing the
Widal agglutination and sheep erythrocyte
agglutination tests and E-rosette formation
in albino rats. The data of the study
indicate an immunostimulation of
humoral immunologie response as
represented by an increase in antibody
titre in both the Widal and sheep
erythrocyte agglutination tests as well as
by the cellular immunologic response
represented by E-rosette formation and
lymphocytosis. The results of the study
indicate a immunostimulant capability for
Ocimum sanctum which may be
contributory in explaining the adaptogenic
action of the plant.23
1.21. Schisandra chinensis:
Schisandra chinensis (Turcz.) Bail is
often referred to as an example of a
medicinal plant with use in modern
Chinese medicine. However, Schisandra
chinensis first gained recognition as an
adaptogen in the official medicine of the
USSR in the early 1960s.
Pharmacological studies on animals have
shown that Schizandra increases physical
working capacity and affords a stress-
protective effect against a broad spectrum
of harmful factors including heat shock,
skin burn, cooling, frostbite,
immobilisation, swimming under load in
an atmosphere with decreased air
pressure, aseptic inflammation,
irradiation, and heavy metal intoxication.
The phytoadaptogen exerts an effect on
the central nervous, sympathetic,
endocrine, immune, respiratory,
cardiovascular, gastrointestinal systems,
on the development of experimental
atherosclerosis, on blood sugar and acid–
base balance, and on uterus myotonic
activity.24
1.22. Eclipta alba:
The present study deals with the
investigation of standardized and
phytochemically evaluated aqueous and
hydroalcoholic extracts of the plant
Eclipta alba for sedative, muscle-relaxant,
anxiolytic, nootropic and anti-stress
activities.The hydrolyzed fraction of the

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aqueous extract was also subjected to
similar studies in rats. The findings
indicated nootropic activity of the
aqueous extract (300 mg/kg, p.o.) and its
hydrolyzed fraction (30 mg/kg, p.o.). The
effect of the extracts on stress-induced
alterations was evaluated. The aqueous
extract and the hydrolyzed fraction
provided protection against cold restraint
induced gastric ulcer formation and also
normalized the white blood cell count in
the milk induced leukocytosis challenge
model.25
1.23. Azadirachta indica:
Azadirachta indica, a plant used widely in
Ayurveda, has been reported to have anti-
inflammatory, immunomodulatory and
adaptogenic properties. The present study
evaluates its hepatoprotective role. Fresh
juice of tender leaves of Azadirachta
indica (200 mg/kg body wt. p.o.) inhibited
paracetamol (2 g/kg body wt. p.o.)-
induced lipid peroxidation and prevented
depletion of sulfhydryl groups in liver
cells. Azadirachta indica pretreatment
stabilized the serum levels of these
enzymes. Histopathological observations
of liver tissues corroborated these
findings.26
1.24. Sutherlandia frutescens:
Sutherlandia frutescens (tribe Galegeae,
Fabaceae), a popular plant in traditional
medicine, is indigenous to South Africa,
Lesotho, southern Namibia and
southeastern Botswana. It is chemically,
genetically and geographically extremely
variable and has been divided into three
subspecies and several regional forms. A
second species, Sutherlandia tomentosa,
is localized along the Cape coast.
Sutherlandia is sometimes treated as part
of the genus Lessertia. There are
numerous vernacular names and a wide
diversity of uses, including poor appetite,
indigestion, stomach complaints,
dysentery, colds, influenza, kidney
conditions, fever, diabetes, internal
cancers, uterine troubles, liver conditions,
backache, rheumatoid arthritis, urinary
tract infections, stress and anxiety, dropsy
and heart failure. Notable is the use as a
bitter tonic (“blood purifier”), anti-stress
medication (‘musa-pelo) and, at least
since 1895, specifically as a cancer tonic
(both as treatment and as prophylaxis).27
1.25. Acanthopanax
senticosus:
To determine whether heat environmental
stress (HES) affects the livers of rats, we
investigated microarray-based expression
profiling using an Affymatrix Gene Chip
Rat genome 230 2.0 Array. We were also
able to examine the effects of
Acanthopanax senticosus extract (ASE)
on the gene expression profile. Heat
environmental stress (HES) induced
changes in gene expression transcript
profiles, including those related to fatty
acid synthase activity, oxidoreductase
activity and lipid peroxidation (LPO). We
observed dramatically increased
malonaldehyde (MDA) levels after HES,
which indicates that HES caused LPO
through the regulation of oxidative stress
and LPO-related transcripts, as revealed
by microarray. When ASE was orally
administered to the HES group, the
number of candidate validation genes as
well as the MDA content decreased in
comparison to rats that did not receive
ASE. 28
1.26. Panax ginseng:
Korean ginseng tea (KGT), prepared from
the roots of Panax ginseng, is widely used
by Korean people for antistress,
antifatigue, and endurance promoting

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effects. In the present study we evaluated
neuroprotective/ cerebro-protective
actions of KGT in stroke, using rat global
and focal models of ischemia. Varied
biochemical/enzymatic alterations,
produced subsequent to the application of
middle cerebral artery (MCAO) and
bilateral carotid artery occlusion (BCAO)
followed by reperfusion viz. increase in
lipid peroxidation (LPO) and decrease in
glutathione (GSH), glutathione reductase
(GR), catalase (CAT), glutathione-S-
transferase (GST), glutathione peroxidase
(GPx) and superoxide dismutase (SOD),
were markedly reversed and restored to
near normal levels in the groups pre-
treated with KGT (350 mg/kg given orally
for 10 days). It is concluded that the
protective action, exhibited by KGT
against hypoperfusion/reperfusion
induced brain injury, suggests its
therapeutic potential in cerebrovascular
diseases (CVD) including stroke. These
findings are important because: (a) the
present treatment strategies for CVD are
far from adequate and (b) KGT with wide
usage is known to be a safe natural
product.29
1.27. Curcuma longa:
The present study was undertaken to
evaluate the cardioprotective potential of
Curcuma longa (Turmeric) in the
ischemia-reperfusion (I/R) model of
myocardial infarction (MI). Wistar rats
were divided into three groups and
received saline orally (sham, control I/R
group) and Curcuma longa 100 mg/kg
(CL-100 treated group) respectively for
one month. On the 31st day, rats of the
control I/R and Cl treated groups were
subjected to 45 min of occlusion of the
LAD coronary artery and were thereafter
reperfused for 1 h. I/R resulted in
significant cardiac necrosis, depression in
left ventricular function, decline in
antioxidant status and elevation in lipid
perodixation in the control I/R group as
compared to sham control. Myocardial
infarction produced after I/R was
significantly reduced in the Cl treated
group. Cl treatment resulted in restoration
of the myocardial antioxidant status and
altered hemodynamic parameters as
compared to control I/R. Furthermore,
I/R-induced lipid peroxidation was
significantly inhibited by Cl treatment.
The beneficial cardioprotective effects
also translated into the functional
recovery of the heart. Cardioprotective
effect of Cl likely results from the
suppression of oxidative stress and
correlates with the improved ventricular
function. Histopathological examination
further confirmed the protective effects of
Cl on the heart.30
1.28.Guduchyadi Ghrita:
This study has been carried out to
compare the Psycho-neuro-
pharmacological basis for the use of
Guduchyadi Ghrita and Bhringarajadi
Ghrita. Guduchyadi Ghrita Rasayana
consisting of Guduchi (Tinospora
cordifolia Linn), Apamarga (Achyrenthus
aspera Linn), Vidanga (Embelia ribes
Burm. F.), Shankhapushpi (Convolvulus
pluricaulis Chois), Vacha (Acorus
calamus Linn), Haritaki (Terminalia
chebula Retz), Kushtha (Saussurea lappa
C.B.Clarke ) and Shatavari (Asparagus
racemosus Willd), has proven mental
health promoting, memory enhancing,
anti-stress, anti- depressant properties that
may slow down the Aging process by
counteracting stress. Bhringarajadi
Rasayana consisting of Bhringaraja
(Eclipta alba Hassk.), Krishna Tila
(Sesamum orientale Linn.), Amalaki
(Embelica officinalis Gaertn.), Mishri

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(Sugar) with proven adaptogenic,
antioxidant, free radicals scavenger,
immuno-modulator properties play a
major role in the management of Aging
process. Both the formulations are
supposed to possess CNS activity, Anti-
stress, adaptogenic and other
pharmacological activities. Based on this
promise the test Ghrita had been studied
on various experimental models such as
Gross behaviour test, Anti depressant test,
Anti-anxiety test and Antistress
adaptogenic test on Swiss Albino Mice
and Charles Foster strain albino rats of
either sex.31
1.29.\Psidium guajava:
Ethanolic extract of leaves of Psidium
guajava was investigated on anoxia stress
tolerance test in Swiss mice. The animals
were also subjected to acute physical
stress (swimming endurance test) and
acute heat induced stress to gauge the
antistress potential of the extract. Further
to evaluate the antistress activity of
Psidium guajava in chronic stress
condition, fresh Wistar rats were
subjected to cold restraint stress (4° for 2
h) for 10 days. Stimulation of
hypothalamus pituitary adrenal axis in
stressful condition alters plasma glucose,
triglyceride, cholesterol, BUN and
corticosterone levels. There is also
alteration in the blood cell counts.The
results indicate that ethanolic extract of
Psidium guajava has significant
adaptogenic activity against a variety of
biochemical and physiological
perturbations in different stress models.32
1.30. Momordica charantia:
The present study was undertaken to
evaluate antistress and
immunomodulatory activity of aqueous
extract of Momordica charantia (MC).
Antistress activity was evaluated by
measuring the swimming time in mice and
cold immobilization induced stress for 10
days in rats, using Withania somnifera
(100mg/kg) as reference standard.
Immunomodulatory activity was
evaluated by carbon clearance assay and
percentage adhesion of neutrophils to
nylon fibers using Levamisole as
reference standard. The degree of
protection was determined by measuring
gastric ulceration, adrenal gland and
spleen weights and by measuring levels of
serum glucose, AST and ALT. Swiss
albino mice of either sex were divided
into 4 groups such as normal control, MC
lower dose (450 mg/kg, p.o), MC higher
dose (900 mg/kg, p.o) and standard group,
treated with standard drug Levamisole (50
mg/kg, p.o). MC increased the swimming
time in mice significantly (P<0.001) and
the results are comparable to that of
standard Withania somnifera.33
1.31. Sida cordifolia:
Ethanol extract of roots of Sida cordifolia
was evaluated for antistress, adaptogenic
activity using cold restraint stress and
swim endurance in mice. Mice pretreated
with extract of Sida cordifolia showed
significant improvement in the swim
duration and reduced the elevated WBC,
blood glucose and plasma cortisone.34
1.32. Morus alba:
The objective of the present study was to
evaluate the adaptogenic property of the
ethyl acetate-soluble fraction of methanol
extract of Morus alba roots against a rat
model of chronic stress (CS).Rats were
exposed to stress procedure for 21 days.
The stress procedure was mild,
unpredictable footshock, administered for
1 h once daily for 21 days. Rats were
administered with the ethyl acetate

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soluble fraction of methanol extract of
M. alba roots (25, 50 and 100 mg/kg p.o)
1 h before footshock for 21 days and
behavioral parameters were evaluated for
cognitive dysfunction and depression
using elevated plus maze and despair
swim test, respectively. On day 21, rats
were sacrificed immediately after stress
and blood was collected for biochemical
estimation. The adrenal gland and spleen
were dissected for organ weight and the
stomach was dissected for ulcer score.CS
significantly induced cognitive deficit,
mental depression and hyperglycemia and
increased blood corticosterone levels,
gastric ulcerations and adrenal gland
weight, but decreased the splenic
weight.The results indicate that M. alba
possesses significant adaptogenic activity,
indicating its possible clinical utility as an
antistress agent.35
1.33. Centella asiatica:
Centella asiatica (CA), a well known
adaptogenic agent in Indian system of
Medicine (Ayurveda), is believed to have
beneficial effects in improving memory,
treating anxiety and eczema. It also
possesses antioxidant, cognitive
enhancing and antiepileptic properties.
Acute ischemia followed by reperfusion is
known to bring about biochemical and
histopathological alterations. In the
present study the effect of Centella
asiatica on acute cerebral reperfusion and
long-term cerebral hypoperfusion in rats
was investigated. Transient cerebral
ischemia was induced under Ketamine
anaesthesia by blocking bilateral common
carotid arteries (BCCAO) for 30 min and
then reperfusion was allowed for 45 min
by releasing the block. Lipid peroxidation,
superoxide dismutase (SOD) and brain
protein were estimated, behavioral and
histopathological studies were done for
both acute ischemia-reperfusion and
chronic hypoperfusion studies. CA
treatment (100 mg/kg p.o. for 28 days)
alleviated these behavioral, cognitive and
histopathological changes. The results
suggest that CA may be useful in
cerebrovascular insufficiency
conditions.36
1.34. Camellia sinensis:
The aim of this study was to study the
ameliorative effects of Ocimum sanctum
and Camellia sinensis on stress-induced
anxiety and depression.The study was
carried out using male albino rats (200 ±
50 g). The effect of O. sanctum and C.
sinensis was evaluated for anxiety and
depression using elevated plus maze
(EPM) test, open field test (OFT), forced
swim test (FST), and tail suspension test
(TST).Restraint stress (3 h/day for six
consecutive days) induced a significant
reduction in both the percentage number
of entries and time spent in open arms in
EPM, and these changes were reversed
with post-treatment of aqueous extract of
O. sanctum and C. sinensis (100 mg/kg
for 6 days). Restraint stress-induced (a)
increased latency and (b) decreased
ambulation and rearing were also reversed
by O. sanctum and C. sinensis in OFT. A
significant increase in immobility period
was observed in FST and TST after
restraint stress. O. sanctum and C.
sinensis significantly reduced the
immobility times of rats in FST and TST.
O. sanctum and C. sinensis possess
anxiolytic and antidepressant activities.37
1.35. Eugenia caryophyllus:
The present study was undertaken to
evaluate the anti-stress effect of the
hydro-alcoholic extract of clove. The anti-
stress effect was evaluated on cold
restraint induced gastric ulcers, sound

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stress induced biochemical changes and
anoxic stress induced convulsions. Clove
extract was administered orally at two
different doses of 100 and 200 mg/kg.
Zeetress, a known anti-stress formulation
(14 mg/kg p.o) was used as the standard
drug. Both the doses of clove extract
showed good anti-stress effect in all the
tested models. The clove extract reduced
the development of cold restraint induced
gastric ulcers and prevented the
biochemical changes induced by sound
stress such as increase in plasma levels of
aspartate aminotransferase, alanine
aminotransferase, alkaline phosphatase,
glucose, cholesterol and corticosterone.
Clove extract was also effective in
increasing the latency of anoxic stress
induced convulsions in mice.38
1.36. Ayurvedic rasayanas:
Siotone (ST) is a herbal formulation
comprising of Withania somnifera,
Ocimum sanctum, Asparagus racemosus,
Tribulus terristris39 and shilajit, all of
which are classified in Ayurveda as
rasayanas which are reputed to promote
physical and mental health, improve
defence mechanisms of the body and
enhance longevity. These attributes are
similar to the modern concept of
adaptogenic agents, which are, known to
afford protection of the human
physiological system against diverse
stressors. The present study was
undertaken to investigate the adaptogenic
activity of ST against chronic
unpredictable, but mild, footshock stress
induced perturbations in behaviour
(depression), glucose metabolism,
suppressed male sexual behaviour,
immunosuppression and cognitive
dysfunction in CF strain albino rats.
Gastric ulceration, adrenal gland and
spleen weights, ascorbic acid and
corticosterone concentrations of adrenal
cortex, and plasma corticosterone levels,
were used as the stress indices. Panax
ginseng (PG) was used as the standard
adaptogenic agent for comparison.
Additionally, rat brain levels of tribulin,
an endogenous endocoid postulated to be
involved in stress, were also assessed in
terms of endogenous monoamine oxidase
(MAO) A and MAOB inhibitory
activity.39
1.37. Rasayana herbs:
Plants from all over the world such as
Eleutherococcus senticosus, Panax
ginseng, Raponticum carthamoides40,
Rhodiola rosea, Withania somnifera and
Ocimum sanctum have been extensively
evaluated for their adaptogenic potential.
However, none of them has been
successfully introduced as an adaptogen
in the clinic. This paper discusses some of
the problems in evaluation of adaptogens
which have precluded their inclusion as
clinically useful drugs. We further discuss
our results with six rasayana plants from
Ayurveda, which were studied for their
adaptogenic potential. The whole,
aqueous, standardized extracts of selected
plants (Tinospora cordifolia, Asparagus
racemosus, Emblica officinalis, Withania
somnifera, Piper longum40 and Terminalia
chebula40) were administered orally to
experimental animals, in a dose
extrapolated from the human dose,
following which they were exposed to a
variety of biological, physical and
chemical stressors. These plants were
found to offer protection against these
stressors, as judged by using markers of
stress responses and objective parameters
for stress manifestations. Using a model
of cisplatin induced alterations in
gastrointestinal motility, the ability of
these plants to exert a normalizing effect,

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irrespective of direction of pathological
change was tested. All the plants reversed
the effects of cisplatin on gastric
emptying, while Tinospora cordifolia and
Asparagus racemosus also normalized
cisplatin induced intestinal hypermotility.
Tinospora cordifolia was also tested for its
ability to modulate the changes occurring
in the phagocytic activity of peritoneal
macrophages after exposure of rats to
either carbon tetrachloride or horse serum.
It was found to normalize the phagocytic
function irrespective to the direction of
change, complying to the definition of an
adaptogen. All the plant drugs were found
to be safe in both acute and subacute
toxicity studies.40
1.38. Clitoria ternatea:
Clitoria ternatea L. (CT) (Family:
Fabaceae) commonly known as 'Butterfly
pea', a traditional Ayurvedic medicine,
has been used for centuries as a memory
enhancer, nootropic, antistress, anxiolytic,
antidepressant, anticonvulsant,
tranquilizing and sedative agent. A wide
range of secondary metabolites including
triterpenoids, flavonol glycosides,
anthocyanins and steroids has been
isolated from Clitoria ternatea Linn. Its
extracts possess a wide range of
pharmacological activities including
antimicrobial, antipyretic, anti-
inflammatory, analgesic, diuretic, local
anesthetic, antidiabetic, insecticidal, blood
platelet aggregation-inhibiting and for use
as a vascular smooth muscle relaxing
properties. This plant has a long use in
traditional Ayurvedic medicine for several
diseases and the scientific studies has
reconfirmed those with modern relevance.
This review is an effort to explore the
chemical constituents, pharmacological
and toxicity studies of CT, which have
long been in clinical use in Ayurvedic
system of medicine along with a critical
appraisal of its future
ethnopharmacological potential in view of
many recent findings of importance on
this well known plant species.41
1.39. Ginkgo biloba:
Lipophilic extracts of Ginkgo biloba L.
leaves were tested for their possible role
on rodent models of depression and stress.
Lipophilic extracts of Ginkgo leaves
(LEG) at (50 and 100 mg/kg, p.o.)
exhibited dose dependent, significant
antidepressant activity in the behavioral
despair test and learned helplessness
rodent model of depression. The activities
were comparable to that of imipramine
(15 mg/kg) and EGb 761 (50 mg/kg). In
the cold immobilization stress induced
gastric ulcer model of stress, only the
LEG showed a significant reduction in the
ulcer index. GC-MS characterization of
this bioactive extract was found to be rich
in a group of 6-alkyl salicylates (6-AS),
along with a fatty alcohol, fatty acids and
cardanols. The n-heptadecenyl salicylate
represented 60% of the 6-AS. Notable
was the absence of dihydroxy
alkylphenols which are linked to allergic
reactions similar to the urushiols present
in poison ivy.42
1.40. Heteropterys
aphrodisiaca:
Literature report is lacking on
pharmacological studies of the plant
Heteropterys aphrodisiaca, endemic to
the scrublands of Brazil. The present
study was carried out to investigate the
effects of oral dosing with extract
BST0298 from this plant, on learning and
on memory, in young (3–6-month-old)
and aged (20–28-month-old) rats. The
aged animals presented significant
memory deficits in both the passive

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avoidance and T-maze left/right
discrimination tests. Treatment for 7 days
(50 mg/kg) or 26 days (100 mg/kg) with
extract BST0298 restored the memory
deficits in the passive avoidance test.
However, no improvement in memory
was observed after acute administration of
extract BST0298 (100 mg/kg) in aged
rats. An improvement in learning was also
observed in the left/right discrimination
test in aged rats treated for 109 days with
BST0298 at a dose of 50 mg/kg. These
results suggest that treatment for 7 days or
more with H. aphrodisiaca improves
learning and memory deficits in aged
rats.43
1.41. Astragalus
membranaceus:
In this study, the haemolytic activities of
Astragalus membranaceus saponins
(AMS) and its adjuvant potentials on the
cellular and humoral immune responses of
ICR mice against OVA were evaluated.
We determined the haemolytic activity of
AMS using 0.5% rabbit red blood cell.
AMS showed a slight haemolytic effect,
with its haemolytic percents being 0.66%
at the concentration of 500 µg/ml.
Furthermore, the adjuvant potentials of
AMS at three dose levels on the cellular
and humoral immune responses of ICR
mice against ovalbumin (OVA) were
investigated. 44
1.42. Curculigo orchioides:
The methanol extract of rhizomes of
Curculigo orchioides Gaertn.
(Amaryllidaceae) holds potential as a
protective agent against cytotoxic drugs.
The extract when studied on humoral and
cell mediated immunity in normal, as well
as cyclophosphamide-induced
immunosuppressed mice produced an
increase in humoral antibody (HA) titre,
delayed type hypersensitivity (DTH) and
levels of WBC in a dose dependent
manner.45
1.43. Tridax procumbens:
The immunomodulatory properties of
ethanol insoluble fraction of aqueous
extract of Tridax procumbens Linn.
(TPEIF) have been investigated. After
intraperitoneal administration of TPEIF in
doses of 0.25 and 0.5 g/kg body weight
(BW) a significant increase in phagocytic
index, leukocyte count and spleenic
antibody secreting cells was noticed.
Stimulation of humoral immune response
was further observed with elevation in
heamagglutination antibody titer.
Heightened delayed type hypersensitivity
reaction suggested convincing evidence
for activation of cellular immune system.
Protective action of herbal medicine in
case of anaphylactic shock was also
studied. In addition, elicitation of specific
antibody titer against tetanus toxoid (TT)
challenge was measured in order to
explore the possible use as adjuvant along
with clinical vaccination program to
reduce number of non-responders. The
results suggest that TPEIF influences both
humoral as well as cell mediated immune
system vis-a-vis assists in genesis of
improved antibody response against
specific clinical antigen.46
1.44. Alium sativum:
It is known as a potent spice and a
medicine with broad therapeutic
properties ranging from antibacterial to
anticancer, and anticoagulant. One major
protein has been isolated and purified, it is
the 14-kDa glycoprotein. This protein has
shown to have immunomodulatory
effects. In this study, two sources of garlic

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(freshly prepared and commercial tablet)
were used. Both sources of garlic were
augmented delayed type hypersensitivity
(DTH) response, the optimum
enhancement were detected at 20 mg/kg.47
2. CONCLUSION
The collections of herbal plant showing
the adaptogenic activity were tabulated
from the various journals and were
reported above. As we can conclude that
herbal plants are very rich source of
substances which are responsible for
increasing the adaptogenic activity.
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