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Bacosides and Neuroprotection

Reference work entry


Bacosides are the putative bioactive component of the Indian medicinal plant Bacopa monnieri which was placed second in the most important medicinal plants’ list by the Export-Import Bank of India. Among the bacoside components, bacoside A was found to be more pharmacologically active than bacoside B. Traditionally, Bacopa has been used in ayurvedic medicines as a cure for mental disorders and loss of memory. Later on, other pharmacological properties like antioxidant, antidepressant, antiulcer, hepatoprotective, anticancerous, vasodilator, smooth muscle relaxant, mast cell stabilizer, and various other functions are revealed. Increasing clinical trials indicate the potential role of bacosides even in Alzheimer’s disease and in epilepsy. Bacosides attribute to the neuroprotective function mainly through modulating antioxidant enzymes, namely, SOD, catalase, etc. Bacosides also regulate the levels of different neurotransmitters in the brain. Interestingly, bacosides do not exert any side effects as proven both in animal models and in human volunteers. These features render B. monnieri as well as bacosides pharmacologically immensely important.


Bacosides Bacopa monnieri neuroprotection antioxidant memory enhancer antidepressant 





Alkaline phosphatase


2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl) propanoic acid


Acute stress


Bacopa monnieri extract


Cornu ammonis 1




Central nervous system


Chronic unpredictable stress






γ-aminobutyric acid


Glutathione peroxidase




Glutathione S-transferase


Heat shock protein 70


Irritable bowel syndrome


Isopentenyl pyrophosphate


Lipid peroxidation




Nitric oxide synthase

PMN cells

Polymorphonuclear cells




Super oxide dismutase

1 Introduction

Bacosides are the mixture of different triterpenoid saponins isolated from the plant Bacopa monnieri Linn., traditionally known for its immense therapeutic value. In ayurvedic medicine in India, it has been used for almost 3,000 years and is classified as medhya rasayana, a drug used to improve memory and intellect (medhya). On the basis of their medicinal importance, commercial value, and potential for further research and development, B. monnieri was placed second in a priority list of the most important medicinal plants by the Export-Import Bank of India. Bacoside A and bacoside B are the major bacosides found in B. monnieri. Bacoside A and bacoside B were elucidated as mixtures of triglycosidic and diglycosidic saponins, respectively. Bacoside A fraction was found to be more biologically active compounds.

B. monnieri is a rich source of many secondary metabolites, namely, alkaloids, glycosides, flavonoids, and triterpenoid saponins (Fig. 120.1). Although different triterpenoid compounds are well distributed in plant kingdom, B. monnieri (popularly known as Brahmi) is the only herbal source of bacosides. B. monnieri is a herbaceous plant, belongs to the family Scrophulariaceae, and grows naturally in the Indian subcontinent. Authentic ayurvedic treatise like Charaka Samhita and Sushruta Samhita, written in the first century AD, prescribed Brahmi as a cure for mental disorder leading to insanity and also beneficial in loss of intellect and memory [1]. Brahmi is recommended in formulations for the management of a range of mental conditions including anxiety, poor cognition, and lack of concentrations [2]. Besides this, it has the potential to act as antioxidant [3], antidepressant [4], antiulcer [5], hepatoprotective, anticancerous [6], Ca+2 antagonist, smooth muscle relaxant [7], vasodilator [8], and mast cell stabilizer [9].
Fig. 120.1

Different types of secondary metabolites obtained from B. monnieri

Bacosides are most popular for their effect on nervous system mainly because of their neuroprotective activities. Neuroprotection signifies the mechanisms and strategies used to protect neuron from degeneration or malfunctioning. Various factors may involve in neuron malfunction (Fig. 120.2). Some of these factors are neuronal injury, exposure to chemical agents, adverse physiological conditions, and different disorders or diseases either decreasing efficiency of proper nervous functions or causing degeneration of neuron. These factors are finally affecting the normal functions of the central nervous system (CNS) in various ways.
Fig. 120.2

Factors involved in neuron malfunction

The goal of neuroprotection is to limit neuronal malfunction or to prevent neuronal death and to maintain the highest possible integrity of cellular interactions in the brain resulting in an undisturbed neural function. There is a wide range of chemical agents available or under investigation, which can potentially be used as neuroprotectant. An immunosuppressive calcineurin inhibitor, NOS inhibitor, σ-1 modulator, AMPA antagonist, and Ca2+ channel blocker have all demonstrated to show neuroprotective activity. An estrogen agonist and two glycoprotein IIb/IIIa antagonists also exhibit neuroprotective activity [10]. Effect of different neuroprotective agents can be achieved by different ways, as shown in the Fig. 120.3.
Fig. 120.3

Various strategies to achieve neuroprotection

Bacosides have been experimentally shown to act as anti-inflammatory agents and free radical scavengers through modulating antioxidant enzymes. Recent studies revealed that bacosides also facilitate proper functioning of CNS through GABA receptor function regulation in the cerebellum, inhibition of acetylcholinesterase, and enhancement of kinase activity in damaged neurons. Unlike other synthetic neuroprotective drugs, bacosides show no apparent toxic effect in experimental animal models as well as in human volunteers. Bacosides are also shown to stimulate thyroxin hormone secretion, have protective function against gastric ulcer, and even have potential to be used as anticancerous agent.

2 Pharmacological Applications

Bacosides are well known for their neuropharmacological effects. Most of the studies on the pharmacological properties were made with the alcoholic extract of whole plant of Bacopa monnieri which chiefly constituted of bacosides A and B [1].

2.1 Memory-Enhancing Ability of Bacosides

B. monnieri extract (BME) has been traditionally used in ayurvedic medicine for the treatment of a number of memory-related disorders, particularly those involving intellect and poor memory [1]. Although bacosides A and B were reported to be active in facilitating effects on learning schedules [11], later on it was found that bacoside A alone was responsible for the facilitation of memory [12].

Bacosides promote the capacity for mental retention and were active in both positive and negative reinforcement experiments [13]. Bacosides are also reported to enhance retention of newly acquired information [14]. Kishore and Singh [15] described that bacosides facilitate anterograde memory and attenuate anterograde experimental amnesia induced by scopolamine and sodium nitrite possibly by improving acetylcholine level and hypoxic conditions, respectively.

2.2 Protective Role of Bacosides in Chronic Cigarette Smoke

Bacoside A was observed to exhibit protective role against chronic cigarette smoke. Cigarette smoke exposure disturbs the tissue defense system by enhancing oxidative stress, inducing mitochondrial dysfunction and membrane damage. Bacoside A works by exerting antioxidant role and maintaining level of trace elements like copper, zinc, and selenium [16]. Moreover, bacoside A maintains the structural and functional integrity of the mitochondrial membrane potential and impulse propagation which depends on membrane enzymes. Disturbances in the electrolyte balance due to cigarette smoke also contribute to membrane damage in brain. Anabarasi and coworkers [17] reported that bacoside A inhibits lipid peroxidation, improves the activities of ATPase, and maintains the ionic equilibrium.

2.3 Antioxidant Properties

The brain is extremely vulnerable to oxidative stress mainly because of abundance of nonheme iron in brain, which involves in the catalysis of oxygen free radical production. Besides, brain also possesses a relatively high amount of polyunsaturated fatty acids that are particularly good substrates for peroxidation reactions [18].

Antioxidant properties of bacoside A were studied by S. K. Bhattacharya [3], and he showed that it increases the activities of antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase in the brain. The results also suggested that the increase in oxidative free radical scavenging activity of bacosides may be associated with cognition-facilitating action. Such cognition-enhancing effects of bacosides were revealed by Vohra et al. [19] and Stough et al. [20]. Both acquisition and retention of memory improvement was found to be associated with bacoside treatment, and the observed cognitive effects were noted to be independent of motor stimulation [19]. The later group of scientists suggested that the bacosides may improve higher-order cognitive processes that are critically dependent on the input of enforcement from the environment such as learning and memory.

2.4 Antistress Effect of Bacosides

Antistress effect of bacosides was studied by Shukia et al. [21] and Sheikh et al. [22]. The first group demonstrated that bacosides of Bacopa monnieri have been postulated to modulate the activities of Hsp70, cytochrome P450, and SOD allowing the brain to be prepared to act under adverse condition such as stress. The later group showed that treatment with bacosides attenuated the stress-induced changes in levels of serotonin and dopamine in cortex and hippocampus regions. The adaptogenic activity of bacosides might be due to the normalization of stress-induced changes in plasma corticosterone and levels of monoamines like noradrenaline, dopamine, and serotonin in cortex and hippocampus region of brain.

2.5 Bacosides as Remedy for Epilepsy and Cognitive Dysfunctions

BME has been indicated as a potential remedy for epilepsy in ayurvedic medicine. Bacoside A was reported to have beneficial effect on epilepsy-associated behavioral deficits [23]. High doses of BME were reported to exhibit anticonvulsive effect.

Hypobaric hypoxia-induced memory impairment has been attributed to several factors including increased oxidative stress, depleted mitochondrial bioenergetics, altered neurotransmission, and apoptosis. Hota et al. [24] expressed that administration of bacosides could be a useful therapeutic strategy in ameliorating hypobaric hypoxia-induced cognitive dysfunctions and other related neurological disorders.

2.6 Other Neuropharmacological Applications

Neuroprotective effect of bacosides was reported by Jyoti and group [25] against aluminium-induced changes in peroxidative products such as thiobarbituric acid-reactive substances and protein carbonyl contents and SOD activity. It was clearly observed that bacoside significantly prevented the aluminium-induced decrease in SOD activity as well as the increased oxidative damage to lipid and proteins. Neuroprotective effects of bacosides were shown to be comparable to those of l-deprenyl at both biochemical and microscopic levels.

It was found to have antidepressant activity and was comparable to that of standard antidepressant drug imipramine [4]. Bacoside was also known to possess potent adaptogenic property.

The role of bacosides on prevention of Alzheimer’s disease has been exclusively studied by Holcomb et al. [26] and Singh et al. [27] concluding that these compounds have potential application in Alzheimer’s disease. Anxiolytic activity of bacosides is also well established.

3 Mechanism of Action

Action of drugs is the biochemical and physiological mechanisms by which the chemical produces a response in living organisms. One major problem of pharmacology is that majority of the drugs produce single effect. The primary effect is the desired therapeutic outcome, and the secondary effects are all other consequences other than the desired effect which may be either beneficial or harmful (popularly known as side effects). The biological effects observed after a drug has been administered are the result of an interaction between that chemical and some part of the organism. Mechanisms of drug action can be viewed from different perspectives, namely, the site of action, the general nature of the drug-cell interactions, etc.

The bacosides aid in repair of damaged neurons by enhancing kinase activity, neuronal synthesis, and restoration of synaptic activity. Ultimately, nerve impulse transmission is relived, and a boost in the synthesis of new proteins in the brain is also observed [1].

Bacosides express antioxidant effect by increasing SOD, catalase (CAT), and GPx activities in all brain regions [3]. Bacoside A has a protective activity against nicotine-induced toxicity by reducing lipid peroxidation (LPO) and restoring SOD (superoxide dismutase), CAT, GSH, ALP, and GST levels [28], protecting the brain from damage by maintaining the structural and functional integrity of the mitochondrial membrane, inhibiting lipid peroxidation, improving the activities of ATPases, and maintaining the ionic equilibrium [17]. Figure 120.4 summarizes mechanism of oxidative damage on nerve cell. Neuroprotective activity of bacosides is mainly attributed to its ability to scavenge ROS.
Fig. 120.4

Mechanism of oxidative damage on nerve cell. Damage can be prevented in two ways: (1) by preventing formation of ROS or (2) by scavenging ROS

Bacosides exhibit antistress effects modifying Hsp70 expression, superoxide dismutase, and cytochrome P450 activity in rat brain. During stressed condition, Hsp70 expression and cytochrome P450–dependent 7-pentoxyresorufin-o-dealkylase (PROD) and 7-ethoxyresorufin-o-deethylase (EROD) activity increase in all brain regions. As a result, the activity of SOD was found to decrease for lower dose of bacosides but increase for higher dose [29].

Bacosides have a positive effect in Alzheimer’s disease. The levels of acrolein (one of the by-products of lipid peroxidation) and amyloid β peptide are much higher in vulnerable brain regions of the patients. This toxicity is due to oxidative stress generation in brain region. BME pretreatment significantly reduces intracellular reactive oxygen species (ROS) generation in the human neuroblastoma cell line SK-N-SH. Additionally, it preserves the mitochondrial membrane potential and activity of several redox-regulated proteins, i.e., NF-kappa β, Sirt1, ERK1/2, and p66Shc, to support cell survival in response to oxidative stress [27].

Shukia B. and coworkers [21] suggested that bacosides protect central nervous system from the nociceptive effect, electroshock seizures, and chemoconvulsions through GABAergic system. Additionally, Das et al. [30] showed that bacosides exert inhibitory effect on acetylcholinesterase activity and anti-dementia properties.

Bacosides have different effects on acute stress (AS)- and chronic unpredictable stress (CUS)-induced changes in plasma corticosterone and monoamines – noradrenaline (NA), dopamine (DA), and serotonin (5-HT) – in cortex and hippocampus regions of brain in rats. AS significantly elevates plasma corticosterone and 5-HT levels in both the brain regions, while DA content significantly increases only in cortex region. On the contrary, AS decreases NA content in both the brain regions and DA content in hippocampus regions. However, treatment with BME lowered the plasma corticosterone levels and increased the levels of 5-HT in both brain regions and DA in cortex. But it decreases DA in hippocampus regions and is also unsuccessful in normalizing the NA levels. CUS causes significant increase in plasma corticosterone levels and decrease in NA, DA, and 5-HT in cortex and hippocampus regions of rat brain. In summary, bacoside treatment weakens the stress-induced changes in levels of 5-HT and DA in cortex and hippocampus regions [22].

Bacosides were found to have a protective effect on morphine-challenged liver toxicity in rats. Also, it protects liver by controlling antioxidant enzyme levels [31].

4 Toxicity

In experimental studies, bacosides did not show any endocrine, metabolic, gastrointestinal, anabolic, or behavioral side effect; no lethality was observed on the oral administration also. Phase I clinical studies confirmed the safety of the bacosides in healthy male volunteers at both single and multiple doses administered over a period of 4 weeks [1]. In addition, bacosides showed no adverse effect on reproductive system in male mouse [32].

5 Bioavailability and Metabolism

Sivaramakrishna et al. [33] used column chromatography to obtain 12 pure saponin compounds from hydroalcohol extract of B. monnieri. Figure 120.5 represents all the saponins reported from B. monnieri. Table 120.1 compiles the chemical names of different saponins.
Fig. 120.5

Different saponins reported from B. monnieri

Table 120.1

Chemical names of some important saponins obtained from B. monnieri


Chemical name

Bacoside A3

3-O-[β-d-glucopyranosyl-(1 → 3)-O-{α-l-arabinofuranosyl-(1 → 2)}-O-(β-d-glucopyranosyl)] jujubogenin

Bacopaside IV

3-O-[β-d-glucopyranosyl-(1 → 3)-α-l-arabinopyranosyl] jujubogenin

Bacopaside X

3-O-[α-l-arabinofuranosyl-(1 → 2)-{β-d-glucopyranosyl-(1 → 3)-}-α-l-arabinopyranosyl] jujubogenin

Bacopasaponin E

3-O-[β-d-glucopyranosyl-(1 → 3)-{α-l-arabinofuranosyl-(1 → 2)}-α-l-arabinopyranosyl]-20-O-(α-l-arabinopyranosyl) jujubogenin

Bacopasaponin F

3-O-[β-d-glucopyranosyl-(1 → 3)-{α-l-arabinofuranosyl-(1 → 2)}-β-d-glucopyranosyl]-20-O-(α-L-arabinopyranosyl) jujubogenin

Bacopaside N1

3-O-[β-d-glucopyranosyl-(1 → 3)-β-d-glucopyranosyl] jujubogenin

Bacopaside I

3-O-[α-l-arabinofuranosyl-(1 → 2)-{6-O-sulphonyl-β-d-glucopyranosyl-(1 → 3)}-α-l-arabinopyranosyl] pseudojujubogenin

Bacopaside II

3-O-[α-l-arabinofuranosyl-(1 → 2)-{β-d-glucopyranosyl-(1 → 3)}-β-d-glucopyranosyl] pseudojujubogenin

Bacopaside III

3-O-[{6-O-sulfonyl-β-d-glucopyranosyl-(1 → 3)}-α-l-arabinopyranosyl] pseudojujubogenin

Bacopaside V

3-O-[β-d-glucopyranosyl-(1 → 3)-α-l-arabinopyranosyl] pseudojujubogenin

Bacopaside N2

3-O-[β-d-glucopyranosyl-(1 → 3)-β-d-glucopyranosyl] pseudojujubogenin

Bacopasaponin C

3-O-[β-d-glucopyranosyl-(1 → 3)-{α-l-arabinofuranosyl-(1 → 2)}-α-l-arabinopyranosyl] pseudojujubogenin

The neuroprotective actions of B. monnieri are mainly attributed by bacosides, which are dammarane type of triterpenoid saponins [34]. Bacosides were initially thought to be the mixture of bacoside A (melting point 250 °C) and B (melting point 203 °C). But later on, it was revealed that they are the stereoisomers of the same compound, where bacoside A was found levorotatory and bacoside B dextrorotatory [35]. The other active agents as extracted from this medicinal plant, namely, bacopasaponins A, B, C, D, E, and F [36] and also bacopasides I, II, III, IV, and V, were isolated and characterized [37, 38]. Figure 120.6 depicts chemical structures of some important saponins obtained from B. monnieri.
Fig. 120.6

Structure of some important saponins obtained from B. monnieri: (a) bacopasaponins A, B, C, D; (b) bacoside A3 and bacopasides II, N1, N2, IV, V; (c) bacopaside III G

Bacoside A and B fractions were further enriched and elucidated as mixtures of triglycosidic and diglycosidic saponins, respectively. Bacoside A fraction comprises of bacoside A3, bacopaside II, bacopaside X, and bacopasaponin C, whereas bacoside B was the mixture of bacopaside N1, bacopaside N2, bacopaside IV, and bacopaside V.

Saponins are a class of triterpene (C30) glycosides, produced by many plant species as secondary metabolite. Like most triterpenoid compounds found in adaptogenic plants, saponins possess an aglycone (glycoside-free) portion, termed as sapogenins, along with various sugar molecules attached to the triterpene unit [39]. Glucose and arabinose are the glycone part, whereas jujubogenin and pseudojujubogenin are the aglycone part in the saponins obtained from B. monnieri.

Terpenoids are classified by the number of five-carbon units they contain like hemiterpenes (C5), monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), triterpenes (C30), tetraterpenes (C40), and polyterpenes (more than 8 isoprene units). All terpenoids are derived by repetitive fusion of branched five-carbon units based on isopentane skeleton, i.e., isoprene units. At suitable chemical conditions, isoprene undergoes polymerization to generate numerous terpenoid skeletons.

At the turn of the twentieth century, structural investigations of many terpenoids led Otto Wallach to formulate the “isoprene rule,” which postulated that most terpenoids could be constructed hypothetically by repetitively joining isoprene units. This principle provided the first conceptual framework for a common structural relationship among terpenoid natural products. Wallach’s idea was refined in the 1930s when Leopold Ruzicka formulated the “biogenetic isoprene rule,” emphasizing mechanistic considerations of terpenoid synthesis in terms of electrophilic elongations, cyclizations, and rearrangements. This hypothesis ignores the precise character of the biological precursors and assumes only that they are “isoprenoid” in structure. As a working model for terpenoid biosynthesis, the biogenetic isoprene rule has been proved to be essentially correct [40].

Despite great diversity in form and function, the terpenoids are unified in their common biosynthetic origin. The biosynthesis of all terpenoids from simple, primary metabolites can be divided into four overall steps: (a) synthesis of the fundamental precursor IPP; (b) repetitive additions of IPP to form a series of prenyl diphosphate homologs, which serve as the immediate precursors of the different classes of terpenoids; (c) elaboration of these allylic prenyl diphosphates by specific terpenoid synthases to yield terpenoid skeletons; and (d) secondary enzymatic modifications to the skeletons (largely redox reactions) to give rise to the functional properties and great chemical diversity of this family of natural products. As bacosides are triterpenoid derivatives, they may probably follow the common biosynthetic pathway of terpenoid production [40].

Proper metabolic pathways that lead to the biosynthesis of bacosides are still not known. But most likely, as soon as the aglycone triterpenoid part is synthesized, the glycone part of the bacosides is then added to the aglycone part to yield different types of saponin molecules.

The following mechanism was proposed by James and Dubery [41] for the catabolism of bacosides. The sugar part of bacosides can easily be cleaved off in the gut by bacteria, allowing the aglycone (triterpene) to be absorbed. This allows them to be inserted into cell membranes and subsequently influence membrane fluidity, which can potentially affect many signaling pathways.

6 Other Biological Activities

6.1 Anti-inflammatory Role of Bacosides

Mast cells play a key role in the inflammatory process. A mast cell quickly releases its granules and various hormonal mediators into the interstitium when activated. Mast cell stabilizers are cromone medications (cromones prevent and relieve swelling of the airways and buildup of mucus. These are used to prevent asthmatic conditions) used to prevent or control certain allergic disorders. They block a calcium channel essential for mast cell degranulation, stabilizing the cell and thereby preventing the release of histamine and related mediators. Bacosides exhibit anti-inflammatory actions by stabilizing mast cells and inhibiting superoxide release from polymorphonuclear (PMN) cells [42].

6.2 Protective Effect of Bacosides Against Heart and Kidney Damage

B. monnieri along with four other herbs shows a considerable reduction of serum markers of heart and kidney damage. In addition, a decrease in lipid peroxidation with a concomitant increase in the enzymatic (SOD and CAT) and nonenzymatic antioxidants (reduced glutathione) suggested a protective effect against both damaged heart and kidneys [43]. Also, B. monnieri possesses broncho-vasodilatory activity, which is mainly characterized by interference with calcium ion movement [8].

6.3 Protective Role Against Gastric Ulcer

Bacoside A has a curative as well as protective effect in gastric ulcer. Sairam and coworkers [44] showed dose-dependent antiulcerogenic effect on various gastric ulcer models promoted by ethanol, acetic acid, aspirin, etc. This effect is due to increased mucin secretion and decreased cell shedding in stressed animals. But the extract does not have any effect on acid-pepsin secretion or cell proliferation. Bacosides were also shown to possess antimicrobial activity against Helicobacter pylori, a bacterium responsible for chronic gastric ulcers in vitro [45]. Accumulation of well-known protective agent for gastric mucosa, namely, prostaglandin E and prostacyclin, was also noted when H. pylori–infected human colonic mucosa cells were incubated with BME [45].

6.4 Bacosides Stimulate Thyroid Hormone Secretion

High doses of bacosides were found to increase thyroid hormone T4, but T3 remained unaffected. This data indicates that bacosides have the potential to induce thyroid stimulation, but probably they have no role in T4 to T3 conversion. Interestingly, this enhanced T4 secretion took place without increasing hepatic lipid peroxidation (LPO). This property of the extract suggests that it can be used as a thyroid-stimulating drug [46].

6.5 Potential Use as Antifertility Agent

Antifertility potential of bacosides has recently been demonstrated. In male mice, bacosides were shown to induce reversible suppression of spermatogenesis and fertility without causing toxic effect [32].

6.6 Anticancerous Property

Elangovan et al. [6] conducted in vitro studies on the anticancer activity of Bacopa extract. They saw that bacosides have cytotoxic activity for sarcoma-180 cells. This might be due to inhibition of DNA replication induced by bacosides in the cancerous cell line. Besides, in vitro studies demonstrated protective role of B. monnieri against DNA damage in astrocytes [47] and fibroblasts [48], which protects them from becoming cancerous.

7 Clinical Trials

Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety (or information about adverse drug reactions and adverse effects of other treatments) and efficacy data to be collected for health interventions (e.g., drugs, diagnostics, devices, therapy protocols). These trials can take place only after satisfactory information has been gathered on the quality of the nonclinical safety, and health authority/ethics committee approval is granted in the country where the trial is taking place. Clinical trials have different phases like phase I, phase II, phase III, and phase IV. After completion of different phases of clinical trial, a potential drug is available in markets for public use.

7.1 On Antioxidant Properties

It is reported that different salts of aluminium caused oxidative damages of lipids, proteins, and nucleic acids. Jyoti et al. [25] experimentally demonstrated that BME at a dose of 40 mg/kg/day shows similar antioxidant properties like l-deprenyl, a standard drug against AlCl3 toxicity, in 8-month-old male Wistar rats. The extract significantly protects lipid and protein in cerebral cortex of rat brain from damage. It also restored the activity of endogenous antioxidant enzymes associated with aluminium administration. It extensively inhibits intraneuronal lipofuscin accumulation and necrotic alteration in the CA1 region of the hippocampus of rat brain [25].

Chronic cigarette smoke exposure also disturbs the tissue defense system by enhancing oxidative stress. Anbarasi and coworkers [16, 17] showed that when adult male albino rats and male Wistar albino rats were exposed to cigarette smoke for a period of 12 weeks, it induced mitochondrial dysfunction in rat brain by the production of ROS molecules. For assay of mitochondrial functional capacity, they used lipid peroxides, cholesterol, phospholipid levels, cholesterol/phospholipid (C/P) ratio, and the activities of isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase, and cytochrome c oxidase as a marker. Aqueous extract of Bacopa monnieri also protects from nicotine-induced toxicity by reducing lipid peroxidation (LPO) and restoring SOD (superoxide dismutase), catalase, GSH, ALP, and GST levels in mice liver [28].

When rats are administered with bacoside A (10 mg/kg), levels of glutathione, vitamin C, vitamin E, and vitamin A were reduced. The activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were also assayed. Copper, iron, zinc, and selenium levels in brain and serum ceruloplasmin activity were also measured. Administration of bacoside A improved the antioxidant status and maintained the levels of trace elements [16].

7.2 On Cognitive Function

One of the significant effects of bacosides is to improve higher-order cognitive processes in human beings. Cognition helps people to function in day-to-day life. It includes concentrating, learning, strategizing, executing plans, comprehending language, etc. When it failed to work properly, people find difficulties in processing information quickly, remembering or recalling information, paying attention in work, solving problems, etc.

Stough and coworkers [20] studied the effect on a double-blind, placebo-controlled independent group. Subjects were indiscriminately assigned to one of two treatment conditions, ethanolic extract of B. monnieri (300 mg) or placebo. Neuropsychological status was monitored pre- and postdrug administration. Subjects were tested for speed of visual information processing, learning rate and memory consolidation, and state anxiety. Treated subjects were significantly improved above neurophysiological conditions compared to placebo.

Bacoside’s capacity to improve cognitive effect has also been studied in Indian children. Tests were performed on 40 children (ages between 6 and 8). Children were grouped into control and treated. One teaspoon Bacopa syrup (350 mg Bacopa powder/teaspoonful) three times daily for 3 months was given to the children undergoing treatment. Visuomotor and perceptual abilities and memory span were measured before and after the treatment. Major improvements were noted in perceptual images of patterns, increased perceptual organization, and reasoning ability [49].

Another trial was done by another group of scientists to prove cognitive effect of bacoside. A double-blind, randomized, placebo-controlled trial was performed on 36 children with diagnosed attention deficit/hyperactivity disorder over a period of 16 weeks. Nineteen children were given Bacopa extract (containing 20 % bacosides) at a dosage of 50 mg twice daily for 12 weeks against a placebo. A significant improvement was observed in Bacopa-treated subjects at 12 weeks proven by an upgradation on sentence repetition and logical memory. Assessment showed that these improvements were maintained at 16 weeks [50].

7.3 On Memory-Enhancing Function

Roodenrys et al. [14] showed that bacosides also have chronic effect on human memory. In a double-blind, randomized, placebo-controlled study, they tested various memory functions and levels of anxiety in 76 adults (aged between 40 and 65 years). This study showed that bacosides help to retain new information, decrease the rate of forgetting newly gained information, increase verbal and short-term memory, and help in recovery of preexperimental knowledge.

7.4 On Anti-inflammatory Function

Carrageenan, a linear sulfated polysaccharide, induces paw edema in mice and rats which is an acute inflammatory model. The ethanolic extract of B. monnieri is injected intraperitoneally (100 mg/kg, 10 ml/kg) into right hind paw of mice. After 30 min, paw edema was induced by a single subplantar injection of 0.1 ml of arachidonic acid (0.5 %, w/v), bradykinin (20 μg/ml), histamine (1 mg/ml), prostaglandin E2 (0.01 μg/ml), or serotonin (1 mg/ml) into the right hind paw of rats. Three hours later, the animals were sacrificed, and paws were quickly amputated at the ankle-joint level and weighed. The edema in the right paw was determined by subtracting its weight from the weight of the left paw [51]. The extract (50 and 100 mg/kg) resulted in a considerable decrease in paw edema (33–95 %) which was 1.6 times more powerful than that caused by aspirin (28–60 %). Hence, B. monnieri has anti-inflammatory action toward paw edema.

7.5 On Gastrointestinal Disorders

Some in vitro animal and human studies have investigated the effect of bacosides on gastrointestinal tract. It has direct spasmolytic activity on intestinal smooth muscle, via inhibition of Ca2+ influx across cell membranes. Also, a similar effect was observed in rabbit’s blood vessels and jejunum.

Bacosides have prophylactic and healing effects in five models of gastric ulcers. BME considerably healed penetrating ulcers induced by acetic acid at a dose of 20 mg/kg for 10 days, notably strengthened the mucosal barrier, and reduced mucosal exfoliation. The extract also reportedly reduces lipid peroxidation and balances SOD and catalase levels in rat gastric mucosa [44, 45].

In vitro studies on animal and human subjects regarding the effect of bacosides on gastrointestinal tract showed that they may have a positive effect on irritable bowel syndrome (IBS). Experiments showed that it has a direct spasmolytic effect on intestinal smooth muscle. A double-blind, randomized, placebo-controlled trial of 169 patients with IBS was done for both standard therapy (clidinium bromide, chlordiazepoxide, and psyllium) and Bacopa extract. Subjects were divided into five subgroups based on type of IBS and randomly assigned to standard drug treatment, BME therapy, or placebo for 6 weeks (5 g of each drug administered orally thrice daily). It was exposed that standard drug therapy is better than BME, except in IBS patients with diarrhea [52].

7.6 On Diabetic Neuropathy

A common complication of diabetes is diabetic neuropathy. It damages the nerves that allow feeling sensations such as pain. Recent treatments are insufficient to provide relief from pain and also cause side effects. Streptozotocin stimulates diabetes in 80 % of animals. Male Sprague Dawley rats were injected streptozotocin (65 mg/kg, i.p.) and subjected to thermal (cold and hot) and chemical (formalin) stimuli. Six weeks after streptozotocin administration, blood glucose levels increased and hyperalgesia developed. Hyperalgesia is an increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves. Ethanolic extract of Bacopa monnieri leaf (500 mg/kg, i.p.) containing bacoside A as main composition significantly set back the responses to thermal and chemical stimuli in diabetic rats [53].

7.7 On Anxiety and Depression

Traditionally, Bacopa was used as antianxiety remedy in ayurvedic medicine and is justified by both animal and clinical research. Lorazepam which is an antianxiety drug has amnesia as side effect. But BME having the same effect did not stimulate amnesia [54]. Thirty five patients diagnosed with anxiety neurosis were treated with Brahmi syrup with a dose of 30 mL twice daily. After this treatment the patients showed significant decrease in level of anxiety, disability, and mental fatigue whereas increase in immediate memory span. Some other positive changes that also occurred during treatment were increased body weight, decreased respiration rate, and decreased systolic blood pressure [55].

7.8 Clinical Trials on Synthetic Drug-Bacosides Interaction

Carbamylcholine chloride (carbachol) exerts bronchoconstrictor action. It is noticed that carbachol significantly increases inspiratory and expiratory pressures and decreases blood pressure and heart rate. Bronchodilation was monitored in anesthetized male albino rats, and ethanolic extract of B. monnieri (50 mg/kg) was administered before and after. The effects of carbachol were reversed within 2–5 min. At a dose of 25 mg/kg, the plant extract repressed the inspiratory pressure, while the doses 37 and 50 mg/kg inhibited both inspiratory and expiratory pressures, respectively. Increase in tracheal pressure due to carbachol reversed in the presence of the plant extract (50 mg/kg). Hence, the ethanolic extract antagonizes the bronchoconstrictor effects of carbachol [7].

Scopolamine is frequently used as amnesic agent. But being a synthetic drug, it has some undesirable effects. Oral dose (at 120 mg kg 1) of ethanolic extract of Bacopa monnieri inverted scopolamine (0.5 mg kg 1 i.p.)-induced adverse effects. The ethanolic extract also stopped scopolamine (0.5 mg kg 1 i.p.)-induced retrograde amnesia [56].

8 Conclusion

With the increasing knowledge on pharmacological applications of bacosides, researchers are now also trying BIOTECHNOLOGICAL tools to obtain higher yields of bacosides from the plant as it is the exclusive source of these immensely useful compounds [57]. Diverse array of neuropharmacological functions of bacosides have the prospect to end the long quest for a neuroprotective drug which has no or minimal side effects. The therapeutic effects of BME were gradually established both in animal models and in human volunteers. But the detailed mechanism through which bacosides execute neuroprotective function or enhance memory is still not clear. Also, the exact functional component of BME as well as its metabolism is yet to be elucidated. Many studies indicated that there may exist interactions between herbal medicines and synthetic drugs. So, stringent clinical trials are necessary to negotiate these issues.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Botany, Centre of Advanced StudyUniversity of CalcuttaKolkataIndia
  2. 2.Department of GeneticsUniversity of CalcuttaKolkataIndia

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