Standardized

Extract of
ASHWAGANDHA
Withania
somnifera
Dunal
for
Stress
Natural solutions for healthy living Natural solutions for healthy living
WITHANIA SOMNIFERA
E-mail : extracts@naturalremedy.com
Mental Stress Advances Aging Process at Cell level
The word adaptogen, coined by Russian Scientist Dr. Nicolai Lazarev in 1947, refers to a natural herb product
that increases the body's resistance to stresses such as trauma, anxiety and bodily fatigue.
The guidelines Lazarev created for an herb to be considered an adaptogen are:
1. It must cause only minimal disorders in the body's physiological functions.
2. It must increase the body's resistance to adverse influences not by a specific action but by a wide range
of physical, chemical and biochemical factors.
3. It must have an overall normalizing effect, improving all kinds of conditions and aggravating none.
Every stress leaves an indelible scar and the organism pays for its survival after a stressful situation by becoming a little older".
Ref: Dr. Hans Selye (1907-1982) internationally acknowledged as "the father of the stress research", authored 1700 scholarly papers and 39 books on stress.
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The study, led by researchers at the University of California, San Francisco determined
that prolonged psychological stress may influence molecules involved in cellular aging
and the onset of disease processes.
The study involved 58 women, aged between 20-50, all of whom were biological
mothers either of a chronically ill child (39 women, so-called "caregivers) or a healthy
child (19 women or "controls")
In the study, the research team determined that chronic stress and the perception of life
stress each had a significant impact on three biological factors; the length of telomeres
(telomeres play a critical role in determining the number of times a cell divides, its
health, and its life span), the activity of telomerase, and levels of oxidative stress in
immune system cells known as "peripheral blood mononucleocytes" in healthy pre-
menopausal women.
As expected, most women who cared for a chronically ill child reported that they were
more stressed than women in the control group.
Ref: Published in the November 30th issue of Proceedings of the National Academy of Sciences, 2006.
Adaptogen

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O S B S E EF H F T E T C N S O
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O S B S E EF H F T E T C N S O
Migraines
Hypertension
Sleep Deprivation
Chronic Fatigue
Eating Disorders
Hives
Atherosclerosis
Acid Reflux Disease
Acne
Depression Diarrhea or Constipation
WITHANIA SOMNIFERA
E-mail : extracts@naturalremedy.com
The Stress Response
When the body experiences stress, a series of biological changes occur. There is
activation of the sympathetic nervous system, which in turn activates the
adrenal medulla, which secretes adrenaline and noradrenaline, leading to
increased physiological arousal. There is also activation of the HPA
(hypothalamic-pituitary-adrenal) axis. Activation of the hypothalamus leads to
the release of hormones that travel through the bloodstream to the pituitary glad,
which in turn secretes other hormones and activates the adrenal gland, which
release the stress hormone, cortisol.
Adaptogen - Rasayana*
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Adaptogen
Anti-aging Rejuvenator Immune Booster
|| Swasthasya urjaskanyastu tad vrishyam tad rasayanam* ||
Rasayana* is the word for rejuvenator or adaptogen in Ayurveda.
Rasayana* are rejuvenators, believed to promote health, immunity, and longevity. According to Ayurveda, they strengthen all tissues of the
body, prevent aging, promote intellect and prevent disease.
Ref: Charaka Samhita - Chikitsa Sthana - 1st Chapter
The main effects of adaptogens are
Increased availability of energy during the day Improvement in mental alertness and promotion of
Increased endurance deep and restful sleep
Immune stimulation Rejuvenation of general health of the body
Reduction of stress feelings
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Psychological Stress and the Human Immune System
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Psychologists have long known that stress affects our ability to fight infection
New meta-analysis a study of studies has elucidated intriguing patterns of how stress affects human
immunity.
Major findings are three-fold.
First, the overlapping findings of 293 independent studies reported in peer-reviewed scientific
journals between 1960 and 2001- with some 18,941 individuals taking part in all, powerfully
confirm the core fact that stress alters immunity.
Second, the authors of the meta-analysis observed a distinctive pattern: Short-term stress actually
revs up the immune system, an adaptive response preparing for injury or infection, but long-term or
chronic stress causes too much wear and tear and the system breaks down.
Third, the immune systems of people who are older or already sick are more prone to stress-related
changes.
Ref: Suzanne CS and Gregory EM Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry, Psychological Bulletin,
(Published by the American Psychological Association), 2004: 130 (4): pp 601-630
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WITHANIA SOMNIFERA
Ashwagandha as adaptogen, immunomodulator & rejuvenator
What ayurveda says about Ashwagandha?
From Rasayana treatment, one attains longevity,
memory, intelligence, freedom from disorders, youthful
age, excellence of luster, complexion and voice
optimum strength of physique and sense organs,
successful words, respectability and brilliance.
Rasayana means the way for attaining
excellent rasa etc.
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Ashwagandha is one of the most highly valuable herb in the ayurvedic medical system.
The use of ashwagandha in ayurvedic medicine dates back over 3000 to 4000 years to
the teachings of the famed ayurvedic rishi (sage) Punarvasu Atreya.
Subsequently, ashwagandha was included in the writings of Charaka, Sushruta and many
other ayurvedic scholars throughout the centuries, where it is widely extolled as a
Rasayana* .
Ref : Charaka Samhita- Chikitsa Sthana-1st Chapter.
While being an energy tonic like ginseng, Ashwagandha is known as Indian Ginseng in
ayurveda.
Ashwagandha is also considered a premiere anti-aging herb due to its rejuvenation and
longevity enhancers.
E-mail : extracts@naturalremedy.com
Withania somnifera
Dunal
FAMILY : Solanaceae
ENGLISH NAME : Ashwagandha,
Winter cherry
PART USED : Roots
WITHANIA SOMNIFERA
(>((--(( (((((`-(-((((((`-()
Anti-aging.....
(((((: ((`( (-(((((( (=( ((:
i(-(((((((( ;(-((-( -(( !!o!!
(((((- i(((`-( (((`-( -(-(( -(( (((-(((!
-((-((-(((( (`; (((-(( (((-(( (((-(( !!t!!
Rasayana*
(>((--((-(( (((-(((-((i()
Balances the mind.....
(>((--(((-( ((((`((-(-(((()
Aphrodisiac.....Muscle promoter.....
(>((--(( (-(( ((((`-( (-((i()
Bestows strength.....Rejuvenator.....
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Effect of ashwagandha on haematological and
biochemical parameters in healthy volunteers
CLINICAL EVIDENCE
Subjects 101 male healthy adults (age group
between 50-59 years)
Dose 3 gm of ashwagandha powder /day
in 3 divided doses along with milk.
Duration One year
Results A significant improvement in
hemoglobin, RBC, hair melanin
and seated stature were observed as
compared to placebo. Serum
cholesterol decreased and nail
calcium was preserved. Erythrocyte
sedimentation rate decreased
significantly and 71.4 percent
reported improvement in sexual
performance
Ref: Kuppurajan K et al , J Res. Ayur. & Siddha, 1980:1: pp 247-258.
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Ashwagandha
Placebo
Effect of ashwagandha on RBC in healthy volunteers
Rejuvenating / growth promoter / haematinic
properties of ashwagandha in normal children
Subjects 60 healthy children (age group
between 8-12 years)
Dose 2 g/day powdered Ashwagandha
with 100 cc of milk
Duration 60 days.
Results A significant increase in mean
corpuscular haemoglobin and total
proteins and there was a slight
increase in haemoglobin, packed
cell volume, mean corpuscular
volume, serum iron, body weight
and hand grip at the end of 60 days
in ashwagandha treated children as
compared to their initial level and
to the placebo group.
Ref: Venkataraghavan S et al, J Res in Ayur & Siddha., 1980:1: pp 370-385.
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Effect of ashwagandha on haemoglobin in normal children
Before ashwagandha After ashwagandha
WITHANIA SOMNIFERA
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Effect of ashwagandha on swimming time, Plasma
corticosterone level, phagocytic index and avidity index
Animals Wistar strain albino rats (150-180g)
Test material Aqueous suspension of
Ashwagandha root.
Dose & 100 mg/kg orally for 7 days.
duration
Results There was a significant increase in
the plasma corticosterone level,
phagocytic index and avidity index
in rats subjected to cold swimming
stress. In the rats pretreated with
ashwagandha, these parameters
were near control value.
Further ashwagandha treatment
showed significant improvement in
swimming time in stress group of
animals.
Ref: Archana R and Namasivayam A, J of Ethnopharmacol. 1999: 64: pp 91-93.
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Plasma corticosterone (g/dl) Phagocytic index
Control Stress Stress + ashwagandha
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Effect of ashwagandha on swimming time
A comparative pharmacological investigation of Ashwagandha and Ginseng
PRE-CLINICAL EVIDENCE
Animals Albino mice (18-20g) for anti stress
activity. Albino rats (40-50g) for
anabolic activity.
Test material Aqueous suspension of
ashwagandha roots.
Dose & 100mg/kg for 7 days, orally.
Duration
Results Ashwagandha exhibited significant
anti-stress (swimming endurance
test) and anabolic activities, the
activities were comparable with
ginseng.
Effect of ashwagandha on swimming time
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Ref: Anuradha G. et al, J of Ethnopharmacol. 1994:44: pp 131-135.
WITHANIA SOMNIFERA
E-mail : extracts@naturalremedy.com
Antioxidant activity of Withania somnifera glycowithanolides (WSG) in
chronic foot-shock stress induced alterations in rat brain
Animals Male albino Wistar rats (180-
220g).
Test material Hydroalcoholic extract of
Withania somnifera roots
containing glycowithanolides
[WSG].
Dose & 50 mg/kg orally once daily for 21
duration days.
Results Treatment with WSG normalized
chr oni c f oot - shock st r ess
induced increase in superoxide
dismutase (SOD) and reversed
the decrease in catalase (CAT)
and glutathione peroxidase
(GPX) values in both the brain
areas ( f ront al cort ex and
striatum), indicating its anti-
stress adaptogenic property.
Anti-stress activity of ashwagandha
Animals Wistar strain albino rats (120-
180g).
Test material The total methanol-water extract
(1:1) extractives of the root of
Withania somnifera (SG-1) and
equi-molar combination of
Sitoindosides VII, VIII and
Withaferin-A (SG-2)
Dose & 100 mg/kg/day, orally for 4 days.
Duration
Results SG-1 and SG-2 were uniformly
effective in attenuating restraint
stress (RS) induced responses
ranging from anxiety, depression,
analgesia, thermic changes,
gastric ulcers, convulsions,
tribulin activity and adreno-
cortical activation.
Effect of Ashwagandha on restraint stress (RS) induced
changes in adrenal weight
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Saline RS SG-1+RS SG-2+RS
Treatment
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Ref: Bhattacharya SK et al, Phytother Res, 1987:1(1): pp 32-37.
Ref: Bhattacharya A et al., J. of Ethnopharmacol. 2001: 74: pp 1-6.
Effect of WSG on chronic foot-shock stress (CS) induced
alterations in rat brain SOD
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WITHANIA SOMNIFERA
Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides
Animals Charles Foster strain male rats
(160-180 g)
Test material Glycowithanolides from Withania
somnifera roots (WSG)
Dose & 50mg/kg, orally, once daily for 5
duration days.
Results Rat brain tribulin activity: Tribulin
activity was assessed in terms of
endogenous monoamine oxidase
(MAO) A and MAO B inhibiting
activity. WSG lowered rat brain
increased tribulin activity induced
by pentylenetetrazole (PTZ -A well
established anxiogenic agent).
This investigation supports the use
of ashwagandha as mood
stabilizer in clinical conditions of
anxi et y and depressi on i n
ayurveda.
Ref: Bhattacharya SK et al., Phytomedicine, 2000: 7(6): pp 463-469.
Effect WSG on rat brain tribulin activity
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MAO A MAO B T
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Vehicle PTZ (20 mg/kg, i.p) WSG (50 mg/kg)+ PTZ
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Immunomodulatory effects of Ashwagandha on
cyclophosphamide induced myelosuppression
Animals Albino mice (30-40g)
Test material Ashwagandha root extract (U.S.
Patent Application No. 08/273,
189, 11,7,1994)
Dose & 100mg/kg body weight orally for
duration 15 days.
Results Cyclophosphamide (3mg/kg)
induced immunosuppressant
effects (decreased haemoglobin,
RBC, WBC and blood platelets
l evel ) wer e r est or ed wi t h
ashwagandha treatment in mice,
indicating its immunomodulatory
effect.
Ref: Ziauddin M et al, J. Ethnopharmacol. 1996: 50: pp 69-76.
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Haemoglobin (g%) RBC (million/cmm) WBC (thousand/cmm)
Control
Chyclophosphamide (3mg/kg)
Ashwagandha + Cyclophosphamide
Effect of Ashwagandha extract on blood cells of
mice treated with cyclophosphamide
PROBABLE MECHANISMS OF ACTION
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Exhibits corticosteroid sparing effect
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Acts as immunostimulant
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Attenuates stress-induced elevation of b-endorphin levels
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Enhances the sensitivity of 5HT2 receptor responsiveness
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Exhibits GABA mimetic activity andantioxidant activity
1. Archana R and Namasivayam A, J of Ethnopharmacol.
1999: 64: pp 91-93.
2. Ziauddin M et al, J. Ethnopharmacol. 1996 : 50 : pp 69-76.
3. Bhattacharya SK et al, Phytother Res, 1987 : 1(1) : pp 32-37.
4. Arun KT et al, Ancient science of life, 1998 : 17 (3) : pp169-181.
5. Mehta AK et al., Indian J Med Res, 1991:94 [B] : pp 312-315.
6. Bhattacharya SK et al, Indian J Exp Biol. 1997: 35(3):
pp 236-239.
WITHANIA SOMNIFERA
E-mail : extracts@naturalremedy.com
PHYTOCHEMISTRY
Major constituents of ashwagandha are :
Free withanolides : Withaferin A, Withanolide A, Withanolide B, 12 - Deoxy Withastramonolide
Withanolide glycosides : Withanoside IV, Withanoside V.
Withaferin A
Withanolide A
Withanolide B
12-deoxy withastramonolide
Withanoside IV
Withanoside V
WITHANIA SOMNIFERA

O
O
OH
O
O
CH
3
CH
3
C H3
O H
CH
3
CH3
Molecular Formula = C
28
H
38
O
6
Formula Weight = 470.598

O
CH
3
O
CH
3
C H
3
CH
3
CH
3
O
OH O
Molecular formula: C H O
28 38 5
Molecular weight: 454.605

O
O
O
O
O
OH
OH
OH
O H
OH
OH
OH
OH
O
H
OH
MOLECULAR FORMULA:C H O
40 62 15
MOLECULAR WEIGHT:782.921

O
O
O
O
O
OH
OH
OH
O H
OH
OH
OH
OH
O
H
MOLECULAR FORMULA:C H O
40 62 14
MOLECULAR WEIGHT:766.921

O
H
O OH
O
O
CH
2
OH
MOLECULAR FORMULA:C H O
28 38 6
MOLECULAR WEIGHT:470.6

O
OH
O
H
CH
3
H
CH
3
O
H
H
OH
CH
3
H
3
C
H
O
Mol. Formula = C
28
H
38
O
6
Mol. Wt. = 470.598
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STANDARDIZATION
HPLC of Ashwagandha extract
TLC of Ashwagandha extract

S1 RE T1 S1 RE T1 S1 RE T1
TLC profile of Ashwagandha extract *
* Details available upon request
WITHANIA SOMNIFERA
HPLC profile of Ashwagandha extract *
254 nm Visible after derivitization 366 nm
Track S1 : Withaferin-A reference standard
Withanolide-A reference standard
Withanolide-B reference standard
Withanoside-IV reference standard
Withanoside-V reference standard
Track
Track
RE : Withania somnifera reference extract
T1 : Withania somnifera extract
Safety
Regulatory status
Why Withania somnifera extract from
?
The available human studies on ashwagandha do
not indicate any significant adverse effects. Both
acute and chronic administration of ashwagandha
has not been found to have any toxic effects in
animal studies. In addition, a strong traditional
support from the point of view of the Ayurveda is
available to substantiate the safety of ashwagandha.
Withania somnifera Dunal is official in Ayurvedic
Pharmacopoeia of India and Indian Pharmacopoeia.
It is listed in American Herbal Pharmacopoeia and
Therapeutic Compendium, Indian Herbal
Pharmacopoeia, Pharmacopoeial standards for
Ayurvedic formulations, Australian Register of
Therapeutic Goods (ARTG) and Herbs of commerce-
American Herbal Products Association (AHPA).
HPLC based quality control: Ensures consistent
chemical profile with known amounts of both free
withanolides and their glycosides in the extract.
Supported with phytochemical reference standards
(with spectroscopic and chromatographic
characterization).
Natural
Remedies
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Disclaimer :
These statements have not been evaluated by the Food and Drug Administration or any other regulatory body. This product is not intended to diagnose, treat, cure or prevent any disease.
"Natural Remedies calls to readers' attention that some of the products, protocols and uses of the product/s described herein are or may be subject to various restrictions or limitations because of patents, exclusive or nonexclusive licenses, confidentiality
agreements and other intellectual property or equivalent rights. Readers are advised to make an early and thorough investigation and inquiry into any product, protocol or use in which they may be interested, to see if any such rights might be applicable".
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Manufactured in a GMP and ISO 9001 - 2000
certified manufacturing facility.
The product is Kosher certified.
Withania somnifera Dunal extract standardized to
free withanolides and their glycosides (total
withanolides >2.5% w/w by HPLC). Standardized
extract of Withania somnifera can be custom
formulated.
Between 600 and 1200mg / adult / day of
standardized extract of Withania somnifera.
Availability
Recommended dose*
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WITHANIA SOMNIFERA
*Basis for arriving at the recommended dose
Dose mentioned in the reported clinical trial is
3 g /day of root powder
Typical yield of ashwagandha root extract is 20 %
i.e. 600 mg extract.
As per American Herbal Pharmacopoeia, dose
range is 3-6 g of ashwagandha root powder.
Hence the recommended dose range for
standardized extract of ashwagandha is between
600 and 1200mg / adult / day.
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