Fitoterapia 81 (2010) 315–322

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Fitoterapia

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Review

Bacopa monnieri and Bacoside-A for ameliorating epilepsy associatedbehavioral deficits

Jobin Mathew, Jes Paul, M.S. Nandhu, C.S. Paulose⁎Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology,Cochin-682 022, Kerala, India

a r t i c l e i n f o

⁎ Corresponding author. Molecular Neurobiology aDirector Centre for Neuroscience, Professor andBiotechnology, Cochin University of Science and Te022, Kerala, India. Tel./fax: +91 484 2575588, +91 4

E-mail addresses: cspaulose@cusat.ac.in, paulosecs(C.S. Paulose).

0367-326X/$ – see front matter © 2009 Elsevier B.V.doi:10.1016/j.fitote.2009.11.005

a b s t r a c t

Article history:Received 23 October 2009Accepted in revised form 13 November 2009Available online 26 November 2009

Bacopa monnieri is an outstanding nervine tonic used for raising the mental performance. Ithelps in concentration, comprehension, recall and alertness, Brahmi is particularly beneficial asit aids in categorizing information in brain and its subsequent expression. Bacopa is also calledas a natural antioxidant which may give details its neuroprotective role seen in the memorycenters of the brain. Epilepsy is neuronal disorder characterized by learning, cognitive andmemory impairments. The present review summarizes information concerning botany,chemistry and beneficial effect of Bacopa monnieri on epilepsy associated behavioral deficits.

© 2009 Elsevier B.V. All rights reserved.

Keywords:EpilepsyBacopa monnieriBacoside-ALearningBehaviour

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3151.1. Botanical description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3151.2. Active constituents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3161.3. Ethnopharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3161.4. Biological activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3161.5. Antioxidant capasity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3171.6. Human studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317

2. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3183. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320

nd Cell Biology Unit,Head Department ofchnology, Cochin-68284 2576267.@yahoo.co.in

All rights reserved.

1. Introduction

1.1. Botanical description

Bacopa monnieri (Linn.) belongs to the family Scrophular-iaceae. It is a prostrate, juicy, succulent, glabrous annual herbrooting at the nodeswith numerous ascending branches. Leavesare simple, opposite, decussate, sessile, obovate–oblong or spat-ulate, entire, fleshy, obscurely veined and punctate. Flowers are

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pale blue or whitish, axillary, solitary, arranged on long slenderpedicels. Fruits are ovoid, acute, 2-celled, 2-valved capsules andtippedwith style base. Seeds areminute and numerous [1]. Thisplant are growing in grasslands occurring in aquatic sites, sandand wet soil occupying in the edges of freshwater or brackishpools and streams and lake beds. Distributed in the major partof the plains of India, Pakistan, Afghanistan, Nepal, Sri Lanka,subtropical US, tropical Asia, Africa and Australia [2]. Bacopamonnieri is commercially cultivated for medicinal purpose andthe annual production is 40,000–50,000 kg per hector.

1.2. Active constituents

Earlier workers have isolated a number of chemical com-pounds from Bacopa monnieri.. Bacopa contains Alkaloids suchas Hydrocotyline, Brahmine and Herpestine. [3] Glycoside suchas Asiaticoside and Thanakunicide. Flavonoids such as Apigeninand Luteonin. Saponins such as D-mannitol, Acid A, Monnierin[C51H82O213H2O] Bacoside A [C41H68O134H2O] and Baco-side B [C41H68O135H2O]. Additional Phytochemicals such asBetulinic acid, Wogonin, Oroxindin, Betulic acid, Stigmastarol,beta-sitosterol, as well as numerous Bacosides and Bacopasa-ponins, and amino acids like alpha alanine, Aspartic acid, Glu-tamic acid, and Serine, and its esters, Heptacosane, Octacosane,Nonacosane, Triacontane, Hentriacontane, Dotriacontane, Nic-otine, [4] 3-formyl-4-hydroxy-2H-pyran (C6H6O3), and its 7-glucoside. Brahamoside, Brahminoside, Brahmic acid, Isobrah-mic acid, Vallerine, pectic acid, fatty acids, tannin, volatile oil,ascorbic acid, thanakunic acid and asiatic acid [5–10]. jujuba-cogenin and pseudojujubacogenin [11]. In a thorough reviewof the chemical composition of Brahmi, Russo and Borrelli [2]point out that the first constituent identified was an alkaloidbrahmine. Saponins are considered to be the major active con-stituents of the plant. Saponins are glycosides, a sugar unitattached to an aglycone portion (the sapogenin). The sapogeninportion describes the type of saponin — either steroidal (4-ringed structure), or triterpenoid (5-ringed structure) [12]. Themain active chemical constituents of Bacopa are the dammar-ane-type triterpenoid saponins [13] with jujubogenin andpseudojujubogenin as the aglycones [14]. The saponins consistof numerous subtypes designated as bacosides, bacopasidesand bacopasaponins. Bacoside-A is considered the major activecomponent,first identified byChatterji et al [15],with bacoside-B being an optical isomer of bacoside-A [16]. Chemical structureof Bacoside-A,B and C are represented as 3-0-α-L-arabinopyr-anosyl-20-0-α-L-arabinopyranosyl-jujubogenin, 3-0-[α-L-arabi-nopyranosyl (1-2)α-L-arabinopyranosy] pseudojujubogeninand3-0-[β-D-glucopyranosyl (1-3){α-L-arabinofuranosyl (1-2)})α-L-arabinopyranosy] pseudojujubogenin respectively [13].

Bacosides can be extracted from the B. monnieri. The wholeplant of B. monnieri was dried in shade and then powderedplant material was extracted with distilled water. The aqueousextract was discarded and the residual plant material wasextracted thrice with 90% ethanol. The residue obtained afterremoving the solventwas dried in vacuum andmaceratedwithacetone to give a free-flowing power. The extract of B. monniericontained 40–50% bacoside estimated as Bacoside A. The es-timation method involves acid hydrolysis of bacosides,whichyields quantitatively a transformed aglycone–ebelin lactonewhich contained a conjugated triene systemandwas estimatedby UV spectrophotometer at 278 nm [17].

1.3. Ethnopharmacology

It is used in traditional Indian medicine, the Ayurveda,for the treatment of anxiety, and in improving intellect andmemory for several centuries [18]. In addition to memoryboosting activity, it is also claimed to be useful in the treat-ment of cardiac, respiratory and neuropharmacological dis-orders like insomnia, insanity, depression, psychosis, epilepsyand stress [2]. It was reported to possess anti-inflammatory,analgesic, antipyretic, sedative, free radical scavenging andanti-lipid peroxidative activities [19,20]. The plant is reportedto have shown barbiturate hypnosis potentiation effect. Theplant is anticancerous and improves learning ability. It is usedas a tranquilliser. The plant is astringent, bitter, sweet, cooling,laxative, intellect promoting, anodyne, carminative, digestive,antiinflammatory, anticonvulsant, depurative, cardiotonic,bronchodialator, diuretic, emmenagogue, sudorfic, febrifugeand tonic [21,22]. The pharmacological properties of B. mon-nieriwere studiedextensively and the activitieswere attributedmainly due to the presence of characteristic saponins calledas bacosides [18]. In animal studies, both purifiedbacosides andextracts of bacopa standardized for bacosides have been foundto enhance several aspects of mental function and learningability [18,23,24]. Additional brain effects of bacopa demon-strated in animal research include reduction of both anxietyand depression [25,26]. Biochemically, these nervous-systemeffects have been attributed to an enhancement of the effectsof the neurotransmitters acetylcholine and [27,28] possibly,serotonin or GABA (gamma aminobutyric acid) [29,30]. Bacopaextracts also appear to have significant antioxidant activity inthe brain [31] and other effects thatmay help protect brain cells[32]. Animal researchhas also reported that bacopaextracts canrelax the muscles that control the blood vessels, the intestine,and the airways of the respiratory system [33–36] and can helpboth prevent and heal ulcers in the stomach [37]. Traditionalherbal references recommend 5 to 10 grams per day of thepowdered herb. Human research has used 300 to 450 mg perday of an extract standardized to contain 55% bacosides. Bacopaappears to be well tolerated when taken in typical amounts[18], although one double-blind study reported significantlymore symptoms of dry mouth, nausea, and muscle fatigue inparticipants taking Bacopa [27].

1.4. Biological activity

The herb has been described in Ayurvedic texts sincearound 800 BC and recorded as a treatment for a range ofmental disorders in the ‘Carak Samhita’ [18], which, according

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to the literature, was written in the 6th century AD [2]. Ay-urvedic medicine classifies Bacopa as belonging to a groupof plant medicines known as medhya rasayana that improvemental health, intellect and memory (medhya) and promotelongevity and rejuvenation (rasayana) [38]. Hence Bacopashares its Sanskrit name, Brahmi, with another herbal ner-vous system restorative Centella asiatica. Learning ability inrats has been significantly enhanced by Bacopa extract as itfacilitated acquisition, consolidation and retention of threenewly learned behavioural responses at an oral dosage of40 mg/kg three times daily [24]. In this study, effects oncognitive function were measured by foot shock motivatedbrightness discrimination reaction, active conditioned flightreaction (jump to avoid shock) and continuous avoidanceresponse (shock avoidance by lever pulling) tests. Bacopafacilitated all parameters of memory acquisition and reten-tion. In a subsequent study the same authors investigatedthe constituents responsible for Bacopa's effect and demon-strated that the isolated bacosides A and B were effective inenhancing memory in rats in learning tasks involving bothpositive and negative reinforcement [18] Additionally, thisstudy demonstrated that the bacosides produced changes inthe hippocampus, cerebral cortex (areas critical to memoryfunction) and hypothalamus regions of the brain and causedenhanced levels of protein kinase activity and increases inprotein levels in these regions. This indicated positive implica-tions for improved neurotransmission and repair of damagedneurons via enhanced regeneration of nerve synapses [18].The neuroprotective effects of Brahmi extract, was tested, itsprotection against the beta-amyloid protein and glutamate-induced neurotoxicity in primary cortical cultured neurons.From this study, the mode of action of neuroprotective effectsof Brahmi appeared to be the results of its antioxidant to sup-press neuronal oxidative stress and the acetylcholinesteraseinhibitory activities. A recent study concurs with Singh andDhawan's findings regarding the effects of isolated Bacopasaponins on memory. Administration of bacosides to mice at-tenuated experimentally induced anterograde amnesia andimproved memory as measured by a well validated learningtask — the morris water maze test [19]. The triterpenoidsaponins and their bacosides are responsible for Bacopa's abil-ity to enhance nerve impulse transmission. The bacosides aidin repair of damaged neurons by enhancing kinase activity,neuronal synthesis, and restoration of synaptic activity, andultimately nerve impulse transmission. Loss of cholinergic neu-ronal activity in the hippocampus is the primary feature ofAlzheimer's Disease. Based on animal study results, bacosidesappear to have antioxidant activity in the hippocampus, frontalcortex, and striatum. Animal research has shown Bacopa ex-tracts modulate the expression of certain enzymes involved ingeneration and scavenging of reactive oxygen species in thebrain.

1.5. Antioxidant capasity

The antioxidant activity of Bacopa has been reported in anumber of laboratory studies [28,32,37,39,41,42,49]. Antioxi-dant effects of Bacopa in areas of the brain that are key mem-ory areas such as hippocampus, frontal cortex and striatumhave been documented by Bhattacharya et al [28] in rat brain.Bacopa was shown to protect the brain [41] and liver [40],

from morphine induced inhibition of antioxidant enzyme sys-tems. Russo et al [2] demonstrated a free radical scavengingactivity which protected against cytotoxicity and DNA damagein human fibroblasts [42]. Further research by Russo et al [32]also demonstrated that Bacopa significantly reduced oxidationand DNA damage in cultured rat astrocytes induced by a nitricoxide donor. Furthermore, Anbarasi et al [20] demonstratedthat isolated bacoside-A protected rat brain tissue from variousparameters of oxidative stress caused by chronic cigarettesmoke exposure. One of the foremost theories of brain ageingasserts that free radical damage results in both ageing-relatedchanges in healthy brains [43] and in neurodegenerative pa-thology, such as Alzheimer's Disease [44]. Good antioxidantstatus is associated with better memory performance in theaged [45] and antioxidant therapy has been targeted as apromising dementia strategy [46]. Thus, the demonstratedantioxidant effects of Bacopa, particularly in brain tissue, sup-port its potential as a therapy in neurodegenerative pathologiesand age-related cognitive decline. Stress elicits a defensiveresponse in living organisms. The defense response involvesseveral mechanisms including stress gene expression, en-hanced antioxidant protection, and enhanced toxin clearance.Bacopa has been shown to facilitate each of these adaptiveresources by modulation of Hsp 70 expression, and enhance-ment of activity of both superoxide dismutase and cytochromeP450 enzymes in stressor exposed rat brain. Thus, Bacopa mayfacilitate the capacity of the brain to withstand stress, and helpthe brain to function under adverse conditions. These findingssupport the afore-mentionedmedhya rasayana classification ofBacopa in ancient Ayurveda in that they imply a brain tonic andadaptogenic effect (adaptogenic meaning improved resistanceto stress). This may indicate some similarities with Panaxginseng,which is considered to be amajor adaptogen and tonic,enhancing resistance to stress in numerous experimentalsituations as well as clinical trials [12,47].

1.6. Human studies

Clinical trials using fresh whole plant extract of Bacopahas been found to improve various aspects of cognitive func-tion in children and adults. Sharma et al [48] found thatlearning, memory, perception and reaction times improved in20 primary school children given Bacopa in syrup form at adosage of 350 mg three times daily for three months. No sideeffects were reported. Negi et al [49] reported children withattention deficit hyperactivity disorder (ADHD) were foundto benefit from Bacopa administration. They have conducteda randomized and double-blind placebo-controlled trial of36 children with ADHD. This study showed logical memoryimprovement. Fresh whole plant extract of Bacopa was givenat a dosage of 50 mg twice daily for 12-weeks, and a batteryof cognitive function tests administered at baseline, 4, 8, 12and 16-weeks (i.e. 4-weeks post trial). Improvements werereported in the active treatment group (n=19) at 12-weeks,as measured by tests of sentence repetition, logical memory,and paired associate learning tasks. Another randomised,double-blind, placebo-controlled study confirmed the effica-cy of Bacopa in improving memory in chronic administration.In this study, seventy six adults 40–65 years of age, weregiven Bacopa (dose 300 mg) placebo and measured on tasksof attention, memory and psychological state at baseline, 12-

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weeks and 6-weeks post trial. Bacopa significantly improvedthe ability to retain information over time as measured bya task requiring delayed recognition all of word pairs. Theauthors commented that this may be due to less informa-tion being lost from memory, that is, the results are dueto decreased forgetting, as opposed to enhanced acquisitionbecause learning trials did not show any effect of Bacopa.Outcome measures in this study which failed to show a sig-nificant effect for Bacopa were tasks of short term memory,working memory, attention, retrieval of prior knowledge andpsychological state (anxiety, stress and depression). In anopen trial, 35 adults with anxiety neurosis were treated withBacopa at the dose of 12 g of dried herb daily in syrup formfor 4-weeks. No significant side effects were observed andresults were highly favourable as overall anxiety levels, con-centration and memory span were all significantly improvedalong with other major anxiety-related physical symptomsand biochemical markers of anxiety [38]. Bacopa's anxiolyticaction was supported in a later animal study in which it wascompared with a major pharmacological anxiolytic agent —the benzodiazepine lorazepam, in validated rat models ofanxiety. It proved to be as effectual as the drug in everyoutcome measured without producing any motor deficits(a common side-effect of lorazepam) [25].

2. Discussion

Epilepsy is a disturbance of the electrical activity of thebrain. When disordered cerebral neurons generate abnormalelectrical discharges in an intermittent manner, the externalmanifestations appear as seizures, fits or convulsions. Whenthese fits occur in a chronic, recurrent manner, it is calledEpilepsy. Neuropsychological impairment is an important co-morbidity of chronic epilepsy [50]. Patients with epilepsyoften experience cognitive dysfunction. Multiple factors canadversely affect cognition in epilepsy, including the etiologyof the seizures, cerebral lesions acquired before the onsetof seizures, seizure type, age at onset of epilepsy, seizurefrequency, duration, and severity, intraictal and interictalphysiologic dysfunction, structural cerebral damage causedby repetitive or prolonged seizures, hereditary factors, psy-chosocial factors, and sequelae of treatment for epilepsy,including antiepileptic drugs (AEDs) and epilepsy surgery[50–55]. All these interrelated factors make complex con-tributions to cognitive deficits[54]. AEDs affect cognition bysuppressing neuronal excitability or enhancing inhibitoryneurotransmission. Patients, and even some clinicians, tendto blame cognitive problems on AEDs because they are moreidentifiable than other factors. However, AED effects shouldnot be overrated. Psychosocial problems which are common,can be overlooked as a source of cognitive impairment. Thestigma of epilepsy and the fear of having seizures in publiccan lead to low self-esteem, social isolation, and depression,all of which can negative affect cognitive function. Similarly,subclinical epileptiform activity is another important con-tributor to cognitive dysfunction that can go unrecognized,especially in patients with infrequent seizures. A rich lit-erature has characterized relationships between adequacyof mental status and a variety of clinical epilepsy factorsincluding etiology, age of onset, seizure type and severity,duration, antiepilepsymedications, and other factors [51–58].

In addition, modal cognitive profiles have been derived forseveral syndromes of epilepsy and efforts have been under-taken to identify the shared versus unique cognitive abnor-malities evident across these syndromes [50,59–65].

The nature, timing and course of cognitive impairments inepilepsy remains an issue of substantial interest and concern,particularly the degree to which chronic medication-resistantepilepsy may lead to progressive cognitive impairment [66].While evidence to this effect has been reviewed [53], theearly cognitive substrate upon which subsequent chronicepilepsy may exert its effects is an important consideration.The possibility that early onset or childhood epilepsy mayadversely alter a child's cognitive substrate in a greater thanexpected fashion despite their increased plasticity is an issueof clinical interest.

Indirect evidence implicating an adverse neuro-develop-mental effect of childhood onset epilepsy has come fromstudies of adults with chronic epilepsy grouped by age ofonset categories where fairly robust relationships have beenreported between earlier age of onset of recurrent seizuresand cognitive abnormality. This relationship, reported early inthe last century [67], confirmed in studies of adult patientswith diverse seizure types [68–72] and observed in neuro-psychological studies of younger patients with complexpartial and other types of seizures [73–76]. In addition, greaterthan expected neuropsychological abnormalities have beenreported in adults with the syndrome of mesial temporal lobeepilepsy [77], a syndrome defined by a focal neuropatholog-ical substrate and early onset of recurrent seizures or initialprecipitating injury [78]. These findings suggest that earlyonset epilepsy, including localization-related syndromes ofepilepsy such as mesial temporal lobe epilepsy, may be asso-ciated with widespread influence on brain development andstructure.

In the case of mesial temporal lobe epilepsy, quantitativevolumetric magnetic resonance (MR) imaging studies havereported abnormalities in neural regions involved in the gen-esis and propagation of seizures, including the hippocampus[79–82], amygdale [83], entorhinal cortex [84], fornix [85],thalamus and basal ganglia [86], and temporal lobe [87–90].Additional investigations have reported abnormalities in morewide ranging volumes of gray and white matter in extra-temporal lobar [88], regional [91] or total brainmorphometrics[89,92] These distributed volumetric abnormalities, interestingin their own right, are also consistent with the widespreadcognitive abnormalities that can be observed in chronictemporal lobe epilepsy. The potential impact of early versuslate age of seizure onset on quantitative MRI volumetrics intemporal lobe epilepsy has however rarely been systematicallyinvestigated, surprising given the neuropsychological literaturereviewed above as well as animal studies demonstrating thatseizures in the immature brain may adversely affect braingrowth and development[93–95].

However, more direct evidence of the neurodevelopmentalimpact of recurrent seizures on cognition has been provided bycontrolled studies of children and adolescents with chronic butsubstantially shorter duration epilepsy. Studies such as thesehave also reported considerable neuropsychological impair-ment [96–99] consistent with an early adverse neurodevelop-mental impact on cognition. However, even these effects couldbe a combination of pre-epilepsy onset (etiological) insults,

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factors which may have contributed to the development ofepilepsy and simultaneously contributed to abnormal mentalstatus. In order to derive perhaps the clearest perspective ofthe natural course of cognitive status in epilepsy, it is importantto characterize the earliest status of the cognitive substrateand to that end, investigation of children with new onset epi-lepsy may contribute to this literature. To date, a modestnumber of studies have examined cognition in children withnew onset epilepsy [100–104]. Three of the five studies iden-tified cognitive impairments at epilepsy onset and these mixedresults may be attributable, at least in part, to the variable ageranges, testbatteries, and epilepsy characteristics across studies.Also interesting and very pertinent to this topic are reports ofacademic underachievement prior to and/or at the onset ofidiopathic/cryptogenic epilepsy[101,105,106] suggestive of anantecedent neurobiological insult of uncertain etiology.

Various animal models of epilepsy are showing cognitive,learning andmemory impairments.Holmes andhis co-workershave studied the role of interictal epileptiform abnormalitiesin cognitive impairment. Most of the studies were performedin adult animals and suggest that epileptiform discharges inolder age groups can impair cognitive abilities through inter-ference with awake learning, and memory, as well as memoryconsolidation during sleep [104–106]. The effects appear tobe more pronounced if the spikes are very frequent andwidespread. In a series of elegant studies, Holmes and co-workers showed that the electrical induction of spikes in thehippocampus impairs recognition and spatial memory in ratsby disrupting the ability of hippocampal place cells to recognizethe position of the animal [106,107]. Genetically epilepticmodel rats, Ihara epileptic rat (IER/F substrain), have neuro-pathologic abnormalities and develop generalized convulsiveseizures when they reach the age of ∼5 months [108]. YoungIER/F rats experiences showed severe learning impairments,genetically programmed microdysgenesis in the hippocampus[108]. Pilocarpine induced temporal lobe epileptic rats showeddeficit in learning tests like morris water maze demonstratedthe impairment in spatial learning during epilepsy [109] androtarod performance demonstrated the impairment in themotor function and coordination [110].

Some anti-epileptic medications can slow down proces-sing of information in some children, while other anti-epileptic medications can induce fatigue that decreases thechild's availability to learn [111]. These are transient beha-vioural abnormalities and falling numbers of patients con-tinuing to take epileptic drugs during long-term treatment.Psychotic reactions have been carefully documented both inpatients receiving standard and new anti-epilepsy drugs, andin up to 6% of patients after epilepsy surgery [112]. As manypsychotic episodes are associated with a dramatic cessationof seizures, it is not surprising that behavioural abnormalitiesare more often seen in patients receiving higher, more ef-fective doses of drugs [113]. Because of the side effects ofchemical drugs, drugs of plant origin are gaining importanceand are being investigated for remedies of a number of dis-orders. Since the introduction of adaptogen concept, severalplants have been investigated, which were used earlier astonics due to their adaptogenic and rejuvenating propertiesin traditional medicine. B. monnieri has been reported topossess anxiolytic, antidepressant and memory enhancingactivity [25,26,114].

Themechanismof action behind thememory and cognitionenhancing effects of B.monnieri is still uncertain, as its multipleactive constituents have multifunctional properties, makingits pharmacology complex. But the antioxidant properties ofB.monnieri have been well documented [21]. Glutamate is oneof the chief excitatory amino acids that mediates excitotoxicneuronal degeneration. Treatment with B. monnieri extractreduced the increase in glutamate dehydrogenase activity tonear-control levels. Hence, it is suggested that B. monnieri has adefinite role in decreasing glutamate excitotoxicity. B. monnieritreatment can induce membrane dephosphorylation and aconcomitant increase in mRNA turnover and protein synthesis.It can also enhance protein kinase activity in the hippocampus,which is critically involved in learning and memory [41]. Thewater maze experiment conducted by Reas et al [109] to studythe neurobiological mechanisms that underlie spatial learningand memory function in epileptic rats. The hippocampal for-mation is critical for computing place representations. TheMorris water maze experiment demonstrated the impairmentin spatial learning during epilepsy. Escape latency was in-creased in epileptic rats as compared with control rats. Treat-ment using Bacopa monnieri and bacoside-A increasing theperformance in morris water maze.

Amee et al. [110] found enhanced immobility during theforced swim test in epileptic rats compared to control. In theforced swim test, the space for rat's movement was restrictedfrom which they cannot escape. Immobility in ratsis considered to be a state of lowed mood or hopelessnesswhich the rodent experience when they are forced to swimin a constrained space from they cannot escape. This isbelieved to indicate a failure or reduced attempts towardsescapedirected behaviour frompersistent stress. It also causesthe development of passive behaviour that disengages theanimal from coping up with stressful stimuli. Studies byMazrati et al [115] also support that rats afflicted withpilocarpine induced epilepsy exhibited increased immobilitytime under forced swim test. This form of immobility whichis a state of despair is reported to be reduced by a broadspectrum of anti-depressant drugs [116]. B. monnieri treat-ment once daily over a period of 15 days decreased the periodof immobility in the epileptic rats which is indicative of itsanti-depressant property. But studies by other workersrevealed that B. monnieri administration also acts as an anti-depressant [25,114,117,118]. Nigel et al., [47] have suggestedshared neurobiological processes leading both to seizuresand to behavioral, emotional and cognitive disturbancewhichcould possibly explain the how B. monnieri is effective as ananti-convulsant and an anti-depressant. It is reported thatthe isolated bacosides A and B were effective in enhancingmemory in rats in learning tasks involving both positive andnegative reinforcement [18,23]. Additionally bacosides pro-duced changes in the hippocampus, cerebral cortex (areascritical to memory function) and hypothalamus regions of thebrain and caused enhanced levels of protein kinase activityand increases in protein levels in these regions. This indicatedpositive implications for improved neurotransmission andrepair of damaged neurons via enhanced regeneration ofnerve synapses [18]. Previous studies showed decreasedRotarod performance demonstrated the impairment in themotor function and coordination in the epileptic rats, sug-gesting impairment in their ability to integrate sensory input

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with appropriate motor commands to balance their pos-ture and at the same time adjust their limb movements onthe metallic rod and is indicative of cerebellar dysfunction[110,119]. Treatment using B. monnieri and its active compo-nent bacoside-A improving cerebellar function [110].

3. Conclusion

Scientific research onB.monnieri revealed its anticonvulsant,antioxidant,memory and cognition improving properties. Theseare transient behavioral abnormalities and cognitive impair-ments in epileptic patients.During long term treatment epilepticdrugs are creating cognitive and memory deficit in patients. B.monnieri can be used as a herbal medicine for ameliorating thememory and cognitive impairments during epilepsy.

Acknowledgement

This work was supported by research grants from DBT,DST, ICMR,Govt. of India andKSCSTE,Govt. of Kerala toDr. C. S.Paulose. Jobin Mathew thanks CSIR for SRF.

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