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Introduction
Bacopa monniera, also
referred to as Bacopa
monnieri, Herpestis
monniera, water hyssop,
and “Brahmi,” has been
used in the Ayurvedic
system of medicine for
centuries.
Traditionally, it was
used as a brain tonic to
enhance memory
development, learning,
and concentration,1 and
to provide relief to
patients with anxiety or
epileptic disorders.2
The plant has also been
used in India and
Pakistan as a cardiac
tonic, digestive aid,
and to improve
respiratory function in
cases of
bronchoconstriction.3
Recent research has
focused primarily on
Bacopa’s
cognitive-enhancing
effects, specifically
memory, learning, and
concentration,
and results support the
traditional Ayurvedic
claims. Research on
anxiety, epilepsy,
bronchitis and asthma,
irritable bowel
syndrome, and gastric
ulcers also supports the
Ayurvedic uses of Bacopa.
Bacopa’s antioxidant
properties may offer
protection from free
radical damage in
cardiovascular disease
and certain
types of cancer.
Description
Bacopa monniera, a
member of the
Scrophulariaceae family,
is a small, creeping
herb with numerous
branches, small oblong
leaves, and light purple
flowers. In India and
the tropics it grows
naturally in wet soil,
shallow water, and
marshes. The herb can be
found at elevations from
sea level to altitudes
of 4,400 feet, and is
easily cultivated if
adequate water is
available. Flowers and
fruit appear in summer
and the entire plant is
used medicinally.2,4
Active Constituents and
Pharmacokinetics
Compounds responsible
for the pharmacological
effects of Bacopa
include alkaloids,
saponins, and sterols.
Many active constituents
– the alkaloids Brahmine
and herpestine, saponins
d-mannitol and
hersaponin, acid A, and
monnierin – were
isolated in India over
40 years ago. Other
active constituents have
since been identified,
including betulic acid,
stigmastarol, beta-sitosterol,
as well as numerous
bacosides and
bacopasaponins. The
constituents responsible
for Bacopa’s cognitive
effects are bacosides A
and B.5-9
Mechanisms of Action
Since Bacopa’s primary
therapeutic use is to
enhance cognitive
function, most research
has focused on the
mechanism behind these
properties. The
triterpenoid saponins
and their bacosides are
responsible for Bacopa’s
ability to enhance nerve
impulse transmission.
The bacosides aid in
repair of damaged
neurons by enhancing
kinase activity,
neuronal synthesis, and
restoration of synaptic
activity, and ultimately
nerve impulse
transmission.10 Loss of
cholinergic neuronal
activity in the
hippocampus is the
primary feature of
Alzheimer’s disease.11
Based on animal study
results, bacosides
appear to have
antioxidant activity in
the hippocampus, frontal
cortex, and striatum.12
Animal research has
shown Bacopa extracts
modulate the expression
of certain enzymes
involved in generation
and scavenging of
reactive oxygen species
in the brain.13 In vitro
research has shown
Bacopa exerts a
protective effect
against DNA damage in
astrocytes14 and human
fibroblasts.15 In
animals Bacopa has a
relaxant effect on
pulmonary arteries,
aorta, trachea, and
ileal and bronchial
tissue, possibly
mediated by inhibition
of calcium-ion influx
into cell membranes.16
Bacopa appears to
stabilize mast cells in
vitro,17 and possesses
anti-inflammatory
activity via inhibition
of prostaglandin
synthesis and lysosomal
membrane stabilization.
18 In vitro research
suggests an anticancer
effect for Bacopa
extracts, possibly due
to inhibition of DNA
replication in cancer
cell lines.19
Clinical Indications -
Cognitive Effects
Adults
Bacopa monniera has been
studied clinically for
its acute and chronic
effects on cognitive
function. In adults, it
appears only chronic
administration is
associated with
cognitive-enhancing
effects. In a
double-blind,
placebo-controlled trial
of 38 healthy volunteers
(ages 18-60), subjects
were given a single dose
of 300 mg Bacopa
monniera extract
(standardized to
55-percent combined
bacosides A and B) or
placebo. Subjects
were tested two hours
after drug
administration,
coinciding with maximum
pharmacodynamic effect.
Acute administration of
this dose of Bacopa
extract resulted in no
significant changes in
cognitive function when
compared to baseline
values. Parameters
assessed included
attention, working and
short-term memory,
verbal learning,
decision making, memory
consolidation, executive
processes, planning and
problem solving, speed
of information
processing, and motor
responsiveness. 20 On
the other hand,
significant
cognitiveenhancing
benefits have been
demonstrated with more
chronic administration
of Bacopa extracts.
Australian researchers
conducted a
double-blind,
placebo-controlled,
12-week trial utilizing
the same patient
selection criteria and
same dose of Bacopa
extract (300 mg daily)
containing 55-percent
combined bacosides.
Forty-six healthy
volunteers (ages 18-60)
were randomly and evenly
divided into treatment
and placebo groups. The
same series of tests
administered in the
acute dosage trial were
administered at
baseline, five, and 12
weeks after treatment
began. At the end of the
12-week study, results
indicated a significant
improvement in verbal
learning, memory
consolidation, and speed
of early information
processing in the
treatment group compared
to placebo. These
effects were not
observed at baseline or
at five weeks. These
results may be
attributed to Bacopa’s
antioxidant properties
and/or its effect on the
cholinergic system.21
Children
Bacopa’s ability to
modulate or enhance
cognitive function has
also been studied in
children. Forty children
from rural India (ages
6-8) were divided into
treatment and placebo
groups of 20 children
each. Children in the
treatment group received
one teaspoon Bacopa
syrup (350 mg Bacopa
powder/teaspoonful)
three times daily for
three months. The
placebo group received
Syrup Simplex (details
not available). A series
of tests measuring
visuomotor and
perceptual abilities and
memory span were
administered at baseline
and at the end of
treatment. Significant
improvements were noted
in strengthened
exploratory drive (as
measured by maze
learning), improved
perceptual images of
patterns, and increased
perceptual organization
and reasoning ability
(as measured by reaction
time). This study,
however, was not
double-blinded.22 A
double-blind,
randomized,
placebocontrolled trial
of 36 children with
diagnosed attention
deficit/hyperactivity
disorder was conducted
over a 16-week period.
Nineteen children
received an extract of
Bacopa (standardized to
contain 20-percent
bacosides) at a dosage
of 50 mg twice daily for
12 weeks, and 17
subjects were given a
placebo. The mean age of
the children in the two
groups was 8.3 years and
9.3 years, respectively.
Active drug treatment
was followed by four
weeks of placebo and the
children were evaluated
on numerous cognitive
function tests at
baseline, four, eight,
12, and 16 weeks. A
significant benefit was
observed in Bacopa-treated
subjects at 12 weeks as
evidenced by improvement
on sentence repetition,
logical memory, and
paired associate
learning tasks.
Evaluation showed these
improvements were
maintained at 16 weeks
(after four weeks
placebo
administration).23
Anxiety and Depression
Bacopa’s traditional use
as an anti-anxiety
remedy in Ayurvedic
medicine is supported by
both animal and clinical
research. Research using
a rat model of clinical
anxiety demonstrated a
Bacopa extract of
25-percent bacoside A
exerted anxiolytic
activity comparable to
Lorazepam, a common
benzodiazapene
anxiolytic drug.
Importantly, the Bacopa
extract did not induce
amnesia, side effects
associated with
Lorazepam, but instead
had a memory-enhancing
effect.24 A one-month,
limited clinical trial
of 35 patients with
diagnosed anxiety
neurosis demonstrated
that administration of
Brahmi syrup (30 mL
daily in two divided
doses, equivalent to 12
g dry crude extract of
Bacopa) resulted in a
significant decrease in
anxiety symptoms, level
of anxiety, level of
disability, and mental
fatigue, and an increase
in immediate memory
span. Other changes
noted were increased
body weight, decreased
respiration rate, and
decreased systolic
blood pressure.25
Epilepsy
Although Bacopa has been
indicated as a remedy
for epilepsy in
Ayurvedic medicine,
research in animals
shows anticonvulsant
activity only at high
doses over extended
periods of time. Early
research in India
demonstrated that
hersaponin (an active
constituent) exhibited
protection against
seizures in mice.26 A
more recent Indian study
also examined the
anticonvulsant
properties of Bacopa
extracts in mice and
rats.
Researchers determined
that intraperitoneal
injections of high doses
of Bacopa extract (close
to 50 percent of LD50)
given for 15 days
demonstrated
anticonvulsant activity.
When administered
acutely at lower doses
(approaching 25 percent
of LD50), anticonvulsant
activity was not
observed.27
Bronchitis and Asthma
Animal studies have
demonstrated Bacopa
extracts have a relaxant
effect on
chemically-induced
bronchoconstriction,
probably via inhibition
of calcium influx into
cell membranes. An
earlier in vitro study
by Dar and Channa
demonstrated the
broncho-vasodilatory
activity of B. monniera
on rabbit and guinea pig
trachea, pulmonary
artery, and aorta.28 A
subsequent rat study
with Bacopa extracts
confirmed the earlier
results. Methanol
subfractions of Bacopa
extracts were given to
anesthetized rats prior
to induction of
bronchoconstriction with
carbachol, an
acetylcholine analogue.
Nearly all of the Bacopa
extract subfractions
inhibited carbachol-induced
bronchoconstriction,
hypotension, and
bradycardia in this
animal model.16 An in
vitro study also
demonstrated a methanol
extract of Bacopa
possessed potent mast
cell stabilizing
activity comparable to
disodium cromoglycate, a
commonly used allergy
medication.17 These
studies indicate
the potential usefulness
of Bacopa extracts in
bronchoconstrictive and
allergic conditions, and
warrant human studies.
Gastrointestinal
Disorders
In vitro, animal, and
human studies have
investigated the effects
of Bacopa extracts on
the gastrointestinal
tract. In vitro
studies28,29 have
demonstrated direct
spasmolytic activity on
intestinal smooth
muscle, via inhibition
of calcium influx across
cell membrane channels.
This property suggests
Bacopa extracts may be
of benefit in conditions
characterized by
intestinal spasm such as
irritable bowel syndrome
(IBS). A double-blind,
randomized,
placebocontrolled trial
of 169 patients with IBS
compared the effects of
an Ayurvedic preparation
containing Bacopa
monniera and Aegle
marmelos to standard
therapy (clidinium
bromide,
chlordiazepoxide, and
psyllium). Subjects were
divided into five
subgroups based on type
of IBS, and randomly
assigned to standard
drug treatment,
botanical treatment, or
placebo for six weeks.
Treatment was
administered orally as 5
g drug, botanical, or
placebo three times
daily. Data analysis
revealed standard
drug therapy to be
superior to the
Ayurvedic preparation,
except in patients with
IBS characterized by
diarrhea. This result
was attributed to the
Aegle marmelos, a
commonly known
antidiarrheal in India,
although the two
botanicals were not
given separately, so
individual effects
cannot be confirmed.
Ayurvedic therapy was
superior to placebo in
all parameters examined,
but no benefit could be
linked specifically to
the Bacopa portion of
the Ayurvedic
preparation.30 Animal
and in vitro studies
suggest Bacopa may have
a protective and
curative effect for
gastric ulcers. In rats
a Bacopa extract
standardized for
bacoside A was evaluated
for its prophylactic and
healing effects in five
models of gastric
ulcers. At a dose of 20
mg/kg for 10 days,
Bacopa extract
significantly healed
penetrating ulcers
induced by acetic acid,
significantly
strengthened the mucosal
barrier, and decreased
mucosal exfoliation. The
extract also alleviated
stress-induced ulcers as
observed by significant
reduction in lipid
peroxidation in rat
gastric mucosa. Bacopa’s
antioxidant properties
and its ability to
balance SOD and catalase
levels may account for
this effect.31 A recent
in vitro study also
demonstrated Bacopa
extract’s specific
anti-microbial activity
against Helicobacter
pylori, a bacteria
associated with chronic
gastric ulcers. When the
extract was incubated
with human colonic
muscosal cells and H.
pylori it resulted in
accumulation of
prostaglandin E and
prostacycline,
prostaglandins known to
be protective for
gastric mucosa.32
Cardiovascular Effects
Use of Bacopa as a
“cardiotonic” is
frequently mentioned in
Ayurvedic medicine
texts, but no clinical
studies have been
conducted. In vitro
research using rabbit
aorta and pulmonary
artery has demonstrated
Bacopa extract exerts a
vasodilatory effect on
calcium chloride-induced
contraction in both
tissues. It is believed
to exert this effect via
interference with
calcium channel flux in
tissue cells.29
Hypothyroidism
A study in mice
demonstrated high doses
(200 mg/kg) of Bacopa
extract increased the
thyroid hormone, T4, by
41 percent when given
orally. T3 was not
stimulated, suggesting
the extract may directly
stimulate synthesis
and/or release of T4 at
the glandular level,
while not affecting
conversion of T4 to T3.
While this study
indicates Bacopa extract
does have a stimulatory
effect on thyroid
function, the doses were
very high and the
typical 200-400 mg daily
dose in humans may not
have the same effect.33
Protection from Drug
Toxicity
In vitro and animal
studies have
demonstrated Bacopa
extracts may have a
protective effect
against certain drugs
and their negative side
effects. An in vitro
study using guinea pig
ileum isolates examined
the effect of Bacopa
extract on drug-induced
morphine withdrawal.
Addition of 1,000 μg/mL
Bacopa extract to the
tissue isolates prior to
injection of morphine
significantly reduced
the naloxone-induced
withdrawal effects,34
an effect that may be
attributed to the
anticholinergic and
calcium antagonistic
activity reported by
other researchers.29 A
second study examined
the effects of an
alcohol extract of
Bacopa on
morphine-induced
hepatotoxicity in rats,
as measured by lipid
peroxide accumulation
and antioxidant enzyme
levels. Administration
of Bacopa extract with
morphine significantly
decreased lipid
peroxidation and
increased levels of
antioxidant enzymes and
glutathione in rat
hepatic tissue, when
compared to morphine
alone. These results
suggest a protective
effect for Bacopa on the
hepatic antioxidant
status in
morphine-treated rats.35
Some of the same
researchers reported a
similar effect for brain
mitochondrial enzyme
activity of
morphinetreated rats.36
It has also been
reported that
antiepileptic drugs,
such as phenytoin, can
result in cognitive
impairment.37 In mice,
Bacopa administration
with phenytoin
significantly reversed
phenytoin-induced
cognitive impairment, as
noted by improved
acquisition and
retention of memory.
These results
suggest a potential
corrective effect of
Bacopa extracts in
phenytoin-induced
cognitive deficit.38
Cancer
In vitro research
demonstrated Bacopa
saponin fractions have
cytotoxic activity for
sarcoma-180 cells. It is
thought this might be
due to Bacopa’s
inhibition of DNA
replication in the
cancerous cell line.19
Research in humans may
be indicated.
Drug/Botanical
Interactions Bacopa has
been noted in animal
models to decrease the
toxicity of morphine35
and phenytoin. 38 It has
also been shown, albeit
inconsistently, to have
a slight sedative
effect, so caution is
advised in combination
with other known
sedatives. Also, since
it appears to stimulate
T4 activity in animals
at high doses, it is
theorized it may
potentiate the activity
of thyroid-stimulating
drugs or inhibit the
effect of
thyroid-suppressant
drugs.
Side Effects and
Toxicity
Therapeutic doses of
Bacopa are not
associated with any
known side effects, and
Bacopa has been used
safely in Ayurvedic
medicine for several
hundred years. A
double-blind,
placebocontrolled
clinical trial of
healthy male volunteers
investigated the safety
of pharmacological doses
of isolated bacosides
over a four-week period.
Concentrated bacosides
given in single (20-30
mg) and multiple
(100-200 mg) daily doses
were well tolerated and
without adverse
effects.10 The LD50 of
Bacopa extracts
administered orally to
rats was
5 g/kg for aqueous
extracts and 17 g/kg of
the alcohol extract.
Neither extract resulted
in gross behavioral
changes at these
concentrations.27
Dosage
Traditional daily doses
of Bacopa are 5-10 g of
non-standardized powder,
8-16 mL of infusion, and
30 mL daily of syrup (Brahmi).
Dosages of a 1:2 fluid
extract are 5-12 mL per
day for adults and 2.5-6
mL per day for children
ages 6- 12. For Bacopa
extracts standardized to
20-percent bacosides A
and B the dosage is
200-400 mg daily in
divided doses for
adults, and for
children, 100-200 mg
daily in divided doses.
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