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stress and inflammation in patients with Mets, the results demonstrated
that supplementation with curcuminoid-piperine combination positively
enhanced serum SOD activities and reduced malondialdehyde (MDA), CRP
plasma C-reactive protein concentration compared with placebo.
80
Atotal
of 37 clinical trials evaluated the significant influence of a single con-
sumption of a CBFI (capsaicinoids, epigallocatechin gallate, piperine and
L-carnitine) on satiety, resting energy expenditure (REE), respiratory quo-
tient, glucagon-like peptide-1 (GLP-1), free fatty acids (FFA) and glycerol in
overweight adults, as described by Rondanelli et al.
81
Abbreviations
P. nigrum Piper nigrum
P. longum Piper longum
Z. officinale Zingiber officinale
T. chebula Terminalia chebula
P. tuberculatum Piper tuberculatum
NaNBBS Sodium n-butyl benzene sulpho nate
NaCS Sodium cumene sulphonate
NaXS Sodium xylene sulphonate
NaPTS Sodium p- toluene sulph onate
SFE Supercritical fluid extraction
UAE Ultrasound-assisted extraction
ILUAE Ionic liquid-based ultrasonic-assisted extraction
HRE Heat-reflux extraction
MAE Microwave-assisted extraction
ILs Ionic liquids
AUC Area under the curve
K
el
Elimination rate constant
PLC Piperine, lycopen e and curcumin
SRP Scaling and root planing
SGRQ St. George Respiratory Questionnaire
CAT COPD Assessment Test
GSH Glutathione
HRQoL Health-related quality of life
CRP C-Reactive protein
REE Resting energy expenditure
FFA Free fatty acids
Conflict of Interest
The authors declare that they have no conflict of interest.
Acknowledgements
The authors are thankful to the Department of Pharmacognosy, ISF College
of Pharmacy, Moga, Punj ab, for providing the necessary facilities.
172 Chapter 7
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Most Modern Approach to the Phytochemical Evaluation 175
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CHAPTER 8
Bacopa monnieri (Brahmi):
Phytochemistry and Use in
Traditional Ayurvedic
Formulations
RENJU KUNJUMON,
a,b
ANIL JOHN JOHNSON
a
AND
SABULAL BABY*
a
a
Phytochemistry and Phytopharmacology Division, Jawaharlal Nehru
Tropical Botanic Garden and Research Institute, Pacha- Palode 695562,
Thiruvananthapuram, Kerala, India;
b
University of Kerala,
Thiruvananthapuram 695034, Kerala, India
*Emails: sabulal@jntbgri.res.in; sabulal@gmail.com
8.1 Ayurveda and Bacopa monnieri
India has one of the oldest folk traditions using medicinal herbs, and the
early records of their use are found in the Sanskrit literature.
1
The main
literary sources of the ancient era are the four Vedas (Sanskrit word meaning
‘knowledge’ or ‘wisdom’) viz.,‘Rig Veda’, ‘Yajur Veda’, ‘Sama Veda ’ and
‘Atharva Veda’. ‘Rig Veda’ and ‘Atharva Veda’, written between 1600 and 400
BCE, describe the uses of plant drugs. ‘Ayurveda’ (considered as ‘Upa Veda’or
applied knowledge; Sanskrit meaning ‘knowledge of life’) deals with the
understanding of the medicinal properties of plant products and their roles
in the treatment of various diseases.
2–4
The initial treatise on ‘Ayurveda’,
‘Charaka Samhita’ written by Charaka in B900 BCE, listing 341 plants and
their products, is an authentic reference to illnesses and medical strategies.
Chemistry, Biological Activities and Therapeutic Applications of Medicinal Plants in Ayurveda
Edited by Augustine Amalraj, Sasikumar Kuttappan and Karthik Varma A. C.
r The Royal Society of Chemistry 2023
Published by the Royal Society of Chemistry, www.rsc.org
176
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‘Susruta Samhita’ written in B600 BCE by Susruta, an ancient surgeon and
teacher of ‘Ayurveda’, is a more inclusive and authentic work which describes
1120 diseases, 700 medicinal plants and 121 preparations.
3,5–7
Ayurveda,
founded on the collective wisdom of ancient Hindu saints and healers,
thrives in the 21st century as a lively healthcare system in India, with a recent
estimate of over 6000 crores (1.3 billion USD) worth of drugs produced
annually.
8,9
Ayurveda emphasizes disease prevention and the promotion of good
health, by adopting a proper lifestyle and assuming measures that re-
juvenate the cells of the body. It is based on the concepts of five elements
(‘panchabhuta’) viz.,‘Vayu’ (air), ‘Jala’ (water), ‘Prithvi’ (earth), ‘Teja’ (fire) and
‘Akasha’ (space), which constitute the physical universe including the human
body, and the three ‘doshas’ (Sanskrit word meaning ‘fault’ or ‘defect’) viz.,
‘Vata’, ‘Pitta’ and ‘Kapha’(Tridoshas), which broadly refer to the functions of
motion, digestion and cumulation.
10,11
In other words, Tridoshas (‘Vata’,
‘Pitta’ and ‘ Kapha’) are the three psychobiological dimensions (energy) or
biological rhythms synchronizing the functio ning of the human body. The
disparity between the three ‘doshas’ leads to diseases. The dominance of
‘Vata’ dosh causes neurological disorders, manifested by memory loss, poor
blood circulation, anxiety and related symptoms. ‘Pitta’ imbalance gives rise
to gastric troubles and imbalanced ‘Kapha’ results in cholesterol-related
diseases. Ayurveda provides medicines of herbal origin to balance the
‘doshas’, aiming to cure diseases.
4,12
Bacopa monnieri (L.) Wettst. (Brahmi; family Plantaginaceae) is a nootropic
herb distributed throughou t the wetlands of the tropics and subtropics.
13,14
The name ‘Brahmi’ is derived from the word ‘Brahma’, the mythical ‘creator’
in the Hindu religion.
15
B. monnieri is one of the herbs used in various
formulations administered in Ayurveda against neurological issues.
4,16
Ancient Vedic scholars often used B. monnieri to memorize lengthy divine
scriptures and hymns.
13,17
In India, in Ayurvedic prescriptions, B. monnieri
has been consumed as ‘Medhya rasayana’ (in Sanskrit, ‘medhya’ – intellect or
cognition, ‘rasayana’ – rejuvenation).
18,19
In Charaka Samhita, B. monnieri is
mentioned as a cure for controlling mental dysfunctions such as poor cog-
nition, lack of concentration and anxiety.
13,15,20–22
Brahmi and its polyherbal
medications are also applied as treatments for various other diseases in
Ayurveda.
21,23
A search of the keywords ‘Bacopa monnieri’ and ‘Brahmi’ in Google
Scholar in November 2021 retrieved 14 900 and 40 500 results, whereas
‘Bacopa monnieri þAyurveda’ and ‘Brahmi þAyurveda’ resulted in 4740 and
5770 articles, respectively. The National Medicinal Plants Board (NMPB) of
India estimate d the annual market demand of B. monnieri in India as 1000
tons in the year 2000.
24–26
Again, in 2004–2005, the NMPB survey quantified
the annual demand of B. monnieri as 6621.8 tons, with an annual growth rate
of 7%.
27
Recent literature reports on the demand of B. monnieri in India
reflect inconsistencies,
16,22
but its demand remains ever-increasing and it is
logical to estimate the annual requirement as above 10 000 tons; and
Bacopa monnieri (Brahmi) 177
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Ayurvedic drugs contribute significantly to this growing demand.
25
NMPB
also listed B. monnieri as one of the ‘medicinal plant species in high trade’ in
2007.
28
Further, the conservation and cultivation of B. monnieri are en-
couraged by NMPB and Technology Information Forecasting and Assessment
Council (TIFAC), Department of Science and Technology (DST), Government
of India.
25
These data indicate the surging research activities on B. monnieri,
including significant contributions from the Ayurvedic drug industry. This
review deals with the phytochemistry of B. monnieri and its uses in Ayurveda.
The need for correlation of the phytochemistry and analytical techniques
(chemical fingerprinting, quantification) in defining the role of bioactive
molecules in Brahmi-based and other Ayurvedic formulations is also dis-
cussed. The neuroprotection of B. monnieri (extracts, bioactive molecules)
achieved through modulation of brain stress hormones, suppression of
neuronal oxidative stress, attenuation of oxidative damage, pro-cholinergic
effect, acetylcholinesterase inhibition, suppression of pro-inflammatory cy-
tokines, calcium channel blocking, b-amyloid reduction, neurotransmitter
modulation, and its other biological effects such as anti-inflammatory, car-
dioprotective, hepatoprotective, antitumor, antiarthritic and antidiabetic ac-
tivities, have been thoroughly reviewed by various authors,
13,15,21,29–35
and
their elaborate assessment is not under the scope of this chapter.
8.2 B. monnieri-based Ayurvedic Formulations
In Ayurveda, rejuvenation of the cells is addressed in the Rasayana shastra.
Rasayana (Sanskrit meaning ‘path of essence’) is defined as a therapeutic
measure which prevents aging, promotes longevity, provides positive health
and mental faculties, increases memory, and imparts immunity and resist-
ance against diseases. Rasayanas are specialized procedures practiced in the
form of rejuvenative ingredients, dietary regimens and definite health-
promoting activities and behavior.
5,8,36
They are basically molecular nutri-
ents and nutrition-enhancing agents acting through three fundamental
mechanisms viz. , Rasa (strengthening nutrient effect), Agni (promoters of
digestion and metabolism) and Srotas (purifying agents or stimulants
of microcirculation and tissue perfusion). These three events individually or
collectively lead to enhanced nutritional status in the body leading to refined
cells and tissues which sustain aging and stress.
36
Rasayanas promote re-
sistance against infections and other diseases by maintaining the balance of
the ‘Tridoshas’, viz.,‘Vata’, ‘Pitta’ and ‘Kapha’. Otherwise, Rasayana drugs
provide actions such as (i) increase in lifespan, (ii) delay the aging process,
(iii) anabolic properties to strengthen the body, (iv) improvement of cogni-
tive ability and (v) gaining immunity and cure from diseases.
37
Doshi and co-
workers provided a list of 34 Rasayana herbs.
38
Some of these Rasayanas are
organ- and tissue-specific; Medhya rasayanas are those specific to the brain
tissues (or neuronutrients). They are a group of drugs widely used in Ayur-
veda since antiquity with several benefits specifically in improving memory
and intellect. Brahmi (B. monnieri) is one of the Medhya rasayanas.
9,36,39
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Other important Medhya rasayana plants are Centella asiatica (Mandukaparni),
Convolvulus pluricaulis (Shankhpushpi), Acorus calamus (Vacha), Withania
somnifera (Ashwagandha), Celastrus paniculatus (Jyotishmati)andNardostachys
jatamansi (Jatamansi). Many Ayurvedic preparations advised for cognitive
dysfunctions contain B. monnieri as a prime constituent.
Brahmi ghrita, which contains B. monnieri, Acorus calamus, Convolvulus
pluricaulis, Saussurea lappa and 10 year-old cows’ clarified butter, is used to
treat memory disorders in Ayurveda. Yadav and co-workers demonstrated
the beneficial effects of Brahmi ghrita in learning and memory at 400 and
800 mg kg
1
body weight in rats. These effects were inferred as due to an
increase in cerebral glutamic acid and gamma-amino butyric acid (GABA),
achieved through the synergistic action of the herbal ingredients.
40
Achliya
and co-workers investigated the effect of Brahmi ghrita (30, 50 and 100 mg
kg
1
, p.o.) on learning and memory processes by various assays in rats and
mice. Brahmi ghrita administration (50 and 100 mg kg
1
, p.o.) showed a
significant decrease in transfer latency and escape latency. This study has
not elucidated the exact mechanism of action of Brahmi ghrita, but inferred
that it may act as a memory enhancer formulation and is useful as a sup-
portive adjuvant in the treatment of impaired memory functions.
41
Bhalerao
and co-workers
42
evaluated the efficacy of Brahmı ghrita against attention
deficit hyperactivity disorder (ADHD) in children. In the pilot study Brahmı
ghrita showed 66% decrease in the total ADHD score. In the therapeutic
confirmatory study, 16% improvement was seen with Brahmı ghrita, which
was comparable to the standard drug (methylphenidate). No side effects
were reported by the authors.
The antiamnesic activity of Brahmı ghrita (400 and 800 mg kg
1
, p.o.) was
evaluated against scopolamine-induced amnesia in rats using elevated
plus maze, passive avoidance and active avoidance tests, with piracetam
(500 mgkg
1
, p.o.) as the standard drug. Brahmı ghrita and piracetam dis-
played significant beneficial effects on scopolamine-induced amnesia.
43
The
antidepressant and psychoactive effects of Brahmi ghrita were studied by
randomized, placebo-controlled clinical trials in 42 patients, and it dem-
onstrated moderate improvement in 40% patients and mild improvement in
55% patients.
44
In another recent clinical study, 72 persons of average age
63.3 6.44 years received either Brahmi ghrita or integrated yoga or com-
bined interventio n for 8 weeks. Both Brahmi ghrita and integrated yoga
intervention were found to be effective in improving cognitive abilities, but
the combined intervention resulted in significantly better improvement in
attention, learning and working memory compared to individual inter-
ventions among elderly persons with mild cognitive impairment.
19
Brahmi rasayana, a rejuvenator, is an Ayurvedic medicinal mixture with
dried Brahmi leaves as its main constituent, along with Eugenia caryophyllus
(flower buds), Elettaria cardamomum (seeds), Cinnamomum zeylanicum (inner
bark of shoots), Piper nigrum (fruits) and P. longum (fruits). It is commonly
used as a nerve tonic and in the treatment of epilepsy. Joshi and Parle
42
demonstrated that Brahmi rasayana improves learning and memory in young
Bacopa monnieri (Brahmi) 179
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mice and it reverses amnesia induced by both scopolamine (0.4 mg kg
1
,
i.p.) and natural aging. Brahmi rasayana significantly decreased whole-brain
acetylcholinesterase activity, and it could be a useful memory-restorative
agent in the treatment of dementia in the elderly. The memory-improving
activity of Brahmi rasayana may be attributed to the phytochemicals in various
ingredients of the multiherbal preparation which exert antioxidant, anti-
inflammatory, neuroprotective, pro-cholinergic and antiacetylcholinesterase
properties, and it may be of use in delaying the onset and reducing the
severity of Alzheimer’s disease.
45
The anti-inflammatory effects of Brahmi
rasayana were studied by Jain and co-workers in rodents (1 and 10 gkg
1
,
p.o.); it suppressed various experimentally induced inflammatory reactions
and displayed activity comparable to indometacin. Brahmi rasayana may
partially mediate its anti-inflammatory activity by interfering with the action
and/or synthesis of prostaglandins and possibly by stabilization of the lyso-
somal membranes.
46
Shukia and co-workers studied the effects of Brahmi
rasayana on the central nervous system in mice and rats (1 and 30 gkg
1
,
p.o.); it displayed significant antinociceptive effect, coupled with the ability to
protect against electroshock seizures and chemoconvulsions. Brahmi rasayana
also showed the potential to antagonize haloperidol-induced catalepsy. These
findings suggested the role of the GABA-ergic system in mediation of the
central nervous system effects of Brahmi rasayana.
47
Brahmi vati is another Ayurvedic formulation comprised of Brahmi and
another 37 herbal and animal ingredients along with nine bhasmas. The
ingredients of Brahmi vati have been listed by Mishra et al.
48
It is one of
the most important formulations primarily used to cure mental disorders,
epilepsy and to improve memory. Mishra and co-workers demonstrated the
memory-enhancing, anticonvulsant and antischizophrenia activities of
Brahmi vati, when compared with bacoside A-rich fraction of B. monnieri and
control groups, and it caused notably higher brain glutathione levels. Acet-
ylcholinesterase activity was found to be significantly lower in the Brahmi
vati-treated group. This study suggested Brahmi vati as a suitable polyherbo-
mineral formulation for the treatment of schizophrenia and memory im-
pairments associated with seizures.
49
A randomized, double-blind clinical
study of Brahmi vati in 68 patients meeting the criteria of essential hyper-
tension (EHTN) (either sex, age group 20–60 years) illustrated it as effective
and safe. Brahmi vati (and similar Ayurvedic formulations) could act on
multiple domains leading to a comprehensive management strategy for
EHTN.
50
Saraswata ghrita is a poly-herbal drug consisting of mainly Brahmi and
Haridra (Curcuma longa), Haritaki (Terminalia chebula), Amlaki (Emblica of-
ficinalis), Vidanga (Embelia ribes), Pippali (Piper longum), Vacha (Acorus ca-
lamus) and Kushta (Saussurea lappa). It is well-known for its nootropic and
memory-enhancing properties. An ultra-fast liquid chromatography/mass
spectrometric (UFLC/MS) investigation of Brahmi, Brahmi vati, Brahmi ghrita
and Saraswata ghrita solutions added to differentiated IMR 32 cells
displayed enhanced levels of neurotransmitters (serotonin, dopamine, GABA).
180 Chapter 8
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Thus, these Ayurvedic medicines when prescribed to children with autism
spectrum disorder (ASD) might alleviate the abnormal behavioural symp-
toms by maintaining neurotransmitter homeostasis. Brahmi in polyherbal
forms increased neurotransmitter levels considerably more than its pure
form.
51
Saraswatarishta, with 18 plant ingredients including Medhya rasayanas
(Brahmi, Ashwagandha, Shatavari), is traditionally used as a brain tonic to
improve memory. It is also used to treat neurosis, psychosis, insomnia, stam-
mering, epilepsy and memory loss, and in vivo assays in rats demonstrated its
antidepressant effects.
52
Giramkar and co-workers studied the anticonvulsant
activity of Brahmi ghrita and Saraswatarishta against seizures induced by
maximal electroshock (MES) in rats with phenytoin (25 mg kg
1
, i.p.) as the
standard. The results indicated that both these formulations are effective in
promoting restorative and neuroprotective actions in convulsion.
53
Recently, an increasing number of studies elucidating the function and
mechanisms of Ayurvedic formulations have emerged. Brahmi-based for-
mulations are subjected to studies illustrating their neuroprotective and
memory-enhancing credentials.
4,20
8.3 Phytochemistry of B. monnieri
So far, there are no comprehensive reviews on the chemistry of B. monnieri.
Over the last eight decades, phytochemistry of B. monnieri has been studied
extensively by several groups (Tables 8.1 and 8.2, and references therein).
An alkaloid [brahmine (76)] was first reported in 1931,
54
and thereafter
two more alkaloids [herpestine (77), nicotine (78)] were isolated from
B. monnieri.
55,56
Chatterji and co-workers deduced the structure of bacoside A
in 1965.
57
Kawai and Shibata in 1978 reported ebelin lactone and
bacogenin A
1
obtained by acid hydrolysis of bacoside A and the sapogenins
(jujubogenin, psuedojujubogenin) by its Smith-de Mayo degradation.
58
They
also inferred bacoside A as leavo- and bacoside B as dextro-rotatory based on
the configurations of their carbohydrate chains.
26,58
Dammarane-type triterpenoid saponins with jujubogenin and psuedoju-
jubogenin aglycone moieties (1–34) are the specialized compounds found in
B. monnieri (Table 8.1). Bacoside A is the most pharmacologically active
constituent reported from B. monnieri. First described in 1965,
57
bacoside A
was later identified as a mixture of four saponins [bacopaside II (2),
bacopasaponin C (9), bacopaside X (20) and bacoside A
3
(29)]
66
(Table 8.1).
Bacoside B was reported by Basu and co-workers in 1967;
97
and in 2005
Sivaramakrishna and co-workers indicated it as a mixture of four saponins
viz., bacopaside V (4), bacopaside N2 (6), bacopaside IV (17) and bacopaside
N1 (22).
61
However, Deepak and Amit (2013)
79
mentioned that the details
given by Sivaramakrishna and co-workers
61
contradicted the original re-
ports
97,98
describing the structure and chromatography of bacoside B.
Chakravarty and co-workers in 2001 reported two new psuedojujubogen in
glycosides, bacopaside I (1) and bacopaside II (2), from B. monnieri methanol
Bacopa monnieri (Brahmi) 181
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