Brahmi

Generic name: Bacopa Monniera (L.) Wettst.
Brand names: Brahmi, Jalanimba, Jalnaveri, Sambrani Chettu, Thyme-leaved Gratiola

Usage of Brahmi

Bacopa has traditionally been used for various conditions but is best known as a neural tonic and cognitive and memory enhancer. Evidence suggests that bacopa acts via the following mechanisms: antioxidant neuroprotection (via redox and enzyme induction), acetylcholinesterase inhibition and/or choline acetyltransferase activation, beta-amyloid reduction, increased cerebral blood flow, and neurotransmitter modulation (acetylcholine, 5-hydroxytryptamine, dopamine).(Aguiar 2013) Long-term bacoside administration (200 mg/kg orally per day for 3 months) can lead to a decrease in proinflammatory cytokines (interleukin 1beta and tumor necrosis factor alpha [TNF-alpha], but not interferon gamma), a significant induction of inducible nitric oxide synthase expression, and a significant reduction in total nitrite and lipofuscin content in the cortex.(Cicero 2018) Bacopa is a well-known neuroprotective herb, and it has been hypothesized that bacopa could be effective in overcoming the Tau-mediated pathology in neurons. Because the aggregates of Tau protein are the predominant cause of Alzheimer disease, it has been suggested that the nootropic herb bacopa could be beneficial in managing Alzheimer disease symptoms and pathology.(Dubey 2019) Supplementation with bacopa extract is likely to support the antioxidant defense pathways altering redox status, which are vital components for normal functioning, while improving cognitive ability. The antioxidant system is believed to be compromised and glutathione levels reduced with age; bacopa extract has potential as a therapeutic antioxidant to reduce oxidative stress and improve cognitive performance.(Simpson 2015)

Antioxidant activity

Animal and in vitro data

In vitro, several bacopa extract fractions have blood clot lysis activity.(Emran 2015) Antioxidant activity may explain the neuroprotective role of bacoside A in increasing brain levels of glutathione and vitamins C, E, and A in rats exposed to cigarette smoke. Zinc and selenium levels were also restored in the brain.(Anbarasi 2006) A bacopa 50 mg/kg/day oral supplement reversed memory impairment in a colchicine-treated rat model of Alzheimer disease; the neuroprotective effects of the bacopa supplement reduced colchicine-induced cognitive decline due to oxidative stress and neural death in the subventricular zone, dentate gyrus, and basal forebrain.(Saini 2012) Animal models also suggest that bacopa protects against neurodegeneration. Bacopa may increase antioxidant activity by protecting central and peripheral neuronal systems, as documented in healthy 3-month-old female Wistar rats and in 4-week-old male mice.(Priyanka 2013, Shinomol 2011) A neuroprotective effect against injury caused by cerebral ischemia was reported for bacopaside I.(Liu 2013) Some animal models report that bacoside constituents have an antioxidant effect on the hippocampus, frontal cortex, and striatum.(Aguiar 2013, Verma 2014)

CNS effects

Analgesic effects

In vitro data

Bacosine, a free triterpene isolated from the aerial parts of B. monnieri, has demonstrated analgesic effects through opioidergic pathways.(Vohora 1997) According to a review article, bacopa's anti-inflammatory effect in chronic pain is mediated via cyclooxygenase-2 inhibition.(Rauf 2013)

Antidepressant effects

Animal data

In a study in mice, B. monnieri displayed antidepressant effects (ie, according to screening models such as the tail suspension and forced swim tests) via interaction with the serotonergic, dopaminergic, and noradrenergic systems. The mixture of bacopaside I and bacoside A isolated from B. monnieri also inhibited activity of monoamine oxidase A and B isoenzymes.(Martins 2018) In a study in rats, bacoside A from a B. monnieri methanolic extract inhibited the effects of morphine withdrawal–induced depression.(Rauf 2014)

Antiepileptic activity

Animal data

Researchers have suggested that high doses of bacopa extract administered via intraperitoneal injection for 15 days results in antiepileptic activity, based on animal studies.(Shinomol 2011) In a rat model study, bacopa and bacoside A treatment reversed epilepsy-associated changes by decreasing gamma-aminobutyric acid (GABA) receptors in the cerebral cortex.(Mathew 2012)

Attention-deficit/hyperactivity disorder

Clinical data

In a randomized, double-blind, placebo-controlled trial of children with attention-deficit/hyperactivity disorder (ADHD) (N=36), fresh whole plant extract of bacopa was given at a dosage of 50 mg twice daily for 12 weeks, and a battery of cognitive function tests were administered at baseline and 4, 8, 12, and 16 weeks (ie, 4 weeks posttrial). Improvements were reported in the active treatment group (n=19) at 12 weeks, as measured by tests of sentence repetition, logical memory, and paired associate learning tasks.(Mathew 2010) In an open study without a placebo or control group, 31 children 6 to 12 years of age diagnosed with ADHD received 225 mg/day of a standardized bacopa extract for 6 months. Seventy-four percent of children experienced a 20% improvement in total subtest scores for ADHD symptoms. Attention-deficit symptoms (ie, restlessness, self-control, learning problems, impulsivity, psychiatric problems) were reduced in 85% of children.(Dave 2014) A systematic review of clinical trials investigated the use of bacopa extract as monotherapy for at least 1 month in children or adolescents; of the 5 studies that met inclusion criteria, 2 were double-blind, randomized, placebo-controlled trials conducted in children with ADHD (n=76; age range, 6 to 12 years). B. monnieri extract 100 mg/day was administered for 3 months in these 2 studies. Significant treatment effects in logical memory, sentence memory, paired associate learning, digit span, word recall, delayed response learning, attention, and hyperactivity were observed with bacopa compared with placebo. Drop-out rates were 22.5% in each trial. No adverse effects were reported by participants.(Kean 2016)

CNS inflammation

In vitro data

According to in vitro studies, bacopa inhibits the release of inflammatory cytokines from microglial cells and inhibits enzymes associated with inflammation in the brain. The tea, infusion, and alkaloid extracts of bacopa, as well as bacoside A inhibited the release of TNF-alpha and interleukin 6 from activated N9 microglial cells in vitro. In addition, the tea, infusion, and alkaloid extracts of bacopa effectively inhibited caspases 1 and 3 and matrix metalloproteinase-3 in the cell free assay.(Nemetchek 2017)

Cognitive effects

Some studies of bacopa demonstrate suppression of acetylcholinesterase activity, which results in enhanced cholinergic function leading to improved attention and memory processing.(Peth-Nui 2012) In other studies, some bacopa compounds showed no inhibitory activity against acetylcholinesterase, but a binding affinity toward the D1 receptor was observed.(Ramasamy 2015) One of these studies demonstrated that bacoside A is not likely to be absorbed through the intestine or to penetrate the blood-brain barrier. Thus, the bacosides may be transformed in vivo, resulting in active metabolites mediating memory-enhancing and cognitive activities.

Animal data

In an older study, oral treatment of rats with bacopa extract for 24 days facilitated an ability to learn mazes.(Dey 1976) The extract has demonstrated improved rat performance in various behavioral models of learning.(Singh 1982) In another study, a bacopa alcoholic extract enhanced learning ability in rats, including retention of newly learned behavioral responses. Bacosides A and B may be associated with the cognition-facilitating effect. Administration of standardized bacopa extract in rats resulted in improvement in spatial learning and enhanced memory retention. Bacopa reversed Diazepam-induced amnesia in mice and restored cognition in a pilocarpine-induced epilepsy rat model. Scopolamine-induced behavior deficits in rats were attenuated due to dose-dependent inhibitory effects of bacopa on acetylcholinesterase activity.(Shinomol 2011)

Clinical data

A systematic review of several randomized, double-blind clinical trials demonstrated efficacy of bacopa in improving memory and some cognitive functions. Adults without dementia or serious cognitive impairment were administered bacopa extracts (300 to 450 mg daily over a 12-week period). Although cognition was not as well documented as other effects, bacopa improved 9 of 17 free recall memory tasks.(Pase 2012)

In a clinical trial of 76 healthy adults, weight-based dosing of bacopa extract resulted in improved retention of new information. However, the results indicated no effect on attention, verbal and visual short-term memory, or retrieval of information from long-term memory. No adverse effects were reported on subjective measures of psychological state (eg, depression, anxiety, stress, everyday memory).(Roodenrys 2002) A double-blind, placebo-controlled study conducted in 46 healthy adults demonstrated statistically significant improvements in visual information processing (P=0.018), learning rate (P=0.042), memory proactive interference (P=0.042), and forgetting rate (P=0.03) after 12 weeks supplementation with bacopa 300 mg/day compared to placebo. Anxiety was also significantly reduced with bacopa (P=0.001). Nausea, dry mouth, and fatigue occurred in a higher percentage of participants in the bacopa group.(Stough 2001) In 2 clinical trials employing a crossover design to assess the short-term effects of bacopa on cognition, healthy subjects were administered 2 doses (320 mg or 640 mg) of bacopa extract. The first trial documented no change in cardiovascular activity or task-related ratings of stress and fatigue.(Downey 2013) The second trial documented some improvement in mood effects and a reduction in cortisol levels.(Benson 2014)

In a 12-week trial, elderly patients received a single daily oral dose of bacopa standardized extract 450 mg for 12 weeks, which resulted in improved cognitive functions (eg, attention, verbal memory).(Harshad 2008) The hematological lab profile was comparable with that of controls.

A systematic review included studies of child and adolescent populations in which bacopa extract monotherapy for at least 1 month was used; ages ranged from 4 to 12 years, and doses ranged from 100 to 1,050 mg/day for 3 to 6 months. Improvements in memory span, visual memory, meaningful memory, and visual perception were reported in children who were healthy, children with ADHD, and children with low intelligence.(Kean 2016)

In another review of clinical trials evaluating the use of bacopa for improvement of cognition, B. monnieri 150 mg twice daily for 90 days improved performance in a spatial working memory task in healthy subjects; B. monnieri treatment for 3 months decreased the rate of forgetting newly acquired information in subjects between 40 and 65 years of age; and standardized B. monnieri extract 300 mg/day for 12 weeks improved performance in a delayed recall and Stroop Task (assessing the ability to ignore irrelevant information) in participants 65 years and older without dementia. Moreover, treatment with B. monnieri 300 mg/day improved verbal learning, memory acquisition, and delayed recall in healthy volunteers older than 55 years.(Farooqui 2018)

According to a meta-analysis of data from 9 chronic-dosage (longer than 12 weeks), randomized, controlled trials (N=518), supplementation with approximately 300 mg/day of bacopa extract (containing 50% triterpene bacosides) improved attention-task performance and speed of processing. One of the included studies also demonstrated a decreased latency of evoked potentials to stimuli (ie, faster cerebro-electrical processing) using electroencephalogram.(Kennedy 2019) In 437 subjects of the same meta-analysis, time taken to complete a task (Trail Making Test part B) was improved (−17.9 ms; 95% CI, −24.6 to −11.2; P<0.001) and choice reaction time was decreased (–10.6 ms; 95% CI, −12.1 to −9.2; P<0.001). The tested extracts were overall well tolerated.(Cicero 2018, Kongkeaw 2014) The meta-analysis suggests that B. monnieri has the potential to improve cognition, particularly speed of attention.(Kongkeaw 2014)

A compiled summary of various clinical studies evaluating the effects of bacopa extracts on cognition showed the effective use of B. monnieri for cognition and neuroprotection.(Abdul Manap 2019) In addition, a review of major studies evaluating effects of bacopa extracts for Alzheimer disease demonstrates brahmi improves memory performance and cognitive function, cardinal symptoms of Alzheimer disease.(Chaudhari 2017)

Nerve tonic

Animal data

In mice, a B. monnieri ethanolic extract increased cerebral levels of GABA 15 minutes after administration.(Dey 1966) In a study evaluating effects of the purified bacosides A and B on avoidance responses in rats, enhanced relearning index and dose-dependent effects on taste aversion response were observed.(Singh 1988) A saponin fraction of B. monnieri reduced spontaneous motor activity in rats and lowered rectal temperatures in mice. The same extract showed tranquilizing effects in rats but did not block the conditioned avoidance response. It also protected against audiogenic seizures.(Ganguly 1967, Ganguly 1967) The ethanolic extract of B. monnieri relaxed smooth muscle preparations of guinea pig and rabbit pulmonary arteries, rabbit aorta, and guinea pig trachea by a mechanism postulated to involve prostacyclins.(Dar 1997) The same investigators found spasmolytic effects of the ethanol extract in guinea pig ileum and rabbit jejunum to be nonspecifically mediated through calcium channels.(Dar 1999)

Parkinson disease

Animal data

In a review evaluating medicinal herbs in Parkinson disease pharmacotherapy, bacopa extracts imparted anti-Parkinsonism effects both in transgenic and toxin-induced animal model systems, thereby suggesting potential efficacy against Parkinson disease.(Srivastav 2017)

Schizophrenia

Animal data

In a rat model, bacopa extracts reduced psychosis by decreasing brain dopamine levels in the frontal cortical region.(Jash 2014) In another study, bacopa restored cognitive deficits in a phencyclidine rat model of schizophrenia.(Piyabhan 2014)

Clinical data

In a case study of a patient with schizophrenia, administration of olanzapine with add-on bacopa extracts of 500 mg/day for 1 month resulted in a reduction in psychopathology.(Sarkar 2012)

Hepatoprotective effects

Animal data

An oral alcoholic extract of bacopa protected against compromised antioxidant status in the liver of morphine-treated rats.(Shinomol 2011) In another study, a bacopa ethanol extract protected against nitrobenzene-induced liver damage in rats.(Menon 2010)

Brahmi side effects

Commonly reported adverse effects are flu-like symptoms, GI irritation, nausea, increased intestinal motility, and muscle fatigue.Calabrese 2008 A phase 1 safety study of 23 volunteers reported mild GI adverse effects (eg, epigastric burning, nausea, fullness, bloating). All adverse effects subsided spontaneously without discontinuation of treatment.Pravina 2007

Before taking Brahmi

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

How to use Brahmi

Numerous bacopa dosage forms and commercial products are available and marketed for improvement of short- and long-term memory; variability among products exists.Saini 2012 In a meta-analysis and reviews of clinical studies evaluating use of bacopa extracts for improvement of cognition and memory in adults, dosages typically ranged from 300 to 450 mg/day; durations of therapy varied, but were typically 12 weeks.Farooqui 2018, Harshad 2008, Kennedy 2019, Pase 2012

Warnings

No clinical data are available regarding toxicity. Toxicity studies in rats reported a median lethal dose of 2,400 mg/kg. Histopathological evidence from a 90-day oral toxicity study in rats did not reveal any evidence of toxicity at bacopa doses of 85, 210, and 500 mg/kg.Joshua 2007

What other drugs will affect Brahmi

None well documented. Bacopa standardized extract inhibited CYP-450 enzymes, and inhibition exhibited by the constituents bacoside A, bacoside A3, bacopaside II, bacopaside X, bacopasaponin C, and bacopaside I was negligible. Bacopa may increase the concentration of drugs metabolized by these isoenzymes.Ramasamy 2014

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