vol-3, issue-4, suppl-3, dec 2012 issn: 0976-7908 … issue-4, suppl-3, dec 2012 issn: 0976-7908...

Vol-3, Issue-4, Suppl-3, Dec 2012 ISSN: 0976-7908 Patil et al

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PHARMA SCIENCE MONITOR

AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES

A REVIEW ON BACOPA MONNIERA: BRAHMI

D. P. Patil*, S. R. Bakliwal, B. R. Rane, S. P. Pawar.

Department of Pharmaceutics, P.S.G.V.P.M’s College of Pharmacy, Shahada, Dist- Nandurbar, Maharashtra - 425409 (India).

ABSTRACT In recent times, the use of herbal products has increased tremendously in the western world as well as in developed countries. One of the most important and valuable medicinal plants, widely used therapeutically in the orient and becoming increasingly popular in the west is Bacopa monniera, a well-known nootropic herb. Bacopa monniera widely known as Brahmi are considered as ‘Medhya rasayanas’ in Ayurveda meaning brain tonic. However, these plants are distinctly different. Brahmi is a spreading creeper, sweet in taste and highly valued classic brain and nervine tonic. It is used in the indigenous system of medicine for the treatment of various disorders of human being such as cardiac, respiratory and neuropsychopharmacological disorders like insomnia, insanity, depression, anxiety, psychosis, epilepsy, and amnesia or memory impairment. It also possesses anti-inflammatory, analgesic, antipyretic, spasmolytic, antirheumatic, anticancer, antiulcer, astringent, bitter, cooling and antidiarrhoeal properties. The present review was undertaken to generate some information regarding pharmacological studies, phytochemical and physicochemical data, major bioactive(s), reported mechanisms of actions, side effects or toxicity, and dosage. Keywords: Brahmi, Bacopa monniera, Herbal medicine, Memory and Nootropic, tonic. INTRODUCTION

Recently, the interest in the use of herbal products has grown dramatically in the western

world as well as in developed countries. [1] In India, Bacopa monniera, known as

"Brahmi", is revered in the indigenous system of medicine as a nerve tonic. [2] The name

Jala-brahmi or water-brahmi assigned to Bacopa monniera in ancient Sanskrit writings

provides the differentiation. [3] Phytochemical studies have shown that B. monniera

contains many active constituents including alkaloids, saponins, bacosides and nicotine.

It is used in the indigenous system of medicine for the treatment of various disorders of

human being such as cardiac, respiratory and neuropsychopharmacological disorders like

insomnia, insanity, depression, anxiety, psychosis, epilepsy, and amnesia or memory



impairment. It also possesses anti-inflammatory, analgesic, antipyretic, spasmolytic,

antirheumatic, anticancer, antiulcer, astringent, bitter, cooling and antidiarrhoeal

properties. [4]

Bacopa monniera- the plant

Brahmi (Bacopa monniera: Scrophulariaceae) is a glabrous succulent, annual, small erect

or spreading creeping herb, small oblong leaves and light purple flowers, trailing around

the ground, distributed in the warmer parts of the world. [5] The name brahmi is derived

from the word 'Brahma', the mythical 'creator' in the Hindu pantheon. Because the brain

is the center for creative activity, any compound that improves the brain health is called

brahmi, which also means 'bringing knowledge of the supreme reality' In India; BM is

largely treasured as a revitalizing herb used by Ayurvedic medical practitioners for

almost 3000 years. It is classified as a medhya rasayana, a drug used to improve memory

and intellect (medhya). The herb has been mentioned in several ancient Ayurvedic

treatises including the 'Charaka Samhita' since sixth century AD, in which it is

recommended in formulations for the management of a range of mental conditions

including anxiety, poor cognition and lack of concentration, as a diuretic and as an

energizer for the nervous system and the heart. [6] The entire plant is used medicinally. [7]

Stem 10-30 cm long, 1-2 mm thick, soft, glabrous; branches ascending. Leaves 0.6-2.5

cm long and 3-8 mm broad, sessile, obovate-oblong or spathulate, entire, nerves obscure

and lower surface dotted, flowers blue or white with purple veins, axillary and solitary on

long pedicles and capsule ovoid glabrous, upto 5 mm long. No distinct odour; taste

slightly bitter. [8, 9]



Figure 1 Bacopa monniera

The scientific classification of the plants is mentioned in Table 1. [10]

TABLE 1: PLANT PROFILE

Scientific Classification Bacopa monniera

Kingdom Plantae

Division Angiospermae

Class Dicotyledonae

Order Tubiflorae

Family Scrophulariaceae

Genus Bacopa

Species monnieri(Linn)

Synonym Herpestis monnieria(Linn)

Common names Brahmi, Nira-brahmi, Jalabrahmi,

Thyme-Leaved Gratiola

SYNONYMS FOR BACOPA MONNIERA:

1. Bacopa monniera (L.) Pennell. Yes



2. Lysimachia monnieri L. Cent.

3. Gratiola monnieri (L.) L.

4. Monniera cuneifolia Michaux

5. Herpestis monniera (L.) Kunth. [11]

CHARACTERISTIC FEATURES OF BRAHMI:

The plant source for Brahmi is Bacopa monniera, a small herb with light purple flowers.

It grows in wet and sandy areas and near streams in tropical regions. It is a creeping herb

with numerous branches and small fleshy, oblong leaves. Flowers and fruits appear in

summer. [12] The whole plant is medicinally useful.

(a) Stem: prostrate, (sub) succulent, herbaceous.

(b) Leaves: decussate, simple, oblong, 1 x 0.4 cm, (sub) succulent, punctate,

penninerved, margin entire, apex obtuse, (sub) sessile.

(c)Flower(s): axillary, solitary, bracteate (2 bracteoles), linear, pedicel to 0.5 cm. purple

in color.

(d) Calyx: 5 lobes (unequal); outer 2 lobes larger, ovate, 7 x 3.5 mm; inner 2 lobes linear,

5.5 x 0.7mm; median 1 lobe oblong, 5.5 x 2 mm, imbricate, (sub)succulent, punctate,

obtuse, acute.

(e) Corolla: white with violet and green bands inside the throat, 0.8 cm across, 5 mm

tube; 5 lobes, obscurely 2-lipped, 2+3, (sub) equal, obtuse or emarginate.

(f) Stamens: 4, didynamous; filament pairs I and 2.5 mm anthers oblong, contiguous, 1. 5

mm.

(g) Ovary: Oblong-globose, 2 mm; style slightly deflexed, 5.5 mm; stigma flat capsule,

oblong globose, 5 x 2.5 mm, septicidal or locilicidal, or 4-valved.

(h) Seeds: oblong; testas striate. [13]



TABLE 2: PHYSICOCHEMICAL DATA OF BACOPA MONNIERA.

TABLE 3: PHYTOCHEMICAL DATA OF BACOPA MONNIERA. [14]

ACTIVE CONSTITUENTS:

Compounds responsible for the pharmacological effects of BM include alkaloids,

saponins and sterols. Detailed investigations first reported the isolation of the alkaloid

'brahmine' from BM. [15] The major chemical entity shown to be responsible for

neuropharmacological effects and the nootropic action or antiamnestic effect of BM is

bacoside A, assigned as 3-(a-L-arabinopyranosyl)-O-b-D-glucopyranoside-10, 20--

dihydroxy-16-keto-dammar-24-ene, while Bacoside A usually co-occurs with bacoside

B. [16,17] Bacosides A and B are the major constituents that impart to enhance nerve

transmission and hence to improve academic performance, consciousness mental

alertness, intellect, memory and cognition in animals and human beings. [18]

Physicochemical parameters Bacopa monniera value Total Ash NMT 18 % Acid insoluble ash NMT 6 % Water soluble extract NLT 15 % Alcohol soluble extract NLT 6 %

Phytoconstituents Pet.Ether Methanol Water Ethyl acetate

Chloroform

Carbohydrates + + + + + Proteins + + + + + Amino acids − − − − − Glycosides + + + + + Alkaloids + + + + + Flavanoids − − − − − Tannins − − − − − Saponins + + + + + Steroids − − − − − Resins − − − − −



Bacoside a (levorotatory)

Bacoside b (dextrorotatory)

MECHANISM OF ACTION:

The other proposal that was put forward was that BM enhances protein kinase activity in

the hippocampus which may also contribute to its nootropic action and thus it would aids

in repair of damaged neurons by enhancing kinase activity, neuronal synthesis and

restoration of synaptic activity and ultimately nerve impulse transmission. [19] The

triterpenoid saponins and their bacosides are said to be responsible for BM's ability to

enhance nerve impulse transmission. It was suggested that bacosides induce membrane

dephosphorylation, with a concomitant increase in protein and RNA turnover in specific

brain areas. [20]

MEDICINAL USES OF BACOPA MONNIERA:

(a) Memory: 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, and to provide relief to patients with anxiety or epileptic disorders. It is



listed as a nootropic, a drug that enhances cognitive ability. [21] Bacopa monniera has

been used to promote memory and intellect, to treat psycho neurological disorders, and as

a rejuvenator. In the last four decades the plant and the compounds isolated from it,

especially the saponins, have been studied extensively regarding their memory-enhancing

activities and their ability to improve cognitive function, including some clinical trials

conducted to establish the activity. [22,23]

(b) Antioxidant activity: Based on animal study results, bacosides were shown to have

antioxidant activity in the hippocampus, frontal cortex and striatum. [24] Animal research

has shown that the BM extracts modulate the expression of certain enzymes involved in

generation and scavenging of reactive oxygen species in the brain. [25] One of the

underlying mechanisms of action of B. monnieri is its antioxidant activity, evident from

several different studies, as discussed above. The whole plant methanolic extracts was

investigated for any in vitro antioxidant properties and total phenolic content. Further, the

antioxidant activity of the plant was studied using three in vitro models. The Nitric oxide

scavenging activity, DPPH free radical scavenging assay and reducing power activity was

also concentration dependent with IC50 value being 455.78±1.03μg/ml,

104.82±1.96μg/ml and 96.13±0.86μg/ml respectively. The total phenolic content was

found out to be 27.76±1.87mg/gm GAE. The methanolic extract of the plant had free-

radical-scavenging activity and provided protection against DNA damage in human

nonimmortalized fibroblasts. [26]

(c) Antispasmodic activity: The plant exhibited a tranquilizing effect in rat and dog.

[27,28] It caused smooth-muscle relaxation and showed antispasmodic activity. [29]

(d) Neuroprotective role: Ethanolic extract of B. monnieri was shown to inhibit lipid

per oxidation, protein oxidation, and lipofuscin accumulation. Co administration of the

extract with aluminium was shown to reverse the aluminium-induced oxidative stress and

ultra-structural changes in the hippocampus 21and prevent the accumulation of lipid and

protein damage. [30] The extract was afforded a neuroprotective role against aluminium-

induced toxicity and prevented



oxidative stress induced by aluminium in the hippocampus of rats. [31] The extract used in

that study comprised 55–60 % bacosides.[32]

(e) Antidepressant properties: Singh and co-workers reported that bacosides A and B

showed antidepressant properties. Recently, Zhou et al. reported that bacopasides I and II

and bacopasaponin C (all three having pseudojujubogenin as aglycone) exhibited

antidepressant activity, while bacopasides VII (having jujubogenin as aglycone) did not

have any antidepressant activity when tested on forced swimming and tail-suspension

models in mice. [33]

(f) Anti-inflammatory activity: The ethanolic extract of B. monnieri (100 mg, i.p.)

exhibited a very good anti-inflammatory activity against carrageenan-induced paw edema

in mice and rats, and it selectively inhibited PGE2-induced inflammation. [34]

(g) Antibacterial activity: Betulinic acid isolated from B. monnieri showed good

antifungal activity against Alternaria alternata and Fusarium fusiformis. Betulinic acid

also showed phytotoxic activity in inhibiting the root growth of wheat seedlings. [35] The

n-butanol extract of the plant was shown to have good antibacterial activity against a

battery of human pathogens and cattle pathogens tested in vitro. [36]

(h) Antileishmanial properties: Bacopasaponin C was tested for its antileishmanial

properties in different delivery modes (i.e., noisome, microspheres, and nanoparticles),

and it was found to be highly active in all forms. However, bacopasaponin C showed

nephrotoxicity, while in vesicular form it was found to be safe. The activity was found to

be parasite specific. [37]

(i) Bronchovasodilatory activity: Several fractions and sub fractions from the ethanolic

extract showed bronchovasodilatory activity, which appears to be mediated by

interference with calcium ion movement. Activity-guided fractionation led to the

isolation of betulinic acid, which exhibited inhibition of tracheal pressure and heart rate

in rats. [38]

(j) Sedative and Tranquillizing Properties: Hersaponins, glycosides isolated from BM

are reported for sedative effect. [39] A subsequent study has found that the alcoholic



extract, and to a lesser extent the aqueous extract of the whole plant exhibited

tranquilizing effects on albino rats and dogs. [40] On the other hand, it has been found that

the alcoholic extract of the plant and chlorpromazine improved the performance of rats in

motor learning. [41]

(k) Anticancer activity: The ethanolic extract of the plant exhibited anticancer activity

against Walker carcinosarcoma 256 in rat. [42] and sarcoma-180 cell culture. [43] In

addition, the bacoside A fraction and its individual components were found to be more

active than the bacoside B fraction. [44,45] Different extracts of the plant, bacosides A and

B, bacopasides I, II, and X, and bacopasaponin C, showed potent activity in a brine

shrimp lethality assay (an assay that is predictive of potential anticancer) activity. [46, 47]

(l) Cell stabilization activity: The methanolic extract was shown to have potent mast

cell stabilization activity; this activity was comparable to that of disodium cromoglycate.

[48]

(m) Alzheimer’s disease: Alzheimer’s is a degenerative disease characterized by the

progressive death of brain cells, which occurs equally in both genders and it is the most

common form of dementia. Most often, it is diagnosed in people over 65 years of age.

Alzheimer described a thinned cortex speckled with unusual brown clumps and irregular

knots that appeared to be growing inside the brain cells that are now called as amyloid

plaques and neurofibrillary tangles. These are the hallmark signs of Alzheimer (AD). [49]

Since it has been claimed that B. monnieri is efficacious in the treatment of memory loss,

its potential benefit in the treatment of Alzheimer’s disease was studied regarding

amyloid plaque pathology in the brain of PSAPP transgenic mice. Short- and long-term

treatment with B. monnieri extract reduced brain Aβ (amyloid beta) 1-40 and 1-42 levels

in the cortex and reversed the behavioral deficits in PSAPP mice; the study indicates the

potential of B. monnieri as a therapeutic agent for :Standardized extract of B. monnieri

(containing 55–60 % bacosides) was shown to have adaptogenic activity. It normalized

the stress-induced elevation in the levels of plasma glucose and creatine kinase, and in

adrenal gland weight. [50] A mixture of bacosides A and B was shown to reduce the stress



by modulating the activities of the 70-kDa heat shock protein (Hsp70), cytochrome P450

and SOD in different regions of the brain in the stress model of cold-hypoxic restraint in

rats. [51]

Figure 2 Normal Neuron and Alzheimer’s Neuron

SIDE EFFECTS AND TOXICITY:

BM has a record of several hundred years of safe therapeutic use in Ayurvedic medicine.

A double-blind, placebo-controlled clinical trial of healthy male volunteers investigated

the safety of pharmacological doses of isolated bacosides over a 4-week period.

Concentrated bacosides given in single (20-30 mg) and multiple (100-200 mg) daily

doses were well tolerated and without adverse effects. [52] The aqueous extract given

orally at a dose of 5 g/kg did not show any toxicity. The LD 50 of the alcoholic extract

was 17 g/kg given orally. Both extracts did not produce any gross behavioural changes at

these levels. [53] The LD 50 of aqueous and alcoholic extracts of BM in rats were 1000 mg

and 15 g/kg by the intraperitoneal route, respectively. [54]

DOSAGE:

For BM extracts standardized to 20%, 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. The

daily doses of BM generally recommended in traditional practice are 5-10 g of non-

standardized powder, 8-16 mL of infusion and 30 mL daily of syrup. [55]



CONCLUSION:

Bacopa monniera is a reputed drug of Ayurveda. Bacopa monniera used for centuries as

a memory enhancing, anti-inflammatory, analgesic antipyretic sedative and antiepileptic

agent. Brahmi has also been used as traditional medicine due to its neurotonic and

memory enhancing property. This study demonstrates that Brahmi extract diminishes

neuronal death induced by amyloid peptide partly through the suppression of AChE

activity. Brahmi extract also exhibited antioxidant properties both in vitro and cell-based

assays. Overall results from the present study support the potential of Brahmi extract as a

remedy to prevent memory loss in natural aging as well as an alternative remedy for

neurodegenerative disorders associated with oxidative stress and amyloid-induced

memory loss.

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For Correspondence: Delia Prakash Patil Email: [email protected]

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