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Bacopa monnieri Increases Cerebral Blood Flow in Rat Independent of Blood Pressure
Abstract
Bacopa monnieri (L.) Wettst. (Brahmi in India and Thailand) is an ayurvedic dementia treatment, but its effect on cerebral blood flow (CBF) is still unknown. We sought to test its chronic and acute effects on CBF compared with Ginkgo biloba and donepezil. CBF was measured by laser Doppler from rat cerebral cortex after 8 weeks of daily oral dosing of these drugs. Systolic blood pressure was also measured using the tail cuff method or via arterial cannulation. In rats treated with B. monnieri (40 mg/kg), CBF was 25% increased [2927 ± 123 perfusion units, (PU)] compared with shams (2337 ± 217 PU, p < 0.05, nine rats). G. biloba (60 mg/kg) also increased CBF (by 29% to 3019 ± 208 PU, p < 0.05, nine rats). No clear effect was obtained with donepezil (1 mg/kg). Chronic administration of the preparations had no effect on blood pressure. In contrast, intravenous acute infusion of these herbals (20-60 mg/kg) had marked dose-dependent hypotensive actions (diastolic ~31 mmHg lower with 40 mg/kg of either extract), which correspondingly reduced CBF by ~15%. Likewise, CBF fell slightly with acute intravenous sodium nitroprusside and rose with noradrenaline. Donepezil (1 mg/kg) was slightly hypotensive without affecting CBF. Increased CBF with B. monnieri may account for its reported procognitive effect, and its further exploration as an alternative nootropic drug is worthwhile. Copyright © 2012 John Wiley & Sons, Ltd.
... There are numerous described mechanisms by which nootropics may exert their effect (for a review, see reference 4). For example, some act by increasing blood flow to the brain, thereby providing more access to glucose and oxygen [3,5]. Others reduce oxidative stress and contribute to eliminating free radicals [6][7][8][9]. ...
... Based on these results, the following working concentrations were used in the subsequent studies: bilberry (0.0001%, 0.001%), blueberry (0.0001%, 0.001%), bacopa (0.0001%, 0.001%), sage (0.0001%, 0.001%, 0.01%), saffron (0.0001%, 0.00005%), arctic root (0.0001%, 0.001%), ginkgo biloba (0.0001%, 0.00005%), ginseng (0.0001%, 0.001%, 0.01%), gotu kola (0.0001%, 0.001%, 0.01%). 5 ...
Brain health is a matter of great importance as we age, where memory loss and other cognitive declines become slowly apparent. There are numerous natural solutions, called nootropics, that can help mitigate this natural process. While some, such as ginkgo biloba, have been traditionally used for centuries, in many cases there is a lack of scientific evidence on their potential mechanisms and efficacy. To this end, the objective of the current study is to evaluate and compare several standardized herb extracts with potential nootropic effects, and from this analysis develop a formula and confirm its effect in healthy volunteers with mild cognitive impairment. A total of 9 standardized herb extracts were chosen based on previous scientific evidence and tested in human neural stem cell cultures exposed to oxidative stress. The expression of nerve growth factor (NGF), NRF2 and vascular endothelial growth factor (VEGF) were also analyzed. As a result, it was observed that an extract from Salvia officinalis revealed to have the most noticeable effect among the herbs analyzed. In further tests it was confirmed that its combination with rutin, a phenolic compound with potential nootropic effects, increased brain derived neurotrophic factor (BDNF) expression, as well as inhibiting acetylcholine esterase (AChE) activity. Finally, a randomized, double-blind placebo-controlled clinical study was conducted, testing the effects of the combination at two different doses, for 12 weeks, in healthy volunteers aged 50+ with mild cognitive impairment. Two questionnaires were applied, the MoCA and ADAS-Cog. As a result, both doses significantly improved several characteristics related to memory, particularly memory recall, with a more noticeable effect in the higher dose. Therefore, the results suggest that the long-term intake, at least 6-12 weeks, of a natural herb blend comprised of Salvia officinalis and rutin can help improve certain brain health-related parameters in healthy subjects with mild cognitive impairment.
... [234] Bacopa has also shown cardio protection, increased coronary blood flow and protection against reperfusion damage to myocardial ischemia [234,241] and regular oral administration of Bacopa monnieri extract (40 mg/kg) to rats for eight weeks has shown a substantial improvement in cerebral blood flow, suggesting cerebrovascular dilation. [242] Furthermore, In vitro thrombolytic activity of ethanolic, methanolic, acetone and aqueous extract of various parts (root, stem and leaf) of Bacopa monnieri is also reported and the study indicated that the ethanolic leaf extract showed the highest thrombolysis followed by aqueous extract, methanol and acetone, and this finding may have important implications for the treatment of cardiovascular disease. [243] Hydro-alcoholic lyophilized extract of entire Brahmi also serves as a cardioprotectant against myocardial necrosis induced by isoproterenol in rats. ...
... Furthermore, these results affirm the effectiveness of this herb in the treatment of neurological disorders. [242] Xoan Thi Le et al., reported that Bacopa monnieri triterpenoid saponins (bacosides I) were also beneficial for the prevention of cognitive deficits related to cerebral ischemia in the mouse model. The neuroprotective effects of bacopaside I were blocked by the PKC inhibitor Ro-31-8220 and the PI3K inhibitor LY294002, but not by the ERK inhibitor U0126. ...
Throughout history, complementary and alternative therapies have been widely utilised. In recent years, there has been a surge in interest in the usage of herbal treatments all around the world. Various natural chemicals, such as those produced from plants, have been investigated as potential therapies for a myriad of ailments. The essence of this review was to methodically describe everything we know about Bacopa monnieri (L.) Pennell, a mysterious holistic Vedic herb belonging to the Plantaginaceae family, a well-known nootropic and effective memory enhancer, which has recently emerged as one of the most important medical herbs, widely used therapeutically in the Orient and growing in popularity around the world. Literature was gathered from sources such as Scopus, PubMed, Google Scholar, and ScienceDirect, and reviewed using the Prisma quality metacritic paradigm. It is now plainly obvious that current therapies fall short of meeting the demands of the vast majority of individuals with health problems, and traditional medicines are gaining appeal as a result of their reduced toxicity. Bacopa is a traditional herb used in Ayurvedic medicine to treat brain and nerve weariness, as well as in Siddha medicine to treat impaired memory. It's also used to cure brain and nerve exhaustion in Unani medicine. We improved Brahmi micropropagation and secondary metabolite biosynthesis by compiling pharmacobotanical and pharmacognostical descriptions, as well as ethnoarchaeological data and nanotechnology domination. This critique also highlights our contemporary information of pharmacological activity, preclinical and clinical investigations, significant bioactives, reported mechanisms of action, clinical effectiveness, safety, and the potential for herb-drug interactions. At the same time, the current incarnation of research at the plant is reviewed, as well as future research possibilities. Brahmi offers a lot of potential for treating a range of illnesses, including neuro-pharmacological, depression, inflammation, hepatoprotective, antidiabetic, and others. According to the presumptions of this review, further clinical trials and research are needed. While the impact of Brahmi as an anxiolytic and antidepressant has to be explored further, its potential as an anti-epileptic therapy and a treatment for antiepileptic drugs side effects is also being researched. Furthermore, Brahmi's antioxidant ability may explain, at least in part, the antistress, immunomodulatory, cognition-facilitating, anti-inflammatory, and anti-aging benefits documented in experimental animals and clinical circumstances, necessitating further study into its other therapeutic characteristics.
... Bacopaside I reduced the neurological deficits, cerebral infarct volume and oedema caused by the induced cerebral ischemia in rats proving it as a neuroprotective drug. Oral administration distinctly increased ATP content in brain, anti-oxidant enzymes, Na + K + ATPase and Ca 2+ Mg 2+ ATPase activities in adult male Sprague-Dawley rats [40]. Cerebral Ischemia induced in mice model when treated with Chlorophyll and aqueous extracts of Brahmi showed decrease in infarct size, increased short term memory and motor coordination [41]. ...
... Transient focal ischemia was induced by middle cerebral artery occlusion (MCAO) and bacopaside was administered in three different doses to rats in three groups at the dose of3, 10 and 30 mg/kg. Groups treated with mg/kg and 10 mg/ kg and 30 mg/kg showed reduction in neurological deficit, reduction in infarct volume, oedema, increased the brain ATP content indicating cerebral energy metabolism, energy charge (EC), total adenine nucleotides (TAN), nitric oxide (NO) level, Na + K + ATPase and Ca2 + Mg2 + ATPase activity along with anti-oxidant activity [40]. An in vitro study conducted using BM as one of the lytic herbs demonstrated that BM has 41.8% thrombolytic activity [89]. ...
Brahmi or aindri is a popular herb in the vast and rich compendium of herbs of Ayurveda and is botanically identified as Bacopa monnieri Linn. (BM). It is extensively used in Ayurveda and other traditional systems of medicine in the management of neurological psychiatric disorders. BM possess active principles belonging to alkaloids, glycosides, flavonoids, saponins categories. Numerous research have been undertaken across the globe to evaluate the neuroprotective potential of this herb. This review collates and summarises current (as on May 2020) published literature on Brahmi as a neuroprotective in neurological and psychiatric disorders. English language articles from databases PubMed, Scopus and Google scholar were searched using appropriate free keywords and MeSH terms related to the topic. The review demonstrates the neuroprotective potential of the Ayurveda herb Brahmi in several disorders including Alzheimer’s disease, epilepsy, Parkinson’s disease, Huntington’s disease, cerebral ischemia and infarct and neoplasms.
... Bacopaside I also reduced the size of infarct volume and cerebral edema. Activation of PKCε by BM could also have protected the hippocampus by maintaining the CBF during ischemia [130] which was in correlation with the study conducted by Kamkaew et al. [133]. Accumulation of Na þ , Ca 2þ , Mg 2þ during dysfunction of respective pumps in cells at incidence of neuronal stress, like ischemia, smoking, neurotoxin exposure, and brain injury, leads to catastrophic enzyme activation resulting in irreversible damage to cells. ...
... BM has been shown to increase the CBF in rat cerebral cortex independent of blood pressure. Chronic administration of BM was demonstrated to improve cognitive function [172] by increasing quiescent CBF up to 25% compared with controls, which implied cerebrovascular dilation [133]. It was hypothesized that the BM acts as a vasodilator by releasing nitric oxide from the endothelium and inhibiting calcium fluctuations in and out of the sarcoplasmic reticulum [173]. ...
The chapter reviews the overall neuronal molecular mechanisms of Bacopa monnieri with respect to cognitive performance. It starts with defining cognition, and how interruption in signal transduction can cause cognitive impairment. Then the factors influencing signal transduction and regulation of those factors are briefed to give a glimpse on cascade involved in signal transduction and their importance in governing the cognitive performance. The drugs and nutraceuticals commonly used as cognition enhancers and their mechanisms of action are covered in brief before taking up details of B. monnieri. Later, effect of B. monnieri on various factors contributing to signal transduction like neurotransmitters, receptors, second messenger system, gene expression, neuronal structural factors, neuronal connections, cerebral blood flow and neuroprotection are detailed to understand the neuronal molecular mechanisms involved in improving cognitive performance. Summary of this review points toward strong scientific substantiation available in the literature to justify the use of B. monnieri in dietary and food supplements intended for cognitive health.
... 134 A study reported by Kamkaew et al. 135 found that BM acted as a vasorelaxant in animal arteries, with potency mostly on basilar artery. Their subsequent follow-up studies 136 reported an increased CBF with improved cognitive function in rats. Classically, cognitive decline is associated with the vascular dysfunction in cerebral cortex and the hippocampus. ...
... As well, hippocampus, being critical in learning and memory, is reported to have increased neocortical blood flow after 8 weeks of BM treatment, which could improve cognition. 136,137 ...
Bacopa monnieri (L.) - (BM) is a perennial, creeping herb which is widely used in traditional ayurvedic medicine as a neural tonic to improve intelligence and memory. Research into the biological effects of this plant has burgeoned in recent years, promising its neuroprotective and memory boosting ability among others. In this context, an extensive literature survey allows an insight into the participation of numerous signaling pathways and oxidative mechanism involved in the mitigation of oxidative stress, along with other indirect mechanisms modulated by bioactive molecules of BM to improve the cognitive action by their synergistic potential and cellular multiplicity mechanism. This multi-faceted review describes the novel mechanisms that underlie the unfounded but long flaunted promises of BM and thereby direct a way to harness this acquired knowledge to develop innovative approaches to manipulate its intracellular pathways.
... monnieri). B. monnieri extract is reported to improve cognition and CBF in a similar fashion to a positive control in rats [24]. In previous papers made by the authors, it was argued that higher doses of BA have a significant effect on in vivo-related hippocampal LTP or neurobehavioral deficits in AD rats through agglomeration of fibril plaques as well as in vitro formation of Aβ monomer to fibril via oligomers' bypassing [36]. ...
... In previous papers made by the authors, it was argued that higher doses of BA have a significant effect on in vivo-related hippocampal LTP or neurobehavioral deficits in AD rats through agglomeration of fibril plaques as well as in vitro formation of Aβ monomer to fibril via oligomers' bypassing [36]. It has been illustrated that cerebral cortex and hippocampus have the dominant role in cognitive performance, and they are vulnerable to dysfunction of vascular responsivity [24]. In addition to AD's obvious signs, electrophysiology or cognitive defect, this study was aimed to further examine other features in AD model with regard to the dual effects of BA on tissue and vessels [21,28,29]. ...
Objective
Alzheimer's disease (AD) is mainly caused by accumulation of β‐amyloid (Aβ) in vessels or parenchyma of the brain. Accordingly, natural compounds such as betulinic acid (BA) might improve the AD signs by increase of blood flow and through reduction of amyloid plaques.
Methods
Intra‐hippocampal injection of BA (0.2 and 0.4μM /10μl DMSO /rat) was done at intervals of 180 and 10 min before co‐microinjection of 0.1μM Aβ dissolved in PBS (5μl/rat, hippocampi) and 1.5 mg/kg Streptozotocin dissolved in aCSF (10μl/rat, lateral ventricles). Cerebro‐vascular responsivity tested by Laser Doppler, BBB leakage, Elisa assays of cytokines (TNF‐α and IL‐10), and western blot analysis of proteins (BDNF and AchE) in the hippocampus were assessed one month after the injections.
Results
Microvascular reaction and BBB function were significantly impaired in AD rats, which were improved via BA pretreatment. BA could increase BDNF expression and decrease cytokine levels in the hippocampus of AD rats (especially 0.1μM Aβ: 0.4μM BA); however, no significant changes were detected in the blotting of AchE among the groups.
Conclusion
BA could have a role in AD through protecting microcirculation, alleviating inflammation and up‐regulating BDNF expression which is clearer toward 1:4 molar ratios of Aβ to BA.
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... It relaxes a wide range of arteries [11], partly through endothelial NO release and in vascular smooth muscle by inhibiting Ca 2+ influx and Ca 2+ release from the sarcoplasmic reticulum [11]. Nevertheless, chronic oral administration of B. monnieri to rats for 12 weeks increased cerebral blood flow without changing blood pressure [12]. This is particularly important because B. monnieri has been traditionally used to enhance memory and several clinical trials suggest that it does have nootropic actions [13,14]. ...
... Similar mechanisms may well operate in the coronary vasculature. Likewise, chronic oral administration of B. monnieri increased cerebral blood flow in normal rats [12]. ...
Background
This study explored Bacopa monnieri, a medicinal Ayurvedic herb, as a cardioprotectant against ischemia/reperfusion injury using cardiac function and coronary flow as end-points. Methods
In normal isolated rat hearts, coronary flow, left ventricular developed pressure, heart rate, and functional recovery were measured using the Langendorff preparation. Hearts were perfused with either (i) Krebs-Henseleit (normal) solution, (control), or with 30, 100 μg/ml B. monnieri ethanolic extract (30 min), or (ii) with normal solution or extract for 10 min preceding no-perfusion ischemia (30 min) followed by reperfusion (30 min) with normal solution. Infarct volumes were measured by triphenyltetrazolium staining. L-type Ca2+-currents (ICa, L) were measured by whole-cell patching in HL-1 cells, a mouse atrial cardiomyocyte cell line. Cytotoxicity of B. monnieri was assessed in rat isolated ventricular myocytes by trypan blue exclusion. ResultsIn normally perfused hearts, B. monnieri increased coronary flow by 63 ± 13% (30 μg/ml) and 216 ± 21% (100 μg/ml), compared to control (5 ± 3%) (n = 8–10, p < 0.001). B. monnieri treatment preceding ischemia/reperfusion improved left ventricular developed pressure by 84 ± 10% (30 μg/ml), 82 ± 10% (100 μg/ml) and 52 ± 6% (control) compared to pre- ischemia/reperfusion. Similarly, functional recovery showed a sustained increase. Moreover, B. monnieri (100 μg/ml) reduced the percentage of infarct size from 51 ± 2% (control) to 25 ± 2% (n = 6-8, p < 0.0001). B. monnieri (100 μg/ml) reduced ICa, L by 63 ± 4% in HL-1 cells. Ventricular myocyte survival decreased at higher concentrations (50–1000 μg/ml) B. monnieri. ConclusionsB. monnieri improves myocardial function following ischemia/reperfusion injury through recovery of coronary blood flow, contractile force and decrease in infarct size. Thus this may lead to a novel cardioprotectant strategy.
... There are numerous mechanisms by which nootropics may exert their effect (for a review, see reference [4]). For example, bacosides present in Bacopa monnieri have been shown to increase blood flow to the brain, thereby providing more access to glucose and oxygen [3,5]. Other active compounds in plants, such as asiaticosides present in gotu kola, ginsenosides from ginseng, or catechins such as those found in guarana, can reduce oxidative stress and contribute to eliminating free radicals [6][7][8][9]. ...
Cognitive decline is a natural process that occurs during aging. Several natural solutions called nootropics exist that can help mitigate this process. However, in some cases, there is a lack of scientific evidence on their potential mechanisms and efficacy. To this end, a total of nine different herb extracts with potential nootropic activity were evaluated. These herb extracts were tested in human neural stem cell cultures exposed to oxidative stress, where reactive oxygen/nitrogen species, cell survival and trophic factor expression were analyzed. Of these extracts, Salvia officinalis (sage) was observed to possess the most significant effect. Its combination with rutin demonstrated additional benefits than with only sage. A randomized, double-blind placebo-controlled clinical study was then performed, testing the effects of the combination at two different doses for 12 weeks in healthy volunteers aged 50+ with mild cognitive impairment. As a result, the blend significantly improved several characteristics related to memory, particularly memory recall, with a more noticeable effect in the higher dose. Therefore, this study reveals the potential nootropic effect of a blend comprising Salvia officinalis and rutin. This blend could be a candidate dietary ingredient with potential nootropic properties.
... Safeguarding this system may help preserve cognitive abilities. Bacopa monnieri has also demonstrated the potential to improve cerebral blood flow, which is essential for supplying oxygen and nutrients to the brain [32]. Enhanced blood flow can enhance brain function and support cognitive processes. ...
Traditional Indian medicine uses the neuroprotective and cognitive-enhancing effects of the spice, Bacopa monnieri, commonly known as Brahmi. This paper provides an overview of the potential neuropharmacological benefits and therapeutic applications of Bacopa monnieri. Bacopa monnieri has therapeutic value due to the inclusion of bioactive compounds, including alkaloids, flavonoids, tannins, and phenolics. Bacoside A, a triterpenoid saponin of the Dammarane family, has been studied most because of its potential to improve memory and cognitive function. Specific brain regions that are affected by bacoside A experience an increase in protein and RNA production, oxidative stress protection, improved cerebral blood flow, and enhanced synaptic activity. By boosting antioxidant defense mechanisms, lowering oxidative stress, and altering neurotransmitter levels, Bacopa monnieri demonstrates neuroprotective effects. By blocking the activity of acetylcholinesterase, lowering the production of β-amyloid plaques, and modifying neurotransmitter levels, it has demonstrated potential for treating neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. As a natural neuroprotective and cognitive-improving agent, Bacopa monnieri is generally found to be promising. To completely comprehend its mechanisms of action and assess its long-term toxicity, more studies are necessary. Further research is needed to determine whether Bacopa monnieri can be used as a possible treatment for neurodegenerative diseases.
... BM-enhanced blood flow was evidenced in the hippocampus of rats suggesting the underlying mechanisms by which BM improves cognition [52]. s0075 2.5 Learning and Memory p0105 Although mechanism/s underlying the neuroprotective properties of BM are rather fairly well known, in-depth understanding does not exist concerning its potential to enhance "memory and learning." ...
... It has antioxidant, antipyretic, antidiabetic, antiarthritic, antihypertensive, anticancer properties and healing properties that have been used in Ayurvedic medicine for the last 3,000 years [12]. It is used as a conventional medicine to cure various nervous problems, as a dietary aid to enhance comprehension, memory, and attention, as well as to reduce anxiety and treat skin disorders, asthma and epilepsy [13,14,15,16]. Bacopa ower also helps in the regeneration of damaged neurons, neuronal growth, and synaptic activity restoration, as well as improving brain function [17,18,19]. ...
Background
Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which amyloid-beta (Aβ) and tau tangles are vital in causing neurodegeneration. Only five FDA-approved drugs are available in the market which manages the symptoms. In this study, 52 novel phytochemicals were selected from the medicinal plant Bacopa monnieri, a medicinal plant with neuroprotective compounds.
Objective
The main aim of this study is to find the most promising compound inhibiting microtubule affinity regulation kinase 4 (MARK 4), which is involved in AD.
Methods
First, an ADMET analysis was conducted, and the selected compounds were molecularly docked against the MARK4-associated protein (5ES1). Based on the top five binding affinities, a molecular dynamics simulation was performed.
Results
Cucurbitacin E, oroxindin, ebelin lactone, cucurbitacin B, and bacosine showed binding affinity of more than − 10.0 kcal/mol, and molecular dynamics (MD) simulations of these molecules in complex with MARK4 was performed. Subsequent trajectory analysis for structural changes and end-state MMGBSA binding energy were performed for Cucurbitacin E, oroxindin, ebelin lactone, cucurbitacin B and bacosine. The MD simulation and MMGBSA calculations showed stable interactions between the screened molecules and MARK4.
Conclusion
This computational study predicted ebelin lactone to be the most promising compound from Bacopa monnieri that can be further developed as a drug to treat AD after pre-clinical and clinical studies.
... The chemical compounds identified as responsible for this positive effect were a mixture of two saponins, bacosides A and B [261]. The reported pro-cognitive effect of B. monnieri on rats may be partially explained by an observed increase in cerebral blood flow independent of a change in blood pressure [262]. ...
Plant-based nootropics are a diverse group of natural drugs that can improve cognitive abilities through various physiological mechanisms, especially in cases where these functions are weakened or impaired. In many cases, the nootropics enhance erythrocyte plasticity and inhibit aggregation, which improves the blood's rheological properties and increases its flow to the brain. Many of these formulations possess antioxidant activity that protects brain tissue from neurotoxicity and improves the brain's oxygen supply. They can induce the synthesis of neuronal proteins, nucleic acids, and phospholipids for constructing and repairing neurohormonal membranes. These natural compounds can potentially be present in a great variety of herbs, shrubs, and even some trees and vines. The plant species reviewed here were selected based on the availability of verifiable experimental data and clinical trials investigating potential nootropic effects. Original research articles, relevant animal studies, meta-analyses, systematic reviews, and clinical trials were included in this review. Selected representatives of this heterogeneous group included Bacopa monnieri (L.) Wettst., Centella asiatica (L.) Urban, Eleutherococcus senticosus (Rupr. & Maxim.) Maxim., Ginkgo biloba L., Lepidium meyenii Walp., Panax ginseng C.A. Meyer, Paullinia cupana Kunth, Rhodiola rosea L., Schisandra chinensis (Turcz.) Baill., and Withania somnifera (L.) Dunal. The species are depicted and described, together with their active components and nootropic effects, and evidence of their efficacy is presented. The study provides brief descriptions of the representative species, their occurrence, history, and the chemical composition of the principle medicinal compounds, with uses, indications, experimental treatments, dosages, possible side effects, and contraindications. Most plant nootropics must be taken at optimal doses for extended periods before measurable improvement occurs, but they are generally very well tolerated. Their psychoactive properties are not produced by a single molecule but by a synergistic combination of several compounds. The available data suggest that including extracts from these plants in medicinal products to treat cognitive disorders can have substantial potential therapeutic benefits.
... Apart from the above myriad of BM actions in vivo, most crucially, it is a vasodilator, and increases cerebral blood ow [43][44][45] . This implies that nootropic actions of BM result from normalising cerebrovascular blood ow that is necessary for maintaining or restoring neuronal function, yet cerebral blood ow and cognitive function are not commonly studied together. ...
Bacopa monnier i (L.) Wettst. (Brahmi) is a traditional memory enhancer partly by improved cerebral blood flow. Here we sought to link improved cognitive function with better blood flow in randomised double-blinded placebo-controlled trial in an elderly cohort. Normotensive Thais, aged 55-80y having mini-mental state examination (MMSE) scores > 25, no dementia or other psycho/neurological disease, normal lipid profile, and blood biochemistry were recruited. The trial design was a 2 week run-in, 12 week intervention of test product or placebo, and 4 week washout. The intervention was an extract of B. monnieri leaves (eBM) in 40 ml of mulberry juice. The placebo contained mulberry juice and other constituents to match gustatory properties. End-points were a battery of memory functions, carotid blood velocity, post-ischemic microvascular blood flow, markers of vascular inflammation, blood pressure and the blood markers. Response latency was reduced by 14.2 ± 4.9% ( p = 0.022 comparing placebo) but only in > 65s. Other memory recall parameters were either unaffected or for ‘accuracy of recall’ was already maximal preventing further improvement. No change was detected in carotid blood velocity while microvascular blood flow marginally increased (by 28.4 ± 8.3%, p = 0.07). This preliminary evidence warrant further studies on selected patients with microvascular cognitive dysfunction using more discriminating protocols.
... Khan et al. showed that pretreatment with BM (30 mg/kg) for two weeks could prevent cognitive impairment by increasing the GSH content and antioxidant enzymes in the intracerebroventricularstreptozotocin (ICV-STZ) rat model [51]. The pro-cognitive role of BM was also attributed to its potential to improve cerebral blood flow [52]. BM also exerted positive effects on body weight, learning skills, memory, and concentration in AD-induced mice [53]. ...
Bacopa monnieri (BM) is of immense therapeutic potential in today’s world. This review is aimed to project the beneficial role of BM in disorders affecting the brain, including Alzheimer’s disease, Parkinson’s disease, stroke, epilepsy and depression. The active constituents and metabolites responsible for the effects of BM could be bacoside A and B, bacopaside I and II, bacopasaponin C, betulinic acid, asiatic acid, loliolide, ebelin lactone and quercetin. The mechanistic role of BM in brain disorders might be related to its ability to modulate neurotransmission, neurogenesis, neuronal/glial plasticity, intracellular signaling, epigenetics, cerebral blood flow, energy metabolism, protein folding, endoplasmic reticulum stress, neuroendocrine system, oxidative stress, inflammation and apoptosis. We have also discussed CDRI-08, clinical trials, safety, emerging formulation technologies, as well as BM combinations and dietary supplements. To propel the clinical translation of BM in disorders affecting the brain, strategies to improve brain delivery via novel formulations and integration of the preclinical findings into large and well-defined clinical trials, in appropriate age groups and sex, specifically in patient population against existing medications as well as placebo, are essentially required.
... 73 Among the plausible mechanisms behind the neuroprotective effect of Brahmi are increasing glutathione expression and enhancing cerebral blood supply. 72,74 Oral administration 300 mg/day of standardized Brahmi extract in healthy elderly participants for 12 weeks significantly enhanced the cognitive tasks, Rey Auditory Verbal Learning Test (AVLT), Stroop test, and depression scores, confirming its safety and memoryenhancing effects. 75 A randomized placebo-controlled trial has been conducted in India and enrolled 60 medical students to assess the impact of Bacopa monnieri on improving cognition among medical students. ...
Dementia is a term that encompasses a group of clinical symptoms affecting memory, thinking and social abilities, characterized by progressive impairment of memory performance and cognitive functions. There are several factors involved in the pathogenesis and progression of dementia, such as old age, brain ischemia, toxin exposure, and oxidative stress. There are extensive similarities between dementia and Alzheimer’s disease (AD) either in clinical manifestations or experimental animal models. AD is the most dominant form of dementia, characterized by the accumulation of beta-amyloid protein and cholinergic neurotransmission deficits in the brain. Currently available medications for the treatment of dementia, such as choline esterase inhibitors, N-methyl-D-aspartate (NMDA) antagonists (memantine), have short-term efficacy and only relieve symptoms rather than targeting the main underlying pathogenesis. Several animal studies and clinical trials are being conducted to provide a rational approach to these medicinal plants in the prevention or treatment of memory deficits. This review highlights the potential effects of medicinal plants and their derived lead molecules, and explains the related mechanisms and effects reviewed from published literature as major thrust aspects and hopeful strategies in the prevention or treatment of dementia.
... Studies in transgenic mice bearing human PS-1 and AβPP mutations have shown that both short and long-term treatment of B. monnieri reduces the amount of β-amyloid found in different regions of the brain 16 . The extract also diminished the neurodegenerative effects of ethylcholine aziridinium ion and colchicine in rats 17,18 , increased cerebral blood flow 19 and decreased the effects of stress in the brains of rats 20 . Many studies also indicate the antioxidant potential of B. monnieri that helps in mitigating the adverse effects of oxidative stress in neurons 6,17,18,[21][22][23][24][25] . ...
Bacopa monnieri (Linn.) Wettst . has been used in traditional medicine as a drug to enhance and improve memory. In this regard, this study aims to provide B . monnieri 's efficacy as a neuroprotective drug and as a nootropic against various neurological diseases. Literatures were collected, following Prisma guidelines, from databases, including Scopus, PubMed, Google Scholar, and Science Direct and were scrutinized using a quality scoring system. Means, standard deviations and ‘n’ numbers were extracted from the metrics and analyzed. Jamovi computer software for Mac was used to carry out the meta-analysis. The selected studies suggested that the plant extracts were able to show some improvements in healthy subjects which were determined in Auditory Verbal Learning Task, digit span-reverse test, inspection time task and working memory, even though it was not significant, as no two studies found statistically significant changes in the same two tests. B . monnieri was able to express modest improvements in subjects with memory loss, wherein only a few of the neuropsychological tests showed statistical significance. B . monnieri in a cocktail with other plant extracts were able to significantly reduce the effects of Alzheimer’s disease, and depression which cannot be solely credited as the effect of B . monnieri . Although in one study B . monnieri was able to potentiate the beneficial effects of citalopram; on the whole, currently, there are only limited studies to establish the memory-enhancing and neuroprotective effects of B . monnieri . More studies have to be done in the future by comparing the effect with standard drugs, in order to establish these effects clinically in the plant and corroborate the preclinical data.
... It is used traditionally to treat various nervous disorders, digestive aid, improve learning, concentration and memory to provide relief to patients with anxiety, and skin diseases; specific uses include the treatment of insanity, asthma and epilepsy (9)(10)(11). ...
Herbal medicines have a history of long therapeutic use and are still serving a lot of the health needs of a big population of the world. However, the quality control still remains a challenge because of the variation of chemical constituents involved. There are numerous compounds in herbal drugs that are in complex matrices in which no single active constituent is responsible for the overall efficacy. This creates a challenge in establishing quality control standards and standardization of finished herbal drugs. Saraswati Panchak is a novel combination given by Pandit Shri Ram Sharma Acharya for mental health. In this study, components of this novel herbal combination were explained for its potential utility in mental illness. In addition, the study also detailed how Saraswati Panchak Churna was converted into tablet form to increase the shelf life, make it easy to dispense, for dose fixation, etc. The tablet was subjected to organoleptic analysis and physico-chemical analysis to establish its efficacy. After performing complete analysis it was found that all the parameters are within the range. The coarse powder of these herbs may be used as havan samagri in brain related disorders because of the presence of nootropic herbs.
... These mechanisms mediated an acute decrease in blood pressure [29]. Also, daily oral BME (40 mg/kg) in rats for 8 weeks showed a significant increase in cerebral blood flow [30], which implies cerebrovascular dilation. BME contains an abundance of bioactive compounds. ...
B. monnieri extract (BME) is an abundant source of bioactive compounds, including saponins and flavonoids known to produce vasodilation. However, it is unclear which components are the more effective vasodilators. The aim of this research was to investigate the vasorelaxant effects and mechanisms of action of saponins and flavonoids on rat isolated mesenteric arteries using the organ bath technique. The vasorelaxant mechanisms, including endothelial nitric oxide synthase (eNOS) pathway and calcium flux were examined. Saponins (bacoside A and bacopaside I), and flavonoids (luteolin and apigenin) at 0.1-100 µM caused vasorelaxation in a concentration-dependent manner. Luteolin and apigenin produced vasorelaxation in endothelial intact vessels with more efficacy (E max 99.4 ± 0.7 and 95.3 ± 2.6%) and potency (EC 50 4.35 ± 1.31 and 8.93 ± 3.33 µM) than bacoside A and bacopaside I (E max 83.6 ± 2.9 and 79.9 ± 8.2%; EC 50 10.8 ± 5.9 and 14.6 ± 5.4 µM). Pretreatment of endothelial intact rings, with L-NAME (100 µM); an eNOS inhibitor, or removal of the endothelium reduced the relaxant effects of all compounds. In K +-depolarised vessels suspended in Ca 2+-free solution, these active compounds inhibited CaCl 2-induced contraction in endothelial denuded arterial rings. Moreover, the active compounds attenuated transient contractions induced by 10 µM phenylephrine in Ca 2+-free medium containing EGTA (1 mM). Thus, relaxant effects occurred in both endothelial intact and denuded vessels which signify actions through both endothelium and vascular smooth muscle cells. In conclusion, the flavonoids have about twice the potency of saponins as vasodilators. However, in the BME, there is~20 × the amount of vaso-reactive saponins and thus are more effective.
... It is a renowned Indian medicinal plant that has been used as a memory booster in the Ayurvedic medicinal system for more than 3000 years [2,3]. It is used in traditional medicine to treat various nervous disorders, digestive aid, improve learning, memory, and concentration and to provide relief to patients with anxiety, and skin disorders; specific uses include the treatment of asthma, insanity and epilepsy [4][5][6]. The Bacopa herb, also called nootropic herb, helps in the repair of damaged neurons, neuronal synthesis, and the restoration of synaptic activity, and improves brain function. ...
Neurological diseases (NDs), especially Alzheimer’s and Spinocerebellar ataxia (SCA), can severely cause biochemical abnormalities in the brain, spinal cord and other nerves of human beings. Their ever-increasing prevalence has led to a demand for new drug development. Indian traditional and Ayurvedic medicine used to combat the complex diseases from a holistic and integrative point of view has shown efficiency and effectiveness in the treatment of NDs. Bacopa monnieri is a potent Indian medicinal herb used for multiple ailments, but is significantly known as a nootropic or brain tonic and memory enhancer. This annual herb has various active compounds and acts as an alternative and complementary medicine in various countries. However, system-level insights of the molecular mechanism of a multiscale treatment strategy for NDs is still a bottleneck. Considering its prominence, we used cheminformatics and system pharmacological approaches, with the aim to unravel the various molecular mechanisms represented by Bacopa-derived compounds in identifying the active human targets when treating NDs. First, using cheminformatics analysis combined with the drug target mining process, 52 active compounds and their corresponding 780 direct receptors were retrieved and computationally validated. Based on the molecular properties, bioactive scores and comparative analysis with commercially available drugs, novel and active compounds such as asiatic acid (ASTA) and loliolide (LLD) to treat the Alzheimer’s and SCA were identified. According to the interactions among the active compounds, the targets and diseases were further analyzed to decipher the deeper pharmacological actions of the drug. NDs consist of complex regulatory modules that are integrated to dissect the therapeutic effects of compounds derived from Bacopa in various pathological features and their encoding biological processes. All these revealed that Bacopa compounds have several curative activities in regulating the various biological processes of NDs and also pave the way for the treatment of various diseases in modern medicine.
... The plant was also used as a cardiac tonic, digestive aid in India and Pakistan, and has been found to improve respiratory function in cases of bronchoconstriction. Clinical studies affirm that bacopa based formulations have positive effects on the reconstruction of mental functions in children suffering from attention deficit hyperactivity disorder (ADHD), and contribute to the enhancement of cognitive functions in stroke and epilepsy patients [6][7][8]. Bacosides and triterpenoids which belong to the saponins are compounds attributed to the above activities [9]. ...
Bacopa monnieri has been used as a reputed drug in the Indian traditional ayurvedic system for centuries. This medicinal herb with important phytopharmaceuticals has been popularly known as "Brahmi". In recent years, B. monnieri has been extensively studied for its bioactive constituents, constituents responsible for memory enhancing effect, and also its diverse other useful effects. It possesses many pharmacological activities such as antioxidant, gastrointestinal, endocrine, antimicrobial, anti-inflammatory etc. The plant has been also used for the treatment of neurological and neuropsychiatric diseases. Due to its multipurpose therapeutic potential, micropropagation using axillary meristems and de novo organogenesis has been extensively studied in the species and is being reviewed. High frequency direct shoot organogenesis can be induced in excised leaf and internode explants in the absence of exogenous phytohormones and the rate of induction is enhanced in the presence of exogenous cytokinins, supplements, growth regulators, etc. Using explants from tissue culture raised plants, direct shoot regeneration leading to production of more than 100 rooted plants/explant within 8-12 weeks period with 85%-100% survival in the field after acclimatization can be expected following optimized protocols. Bioreactor based micropropagation was found to increase the multiplication rate of shoot cultures for the commercial propagation of B. monnieri plants. The maximum content of bacosides has been recorded in shoot biomass using an airlift bioreactor system. Further studies for the biosynthesis of bacosides and other secondary metabolites need to be conducted in the species utilizing untransformed shoot cultures in bioreactors.
... These mechanisms mediated an acute decrease in blood pressure [29]. Also, daily oral BME (40 mg/kg) in rats for 8 weeks showed a significant increase in cerebral blood flow [30], which implies cerebrovascular dilation. BME contains an abundance of bioactive compounds. ...
B. monnieri extract (BME) is an abundant source of bioactive compounds, including saponins and flavonoids known to produce vasodilation. However, it is unclear which components are the more effective vasodilators. The aim of this research was to investigate the vasorelaxant effects and mechanisms of action of saponins and flavonoids on rat isolated mesenteric arteries using the organ bath technique. The vasorelaxant mechanisms, including endothelial nitric oxide synthase (eNOS) pathway and calcium flux were examined. Saponins (bacoside A and bacopaside I), and flavonoids (luteolin and apigenin) at 0.1–100 µM caused vasorelaxation in a concentration-dependent manner. Luteolin and apigenin produced vasorelaxation in endothelial intact vessels with more efficacy (Emax 99.4 ± 0.7 and 95.3 ± 2.6%) and potency (EC50 4.35 ± 1.31 and 8.93 ± 3.33 µM) than bacoside A and bacopaside I (Emax 83.6 ± 2.9 and 79.9 ± 8.2%; EC50 10.8 ± 5.9 and 14.6 ± 5.4 µM). Pretreatment of endothelial intact rings, with L-NAME (100 µM); an eNOS inhibitor, or removal of the endothelium reduced the relaxant effects of all compounds. In K+-depolarised vessels suspended in Ca2+-free solution, these active compounds inhibited CaCl2-induced contraction in endothelial denuded arterial rings. Moreover, the active compounds attenuated transient contractions induced by 10 µM phenylephrine in Ca2+-free medium containing EGTA (1 mM). Thus, relaxant effects occurred in both endothelial intact and denuded vessels which signify actions through both endothelium and vascular smooth muscle cells. In conclusion, the flavonoids have about twice the potency of saponins as vasodilators. However, in the BME, there is ~20 × the amount of vaso-reactive saponins and thus are more effective.
... According to the quality standard of Chinese Pharmacopoeia, the contents of flavonoids and terpene lactones in GBE should be more than 24% and 6%, respectively (Cheng et al., 2014). Many research results have shown that GBE exhibits the significant effect on the treatment of cardiovascular disease (Tian et al., 2017), brain dysfunction (Gong et al., 2005), hypertension (Huang et al., 2004;Kamkaew et al., 2013;Maeda et al., 2015), inflammation (Chan et al., 2007;Zahradnikova et al., 2007;Tsuruda, 2010;Sati & Joshi, 2011) and carcinogenesis (Ma et al., 2015). Moreover, in view of so many advantages of GBE, the various derivative products based on the GBE are widely used as the medicine, health products, food additives, functional beverages and cosmetics. ...
The ginkgo biloba extract (GBE) nanoparticles were successfully prepared by adopting the liquid anti‐solvent precipitation (LASP) method to enhance the antioxidant activity and oral bioavailability of GBE. Under the optimum preparation conditions, the particle size of GBE nanoparticles had reached 76.90 nm. Moreover, the antioxidant activity and intestinal transmittance of GBE nanoparticles were tested before and after the simulated in vitro digestion, which were both significantly higher than that of raw GBE. Significantly, the AUC(0→t) value of flavonoids and terpene lactones in GBE nanoparticles were 2.20 and 2.24 times of that in raw GBE, respectively. What cannot be ignored was that the residual amount of ethanol and n‐hexane meets the safety standards for food.
... Bacopa monerii (L.) Wettst (Family: Scrophulariaceae), is a wellknown nootropic herb, commonly used for longevity and to enhance cognition. The ethanolic extract of this plant possesses anti-convulsant [3], anti-inflammatory [4], cholinesterase inhibition [5] and prevents dementia by improving cerebral blood flow in rats [6]. Recent studies reported that extracts of Bacopa monerii (L.) protected against allodynia and hyperalgesia in neuropathic pain induced rats [7]. ...
Chronic inflammation of the myelin sheath is the crucial event behind the progression of multiple sclerosis (MS). Bacoside-A is one of the major constituents obtained from Bacopa monerii (L.) Wettst., and possess neuropro-tective as well as anti-inflammatory actions. The current study explores the effect of Bacoside-A in acute and chronic models of Experimental Autoimmune Encephalomyelitis (EAE). The results indicate that the Bacoside-A treated mice produced a significant reduction in disease score compared to disease control in both models. The treatment with Bacoside-A downregulated the inflammatory cytokines (IL-6, IL-17a, and TNFα) and in-flammatory chemokine CCL-5 in EAE mice. On the other hand, Bacoside-A treated mice showed a nonsignificant effect on promoting the expressions of NCAM, BDNF1, and FOXP3 in acute and chronic models of EAE. Histopathological analysis revealed that the Bacoside-A treated mice at a dose of 10 mg/kg exhibited a significant reduction in cellular infiltrations, cellular changes, and demyelination in cerebral tissues, but unable to protect at a higher dose in both models. In conclusion, Bacoside-A can able to inhibit the progression of EAE may be by the inhibition of inflammatory cytokines and chemokine evolved during active EAE.
... brain function, increase the ability to concentrate, and improve memory in all the population groups. Clinical studies have shown that brahmi is involved in the reconstruction of mental functions in children suffering from attention deficit hyperactivity disorder (ADHD) and improves cognitive functions in patients after strokes and in epilepsy (Jyoti and Sharma 2006;Calabrese et al. 2008;Kamkaew et al. 2013). Most of these effects are due to the ability of the plant extracts to modulate the cholinergic system (Peth-nui et al. 2012). ...
Bacopa monnieri (L.) Wettst. (Plantaginaceae) is an important Ayurvedic medicinal herb commonly known as brahmi, growing in the region of Indian subcontinent. Bacosides are the major chemical component having the major role in the biological and pharmacological field. Bacopa cultivation is time-consuming, requires labor team, and needs great efforts to maintain the quality of bacosides as growths are affected by environmental factors such as soil, water, temperature, climate, pests, and pathogens. To solve these problems, organ and cell cultures have been adopted for swift and efficient production of Bacopa biomass and bacosides. In the current chapter, various parameters, such as types of media, media composition, elicitors, salinity, drought, types of vessels used, and effect of heavy metals, were investigated against the in vitro production of bacosides from Bacopa monnieri.
... Bacopamonnieri extract has been reported to exhibit several pharmacological activities, for example, neuroprotective effect [13][14][15], an antioxidant [16][17][18], an antiparkinsonian agent [19], hepatoprotective agent [20], anti-depressant [21], anti-stress [22], anti-cancer [23], antimicrobial effect [24,25], endocrine effect [26,27], antiinflammatory agent [28], gastrointestinal effect [29] and antiulcerogenic agent [30]. ...
Bacopa monnieri (L) is a renowned medicinal plant for its numerous therapeutic activities against a number of ailments. Bangladeshi species of B. monnieri has been previously reported for its anti-inflammatory activities. Therefore, the present investigation involves phytochemical screening and evaluation of antiulcerogenic activity of B. monnieri extracts of different solvent medium by in-vivo analysis. The study was conducted by using ethanol-induced gastric injury in Swiss albino mice model to evaluate anti-ulcer effect of B. monnieri (whole plant). Three different solvent systems (water, ethanol and carbon tetrachloride) were used to prepare plant extract. Animals were pretreated with 200mg/kg and 400mg/kg (body weight, p.o.) of the plant extracts in 0.2% tween 80 where omeprazole (20 mg/kg b.w. in 0.2% tween 80, p.o.) was used as the reference drug. The extent of gastric injury was evaluated by assessment of gross appearance of gastric areas to determine ulcer index and histology of stomach. A dose-dependent therapeutic effect against gastric ulcer was found with all three extracts of Bacopa monnieri where ethanolic extract of the plant showed statistically significant result(** p< 0.01) when compared with ulcerogenic animal group. Furthermore, the therapeutic effect of 400mg/kg (b.w. p.o.) of B. monnieri ethanolic extract exhibited close relation with pretreatment by omeprazole. The present study suggests ethanol as a suitable extraction medium for Bacopa monnieri (L) in order to evaluate its antiulcerogenic activity. Treatment with this extract leads to extensive protection against gastric ulcer providing a scientific basis for its traditional uses as a cure for ulcer.
... After a 15-min stabilization period, systolic arterial blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded before and during intravenous infusion (at 1 ml/min) of 1 ml/kg of saline, vehicle (a saline solution containing 5% DMSO), EM extract (1, 5, 20, 70 mg/kg), or the NO donor SNP (25 µg/kg). The dose of SNP was chosen as a dose inducing a maximum lowering effect on blood pressure (Pagani et al., 1978;Kamkaew et al., 2013). The EM extract was dissolved in DMSO, diluted in saline and filtered through 0.2 µM syringe filter. ...
Background: Ethnopharmacological studies demonstrated the potential for Eulophia species to treat inflammation, cancer, and cardio-metabolic diseases. The aim of the study was to investigate the vasorelaxant effect of ethanolic Eulophia macrobulbon (EM) extract and its main phenanthrene on rat isolated mesenteric artery and to investigate the hypotensive effect of EM.
Methods: The vasorelaxant effects of EM extract or phenanthrene and the underlying mechanisms were evaluated on second-order mesenteric arteries from Sprague Dawley rats. In addition, the acute hypotensive effect was evaluated in anesthetized rats infused with cumulative concentrations of the EM extract.
Results: Both EM extract (10⁻⁴–1 mg/ml) and phenanthrene (10⁻⁷–10⁻⁴ M) relaxed endothelium-intact arteries, an effect that was partly reduced by endothelium removal (p < 0.001). A significant decrease in the relaxant effect of the extract and the phenanthrene was observed with L-NAME and apamin/charybdotoxin in endothelium-intact vessels, and with iberiotoxin in denuded vessels. SNP (sodium nitroprusside)-induced relaxation was significantly enhanced by EM extract and phenanthrene. By contrast, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one), 4-aminopyridine and glibenclamide (endothelium-denuded vessels) and indomethacin (endothelium-intact vessels) had no effect. In calcium-free solution, both the EM extract and phenanthrene inhibited extracellular Ca²⁺-induced contraction in high KCl and phenylephrine (PE) pre-contracted rings. They also inhibited the intracellular Ca²⁺ release sensitive to PE. The acute infusion of EM extract (20 and 70 mg/kg) induced an immediate and transient dose-dependent hypotensive effect.
Conclusion: The ethanolic extract of EM tubers and its main active compound, 1-(4′-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (phenanthrene) induced vasorelaxant effects on rat resistance vessels, through pleiotropic effects including endothelium-dependent effects (NOS activation, enhanced EDH production) and endothelium-independent effects (opening of KCa channels, inhibition of Ca²⁺ channels, inhibition of intracellular Ca²⁺ release and PDE inhibition).
... 15 Evidence exists for other mechanisms of action including increasing cerebral blood flow, restoring cholinergic function, modulating GABA and/or serotonin levels, reducing b-amyloid levels and blocking nerve damage caused by it, reducing free radical damage, altering brain stress hormone levels, and decreasing neuroinflammation. 16,17 Centella asiatica (gotu kola) shares numerous similarities with bacopa, though it is in the Apiaceae family. Gotu kola is also a tropical species that likely originated in Southeast Asia, but has now become quite a bit more widespread. ...
Nootropic herbs can be very helpful in people with attention-deficient/hyperactivity disorder (ADHD). Two herbs both called brahmi in the Ayurvedic tradition, Bacopa monnieri (bacopa) and Centella asiatica (gotu kola), as well as formulas featuring these herbs, are discussed in great depth for this purpose. Additional general nootropic herbs discussed are Ginkgo biloba (ginkgo) and Acorus calamus (sweetflag), including both American and Eurasian varieties. Nootropic herbs from the Lamiaceae (mint) family with a focus on Rosmarinus officinalis (rosemary) and various species of Salvia (sage) are also reviewed. The general failure of nervine herbs such as Hypericum perforatum (St. John's wort) and Valeriana officinalis (valerian) for ADHD is highlighted, giving further impetus for the need to focus on nootropic herbs instead. The safety and clinical use of all relevant herbs is highlighted.
... Pennell [family: Scrophulariaceae] has been considered as a reputable nootropic medicine and is traditionally used for memory enhancing, rejuvenating, increasing longevity and promoting progeny [4]. Experimental studies have shown that Bacopa monnieri possesses anti-dementia [5], cognitive enhancing [6,7], antidepressant [8], anti-anxiety [9], antiepileptic [10][11][12], antiparkinson [13,14], antiamnesic [15][16][17], antibacterial [18], antidiabetic [19], anti-inflammatory [20][21][22], anti-arthritis [23], antihypertensive [24], anticancer [25], anti-asthmatic [26], spasmolytic [27], antiulcer [28,29], analgesic [30][31][32], anti-aging [33], antifungal [34], antioxidant [35][36][37], adaptogenic [38,39], anti-addictive [40,41], lessened narcotics-induced toxicity [42], neuroprotective [35,[43][44][45], antiemetic [46,47], cardioprotective [48,49], hepatoprotective [50][51][52][53] and nephroprotective [53,54] properties. Clinical trials have shown that Bacopa monnieri has both acute [55,56] and chronic [55][56][57][58][59] cognitive enhancing effects and improves memory performance in older persons [60,61] and patients with Alzheimer's disease [62]. ...
Background:
The current therapy of neuropathic pain is inadequate and is limited by the extent of pain relief and the occurrence of dose dependant side effects. Insufficient control of pain with conventional medications prompts the use of complementary and alternative medicine therapies by patients with neuropathic pain. This study therefore investigated a standardized methanolic extract of Bacopa monnieri, a widely reputed nootropic plant, for prospective antinociceptive effect in the chronic constriction injury (CCI) model of neuropathic pain.
Methods:
Placement of four loose ligatures around the sciatic nerve produced partial denervation of the hindpaw in rats. Bacopa monnieri (40 and 80 mg/kg, p.o) and the positive control, gabapentin (75 mg/kg, i.p), were administered daily after CCI or sham surgery and the behavioral paradigms of static- and dynamic-allodynia (paw withdrawal threshold to von Frey filament stimulation [PWT] and paw withdrawal latency to light-brushing [PWL]), cold-allodynia (paw withdrawal duration [PWD] to acetone), heat- (PWL to heat-stimulus) and punctate-hyperalgesia (PWD to pin-prick) were assessed on days 3, 7, 14 and 21.
Results:
CCI consistently generated static- (days 3-21), dynamic- (days 14-21) and cold-allodynia (days 3-21) plus heat- and mechano-hyperalgesia (days 3-21). The tested doses of Bacopa monnieri significantly attenuated the CCI-induced allodynia and hyperalgesia, exemplified by increased PWT (days 7-21), PWL to light brushing (days 14-21) and heat (days 7-21) as well as decreased PWD to pin prick and cold stimuli (days 3-21). The extract also counterbalanced the CCI-induced aberrations in the nociceptive behaviors by increasing the pain threshold to that of pre-surgery baseline. Gabapentin also afforded analogous beneficial behavioral profile but of higher magnitude.
Conclusions:
Our findings suggest that Bacopa monnieri can be used as adjuvant therapy for neuropathic pain conditions afflicted with allodynia and hyperalgesia.
... Another study conducted by Kamkaew et al. [57] in which they compared the cerebral blood flow (CBF) augmenting property of EBm and Ginkgo biloba . They administered EBm, G. biloba (standardized extract) and donepezil to 3 test groups and water to the control group for 8 weeks. ...
... Bacopa monnieri (Brahmi) has been traditionally used in Ayurvedic medicine to treat conditions including pain, asthma, fever, inflammation, and memory decline [66]. Various mechanisms may be involved in the neuroprotective and memory enhancing effects of Brahmi such as increasing antioxidant activity [67], free radical scavenging [68], binding and detoxification of metal ions [69], modifying levels of acetylcholine [68], and increasing cerebral blood flow via vasodilation [70]. The constituents responsible for improving learning and memory are attributed to steroidal saponins and bacosides A and B [71]. ...
Dementia is a leading cause of mental and physical disability. Vascular dementia (VaD) is the second most common cause of dementia after Alzheimer’s disease (AD) constituting 10–15% of the dementia population. Currently there are no approved pharmaceutical options for VaD and the conventional anti-AD therapies provide only modest, short-term relief of symptoms associated with VaD. Herbal medicines have been used for the management of dementia-like symptoms for centuries and may provide viable therapies for VaD due to their multicomponent and multitarget approach. This review is designed to provide an updated overview on the current status of herbal medicine research, with an emphasis on Chinese herbal medicine, for the treatment of VaD or dementia. A case study is also provided to demonstrate the development process of a novel standardized complex herbal formulation for VaD. The article reveals some preliminary evidence to support the use of single and complex herbal preparations for VaD and dementia. Multiple issues in relation to clinical and preclinical research have been identified and future research directions are discussed.
... Bacopa monnieri (L.) Wettst, known as Brahmi or water hyssop, (Family Plantaginaceae), is a perennial creeper found in marshy areas throughout Asia where it is used in Ayurvedic medicine for enhancing memory and improving brain function [1]. It has recently been reported that B. monnieri extract has several pharmacological activities, e.g., a neuroprotective effect [2,3], ameliorating cognitive dysfunction [4][5][6], increasing cerebral blood flow [7], enhancing the activity of antioxidant enzymes and intracellular signaling pathways [8], an antiparkinsonian agent [9], reducing blood pressure [10], hepatoprotection [11], anti-fertility [12], anti-addiction [13], antioxidant [14,15], antidepressant [16], anti-stress [17], anti-ulcer [18], anti-cancer [19], and anti-inflammation [20]. ...
Background
Bacopa monnieri is a medicinal plant which has long been used in Ayurvedic medicines to augment brain function and to improve memory. The purpose of our study was to identify and evaluate possible toxic effects of B. monnieri extract in rats by assessing hematological, biochemical, and histopathological parameters.
Methods
Acute oral toxicity of Bacopa monnieri extract was studied in female rats by giving a single orally administered dose at a level of 5,000 mg/kg. The rats were monitored for toxic signs for 14 days. In the chronic toxicity test, groups of both female and male rats were given daily oral doses of B. monnieri extract at dose levels of either 30, 60, 300 or 1,500 mg/kg for 270 days. The behavior and health of the animals was then monitored. At the end of the observation period, the body and organ weights of the rats in each group were measured. Blood was collected and necropsy was performed to evaluate their hematology, blood clinical chemistry, and microanatomy.
Results
The acute toxicity test found no significant differences between the experimental and the control group rats. In the chronic toxicity test, animal behavior and health of the experimental groups were normal, just as in the control rats. All values of other parameters assessed remained within the normal range.
Conclusion
A single oral administration of B. monnieri extract at the dose of 5,000 mg/kg did not cause any serious undesirable effects. B. monnieri extract at doses of 30, 60, 300 and 1,500 mg/kg given for 270 days did not produce any toxicity in rats.
... We studied its effect on human memory and forgetfulness in dementia of various gradesfrom mild to severe. There are reports of its efficacy in various publications: Many relate to its effect in animals, [1][2][3][4][5] some to its effect in human beings too. One such study showed that it decreased the rate of forgetting newly acquired information in humans while the rate of learning remained unaffected. ...
... Based on the previous studies, it is believed that these effects are due to the ability of the plant extracts to modulate humans' cholinergic system (Jyoti and Sharma 2006). Plant extracts increase blood flow in brain, improve concentration, they have antioxidant, antiinflammatory, antibacterial, and antitumor effects, and they are also used as a support in neurodegenerative diseases (such as Alzheimer's and Parkinson's diseases) therapies (Kamkaew et al. 2013;Shah et al. 2012;Wasnik 2012, Ravikumar et al. 2005Sumathi et al. 2012). Compounds, which are attributed to the abovementioned actions are bacosides and triterpenoids, belonging to the saponins (Gohil and Patel 2010). ...
The experiments on Bacopa monnieri from Scrophulariaceae family were performed in in vitro shoot cultures conditions in media enriched with Mg ions and serine or anthranilic acid (L1 vitamin). As there is limited literature data available on the content of elements in shoots from B. monnieri in vitro cultures, analyses of magnesium, zinc, potassium, calcium, copper, sodium and iron in plant shoots constituted the aim of the present study. The next aim of the work, for the first time, consists of evaluation of the content and concentration of magnesium and other metals in in vitro shoot cultures of B. monnieri and their influence on bacoside levels, as well as establishment of interactions between the listed analytes. The highest accumulation of magnesium was determined in the plant tissues cultured in media doped with 0.1 g/L serine and 0.5 g/L Mg (2104 µg/g dry weight), and 0.5 mg/g of anthranilic acid and 1.0 g/L Mg (2163 µg/g). The highest concentration of bacosides in the obtained in vitro shoot cultures of B. monnieri (37.3 mg/g dry weight) was found in cultures of the following media composition: MS1 with addition of 0.25 g/L serine and 0.1 g/L Mg, and MS1 with addition of 0.5 g/L serine and 0.5 g/L magnesium. Considering the observed shortage of plant reserves in the natural environment and its curative properties, it seems to be of utmost importance to obtain, as a result of the presented experiment, in vitro shoot cultures of B. monnieri characterized by optimal and reproducible composition of the physiologically active elements and metabolites.
... Commercially available preparations of B. monnieri improve brain function, increase the ability to concentrate and improve memory in both young and older people. Clinical studies confirm the positive effects of this material in the reconstruction of mental functions in children suffering from attention deficit hyperactivity disorder (ADHD), and to improve cognitive functions in patients after strokes and in epilepsy (Jyoti & Sharma 2006;Calabrese et al. 2008;Kamkaew et al. 2013). Based on previous studies, these effects are due to the ability of the plant extracts to modulate the cholinergic system (Peth-nui et al. 2012). ...
Context:
Bacopa monnieri L. Pennell (Scrophulariaceae) is one of the most important plants in the system of Indian medicine (Ayurveda).
Objective:
This paper studies the optimal growth of B. monnieri for effective accumulation of metabolites. Biomass growth of this plant could be accomplished in liquid cultures on Murashige & Skoog medium.
Materials and methods:
Powdered shoots of in vitro cultures of B. monnieri were extracted by methanol for indole compounds, phenolic compounds and bacosides for RP-HPLC analysis. Fatty acid analysis was performed via gas chromatography. Anti-inflammatory effect of B. monnieri extracts was evaluated in the A549 cells. COX-2 and cPGES expression was analyzed using Western blots.
Results:
l-Tryptophan and serotonin were found in biomass from in vitro cultures of B. monnieri on MS medium and in biomass from the MS mediums enriched with the different additions such as of 0.1 g/L magnesium sulphate, 0.1 g/L zinc hydroaspartate, 0.1 g/L l-tryptophan, 0.25 g/L serine, 0.5 g/L serine and 0.5 mg/L anthranilic acid. The content of l-tryptophan and serotonin compounds was significant in biomass from medium with the addition of 0.1 g/L zinc hydroaspartate (0.72 mg/g dry weight and 1.19, respectively). Phenolic compounds identified in biomass from the same variants of MS medium were chlorogenic acid (ranging from 0.20 to 0.70 mg/g dry weight), neochlorogenic acid (ranging from 0.11 to 0.40 mg/g dry weight) and caffeic acid (ranging from 0.01 to 0.04 mg/g dry weight). The main group of fatty acids in biomass was saturated fatty acids (53.4%). The predominant fatty acid was palmitic acid. A significant decrease of COX-2 and cPGES expression was observed in the A549 cells activated with LPS and treated with B. monnieri extracts.
Discussion and conclusions:
As far as we know, this is the first analysis of indole compounds and phenolic acids in this plant. The multi-therapeutic effect of B. monnieri is expressed by the activity of bacosides. Information about the presence of indole and phenolic compounds, and fatty acids in this plant is limited, but the content of these compounds might participate in the physiological activity of B. monnieri.
... Commercially available preparations of B. monnieri improve brain function, increase the ability to concentrate and improve memory in both young and older people. Clinical studies confirm the positive effects of this material in the reconstruction of mental functions in children suffering from attention deficit hyperactivity disorder (ADHD), and to improve cognitive functions in patients after strokes and in epilepsy (Jyoti & Sharma 2006;Calabrese et al. 2008;Kamkaew et al. 2013). Based on previous studies, these effects are due to the ability of the plant extracts to modulate the cholinergic system (Peth-nui et al. 2012). ...
... Furthermore, brain ischemia reduces blood flow in cerebral arteries due to the lack of oxygen supply. To investigate whether Brahmi exerts any effect on cerebral blood flow (CBF) Kamkaew et al., measured this parameter in rats (Kamkaew et al., 2013). Rats were treated with a dose of 40 mg of Brahmi for a period of 8 weeks and thereafter, the CBF was measured via Doppler. ...
The convolution associated with memory is being resolved with advancement in neuroscience. According to the concurrent assumptions, synaptic plasticity forms one of the basis of memory formation, stabilization and strengthening. In Alzheimer's disease (AD), which is generally characterized by memory dysfunction, connections amongst the cells in the brain are attenuated or lost leading to degeneration of neural networks. Numerous attempts have been made to find new therapies for memory dysfunction with increasing attention and investments being laid on herbal drugs. Many herbal plants and extracts have already documented beneficial results when tested for antiamnesic effects. Brahmi (Bacopa monniera) is one such common herbal drug, which is employed for a long time in the Indian and Chinese medical system in order to treat several disorders. Previous research has shown that Brahmi exerts many pharmacological effects including memory boosting capacity in the treatment of Alzheimer's disease and Schizophrenia, exhibiting antiparkinsonian, antistroke, and anticonvulsant potentials. The present review discusses the chemical constituents of Brahmi along with in vitro and in vivo studies based on the pharmacological effects exerted by it. The efficacy of Brahmi in treating various disorders has evoked sufficient research in recent years and now it is a time to launch multiple clinical trials.
... This plant also induces vasodilatation in basilar and mesenteric artery, but poorly influences femoral and kidney arteries. Lack of hypertensive or hypotensive effect determines that B. monnieri can be applied as a food supplement with nootropic effect [27]. B. monnieri extract decreases morphine and phenytoin toxicity. ...
The use of herbs or their parts: leaves, roots, rhizomes, flowers, seeds, natural strains, as well as extracts or isolated metabolites is becoming more and more popular. Natural remedies not only act prophylactically, but also help to alleviate symptoms of many diseases and enhance the overall functioning of the internal organs. Many raw materials of natural origin plays a role in treatment of health problems, and also in case of serious diseases such as depression. Depression (affective disorder) now affects about 10% of the population, but in next few years due to the development of civilization and increasing pace of life, the probable number of people suffering from this disease can grow rapidly. Natural raw materials such as Bacopa monnieri, Crocus sativus, Eleutherococcus senticosus, Griffonia simplicifolia, Hypericum perforatum, Sceletium tortuosum, Piper methysticum, Rhodiola rosea, Aspalathus linearis, Camellia sinensis, Ficus carica, Lycium chinense, Cuminum cyminum, Panax Ginseng can effectively assist the prevention and treatment of depression. Daily diet may also have positive effect in prevention of this disease. It was found that 5-hydroxy-L-tryptophan, L-tryptophan (which are precursors of serotonin in the CNS), omega-3 fatty acids and anthranilic acid (vitamin L1) are able to improve mood. L-Tryptophan, 5-hydroxy-L-tryptophan are present in the largest quantities in the fruiting bodies of edible mushrooms. Omega-3 fatty acids are found in the flesh of fish, walnuts, soybeans, beans and chicken egg protein, while the anthranilic acid is commonly found in plants.
... Based on the previous studies, it is believed that these effects are due to the ability to modulate the cholinergic system of the plant extracts [11]. Their main action is to increase blood flow in the brain, improving concentration, they also have antioxidant, anti-inflammatory, antibacterial, and antitumor effects, and they are also used as support in neurodegenerative diseases (such as Alzheimer's and Parkinson's diseases) treatment [12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Based on studies of patients with depression, it was shown that B. monnieri exhibits an antidepressant activity [1,11]. ...
Bacopa monnieri is one of the most interesting plants from the Ayurveda system. The aims of present research were, basing on in vitro shoot culture of B. monnieri, to determine content and to evaluate the influence of physiologically important metabolites on the selected bioelements accumulation in biomass. The most significant increase in biomass production was observed in the culture medium enriched with 0.5 mg/L of anthranilic acid. In this medium also, the highest accumulation of Mg was noted. The highest concentration of iron was determined in B. monnieri in vitro culture enriched with 0.25 g/L of serine. The addition of L-tryptophan, magnesium sulfate, and zinc hydroaspartate caused only a small increase in the accumulation of copper in B. monnieri. Increase in Zn accumulation was obtained in biomass from in vitro culture of B. monnieri with the addition of magnesium sulfate and zinc hydroaspartate. In the case of Na, the maximum level of this element was in biomass from medium enriched with zinc hydroaspartate. Twofold increase in K concentration was obtained in biomass from cultures on medium with addition of serine and magnesium sulfate. The concentrations of Ca in biomass of all studied media were at the similar level.
... However, many potential mechanisms of action have been identified and extensively reviewed (Aguiar and Borowski, 2013). These mechanisms include as follows: reducing β-amyloid levels and neuronal damage induced by β-amyloid; restoration of cholinergic function; GABA modulation; promoting anti-oxidant defenses; augmentation of 5-HT levels; modulation of brain stress hormones; neuroprotection; reducing neuroinflammation ( Rastogi et al., 2012); and increasing cerebral blood flow ( Kamkaew et al., 2013). Such a complex spectrum of actions, in mostly animal studies, might reflect varying activity profiles of individual components contained in the Bacopa monnieri extracts. ...
ETHNOPHARMACOLOGICAL RELEVANCE:
Bacopa monnieri has a long history in Ayurvedic medicine for neurological and behavioral defects. To assess its efficacy in improving cognitive function.
MATERIALS AND METHODS:
MEDLINE, EMBASE, CINAHL, AMED, Cochrane Central of clinical trial, WHO registry, Thai Medical Index, Index Medicus Siriraj library and www.clinicaltrial.gov were searched from the inception date of each database to June 2013 using scientific and common synonyms of Bacopa monnieri, cognitive performance or memory. The reference lists of retrieved articles were also reviewed. Randomized, placebo controlled human intervention trials on chronic ≥12 weeks dosing of standardized extracts of Bacopa monnieri without any co-medication were included in this study. The methodological quality of studies was assessed using Cochrane's risk of bias assessment and Jadad's quality scales. The weighted mean difference and 95% confidence interval (95% CI) were performed using the random-effects model of the Dersimonian-Laird method.
RESULTS:
Nine studies met the inclusion criteria using 518 subjects. Overall quality of all included trials was low risk of bias and quality of reported information was high. Meta-analysis of 437 eligible subjects showed improved cognition by shortened Trail B test (-17.9ms; 95% CI -24.6 to -11.2; p<0.001) and decreased choice reaction time (10.6ms; 95% CI -12.1 to -9.2; p<0.001).
CONCLUSION:
This meta-analysis suggests that Bacopa monnieri has the potential to improve cognition, particularly speed of attention but only a large well designed 'head-to-head' trial against an existing medication will provide definitive data on its efficacy on healthy or dementia patients using a standardized preparation
... ); and increasing cerebral blood flow (Kamkaew et al., 2013). ...
Bacopa monnieri has a long history in Ayurvedic medicine for neurological and behavioral defects.
To assess its efficacy in improving cognitive function.
MEDLINE, EMBASE, CINAHL, AMED, Cochrane Central of clinical trial, WHO registry, Thai Medical Index, Index Medicus Siriraj library and www.clinicaltrial.gov were searched from the inception date of each database to June 2013 using scientific and common synonyms of B. monnieri, cognitive performance or memory. The reference lists of retrieved articles were also reviewed. Randomized, placebo controlled human intervention trials on chronic ≥12 weeks dosing of standardized extracts of B. monnieri without any co-medication were included in this study. The methodological quality of studies was assessed using Cochrane's risk of bias assessment and Jadad's quality scales. The weighted mean difference and 95% confidence interval (95%CI) was performed using the random-effects model of Dersimonian-Laird method.
Nine studies met the inclusion criteria using 518 subjects. Overall quality of all included trials was low risk of bias and quality of reported information was high. Meta analysis of 437 eligible subjects showed improved cognition by shortened trail B test (-17.9ms; 95% CI -24.6 to -11.2; p<0.001) and decreased choice reaction time (10.6ms; 95% CI-12.1 to -9.2; p<0.001).
This meta-analysis suggests that B. monnieri has the potential to improve cognition, particularly speed of attention but only a large well designed 'head-to-head' trial against an existing medication will provide definitive data on its efficacy on healthy or dementia patients using a standardized preparation.
Bacopa monnieri, a valuable medicinal herb, is endangered and is often propagated vegetatively. It is well-known for its versatility in applications. Bacopa monnieri ,a plant with strong roots in the Indian ancient Ayurvedic system, has long been known as an effective treatment. Commonly known as "Brahmi," this medicinal plant contains important phytopharmaceuticals substances. Given its importance in treating a variety of disorders, producing Bacopa monnieri via in vitro cultivation is crucial. Aseptic cultures were produced and begun on Murashige and Skoog (MS) media enriched with 6-benzyl adenine (0.5μM). For shoot multiplication, a combination of BA, Kinetin (KIN), and Thidizuron (TDZ) was used. BA surpassed KIN and TDZ in terms of multiplication of shoots and elongation.MS medium with 2.5μM of BA resulted in the maximum shoot multiplication. Furthermore, the greatest shoot regeneration frequency was found on MS medium enriched with 5.0μM of BA and 1.0μM of α-naphthalene acetic acid (NAA). This plant is suggested in the Indian Materia Medica (Bhavaprakasha Nighantu AD 1500) for treating a wide range of mental illnesses, including stress, poor cognition, lack of focus, sleeplessness, insanity, depression, psychosis, epilepsy, and Alzheimer's disease [1,2]. Commercially accessible extracts of B. monnieri have been shown to improve memory focus, cognitive development, and general brain function in young as well as older people. Furthermore, the plant has a long history of usage as a heart tonic and digestive aid in India and Pakistan, with reports of improved respiratory performance during bronchoconstriction. Clinical studies demonstrate the favorable benefits of bacopa-based compounds in the recovery of brain functions in children with diagnoses of attention deficit hyperactivity disorder (ADHD), as well as the augmentation of cognitive capacities in patients recovering from stroke. It is also used in cosmetic industries as it contains essential oils, sterols, flavonoids, glycosides, as well as triterpenoid saponins. Two commercially available hair care formulations—Brahmi oil and soft extract—make use of Brahmi's positive characteristics. It is also classified as classified as a Rasayana in Ayurveda, is known for its ability to postpone indications of aging in the body, such as hair graying. Furthermore, Brahmi helps to alleviate mental weariness, which contributes to the preservation of a favorable body environment for healthy hair [3].
The cholinergic transmission in the medial septum and ventral limb of the diagonal band of broca (MS/VDB)-hippocampal circuit and its associated theta oscillations play a crucial role in chronic cerebral hypoperfusion (CCH)-related cognitive impairment. However, the contribution and mechanism of the vesicular acetylcholine transporter (VAChT), a vital protein that regulates acetylcholine (ACh) release, in CCH-related cognitive impairment are not well understood. To investigate this, we established a rat model of CCH by performing 2-vessel occlusion (2-VO) and overexpressed VAChT in the MS/VDB via stereotaxic injection of adeno-associated virus (AAV). We evaluated the cognitive function of the rats using the Morris Water Maze (MWM) and Novel Object Recognition Test (NOR). We employed enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and immunohistochemistry (IHC) to assess hippocampal cholinergic levels. We also conducted in vivo local field potentials (LFPs) recording experiments to evaluate changes in hippocampal theta oscillations and synchrony. Our findings showed that VAChT overexpression shortened the escape latency in the hidden platform test, increased swimming time in the platform quadrant in probe trains, and increased the recognition index (RI) in NOR. Moreover, VAChT overexpression increased hippocampal cholinergic levels, improved theta oscillations, and improved the synchrony of theta oscillations between CA1 and CA3 in CCH rats. These results suggest that VAChT plays a protective role in CCH-induced cognitive deficits by regulating cholinergic transmission in the MS/VDB-hippocampal circuit and promoting hippocampal theta oscillations. Therefore, VAChT could be a promising therapeutic target for treating CCH-related cognitive impairments.
Degenerative nerve diseases are age-related, progressive and cause irreversible neurological loss that may lead to death. Chronic diseases like amyotrophic lateral sclerosis, Huntington's disease, Alzheimer's disease, and Parkinson's disease are associated with insoluble protein depositions and pose serious health challenges that may intensify in the coming decades. Current therapies only help to alleviate some of the physical or mental symptoms associated with neurodegenerative diseases, although there is currently no remedy for slow disease progression. In recent years, attempts have been made to discover a mechanism for neurodegenerative diseases and prospective treatment that may help mitigate aging effects and prevent these diseases. Natural products have been a constant source of new approaches for the treatment of neurodegenerative diseases, in particular plant alkaloids and polyphenolic compounds. Indopathy for Neuroprotection: Recent Advances highlights herbal treatments that are preferred over conventional treatments in some regions. Book chapters focus on the effects of various medicinal plants that have shown promise in reversing pathological symptoms of neurodegenerative disease and highlight the neuroprotective role of medicinal herbal phytochemicals and their mechanism of action. The book serves as a reference for pharmacology and herbal medicine scholars as well as healthcare workers interested in information about alternative and complementary therapies for neurological disorders.
Brahmi essence, developed from Bacopa monnieri (L.) Wettst. standardized extract and mulberry juice, was proven to improve the memory speed of healthy participants aged 55–80 years old, following a 12-week dietary program. However, the metabolites have not yet been reported. Our objective was to characterize the altered metabolites in the plasma, urine, and feces of healthy volunteers after consumption of Brahmi essence for 12 weeks, using the LC-MS metabolomics approach. The altered metabolites were selected from OPLS-DA S-plots; 15 metabolites in the plasma, 7 in the urine, and 17 in the feces samples were tentatively identified by comparison with an online database and literature. The metabolites in the plasma samples were in the classes of amino acids, acylcarnitine, and phospholipids. Benzeneactamide-4-O-sulphate and 3-hydroxyhippuric acid were found in urine samples. The metabolites in the class of amino acids, together with jujubogenin and pseudojujubogenin, were identified in the fecal samples. The aminoacyl-tRNA, aromatic amino acids, and branched-chain amino acid biosynthetic pathways were mainly related to the identified metabolites in all three samples. It could be implied that those metabolites and their pathways might be linked with the effect of Brahmi essence on memory speed.
Dementia is a chronic condition characterized by the decreased cognitive capacity, which is more severe than in case of normal aging. Cognitive impairment is a major social and economic problem of modern society, which affects about 47 million people worldwide. The first stage of dementia (mild cognitive impairment) is characterized by the decline of memory, executive function, attention, visuospatial skills and speech. Pathogenic links of cognitive impairment are represented by neuroinflammation, excessive amyloid-β protein deposition, oxidative stress, hyperphosphorylation etc. In the recent years, the interest in natural plant-derived compounds for the treatment of cognitive decline has increased. In this chapter, we summarize the available evidence supporting the benevolent action of some botanicals and phytochemicals on cognitive function. The most widely studied plants include Ginkgo biloba, Panax ginseng and Camellia sinensis (green tea), but there also some other promising ones like guarana, grape, soy etc. These nutraceuticals mostly influence memory, learning and attention. At the moment it is quite difficult to make a definite conclusion on the effects of nutraceuticals on cognitive decline, because human trials show significant discrepancies. This underpins the need of future trials and scientific analysis.
Alzheimer's disease (AD) is caused by accumulation of senile plaques and neurofibrillary tangles in hippocampus and temporal lobe and the progressive, irreversible, immunooxidative (neurodegenerative) cascades initiated by them. Availability of merely two classes of drugs targeting symptoms rather than underlying pathomechanisms while newer molecules show 99.6% failure rate makes AD an unyielding dementia syndrome. Considering the tremendous disability weight and healthcare burden posed by AD, it is worth exploring the relatively safe and disease-modifying plant-derived nootropics in AD. This chapter summarizes the research on existing, withdrawn, and under-trial synthetic and plant-derived molecules with key focus on the targeted pathomechanisms, efficacy, and safety outcomes. Actions of Bacopa monnieri extract (EBm) as an antioxidant, cholinomimetic, and on neuronal and glial plasticity, cerebral blood flow, memory impairment, and cognitive defects are reviewed extensively with current research. Meticulous standardization of EBm extract and further metacentric clinical trials are vital to drug development in AD.
Bacopa monnieri (L.) Wettst. (Scrophulariaceae), commonly known as water hyssop, is an extensively used herb in Ayurveda. The bioactive phyto-constituents like the dammarane-type triterpenoid saponins such as bacosides A, B, and C were reported mostly for neuroprotective, nootropic, and memory-enhancing properties. Furthermore, B. monnieri also acts as a natural antioxidant, which can ameliorate morphine dependence, memory deficit in epilepsy, hepatocarcinogenesis, hepatotoxicity, β-amyloid cytotoxicity, inflammation, and oxidative stress (Singh et al., Physiol Plant. 2019). The neuroprotective role of the plant was manifested against neurodegenerative disorders like Parkinson’s disease (PD), Alzheimer’s disease (AD)-associated dementia, attention-deficit hyperactivity disorder in children, and anxiety. Somer report also found the traces of heavy metals in various species of Bacopa monnieri. Inadequate knowledge regarding underlying mechanism of neuroprotection and associated systematic structure-activity relationship (SAR) studies and development of semisynthetic derivatives of saponins are of high importance to facilitate rational designing of novel drugs based on leads from bacopasaponins. This review systematically summarizes the origin, analysis of the pharmacotherapeutic properties, and structural significance of bioactivities exerted by the bacopasaponins. Moreover, future research arenas, lacunae in the present understanding, are also highlighted in this work. Together, this book chapter may further direct to the synthetic optimization of bacopasaponins as lead compounds for the designing of efficacious and clinically acceptable analogues.
Eating is a lifelong necessity and, as many people experience, eating behaviors can also lead to health problems. Attention to diet and nutrition should enable development of dietary and therapeutic measures that can arrest, resist, delay, or reverse disease risk factors, including aging, by regenerating, rejuvenating, or revitalizing the metabolic functional dynamics of the bodily organs. Within this context, this review examines the appealing potential for chemoprevention and the function and contribution of the most frequently used dietary herbs. These herbs may serve as long-term dementia prevention treatments that can complement the daily diet to improve quality of life. Expanded coverage of the evidence for the antidementia effects and cognitive improvement provided by huperzine A and Bacopa monnieri is also presented.
Extract of Ginkgo biloba (EGb), a dietary supplement used for a number of conditions including dementia, has been suggested to increase cerebral bloodflow (CBF). The purpose of this study was to determine if changes in CBF could be detected by dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI)in elderly human subjects taking EGb.
DSC-MRI was performed in nine healthy men(mean age 61±10 years) before and after 4 weeks of 60 mg EGb taken twice daily. One subject underwent six consecutive scans to evaluate intrasubject reproducibility. CBF values were computed before and after EGb, and analyzed at three different levels of spatial resolution, using voxel-based statistical parametric mapping (SPM), and regions of interest in different lobes, and all regions combined.
Normalized intrasubject CBF (nCBF) measurements had a standard deviation of 7% and 4% in gray and white matter (WM) regions, respectively. SPM using an uncorrected, voxel-level threshold of P≤0.001 showed a small CBF increase in the left parietal-occipital region.CBF in individual lobar regions did not show any significant change post-EGb, but all regions combined showed a significant increase of non-normalized CBF after EGb (15% in white and 13% in gray matter, respectively, P≤0.0001).
nCBF measured by DSC-MRI has good intrasubject reproducibility. In this small cohort of normal elderly individuals, a mild increase in CBF is found in the left parietal-occipital WM after EGb, as well as a small but statistically significant increase in global CBF.
W. R. Brown and C. R. Thore (2011) Neuropathology and Applied Neurobiology37, 56–74 Cerebral microvascular pathology in ageing and neurodegeneration
This review of age-related brain microvascular pathologies focuses on topics studied by this laboratory, including anatomy of the blood supply, tortuous vessels, venous collagenosis, capillary remnants, vascular density and microembolic brain injury. Our studies feature thick sections, large blocks embedded in celloidin, and vascular staining by alkaline phosphatase. This permits study of the vascular network in three dimensions, and the differentiation of afferent from efferent vessels. Current evidence suggests that there is decreased vascular density in ageing, Alzheimer's disease and leukoaraiosis, and cerebrovascular dysfunction precedes and accompanies cognitive dysfunction and neurodegeneration. A decline in cerebrovascular angiogenesis may inhibit recovery from hypoxia-induced capillary loss. Cerebral blood flow is inhibited by tortuous arterioles and deposition of excessive collagen in veins and venules. Misery perfusion due to capillary loss appears to occur before cell loss in leukoaraiosis, and cerebral blood flow is also reduced in the normal-appearing white matter. Hypoperfusion occurs early in Alzheimer's disease, inducing white matter lesions and correlating with dementia. In vascular dementia, cholinergic reductions are correlated with cognitive impairment, and cholinesterase inhibitors have some benefit. Most lipid microemboli from cardiac surgery pass through the brain in a few days, but some remain for weeks. They can cause what appears to be a type of vascular dementia years after surgery. Donepezil has shown some benefit. Emboli, such as clots, cholesterol crystals and microspheres can be extruded through the walls of cerebral vessels, but there is no evidence yet that lipid emboli undergo such extravasation.
Bacopa monniera and Ginkgo biloba are well-known cognitive enhancers in Indian and Chinese traditional medicine systems. Standardized extracts of B. monniera and G. biloba were used to evaluate the antidementic and anticholinesterase activities in adult male Swiss mice. Antidementic activity was tested against scopolamine (3 mg/kg ip)-induced deficits in passive avoidance test. Three different extracts of B. monniera (30 mg/kg) and extract of G. biloba (15, 30 and 60 mg/kg) were administered postoperatively, daily for 7 days and 60 min after the last dose, i.e., on Day 7, first trial was conducted. In passive avoidance test, increased transfer latency time (TLT) and no transfer response (NTR) were taken as criteria for learning. TLT and NTR were significantly increased and decreased in second trial, 24 h after the first trial in control group and scopolamine-dementia group, respectively. The B. monniera- and G. biloba-treated groups produced significant increase in TLT and NTR on second trial (40-80%) after scopolamine treatment, thus, attenuating its antidementic effect. Both the extracts showed a dose (10-1000 microg)-dependent inhibitory effect on acetylcholinesterase (AChE) activity (in vitro), performed spectrophotometrically. IC(50) of G. biloba was 268.33 microg, whereas none of the extracts of B. monniera showed more than 50% inhibition. At a dose concentration of 30 and 60 mg/kg, extracts of G. biloba showed a cognitive enhancing property and, at the same time, a significant decrease in AChE-specific activity in both per se and scopolamine-dementia groups. These extracts possess a significant anticholinesterase and antidementic properties, which may be useful in the treatment of dementia.
Beneficial effects of Ginkgo biloba on peripheral arterial occlusive disease have been repeatedly shown in clinical trials, especially after use of EGb 761, a standardized special extract. Since the underlying mechanisms are widely unknown, we aimed to elucidate the molecular basis on which EGb 761 protects against endothelial dysfunction in vitro and in vivo. Application of therapeutically feasible doses of EGb 761 for 48 h caused endothelial nitric oxide (NO) production by increasing endothelial nitric oxide synthase (eNOS) promoter activity and eNOS expression in vitro. Phosphorylation of eNOS at a site typical for Akt (Ser 1177) was acutely enhanced by treatment with EGb 761, as was Akt phosphorylation at Ser 478. Furthermore, the extract caused acute relaxation of isolated aortic rings and NO-dependent reduction of blood pressure in vivo in rats. These influences on eNOS represent a putative molecular basis for the protective cardiovascular properties of EGb 761.
Bacopa monnieri (Brahmi) provides traditional cognitive treatments possibly reflecting improved cerebral hemodynamics. Little is known about the cardiovascular actions of Brahmi. We sought to assess its effects on blood pressure and on isolated arteries, thus providing insights to clinical applications.
Intravenous Brahmi (20-60 mg/kg) was tested on arterial blood pressure and heart rate of anaesthetized rats. In vitro vasorelaxation was assessed in arteries, with and without blockers of nitric oxide synthase (L-NAME), cyclooxygenase (indomethacin), and mechanical de-endothelialisation. The effects of Brahmi on Ca(2+) influx and release from stores were investigated.
Intravenous Brahmi extract (20-60 mg/kg) decreased systolic and diastolic pressures without affecting heart rate. Brahmi evoked relaxation in isolated arteries in order of potency: basilar (IC50=102 ± 16 μg/ml)>mesenteric (171 ± 31)>aortae (213 ± 68)>renal (IC50=375 ± 51)>tail artery (494 ± 93)>femoral arteries (>1,000 μg/ml). Two saponins, bacoside A3 and bacopaside II, had similar vasodilator actions (IC50=8.3 ± 1.7 and 19.5 ± 6.3 μM). In aortae, without endothelium or in L-NAME (10-4M), Brahmi was less potent (IC50=213 ± 68 to 2170 ± 664 and 1192 ± 167 μg/ml, respectively); indomethacin (10-5M) was ineffective. In tail artery, Brahmi inhibited K(+)-depolarization induced Ca(2+) influx and Ca(2+) release from the sarcoplasmic reticulum by phenylephrine (10-5M) or caffeine (20mM).
Brahmi reduces blood pressure partly via releasing nitric oxide from the endothelium, with additional actions on vascular smooth muscle Ca(2+) homeostasis. Some Brahmi ingredients could be efficacious antihypertensives and the vasodilation could account for some medicinal actions.
Bacopa monnieri (L.) Wettst., a plant belonging to the family Scrophulariaceae, has been used in the traditional system of Ayurvedic medicine to improve intelligence and memory for a long time. Therefore, the potential of this plant to protect against Alzheimer's disease has been raised but less supported document is available.
To determine the effect of alcoholic extract of Bacopa monnieri on cognitive function and neurodegeneration in animal model of Alzheimer's disease induced by ethylcholine aziridinium ion (AF64A).
Male Wistar rats were orally given the alcoholic extract of Bacopa monnieri at doses of 20, 40 and 80 mg/kg BW via feeding needle for a period of 2 weeks before and 1 week after the intracerebroventricular administration of AF64A bilaterally. Rats were tested for spatial memory using Morris water maze test and the density of neurons and cholinergic neurons was determined using histological techniques 7 days after AF64A administration.
Bacopa monnieri extract improved the escape latency time (p<.01) in Morris water maze test. Moreover, the reduction of neurons and cholinergic neuron densities were also mitigated.
These findings suggest that Bacopa monnieri is a potential cognitive enhancer and neuroprotectant against Alzheimer's disease.
Early postnatal maternal deprivation is known to cause long-lasting neurobiological effects. Here, we investigated whether some of the cognitive aspects of these deficits might be related to a disruption of the cholinergic system. Pregnant Wistar rats were individually housed and maintained on a 12:12h light/dark cycle with food and water freely available. The mothers were separated from their pups for 3h per day from postnatal day 1 (PND-1) to PND-10. To do that, the dams were moved to a different cage and the pups maintained in the original home cage, which was transferred to a different room kept at 32 degrees C. After they reached 120-150 days of age, maternal-deprived and non-deprived animals were either sacrificed for brain acetylcholinesterase measurement, or trained and tested in an object recognition task and in a social recognition task as described by Rossato et al. (2007) [Rossato, J.I., Bevilaqua, L. R.M., Myskiw, J.C., Medina, J.H., Izquierdo, I., Cammarota, M. 2007. On the role hippocampal synthesis in the consolidation and reconsolidation of object recognition memory. Learn. Mem. 14, 36-46] and Lévy et al. (2003) [Lévy, F., Melo. A.I., Galef. B.G. Jr., Madden, M., Fleming. A.S. 2003. Complete maternal deprivation affects social, but not spatial, learning in adult rats. Dev. Psychobiol. 43, 177-191], respectively. There was increased acetylcholinesterase activity in hippocampus and perirhinal cortex of the deprived animals. In addition, they showed a clear impairment in memory of the two recognition tasks measured 24h after training. Oral administration of the acetylcholinesterase inhibitors, donepezil or galantamine (1mg/kg) 30min before training reversed the memory impairments caused by maternal deprivation. The findings suggest that maternal deprivation affects memory processing at adulthood through a change in brain cholinergic systems.
The normal anatomical position of the point of junction of the superficial cerebral veins with the superior sagittal and transverse sinuses of the rat was studied with an analytical mathematical method. There were eight fixed veins, each characterized by a constant point of juncture having minimal variance. The findings indicate that the points of juncture between large veins and sinuses are developmentally fixed and that there is a definite order in the number and the territories of the large veins.
Background:
The recent introduction of acetylcholinesterase inhibitors (AChEIs) therapy for Alzheimer's Disease (AD) has led to the need to assess the brain's response to the therapy on an objective, neurophysiological basis. Brain perfusion single photon emission computed tomography (SPECT) was used in an open-label study to evaluate the effect of chronic Donepezil administration to a group of patients affected by mild to moderate AD, compared to a group of AD patients not receiving AChEIs and kept under observation for a similar period.
Methods:
Twenty-five consecutive patients with probable AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria) (19 women, 6 men; mean age: 74.2+/-7.2; mean Mini-Mental State Examination score, MMSE: 19.8+/-3.5) underwent (t0) brain SPECT with 99mTc-hexamethylpropylene-amine-oxime by a brain-dedicated, high-resolution camera and were re-evaluated (t1) after 11+/-2.6 months of chronic Donepezil administration (5mg/day) (treated group). Thirteen AD patients (9 women, 4 men, mean age: 71.4+/-5.7, MMSE score: 20.6+/-3.5) were not treated with AChEIs and served as controls (untreated group). They were subjected to the same evaluation after 13+/-1.4 months as the treated group. Statistical parametric mapping (SPM) was employed to analyse SPECT findings.
Results:
The MMSE score declined significantly (P<0.01) from t0 to t1 both in untreated (from 20.6+/-3.5 to 17.8+/-4.4) and in treated (from 19.8+/-3.5 to 17.8+/-4.1) group. At t(0), the untreated group showed higher regional cerebral blood flow (rCBF) than the treated group in a frontal and a frontal-parietal region of the left hemisphere. Between t0 and t1, significant rCBF reduction was observed in the temporal lobe and occipital-temporal cortex of the left hemisphere in the untreated group, whereas no significant change was observed in the treated group. The rCBF of the two groups did not significantly differ at t1. By covariate SPM analysis between t0 and t1 in treated patients, MMSE score changes correlated significantly with rCBF changes in a large left frontal-temporal region.
Conclusions:
Brain perfusion is preserved in AD patients undergoing chronic Donepezil therapy while it is reduced in untreated patients. SPECT is a promising tool with which to assess the impact of AChEI therapy on brain functioning of AD patients.
Dementia of Alzheimer's type (DAT), together with vascular dementia, is the most important indication for Ginkgo biloba extract (EGb). The therapeutic efficacy of this extract is founded on neuroprotective, metabolic and rheological effects. In addition to these mechanisms--which also form the basis of the activity of the older synthetic nootropics--the hypothesis that DAT is due to a "cholinergic deficit" at central synapses has led, over the last decade, to the development of a new group of drugs for this indication, the cholinesterase (ChE) inhibitors. Thus nowadays, EGb is competing, on the synthetic side, with the ChE inhibitors tacrine, donepezil, rivastigmine and galantamine. No direct comparative trials have been undertaken, but long-term studies lasting 24-56 weeks to demonstrate efficacy have been carried out with both groups of substances in accordance with current EU guidelines. To date, only one psychometric scale has gained general acceptance as the primary criterion of efficacy, namely the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), whose scores range from 0 to 70 (the lower the better). The initial scores of patients in the trials were between 20 and 30; the improvements after 6 months treatment (less those seen with placebo) were about 2 points under Ginkgo extract and 2 to 4 points with the ChE inhibitors. However, the relatively small differences are called into question by the occurrence of drug-specific side effects with the ChE inhibitors. Unlike the treatment with EGb, up to 90% of the patients given the ChE inhibitors developed nausea and vomiting, so there is a suspicion that methodological reasons in the sense of an "unblinding" of the treatment groups caused the apparent superiority in the intensity of the effect. In addition, the benefits of treatment were rapidly reversed after ending administration of ChE inhibitors, which did not occur to the same extent with EGb. Adverse drug reactions are more than 10 times more common with the ChE inhibitors and the treatment costs about five times higher than with EGb. Given the limited therapeutic options for DAT, treatment with EGb still appears to be the method of choice compared to the ChE inhibitors.