Methyl jasmonate inducible UGT79A18 is a novel glycosyltransferase involved in the bacoside biosynthetic pathway in Bacopa monnieri.

Bacosides are dammarane-type triterpenoidal saponins in Bacopa monnieri and have various pharmacological applications. All the bacosides are diversified from two isomers, i.e., jujubogenin and pseudojujubogenin. The biosynthetic pathway of bacoside is not well elucidated. In the present study, we characterized a UDP-glycosyltransferase, UGT79A18, involved in the glycosylation of pseudojujubogenin. UGT79A18 shows higher expression in response to 5 h of wounding, and 3 h of MeJA treatment. The recombinant UGT79A18 shows in vitro activity against a wide range of flavonoids and triterpenes and has a substrate preference for protopanaxadiol, a dammarane-type triterpene. Secondary metabolite analysis of overexpression and knockdown lines of UGT79A18 in B. monnieri identify bacopasaponin D, bacopaside II, bacopaside N2 and pseudojujubogenin glucosyl rhamnoside as the major bacosides that were differentially accumulated. In the overexpression lines of UGT79A18, we found 1.7-fold enhanced bacopaside II, 8-fold enhanced bacopasaponin D, 3-fold enhanced pseudojujubogenin glucosyl rhamnoside, and 1.6-fold enhanced bacopaside N2 content in comparison with vector control plant, whereas in the knockdown lines of UGT79A18, we found 1.4-fold reduction in bacopaside II content, 3-fold reduction in the bacopasaponin D content, 2-fold reduction in the pseudojujubogenin glucosyl rhamnoside content, and 1.5-fold reduction in bacopaside N2 content in comparison with vector control. These results suggest that UGT79A18 is a significant UDP glycosyltransferase involved in glycosylating pseudojujubogenin and enhancing the pseudojujubogenin-derived bacosides.

Discovery of Molecular Networks of Neuroprotection Conferred by Brahmi Extract in Aß42-Induced Toxicity Model of Drosophila melanogaster Using a Quantitative Proteomic Approach.

Accumulation of Aß42 peptides forming plaque in various regions of the brain is a hallmark of Alzheimer's disease (AD) progression. However, to date, there is no effective management strategy reported for attenuation of Aß42-induced toxicity in the early stages of the disease. Alternate medicinal systems such as Ayurveda in the past few decades show promising results in the management of neuronal complications. Medhya Rasayana such as Brahmi is known for its neuroprotective properties via resolving memory-related issues, while the underlying molecular mechanism of the same remains unclear. In the present study, we aimed to understand the neuroprotective effects of the aqueous extract of Bacopa monnieri and Centella asiatica (both commonly known as Brahmi) against the Aß42 expressing model of the Drosophila melanogaster. By applying a quantitative proteomics approach, the study identified > 90% of differentially expressed proteins from Aß42 expressing D. melanogaster were either restored to their original expression pattern or showed no change in expression pattern upon receiving either Brahmi extract treatment. The Brahmi restored proteins were part of neuronal pathways associated with cell cycle re-entry, apoptosis, and mitochondrial dynamics. The neuroprotective effect of Brahmi was also validated by negative geotaxis behavioral analysis suggesting its protective role against behavioral deficits exerted by Aß42 toxicity. We believe that these discoveries will provide a platform for developing novel therapeutics for AD management by deciphering molecular targets of neuroprotection conferred by an aqueous extract of Bacopa monnieri or Centella asiatica.

Computational Analysis of Bacopa monnieri (L.) Wettst. Compounds for Drug Development against Neurodegenerative Disorders.

AIM: With several experimental studies establishing the role of Bacopa monnieri as an effective neurological medication, less focus has been employed to explore how effectively Bacopa monnieri brings about this property. The current work focuses on understanding the molecular interaction of the phytochemicals of the plant against different neurotrophic factors to explore their role and potential as potent anti-neurodegenerative drugs. BACKGROUND: Neurotrophins play a crucial role in the development and regulation of neurons. Alterations in the functioning of these Neurotrophins lead to several Neurodegenerative Disorders. Albeit engineered medications are accessible for the treatment of Neurodegenerative Disorders, due to their numerous side effects, it becomes imperative to formulate and synthesize novel drug candidates. OBJECTIVE: This study aims to investigate the potential of Bacopa monnieri phytochemicals as potent antineurodegenerative drugs by inspecting the interactions between Neurotrophins and target proteins. METHODS: The current study employs molecular docking and molecular dynamic simulation studies to examine the molecular interactions of phytochemicals with respective Neurotrophins. Further inspection of the screened phytochemicals was performed to analyze the ADME-Tox properties in order to classify the screened phytochemicals as potent drug candidates. RESULTS: The phytochemicals of Bacopa monnieri were subjected to in-silico docking with the respective Neurotrophins. Vitamin E, Benzene propanoic acid, 3,5-bis (1,1- dimethylethyl)- 4hydroxy-, methyl ester (BPA), Stigmasterol, and Nonacosane showed an excellent binding affinity with their respective Neurotrophins (BDNF, NT3, NT4, NGF). Moreover, the molecular dynamic simulation studies revealed that BPA and Stigmasterol show a very stable interaction with NT3 and NT4, respectively, suggesting their potential role as a drug candidate. Nonacosane exhibited a fluctuating binding behavior with NGF which can be accounted for by its long linear structure. ADME-Tox studies further confirmed the potency of these phytochemicals as BPA violated no factors and Vitamin E, Stigmasterol and Nonacosane violated 1 factor for Lipinski's rule. Moreover, their high human intestinal absorption and bioavailability score along with their classification as non-mutagen in the Ames test makes these compounds more reliable as potent antineurodegenerative drugs. CONCLUSION: Our study provides an in-silico approach toward understanding the anti-neurodegenerative property of Bacopa monnieri phytochemicals and establishes the role of four major phytochemicals which can be utilized as a replacement for synthetic drugs against several neurodegenerative disorders.

Bio-Computational Evaluation of Compounds of Bacopa Monnieri as a Potential Treatment for Schizophrenia.

Schizophrenia is a horrible mental disorder characterized by distorted perceptions of reality. Investigations have not identified a single etiology for schizophrenia, and there are multiple hypotheses based on various aspects of the disease. There is no specific treatment for schizophrenia. Hence, we have tried to investigate the updated information stored in the genetic databases related to genes that could be responsible for schizophrenia and other related neuronal disorders. After implementing combined computational methodology, such as protein-protein interaction analysis led by system biology approach, in silico docking analysis was performed to explore the 3D binding pattern of Bacopa monnieri natural compounds while interacting with STXBP1. The best-identified compound was CID:5319292 based on -10.3 kcal/mol binding energy. Further, selected complexes were dynamically evaluated by MDS methods, and the output reveals that the STXBP1-CID:5281800 complex showed the lowest RMSD value, i.e., between 0.3 and 0.4 nm. Hence, identified compounds could be used to develop and treat neuronal disorders after in vivo/in vitro testing.

Investigating neuroprotective roles of Bacopa monnieri extracts: Mechanistic insights and therapeutic implications.

Bacopa monnieri (Brahmi) is a well-known perennial, creeping herb of the Indian Ayurveda system; it contains numerous bioactive phytoconstituents implicated in the therapeutic management of several life-threatening diseases. This herb was used by Ancient Vedic scholars due to its pharmacological effect, especially as a nerve tonic and nootropic booster. However, to better understand the roles of Bacopa monnieri extract (BME) in neurological disorders and memory-related diseases, it is necessary to understand its active phytochemical constituents and their molecular mechanisms. Several clinical studies suggested that BME have neuroprotective effects, making it worth revising a notable herb. Here we investigated the contours of BME's phytochemistry and pharmacological features, focusing on neuronal disorders. We further analyzed the underlying molecular mechanisms in therapeutic intervention. Various clinical concerns and synergistic potential of BME were explored for their effective use in cognition and neuroprotection. The generation of reactive oxygen species increases neuroinflammation and neurotoxicity and is associated with Tau and amyloid-beta (Aß) aggregation, leading to a neurological disorder. Our findings provide deeper mechanistic insights into the neuroprotective roles of BME, which can be further implicated in the therapeutic management of neurological disorders and exerting cognitive-enhancing effects.

Antibacterial Potential of Bacopa monnieri (L.) Wettst. and Its Bioactive Molecules against Uropathogens-An In Silico Study to Identify Potential Lead Molecule(s) for the Development of New Drugs to Treat Urinary Tract Infections.

Urinary tract infections (UTIs) are becoming more common, requiring extensive protection from antimicrobials. The global expansion of multi-drug resistance uropathogens in the past decade emphasizes the necessity of newer antibiotic treatments and prevention strategies for UTIs. Medicinal plants have wide therapeutic applications in both the prevention and management of many ailments. Bacopa monnieri is a medicinal plant that is found in the warmer and wetlands regions of the world. It has been used in Ayurvedic systems for centuries. The present study aimed to investigate the antibacterial potential of the extract of B. monnieri leaves and its bioactive molecules against UTIs that are caused by Klebsiella pneumoniae and Proteus mirabilis. This in vitro experimental study was conducted by an agar well diffusion method to evaluate the antimicrobial effect of 80% methanol, 96% ethanol, and aqueous extracts of B. monnieri leaves on uropathogens. Then, further screening of their phytochemicals was carried out using standard methods. To validate the bioactive molecules and the microbe interactions, AutoDock Vina software was used for molecular docking with the Klebsiella pneumoniae fosfomycin resistance protein (5WEW) and the Zn-dependent receptor-binding domain of Proteus mirabilis MR/P fimbrial adhesin MrpH (6Y4F). Toxicity prediction and drug likeness were predicted using ProTox-II and Molinspiration, respectively. A molecular dynamics (MD) simulation was carried out to study the protein ligand complexes. The methanolic leaves extract of B. monnieri revealed a 22.3 mm ± 0.6 mm to 25.0 mm ± 0.5 mm inhibition zone, while ethanolic extract seemed to produce 19.3 mm ± 0.8 mm to 23.0 mm ± 0.4 mm inhibition zones against K. pneumoniae with the use of increasing concentrations. In the case of P. mirabilis activity, the methanolic extracts showed a 21.0 mm ± 0.8 mm to 24.0 mm ± 0.6 mm zone of inhibition and the ethanol extract produced a 17.0 mm ± 0.9 mm to 23.0 mm ± 0.7 mm inhibition zone with increasing concentrations. Carbohydrates, flavonoids, saponin, phenolic, and terpenoid were common phytoconstituents identified in B. monnieri extracts. Oroxindin showed the best interactions with the binding energies with 5WEW and 6Y4F, -7.5 kcal/mol and -7.4 kcal/mol, respectively. Oroxindin, a bioactive molecule, followed Lipinski's rule of five and exhibited stability in the MD simulation. The overall results suggest that Oroxindin from B. monnieri can be a potent inhibitor for the effective killing of K. pneumoniae and P. mirabilis. Additionally, its safety has been established, indicating its potential for future drug discovery and development in the treatment for UTIs.

Neuroprotective effect of the standardised extract of Bacopa monnieri (BacoMind) in valproic acid model of autism spectrum disorder in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Bacopa monnieri (BM) is commonly employed in the Indian traditional system of medicines, i.e. Ayurveda as a memory booster, antioxidant, anti-inflammatory, antipyretic, analgesic, sedative and anti-epileptic for decades. AIM OF THE STUDY: To evaluate the neuroprotective effect of Bacopa monnieri (BM) in experimental model of autism spectrum disorder (ASD) in Wistar rats and explore its mechanism of action. MATERIALS AND METHODS: BacoMind, was evaluated for its neuroprotective effect in valproic acid (VPA) model of ASD. For in-vivo study, the pregnant female Wistar rats were divided in two groups; normal control (NC) and VPA group who received single dose of normal saline (0.9%) or 600 mg/kg dose of VPA respectively on gestation day (G.D) 12.5. After the birth, all pups were segregated according to the sex. All the male pups from the dams were divided into six groups: Group 1 (NC, treated with only 0.9% normal saline, group 2 (VPA, treated 600 mg/kg on G.D12.5 and normal saline from post natal day (PND) 23 to 43), group 3 (risperidone 2.5 mg/kg, PND 23 to 43) and groups 4, 5 and 6 (BM 20, 40, 80 mg/kg, PND 23 to 43). All experimental groups were subjected to batteries of behavior parameters (three chamber sociability test, Morris Water Maze, elevated plus maze, open field and rota rod test), biochemical parameters such as oxidative stress (GSH, SOD, Catalase, MDA), inflammatory cytokines (Il-1ß, IL-6, IL-10, TNF-α), histopathological examination (cresyl violet staining) of hippocampus (HC) and prefrontal cortex (PFC) regions. Further, the mRNA as well as protein expression of AMPA receptor was evaluated using RT-PCR and western blot respectively to study the mechanism of neuroprotective effect of BM. The in-silico analysis followed evaluating the binding profile of different constituents of BacoMind with AMPA receptor. RESULTS: The results of the in-vivo study indicated BM at 80 mg/kg ameliorated abnormal behavioral paradigms such as social deficits, repetitive behavior, learning and memory impairments, and motor coordination exhibited by the VPA model of ASD in rats. Furthermore, BM was found to have a significant anti-oxidant (increasing GSH, SOD, and catalase and decreasing MDA levels) and anti-inflammatory properties (decreasing IL-1ß, 6, TNF- α). The histopathological score was also found to be significantly improved by BM in a dose dependent manner in both HC and PFC. In addition to this, the up-regulated mRNA as well as protein expression of AMPA receptor was significantly reduced by 80 mg/kg dose of BM in both HC and PFC. Further, the in-silico analysis of different constituents of BacoMind with AMPA receptor demonstrated that luteolin and apigenin showed good binding to both the competitive antagonist binding site, non-competitive antagonist binding site and allosteric modulator site while Bacosaponin C showed good binding to the non-competitive antagonist binding site. CONCLUSION: The present study concluded that BM can be a potential candidate for ameliorating the ASD symptoms in rats and acts via modulating the up-regulated AMPA receptor expression.

Bacopa monnieri: historical aspects to promising pharmacological actions for the treatment on central nervous system diseases / Bacopa monnieri: aspectos históricos de las acciones farmacológicas prometedoras para el tratamiento de enfermedades del sistema nervioso central

Bacopa monnieri(L.) Wettst. (Plantaginaceae), also known as Brahmi, has been used to improve cognitive processes and intellectual functions that are related to the preservation of memory. The objective of this research is to review the ethnobotanical applications, phytochemical composition, toxicity and activity of B. monnieri in the central nervous system. It reviewed articles on B. monnieri using Google Scholar, SciELO, Science Direct, Lilacs, Medline, and PubMed. Saponins are the main compounds in extracts of B. monnieri. Pharmacological studies showed that B. monnieri improves learning and memory and presents biological effects against Alzheimer's disease, Parkinson's disease, epilepsy, and schizophrenia. No preclinical acute toxicity was reported. However, gastrointestinal side effects were reported in some healthy elderly individuals. Most studies with B. monnieri have been preclinical evaluations of cellular mechanisms in the central nervous system and further translational clinical research needs to be performed to evaluate the safety and efficacy of the plant.

Bacopa monnieri (L.) Wettst. (Plantaginaceae), también conocida como Brahmi, se ha utilizado para mejorar los procesos cognitivos y las funciones intelectuales que están relacionadas con la preservación de la memoria. El objetivo de esta investigación es revisar las aplicaciones etnobotánicas, composición fitoquímica, toxicidad y actividad de B. monnieri en el sistema nervioso central. Se revisaron artículos sobre B. monnieri utilizando Google Scholar, SciELO, Science Direct, Lilacs, Medline y PubMed. Las saponinas son los principales compuestos de los extractos de B. monnieri. Los estudios farmacológicos mostraron que B. monnieri mejora el aprendizaje y la memoria y presenta efectos biológicos contra la enfermedad de Alzheimer, la enfermedad de Parkinson, la epilepsia y la esquizofrenia. No se informó toxicidad aguda preclínica. Sin embargo, se informaron efectos secundarios gastrointestinales en algunos ancianos sanos. La mayoría de los estudios con B. monnieri han sido evaluaciones preclínicas de los mecanismos celulares en el sistema nervioso central y es necesario realizar más investigaciones clínicas traslacionales para evaluar la seguridad y eficacia de la planta.

Biotechnology for propagation and secondary metabolite production in Bacopa monnieri.

Bacopa monnieri (L.) Wettst. or water hyssop commonly known as "Brahmi" is a small, creeping, succulent herb from the Plantaginaceae family. It is popularly employed in Ayurvedic medicine as a nerve tonic to improve memory and cognition. Of late, this plant has been reported extensively for its pharmacologically active phyto-constituents. The main phytochemicals are brahmine, alkaloids, herpestine, and saponins. The saponins include bacoside A, bacoside B, and betulic acid. Investigation into the pharmacological effect of this plant has thrived lately, encouraging its neuroprotective and memory supporting capacity among others. Besides, it possesses many other therapeutic activities like antimicrobial, antioxidant, anti-inflammatory, gastroprotective properties, etc. Because of its multipurpose therapeutic potential, it is overexploited owing to the prioritization of natural remedies over conventional ones, which compels us to conserve them. B. monnieri is confronting the danger of extinction from its natural habitat as it is a major cultivated medico-botanical and seed propagation is restricted due to less seed availability and viability. The ever-increasing demand for the plant can be dealt with mass propagation through plant tissue culture strategy. Micropropagation utilizing axillary meristems as well as de novo organogenesis have been widely investigated in this plant which has also been explored for its conservation and production of different types of secondary metabolites. Diverse in vitro methods such as organogenesis, cell suspension, and callus cultures have been accounted for with the aim of production and/or enhancement of bacosides. Direct shoot-organogenesis was initiated in excised leaf and internodal explants without any exogenous plant growth regulator(s) (PGRs), and the induction rate was improved when exogenous cytokinins and other supplements were used. Moreover, biotechnological toolkits like Agrobacterium-mediated transformation and the use of mutagens have been reported. Besides, the molecular marker-based studies demonstrated the clonal fidelity among the natural and in vitro generated plantlets also elucidating the inherent diversity among the natural populations. Agrobacterium-mediated transformation system was mostly employed to optimize bacoside biosynthesis and heterologous expression of other genes. The present review aims at depicting the recent research outcomes of in vitro studies performed on B. monnieri which include root and shoot organogenesis, callus induction, somatic embryogenesis, production of secondary metabolites by in vitro propagation, acclimatization of the in vitro raised plantlets, genetic transformation, and molecular marker-based studies of clonal fidelity. KEY POINTS: • Critical and up to date records on in vitro propagation of Bacopa monnieri • In vitro propagation and elicitation of secondary metabolites from B. monnieri • Molecular markers and transgenic studies in B. monnieri.

Biotechnological production of bacosides from cell and organ cultures of Bacopa monnieri.

Bacopa monnieri (L.) Wettst. (BM), also known as 'Brahmi' or 'Water Hyssop', has been utilized as a brain tonic, memory enhancer, sensory organ revitalizer, cardiotonic, anti-anxiety, antidepressant and anticonvulsant agent in the Indian system of medicine Ayurveda for centuries. BM is beneficial in the treatment of Parkinson's disease, Alzheimer's disease, epileptic seizures and schizophrenia in recent pharmacological research. Dammarane-type triterpenoid saponins containing jujubogenin and pseudojujubogenin as aglycones, also known as bacosides, are the principal chemical ingredients identified and described from BM. Bacosides have been shown to have anti-ageing, anticancer, anticonvulsant, antidepressant, anti-emetic, anti-inflammatory and antibacterial properties in a variety of pre-clinical and clinical studies. The pharmaceutical industry's raw material comes from wild sources; nevertheless, the concentration of bacosides varies in different regions of the plants, as well as seasonal and genotypic variation. Cell and tissue cultures are appealing alternatives for the long-term manufacture of bioactive chemicals, and attempts to produce bacosides using in vitro cultures have been made. This review discusses the biotechnological approaches used to produce bacosides, as well as the limitations and future potential. KEY POINTS: • Bacosides extracted from Bacopa monnieri are important pharmaceutical compounds. • The current review provides insight into biotechnological interventions for the production of bacosides using in vitro cultures. • Highlights the prospects improvement of bacoside production through metabolic engineering.

Saponins and flavonoids from Bacopa floribunda plant extract exhibit antioxidant and anti-inflammatory effects on amyloid beta 1-42-induced Alzheimer's disease in BALB/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Bacopa floribunda (BF), a locally available plant has been employed traditionally as memory enhancer in Southwestern, Nigeria. It has been utilized in traditional and Ayurvedic medicine as brain tonic for enhancing memory, anti-aging and forestalling series of psychological disorders. However, there is a dearth of scientific information on the mechanism(s) of action of important phytochemicals from BF extract on dementia. AIM OF THE STUDY: Alzheimer's disease, the commonest form of dementia has been postulated to triple by 2050 as a result of increase in life expectancy. This study therefore assessed and compared the possible mechanism(s) of action of flavonoids and saponins from BF on Amyloid beta (Aß1-42)-induced dementia in male BALB/c mice. MATERIALS AND METHODS: Eighty (80) healthy BALB/c mice divided into 10 groups (n = 8) were given a single bilateral ICV injection of Aß1-42 or normal saline. Graded doses of Saponins and flavonoids (50, 100 and 200 mg/kg) were used as treatment for 21 days. Hippocampal homogenates were assayed for the levels of antioxidants, oxidative stress and neuroinflammatory markers. In vitro antioxidant activity of flavonoids and saponins were equally assessed using standard procedures. The extent of microglial activation was quantified through immunohistochemistry procedure. RESULTS: Aß1-42 successfully caused a spike in hippocampal levels of MDA, IL1ß, TNF-α including MPO levels and invariably decreased antioxidant activities. Likewise an increase in reactive microglia (microgliosis) was observed. However, crude saponins and flavonoids from BF were able to suppress microgliosis, oxidative stress and neuroinflammation induced by Aß1- 42 and were observed to be more effective at higher doses of saponins (100 mg/kg and 200 mg/kg) and flavonoid (100 mg/kg). CONCLUSIONS: Phytochemicals from BF efficiently exhibited dose dependent alleviation of some symptoms associated with Alzheimer's disease.

Characterization of Metabolites in Plasma, Urine and Feces of Healthy Participants after Taking Brahmi Essence for Twelve Weeks Using LC-ESI-QTOF-MS Metabolomic Approach.

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.

Chemical-Genetic Interactions of Bacopa monnieri Constituents in Cells Deficient for the DNA Repair Endonuclease RAD1 Appear Linked to Vacuolar Disruption.

Colorectal cancer is a common cancer worldwide and reduced expression of the DNA repair endonuclease XPF (xeroderma pigmentosum complementation group F) is associated with colorectal cancer. Bacopa monnieri extracts were previously found to exhibit chemical-genetic synthetic lethal effects in a Saccharomyces cerevisiae model of colorectal cancer lacking Rad1p, a structural and functional homologue of human XPF. However, the mechanisms for B. monnieri extracts to limit proliferation and promote an apoptosis-like event in RAD1 deleted yeast was not elucidated. Our current analysis has revealed that B. monnieri extracts have the capacity to promote mutations in rad1∆ cells. In addition, the effects of B. monnieri extracts on rad1∆ yeast is linked to disruption of the vacuole, similar to the mammalian lysosome. The absence of RAD1 in yeast sensitizes cells to the effects of vacuole disruption and the release of proteases. The combined effect of increased DNA mutations and release of vacuolar contents appears to induce an apoptosis-like event that is dependent on the meta-caspase Yca1p. The toxicity of B. monnieri extracts is linked to sterol content, suggesting saponins may be involved in limiting the proliferation of yeast cells. Analysis of major constituents from B. monnieri identified a chemical-genetic interaction between bacopasaponin C and rad1∆ yeast. Bacopasaponin C may have potential as a drug candidate or serve as a model for the development of analogs for the treatment of colorectal cancer.

The effectiveness of Bacopa monnieri (Linn.) Wettst. as a nootropic, neuroprotective, or antidepressant supplement: analysis of the available clinical data.

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.

The Evolving Roles of Bacopa monnieri as Potential Anti-Cancer Agent: A Review.

The intermingled interrelationship of Bacopa monnieri and human health dates backs to the ancient times in the history of ayurveda making the plant an enriched source of alternative drug development in a nontoxic manner. In recent years, research on the biological effects of Bacopa monnieri has flourished as promising neuroprotective, memory boosting and more importantly as both chemopreventive and anti-neoplastic agent. Each naturally synthesized chemical constituent identified from Bacopa monnieri leaf extract with different solvents, has significant anti-metastatic, anti-angiogenic and anti-proliferative activity on different type of cancer cells. In this context, a substantial literature survey allows a deep understanding of the involvement of specific bioactive molecules along with the whole plant extract of Bacopa monnieri with their divergent effective molecular pathways. This comprehensive review covers literature up to the year 2020 highlighting all the anticancer efficacy along with signaling pathways activated by secondary metabolites found in bacopa plant.

Acute effects of combined Bacopa, American ginseng and whole coffee fruit on working memory and cerebral haemodynamic response of the prefrontal cortex: a double-blind, placebo-controlled study.

Objective: This study assessed whether a multi-ingredient herbal supplement containing Bacopa monniera (BM), Panax quinquefolius ginseng (PQ) and whole coffee fruit extract (WCFE) could enhance cognitive performance and cerebral-cortical activation during tasks of working memory and attention.Method: In a randomised, double-blind, placebo-controlled, between-group study, 40 healthy adults between 18-60 years (M = 34.46 SD = 12.95) completed tasks of working memory and attention at baseline and 45 min post active or placebo supplement consumption. During the cognitive testing, changes in hemodynamic response in the prefrontal cortex (PFC) were continuously measured using functional near-infrared spectroscopy (fNIRS).Results: Working memory task performance on the N-back task was significantly improved following active supplement consumption compared to placebo in terms of accuracy (p < .01) and response time (p < .05). Improved performance was associated with a reduction of PFC activation (p < .001) related to effortful mental demand, reflecting increased neural efficiency concomitant with improved cognitive performance. The effects were independent of background demographics variables and changes in blood glucose response and mood.Discussion: This is the first report of acute effects on cognitive performance in healthy adults following intake of a combined, multi-ingredient herbal supplement with concomitant changes in cerebral haemodynamic response. The potential synergistic effects of polyphenolic compounds on neurocognitive function and fNIRS use in nutritional intervention studies, poses a significant increase in the capacity to understand the effects of dietary compounds on the brain.

Improvement of Executive Function after Short-Term Administration of an Antioxidants Mix Containing Bacopa, Lycopene, Astaxanthin and Vitamin B12: The BLAtwelve Study.

During the last few years increasing interest has been focused on antioxidants as potentially useful agents in the prevention of the onset and progression of cognitive dysfunction. In this randomized, double-blind, controlled, parallel arm study, the effects of daily consumption of an antioxidant mix on cognitive function in healthy older adults were evaluated. After a 1 week run-in period, 80 subjects aged 60 years or more, and with no evidence of cognitive dysfunction, were randomly allocated to a mix of four bioactive compounds (bacopa, lycopene, astaxanthin, and vitamin B12) or matched placebo, taken orally once a day for 8 weeks. The primary objective of the study was to evaluate the changes in trial making test (TMT) scores from baseline to 8 weeks of treatment, analyzed in the following hierarchical order: TMT-B, TMT-A, and TMT-B minus TMT-A. TMT-B increased in the control group (+3.46 s) and decreased in the active group (-17.63 s). The treatment difference was -21.01 s in favor of the active group (95% C.I. -26.80 to -15.2, p < 0.0001). The decrease in TMT-A was significantly higher in the active group (-6.86 s) than in the control group (-0.37 s). TMT-B minus TMT-A increased in the control group (+3.84 s) and decreased in the active group (-10.46 s). The increase in letter fluency in the verbal fluency test (VFT) was also significantly higher in the active group and statistically significant (+5.28 vs. +1.07 words; p < 0.001). Our findings provide encouraging evidence that regular dietary supplementation with bacopa, lycopene, astaxanthin, and vitamin B12 may be an effective dietary approach for counteracting cognitive changes associated with brain aging.

Chemical composition of Polish propolis and its antiproliferative effect in combination with Bacopa monnieri on glioblastoma cell lines.

Propolis and Bacopa monnieri (L.) Wettst. (Brahmi) are natural products that contain many active substances and possess anticancer properties. The aim of this study was to investigate the chemical composition of Polish propolis extract (PPE) by gas chromatography-mass spectrometry (GC-MS), B. monnieri extracts (BcH, BcS) by high performance liquid chromatography with diode array detector and mass spectrometry coupled with electrospray ionization (LC-ESI-MS) and finally determine its anti-proliferative potential combined with BcH and BcS in glioblastoma cell lines (T98G, LN-18, U87MG). The antiproliferative activity of PPE, BcH, BcS and their combination (PPE + BcH) was determined by a cytotoxicity test, and DNA binding was determined by [3H]-thymidine incorporation. Flavonoids and phenylpropenoids were the main components of PPE. BcH and BcS samples were also successfully analyzed. Their main constituents were saponins such as bacoside A3, bacopaside II, X and bacopasaponin C and its isomer. The inhibitory effects on the viability and proliferation of the tested glioma cells observed after incubation with the combination of PPE and BcH were significantly stronger than the effects of these two extracts separately. These findings suggest that propolis in combination with B. monnieri shows promising anticancer activity for the treatment of glioblastoma. However, further studies are still required.

Bacopa monnieri (L.) Wettst. Extract Improves Memory Performance via Promotion of Neurogenesis in the Hippocampal Dentate Gyrus of Adolescent Mice.

Bacopa monnieri L. Wettst. (BM) is a botanical component of Ayurvedic medicines and of dietary supplements used worldwide for cognitive health and function. We previously reported that administration of BM alcoholic extract (BME) prevents trimethyltin (TMT)-induced cognitive deficits and hippocampal cell damage and promotes TMT-induced hippocampal neurogenesis. In this study, we demonstrate that administration of BME improves spatial working memory in adolescent (5-week- old) healthy mice but not adult (8-week-old) mice. Moreover, improved spatial working memory was retained even at 4 weeks after terminating 1-week treatment of adolescent mice. One-week BME treatment of adolescent mice significantly enhanced hippocampal BrdU incorporation and expression of genes involved in neurogenesis determined by RNAseq analysis. Cell death, as detected by histochemistry, appeared not to be significant. A significant increase in neurogenesis was observed in the dentate gyrus region 4 weeks after terminating 1-week treatment of adolescent mice with BME. Bacopaside I, an active component of BME, promoted the proliferation of neural progenitor cells in vitro in a concentration-dependent manner via the facilitation of the Akt and ERK1/2 signaling. These results suggest that BME enhances spatial working memory in healthy adolescent mice by promoting hippocampal neurogenesis and that the effects of BME are due, in significant amounts, to bacopaside I.

Bacopa monnieri and Their Bioactive Compounds Inferred Multi-Target Treatment Strategy for Neurological Diseases: A Cheminformatics and System Pharmacology Approach.

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.