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Nootropic Activity of Bacomind™, an Enriched Phytochemical Composition from Bacopa Monnieri

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Nootropic Activity of Bacomind™, an Enriched Phytochemical Composition from Bacopa Monnieri Vol. 7/1 (2007) 166 - 173 JOURNAL OF NATURAL REMEDIES Nootropic activity of BacoMind™, an enriched phytochemical composition from Bacopa monnieri S. B. Kasture1#, V. S. Kasture1, A. J. Joshua2, A. Damodaran2, A. Amit3* 1. MGV’s Pharmacy College, Panchavati, Nashik - 422 003, India. 2. R & D centre, Natural Remedies Pvt. Ltd., Bangalore - 560 100, India. Abstract The objective of this study was to evaluate the nootropic activity of BacoMind™, an enriched phytochemical composition from Bacopa monnieri, in different learning and memory paradigms viz., elevated plus maze, passive shock avoidance test and object recognition test. BacoMind™ was administered for 7 days at the dose of 40, 60 and 80 mg/kg to mice in elevated plus maze and passive shock avoidance test and 27, 40 and 54 mg/kg to rats in object recognition test. Scopolamine (0.3 mg/kg) was used to induce amnesia and piracetam (100 mg/kg) served as reference standard. In elevated plus maze test, BacoMind™ significantly (p<0.01) increased the inflexion ratio in scopolamine treated mice. In passive shock avoidance test, BacoMind™ significantly (p<0.001) reduced the latency to reach the shock free zone and number of mistakes in 15 min in both normal as well as scopolamine treated mice. In object recognition test, BacoMind™ significantly (p<0.001) increased the discrimination index in both normal as well as scopolamine treated rats. Thus, the findings of the present study revealed the nootropic activity of BacoMind™. Keywords: BacoMind™, Bacopa monnieri, Nootropic activity, Bacosides, Elevated plus maze, Passive shock avoidance test, Object recognition test. 1. Introduction Bacopa monnieri (B. monnieri), also referred folklore as a nerve tonic [3]. Traditionally, it to as Bacopa monniera, Herpestis monniera, was used as a brain tonic to enhance memory water hyssop, and “Brahmi,” has been in use development, learning and concentration [4] and since time immemorial as nerve tonic for to provide relief to patients with anxiety or improvement of memory. B. monnieri is a epileptic disorders [5]. perennial creeping plant found throughout India in wet, damp and marshy areas [1, 2]. An The plant, plant extracts and isolated bacosides infusion of the plant has been used in Indian have been investigated for nootropic activity. * Corresponding author # Currently available at : Department of Toxicology, Email : [email protected] University of Cagliary, Italy. S. B. Kasture et al. / Journal of Natural Remedies, Vol. 7/1 (2007) 166 - 173 167 Preliminary studies revealed that the treatment Based on the above, an enriched phytochemical with B. monnieri plant [6, 7], its aqueous composition, BacoMind™, was developed from decoction [8] and the alcoholic extract [9] B. monnieri extract for use as a cognition enhanced learning ability in rats. Alcoholic extract enhancing agent and it differs from the of B. monnieri has shown cognition facilitating previously reported standardized extracts, in that effect in normal rats [10] and inhibited the it has been standardized to nine different amnesic effects of scopolamine, electroshock and bioactive constituents and with reference to immobilization stress [11]. In different in vitro bioassays. Hence, in order to establish behavioural response studies, alcoholic extract the nootropic activity of this phytochemical of B. monnieri facilitated the cognitive function composition, BacoMind™, the current study and augmented the mental retention capacity [12]. was undertaken in different learning and Vohora et al., (2000) [13] have shown the memory paradigms. potential protective effect of B. monnieri in 2. Materials and methods phenytoin-induced cognitive deficit in mice by 2.1 Test substance both acquisition and retention of memory without affecting its anticonvulsant activity. The butanolic BacoMind™, an enriched phytochemical extract of B. monnieri has shown memory composition of B. monnieri extract was obtained enhancing effect in rats by increasing recognition from Natural Remedies Pvt. Ltd, Bangalore. index in differential exploration of familiar and BacoMind™ (patent pending) was standardized new objects test [14]. to the content of the following bioactive constituents viz., bacoside A3 (>5.0% w/w), Recently, Kishore and Singh (2005) [15] have bacopaside I (>7.0% w/w), bacopaside II reported that anterograde administration (before (>5.5% w/w), jujubogenin isomer of training) of alcoholic extract of B. monnieri in bacopasaponin C (>7.0% w/w), bacopasaponin mice facilitated anterograde memory and C (>4.5% w/w), bacosine (>1.5% w/w), luteolin attenuated anterograde experimental amnesia (>0.2% w/w), apigenin (>0.1% w/w) and induced by scopolamine and sodium nitrite. The β-sitosterol-D-glucoside (>0.3% w/w). It was standardized extract of B. monnieri has also further standardized using the following in vitro shown potent cognitive enhancing activity by bioassays viz., lipoxygenase inhibition assay attenuating the dementia effect of scopolamine (IC50< 600 µg/ml), ABTS radical scavenging in passive avoidance test [16]. A recent study assay (IC50< 100 µg/ml), DPPH assay reveals B. monniera extract is able to reduce (IC50< 200 µg/ml) and butyrylcholinesterase amyloid levels in PSAPP mice which is a inhibition assay (IC50< 3000 µg/ml). transgenic mice expressing the “Swedish” 2.2 Animals amyloid precursor protein and M146L presenilin-1 mutations [17]. Albino Wistar rats (150-175 g) and albino Swiss mice (20-22 g) of either sex were procured from The major chemical constituents shown to be National Toxicology Center, Pune and housed responsible for the memory-facilitating action three animals per cage with paddy husk as of B. monnieri are the steroidal saponins bedding. Animals were housed at a temperature bacoside A and B, as these compounds of 24 ± 2°C and relative humidity of 30-70 %. have shown to exert facilitatory effects on A 12:12 h light and dark cycle was followed. mental retention in avoidance response in rats The animals had free access to feed and water [18]. ad libitum. 168 S. B. Kasture et al. / Journal of Natural Remedies, Vol. 7/1 (2007) 166 - 173 2.3 Drugs and Chemicals transferred to their home cages. The TL (L0) Piracetam and scopolamine obtained from UCB was again measured after 24 h i.e. 30 min after India Ltd., Mumbai as gratis were used for this the administration of BacoMind™ on day 7. The study. TL was expressed as inflexion ratio. L – L 2.4 Assessment of nootropic activity Inflexion ratio = 1 0 L 2.4.1 Treatment schedule 0 Where L0 is the TL after 24 h and L1 is the initial In elevated plus maze and passive shock TL. avoidance test, mice in groups of six were treated with vehicle or BacoMind™ (40, 60 and 2.4.3 Passive shock avoidance test 80 mg/kg for 7 days, p.o.). Scopolamine (0.3 The apparatus consisted of an electric grid with mg/kg, single dose, i.p.) was used to induce a shock free zone (SFZ, 2 x 3 x 1 cm) in the amnesia and piracetam (100 mg/kg, single center and the entire grid having a perplex dose, i.p.) served as reference standard. enclosure. After 20 min of treatment on day 7, Another group was treated both with mice were placed individually on the electric grid BacoMind™ (60 mg/kg, 7 days, p.o.) and and allowed to explore for one minute. A stimulus scopolamine (0.3 mg/kg, single dose, i.p.). of 20 V with AC current of 5 mA was given and In object recognition test, rats in groups of latency to reach SFZ was recorded for three six were treated with vehicle or BacoMind™ consecutive times and considered as basal value. (27, 40 and 54 mg/kg, 7 days, p.o.). After 1 h of the first trial, each animal was Scopolamine (0.3 mg/kg, single dose, i.p.) was placed on the electric grid again and the latency used to induce amnesia and piracetam (100 mg/ to reach SFZ and the mistakes (descents) the kg, single dose, i.p.) served as reference animal made in 15 min were recorded and standard. Another group was treated both with considered as parameters for acquisition and BacoMind™ (40 mg/kg, 7 days, p.o.) and retention respectively. scopolamine (0.3 mg/kg, single dose, i.p.). 2.4.4 Object recognition test 2.4.2 Elevated plus maze test Object recognition test apparatus consisted of The elevated plus maze consisted of two open white coloured box (60 x 60 x 30 cm). The arms (25 x 5 cm) crossed with two enclosed apparatus was illuminated by a 60 W bulb arms (25 x 5 x 20 cm). The arms were suspended 50 cm above the box. The objects connected to a central platform (5 x 5 cm). The of different shapes to be discriminated were apparatus was elevated to a height of 25 cm in made of plywood but coloured black. The height a dimly illuminated (25 W) room [19]. of the objects was 8 cm [20]. The mice were placed individually at the end of The day before testing, the animals were allowed open arm of the elevated plus maze facing away to explore the box for 2 min. On day 7 after 30 from the center. The time taken by the mouse min of last dose, a session of two trials were to move into the enclosed arm was noted as given. An intertrial interval of 60 min was kept. transfer latency (TL). On day 6, TL (L1) was In the first trial (T1), two identical objects were recorded before administration of BacoMind™. presented in the opposite corners of the After determination of the TL, mice were apparatus and the amount of time taken by each allowed to explore the maze for 2 min and then animal to complete 20 sec of object exploration S.
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