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Alzheimer's disease, a prevalent neurodegenerative disorder in the elderly, is characterized by the accumulation of senile plaques and neurofibrillary tangles, triggering oxidative stress, neuroinflammation, and neuronal apoptosis. Current therapies focus on symptomatic treatment rather than targeting the underlying disease-modifying molecular mechanisms and are often associated with significant side effects. Bacopa monnieri, a traditional Indian herb with nootropic properties, has shown promise in neurological disorder treatment from ancient times. However, its mechanisms of action in Alzheimer's disease remain elusive. In this study, a cellular model for Alzheimer's disease was created by treating differentiated IMR-32 cells with beta-amyloid, 1-42 peptide (Aβ 42 ). Additionally, a recovery model was established through co-treatment with Bacopa monnieri to explore its protective mechanism. Co-treatment with Bacopa monnieri extract recovered Aβ 42 induced damage as evidenced by the decreased apoptosis and reduced reactive oxygen species production. Mass spectrometry-based quantitative proteomic analysis identified 21,674 peptides, corresponding to 3626 proteins from the Alzheimer's disease model. The proteins dysregulated by Aβ 42 were implicated in cellular functions, such as negative regulation of cell proliferation and microtubule cytoskeleton organization. The enriched pathways include extracellular matrix organization and interleukin-4 and interleukin-13 signaling. Bacopa monnieri co-treatment showed remarkable restoration of Aβ 42 altered proteins, including FOSL1, and TDO2. The protein-protein interaction network analysis of Bacopa monnieri restored proteins identified the hub gene involved in Alzheimer's disease. The findings from this study may open up new avenues for creating innovative therapeutic approaches for Alzheimer's disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study assessed whether polyphenolic rich supplement containing Bacopa monnieri (BM: 300 mg), Panax quinquefolius ginseng (PQ: 100 mg) and whole coffee fruit extract (WCFE: 100 mg) could enhance cognitive performance, affect and cerebral-cortical activation over 28-days of intervention. Method: A randomised, double-blind, placebo-controlled, between-group study of 52 healthy adults between 35 and 65 years (M = 50.20, SD = 9.37) was conducted. Measures of cognition, affect and brain activity were measured at three time points: baseline, 28 days post intervention and 14 days post washout. At each time point, haemodynamic response in the prefrontal cortex (PFC) was measured using functional near-infrared spectroscopy (fNIRS), and serum brain-derived neurotrophic factor (BDNF). Results: The polyphenolic-rich supplement reliably improved positive affect and delayed recall compared to placebo following 28 days of supplementation. For the brain, those in the active condition showed greater PFC activation on performance of the 2-back tasks post supplementation compared to placebo ( p  < .05, d = 0.6). Discussion: This is the first report of a 28-day supplement intervention and 2-week follow-up study to assess changes in affect, cognition, cerebral haemodynamic response and BDNF in healthy middle-aged adults. The potential synergistic effects of polyphenolic compounds on neurocognitive function in middle-aged adults through emotional-cognitive processing and cognitive reserve are important for promoting brain and cognitive health.

Bacopa monnieri (L.) Wettst (Plantaginaceae), is traditionally used in many countries as neural tonic and memory enhancer, or to relieve acute pain and inflammation. This study described the isolation and identification of one new, bacomoside D 3 ( 1 ), and seven known phenyl glycosides ( 2  -  8 ). The structures of isolates were established by analysis of their spectroscopic data or hydrolysis followed by HPLC analysis together with a comparison to those reported in the literature. These compounds were evaluated for antioxidant and anti-inflammatory activities. Among them, compounds 4 and 5 exhibited strong DPPH radical scavenging activity with IC 50 values of 9.77 ± 0.08 and 3.50 ± 0.04 µM, respectively. Compounds 2 and 5 significantly inhibited TNF- α production in LPS-stimulated RAW264.7 cells with IC 50 values of 40.60 ± 3.05 and 38.19 ± 1.75 µM, respectively. Furthermore, the active compounds could be efficient inhibitors of oxidants by interfering with the DPPH activity in silico study.

Cerebroside sulfotransferase (CST) is considered a target protein in developing substrate reduction therapy for metachromatic leukodystrophy. This study employed a multistep virtual screening approach for getting a specific and potent inhibitor against CST from 35 phytoconstituents of Bacopa monnieri (L.) Pennell and 31 phytoconstituents of Mucuna pruriens (L.) DC. from the IMPPAT 2.0 database. Using a binding score cutoff of -8.0 kcal/mol with ADME and toxicity screening, four phytoconstituents IMPHY009537 (Stigmastenol), IMPHY004141 (alpha-Amyrenyl acetate), IMPHY014836 (beta-Sitosterol), and IMPHY001534 (jujubogenin) were considered for in-depth analysis. In the binding pocket of CST, the major amino acid residues that decide the orientation and interaction of compounds are Lys85, His84, His141, Phe170, Tyr176, and Phe177. The molecular dynamics simulation with a 100ns time span further validated the stability and rigidity of the docked complexes of the four hits by exploring the structural deviation and compactness, hydrogen bond interaction, solvent accessible surface area, principal component analysis, and free energy landscape analysis. Stigmastenol from Bacopa monnieri with no potential cross targets was found to be the most potent and selective CST inhibitor followed by alpha-Amyrenyl acetate from Mucuna pruriens as the second-best performing inhibitor against CST. Our computational drug screening approach may contribute to the development of oral drugs against metachromatic leukodystrophy., Competing Interests: The authors declare that there are no competing interests associated with the manuscript., (Copyright: © 2024 Singh, Singh. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Modulation of in vivo adult neurogenesis (AN) is an evolving concept in managing neurodegenerative diseases. CDRI-08, a bacoside-enriched fraction of Bacopa monnieri, has been demonstrated for its neuroprotective actions, but its effect on AN remains unexplored. This article describes the status of AN by monitoring neuronal stem cells (NSCs) proliferation, differentiation/maturation markers and BDNF-TrkB levels (NSCs signalling players) vs. the level of neurodegeneration and their modulations by CDRI-08 in the hippocampal dentate gyrus (DG) of male rats with moderate grade hepatic encephalopathy (MoHE). For NSC proliferation, 10 mg/kg b.w. 5-bromo-2'-deoxyuridine (BrdU) was administered i.p. during the last 3 days, and for the NSC differentiation study, it was given during the first 3 days to the control, the MoHE (developed by 100 mg/kg b.w. of thioacetamide i.p. up to 10 days) and to the MoHE male rats co-treated with 350 mg/kg b.w. CDRI-08. Compared with the control rats, the hippocampus DG region of MoHE rats showed significant decreases in the number of Nestin + /BrdU + and SOX2 + /BrdU + (proliferating) and DCX + /BrdU + and NeuN + /BrdU + (differentiating) NSCs. This was consistent with a similar decline in BDNF + /TrkB + NSCs. However, all these NSC marker positive cells were observed to be recovered to their control levels, with a concordant restoration of total cell numbers in the DG of the CDRI-08-treated MoHE rats. The findings suggest that the restoration of hippocampal AN by CDRI-08 is consistent with the recovery of BDNF-TrkB-expressing NSCs in the MoHE rat model of neurodegeneration., (© 2024 International Society for Developmental Neuroscience.)

Objective: To evaluate synergistic antiulcer activity of ethanolic extracts of Tephrosia purpurea and Bacopa monnieri in ulcer induced rats., Methods: Ethanolic leaf extracts of both the plants were administered individually and in combination at a dose of 200mg/kg to ulcer induced male albino rats. Omeprazole 10mg/kg was used as standard. Pylorus ligation method, ethanol and indomethacin induced gastric ulcer models were the different gastric ulcer models selected for the induction of ulcer in rats. Ulcer index, ulcer score, total acidity, pH, percentage protection, volume of gastric juice were the parameters evaluated and compared in different groups in all the models., Results: Decrease in the ulcer score, ulcer index, total acidity was observed and percentage protection was significant(*p<0.05 and p<0.01) with the combination extract compared to group received individual plant extracts., Conclusion: Our results suggested that combination of two medicinal plants showed synergistic anti ulcer activity and decreased the formation of ulcer lesions in rats.

Background: Alzheimer's disease (AD) is the most prevalent dementia, affecting a large number of populations. Despite being under scrutiny for decades, an effective therapeutic option is still not available., Methods and Results: This study explores the therapeutic role of a nootropic herb Bacopa monnieri (BM) in AD-like pathological conditions produced by injecting preformed amyloid-β 42 (Aβ 42 ) fibril bilaterally into hippocampus of Wistar rats, and ethanolic extract of BM is orally administered for 4 weeks. Assessment of behavioral changes reveals that BM treatment ameliorates Aβ 42 -induced cognitive impairment and compromised explorative behavior. Supplementation of BM also reduces oxidative stress biomarkers, proinflammatory cytokines, and cholinesterase activity in the AD rats. Additionally, BM treatment restores Bcl-2-associated X protein (Bax)/ B-cell lymphoma 2 (Bcl-2) imbalance, increases neurotrophic factors expression, and prevents neurodegeneration validated by quantifying Nissl-positive hippocampal neurons. Interestingly, BM administration eliminates amyloid plaques in the hippocampal region and normalizes the Aβ 42 -induced increase in phospho-tau and total tau expression. Mechanistic investigations reveal that BM interacts with glycogen synthase kinase (GSK-3β) and restores Wnt/β-catenin signaling., Conclusion: BM has been used in diet as a nootropic herb for several centuries. This study highlights the anti-Alzheimer activity of BM from the behavioral to the molecular level by modulating mitochondrial dysfunction, and GSK-3β mediates the Wnt/β-catenin signaling pathway., (© 2023 Wiley‐VCH GmbH.)

The aim of the present study was to evaluate the role of Bacopa monnieri in acetic-acid-induced ulcerative colitis in mice. Acetic acid (3%v/v, in 0.9% saline) was infused intrarectally to induce ulceration in mice. Administration of acetic acid resulted in severe inflammation of the colon along with an increase in the myeloperoxidase (MPO) activity assessed on 7 th day. Treatment with Bacopa monnieri extract (20 mg/kg and 40 mg/kg, p.o) and saponin-rich fraction (5 mg/kg and 10 mg/kg; p.o) for 7 days i.e. 2 days before and 5 days after acetic acid infusion, significantly attenuated the colonic inflammation in a dose-dependent manner. Furthermore, it also reduced the MPO levels and the disease activity score as compared to the control group. It may be concluded that Bacopa monnieri has the potential for ameliorating acetic-acid-induced colitis and its saponin-rich fraction may be responsible for this effect.

Using combined chromatographic methods, two new triterpenoid glycosides, bacopasaponin K ( 1 ) and bacopasaponin L ( 2) , along with eight known compounds, bacopaside IV ( 3 ), bacopaside VII ( 4 ), bacopasaponin E ( 5 ), bacoside A 3 ( 6 ), bacopasaponin F ( 7 ), bacopasaponin C ( 8 ), bacopaside I ( 9 ), and bacopaside II ( 10 ) were isolated from the methanol extract of the Bacopa monnieri . Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis, HR-ESI-MS and comparing with the NMR data reported in the literature. All these compounds were evaluated for their cytotoxic activity using the cell counting kit-8 (CCK-8) assay. Compounds 4 , 6 , 8 , and 10 exhibited potential cytotoxic effects against human lung cancer cells (PC9) and human colon cancer cells (SW620).

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., (© 2024 Scandinavian Plant Physiology Society.)

The popular perennial creeping plant known as Bacopa monnieri (also known as Brahmi) is being utilized in the Indian Ayurvedic medicine practice. It has a variety of bioactive phytoconstituents that have been used therapeutically to treat a number of serious illnesses. Ancient Vedic scholars used this herb because of its pharmacological effects, particularly as a nerve booster and nootropic supporter. However, it is vital to comprehend the active phytochemical components of Bacopa monnieri extract (BME) and their molecular mechanisms in order to better grasp the effect of BME on neurological illnesses and diseases. Understanding its active phytochemical constituents and their molecular processes is essential. Numerous clinical investigations indicated that BME may have neuroprotective benefits, so it is worthwhile to re-evaluate this wellknown plant. Here, we focused on neurological problems as we examined the pharmacological and phytochemical characteristics of BME. For their effective usage in neuroprotection and cognition, many clinical concerns and the synergistic potential of Bacopa extract have been investigated. Alzheimer's disease is a neurological condition caused by the production of reactive oxygen species, which also causes amyloid-beta (Aβ) and tau protein aggregation and increases neuro-inflammation and neurotoxicity. Our review offers a more indepth molecular understanding of the neuroprotective functions of BME, which can also be connected to its therapeutic management of neurological illnesses and cognitive-improving effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Millions of people around the globe are affected by Alzheimer's disease (AD). This crippling condition has no treatment despite intensive studies. Some phytocompounds have been shown to protect against Alzheimer's in recent studies., Methods: Thus, this work aimed to examine Bacopa monnieri phytocompounds' synergistic effects on neurodegeneration, antioxidant activity, and cognition in the scopolamine-induced AD mice model. The toxicity study of two phytocompounds: quercetin and bacopaside X revealed an LD 50 of more than 2000 mg/kg since no deaths occurred., Results: The neuroprotection experiment consists of 6 groups i.e., control (saline), scopolamine (1 mg/kg), donepezil (5 mg/kg), Q (25 mg/kg), BX (20 mg/kg), and Q + BX (25 mg/kg + 20 mg/kg). Visual behavioral assessment using the Morris water maze showed that animals in the diseased model group (scopolamine) moved more slowly toward the platform and exhibited greater thigmotaxis behavior than the treatment and control groups. Likewise, the concentration of biochemical NO, GSH, and MDA improved in treatment groups concerning the diseased group. mRNA levels of different marker genes including ChAT, IL-1α, IL-1 β, TNF α, tau, and β secretase (BACE1) improved in treatment groups with respect to the disease group., Conclusion: Both bacopaside X and quercetin synergistically have shown promising results in neuroprotection. Therefore, it is suggested that Q and BX may work synergistically due to their antioxidant and neuroprotective property., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Bacteria that enhance plant growth and development and are found in the vicinity of roots are referred to as plant growth-promoting rhizobacteria. Some beneficial bacteria help plant tolerance to many hazardous chemical elements. In this context, Cupriavidus basilensis , Novosphingobium humi , Bacillus zanthoxyli , Bacillus sp., Paenibacillus alvei , Ancylobacter aquaticus and Ralstonia syzygii metal-tolerant rhizospheric bacteria were isolated from rhizospheric soil associated with Bacopa monnieri . The beneficial effects of rhizospheric bacteria on B. monnieri plant physiology and biochemical responses were investigated under pot conditions at two levels (100μM and 500μM) of CuSO4 or FeCl3 . N. humi , A. aquaticus and R. syzygii bacterial strains were associated with significantly increased height and biomass under normal and stress conditions. An assay for indole acetic acid in isolated rhizospheric bacteria found differential secretion except Bacillus zanthoxyli . Bacoside A is a major phytocompound in B. monnieri with medicinal value; maximum induction was observed in the R. syzygii treatment. High concentration of copper and iron salts negatively influenced height, biomass and photosynthetic pigments; however N. humi , A. aquaticus , Bacilllus sp. and R. syzygii beneficial bacterial helped plants under stress conditions. Moreover, a significant enhancement in chlorophyll a and b was noticed in C. basilensis , B. zanthoxyli , Bacilllus sp., P. alvei and R. syzygii treatments, without much influence on carotenoid levels. Therefore, the present study emphasises the importance of isolating plant growth-promoting rhizobacteria for use in bacopa plants exposed to metals such as copper and iron in soil.

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Accumulation of Aβ 42 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 Aβ 42 -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 Aβ 42 expressing model of the Drosophila melanogaster. By applying a quantitative proteomics approach, the study identified > 90% of differentially expressed proteins from Aβ 42 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 Aβ 42 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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

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 (Aβ) 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The neurotoxins methamphetamine (METH) and 1-methyl-4-phenylpyridinium (MPP + ) damage catecholamine neurons. Although sharing the same mechanism to enter within these neurons, METH neurotoxicity mostly depends on oxidative species, while MPP + toxicity depends on the inhibition of mitochondrial activity. This explains why only a few compounds protect against both neurotoxins. Identifying a final common pathway that is shared by these neurotoxins is key to prompting novel remedies for spontaneous neurodegeneration. In the present study we assessed whether natural extracts from Bacopa monnieri (BM) may provide a dual protection against METH- and MPP + -induced cell damage as measured by light and electron microscopy. The protection induced by BM against catecholamine cell death and degeneration was dose-dependently related to the suppression of reactive oxygen species (ROS) formation and mitochondrial alterations. These were measured by light and electron microscopy with MitoTracker Red and Green as well as by the ultrastructural morphometry of specific mitochondrial structures. In fact, BM suppresses the damage of mitochondrial crests and matrix dilution and increases the amount of healthy and total mitochondria. The present data provide evidence for a natural compound, which protects catecholamine cells independently by the type of experimental toxicity. This may be useful to counteract spontaneous degenerations of catecholamine cells.

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.

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-1β, 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-1β, 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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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 (Aβ1-42)-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 Aβ1-42 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: Aβ1-42 successfully caused a spike in hippocampal levels of MDA, IL1β, 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 Aβ1- 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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Parkinson's disease is a chronic and gradually progressive neurodegenerative disorder triggered due to the loss of dopamine-releasing neurons in the region of substantia nigra pars compacta characterized by the motor symptoms, such as tremor, bradykinesia, akinesia, and postural instability. Proteinopathies, mitochondrial dysfunction induced dopaminergic neuronal deterioration, and gene mutations are the hallmarks of Parkinson's disease. The bioactive components of Brahmi, such as Bacoside A, Bacoside B, and Bacosaponins, belong to various chemical families. Brahmi's neuroprotective role includes reducing neuronal oxidative stress, dopaminergic neuronal degeneration, mitochondrial dysfunction, inflammation, inhibition of α-synuclein aggregation, and improvement of cognitive and learning behaviour. Researchers found that Bacopa monnieri significantly increased brain levels of glutathione, vitamin C, vitamin E, and vitamin A in rats exposed to cigarette smoke. Brahmi has a potent antioxidant property and neuroprotective effects against PD that help reduce oxidative stress and neuroinflammation and enhance dopamine levels. The review collates all the preclinical studies that prove the beneficial neuroprotective effect of Brahmi for treating PD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.

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.

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.

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.

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 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.

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.

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 [ 3 H]-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.) is widely used in Ayurvedic medicine as a neural tonic for improving intelligence and memory. Several studies highlighted its efficacy in neuropsychiatric diseases but there is no evidence regarding anhedonia. Aim of the present work was to preclinically and clinically test against anhedonia a standardized B. monnieri extract (20% bacosides). In a mouse model of a depressive-like syndrome induced by lipopolysaccharide (LPS), the daily administration of the extract (50-200 mg kg -1 , p.o.) for 1 week, dose-dependently counteracted the immobility time in Porsolt and Tail suspension tests (p < .01). At the sucrose preference test (directly related to the ability for feeling pleasure) the extract treatment (100 and 200 mg kg -1 ) counteracted the reduction of sucrose intake induced by LPS (p < .01). Moreover, B. monnieri significantly reduced cytokines, cortisol, and artemin LPS-dependent alterations in plasma while increased the brain-derived neurotrophic factor levels (p < .05). The efficacy of the same extract was tested in a clinical study in which 42 patients with significant degree of anhedonia (evaluated as Snaith-Hamilton Pleasure Scale [SHAPS] score ≥ 3) were enrolled. Patients were divided into two groups and treated with citalopram or citalopram associated with B. monnieri (300 mg bid) for 4 weeks. The Pears Sample T-test showed a significant improvement (p < .05) in relevant scales (Hamilton depression rating scale, SHAPS, and strength and difficulties questionnaire) in the extract-treated group in comparison to citalopram alone was recorded. These data suggest that B. monnieri extract may be effective for the management of anhedonia and therefore should be considered for future controlled trials., (© 2020 John Wiley & Sons, Ltd.)

Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon, is a potent neurotoxic agent that is responsible for impaired neuronal development and is associated with aging. Here, it was demonstrated that extracts of Bacopa monnieri (BM), a traditional Ayurvedic medicine, diminished the B[a]P-induced apoptosis and senescence in human astrocytes. BM was demonstrated to protect the immortalized primary fetal astrocytes (IMPHFA) from B[a]P-induced apoptosis and senescence by reducing the damaged mitochondria that produced reactive oxygen species (ROS). Furthermore, it was shown that B[a]P-triggered G2 arrest could be altered by BM, thus indicating that BM could reverse the cell cycle arrest and mediate a normal cell cycle in IMPHFA cells. In addition, the lifespan of Caenorhabditis elegans was assessed, which confirmed these effects in the presence of BM, compared to the B[a]P-treated group. Furthermore, the anti-senescence and anti-apoptotic activities of BM were observed to be mediated through the protective effect of mitophagy, and inhibition of mitophagy could not protect the astrocytes from mitochondrial ROS-induced apoptosis and senescence in BM-treated cells. Moreover, it was revealed that BM induced Parkin-dependent mitophagy to exert its cytoprotective activity in IMPHFA cells. In conclusion, the anti-senescence and anti-apoptotic effects of BM in astrocytes could combat pollution and aging-related neurological disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors declare no conflict of interest.

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 present study demonstrates the epigenetic mechanisms underlying the effect of Bacoside rich extract of Bacopa monniera-a nootropic herb, on scopolamine treated amnesic mice conferred via chromatin modifying enzymes. The focus of the work was to elucidate the modulation of the chromatin modifying enzymes: DNMT1, DNMT3a, DNMT3b, HDAC2, HDAC5 and CPB in scopolamine induced amnesic mice after treatment with bacoside rich extract of Bacopa monniera (BA) and BA encapsulated in lactoferrin conjugated PEG-PLA-PCL-OH based polymersomes (BAN). We observed remarkable difference between the results obtained after the treatment with BA and BAN. Interestingly BAN was found to be more efficient in downregulating DNA methylation and histone chain deacetylation. Scopolamine treatment showed up-regulation of DNMT1 expression in qRT-PCR by 3.14-fold as compared to the control, which was considerably decreased by 1.5-fold after treatment with BA and remarkably decreased 0.11-fold by BAN treatment. Scopolamine treatment up-regulated the expression of DNMT3a by 1.6-fold while for DNMT3b by 3.13-fold. In DNMT3a and DNMT3b the fold change decreased to 0.64 and 0.76 after BA treatment, whereas the BAN treatment further down-regulated to 0.32- and 0.63-fold, respectively. Similarly scopolamine up-regulated HDAC2 and HDAC5 by 3.12 fold and 3.64-fold, respectively. BA treatment reversed the changes by reducing HDAC2 mRNA to 0.89-fold and HDAC5 mRNA 0.83-fold. BAN further reduced expression of HDAC2 further to 0.39-fold and HDAC5 to 0.31-fold. On the other hand scopolamine down-regulated CBP mRNA expression by 0.28-fold and increased by 1.09 after BA treatment. BAN significantly increased the CPB expression by 1.65-fold as compared to BA treatment. These findings were consolidated by DNMT and HDAC enzyme activity assay, methylation in the promoter region of the memory related genes: ARC and BDNF and Dot blot assay for DNA methylation. The percent activity increase of DNMT and HDAC after scopolamine administration was 375.74 and 240.90 respectively. After treatment with BA the downfall in percent activity was observed as 167.99 in DMNT and 130.57 in HDAC. BAN treatment further decreased the percent enzyme activity of DNMT and HDAC significantly by 30.0 and 61.81 respectively. The potency of BAN in reversing the epigenetic changes of scopolamine induced amnesic mouse brain, can be attributed to the brain specific delivery of BA through polymersomes which are able to cross the blood brain barrier (BBB) via receptor mediated endocytosis.

The use of herbs as medicine is an ancient form of healthcare known to mankind. Standardization of herbal medicines is however a challenging task and is the major bottleneck in their acceptance as the primary therapeutic option. The aim of this study was to develop and validate a simple, rapid HPLC method for standardizing the mixture of extracts of three Medhya Rasayanas (neurotonic), Convolvulus pluricaulis, Withania somnifera and Bacopa monnieri. Simultaneous estimation of the respective bioactive markers of these plants viz., scopoletin, withaferin A, bacoside A 3, bacopaside II, jujubogenin and bacosaponin C has been reported for the first time. The method was developed using Waters Hybrid X-Bridge shield with BEH technology 2.5 μm, 4.6 × 75 mm column and validated according to ICH guidelines. The 20 minutes run time makes the method eco-friendly. The method was linear over a range of 12.5-400 ng/10 μL for scopoletin and 62.5-2,000 ng/10 μL for withaferin A, bacoside A 3, bacopaside II, jujubogenin and bacosaponin C with detection limits of 8.0, 48.3, 30.4, 40.7, 15.6 and 18.9 ng/10 μL and quantification limits of 24.5, 146.5, 92.2, 123.4, 47.4 and 57.4 ng/10 μL, respectively. The correlation coefficient for each analyte was >0.999. The intra-day and inter-day precision was <2%. These results confirmed the precision, accuracy and robustness of the proposed method., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Keeping in view the public health-related issues of Alzheimer's disease (AD), its unpredictable occurrence and progression indicate the needs for best treatment options. The present bioinformatics study explores the binding pattern and molecular interactions between human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes with natural compounds from Bacopa monnieri. The docking analysis between natural compounds as a ligand and AChE, BuChE as a receptor was completed using MGL tools Autodock 4.2 module. The analysis of the hydrophobic interactions, inhibition constants, and hydrogen bonds may indicates that they play a significant role in finding out the interacting position at the active site. However, after analyzing the binding energy (ΔG), the documented data shows that bacoside X, bacoside A, 3-beta-D-glucosylstigmasterol and daucosterol could be good inhibitors in the inhibition of AChE and BuChE activities. Therefore, our study indicates that the inhibition constants of the aforesaid natural compounds of Bacopa can be utilized for the development of inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The homotetrameric plasma protein transthyretin (TTR), is responsible for a series of debilitating and often fatal disorders in humans known as transthyretin amyloidosis. Currently, there is no cure for TTR amyloidosis and treatment options are rare. Thus, the identification and development of effective and safe therapeutic agents remain a research imperative. The objective of this study was to determine the effectiveness of Bacopa monnieri extract (BME) in the modulation of TTR amyloidogenesis and disruption of preformed fibrils. Using aggregation assays and transmission electron microscopy, it was found that BME abrogated the formation of human TTR aggregates and mature fibrils but did not dis-aggregate pre-formed fibrils. Through acid-mediated and urea-mediated denaturation assays, it was revealed that BME mitigated the dissociation of folded human TTR and L55P TTR into monomers. ANS binding and glutaraldehyde cross-linking assays showed that BME binds at the thyroxine-binding site and possibly enhanced the quaternary structural stability of native TTR. Together, our results suggest that BME bioactives prevented the formation of TTR fibrils by attenuating the disassembly of tetramers into monomers. These findings open up the possibility of further exploration of BME as a potential resource of valuable anti-TTR amyloidosis therapeutic ingredients.

Ayurveda is the medicinal science, dealing with utilization of naturally available plant products for treatment. A wide variety of neuroprotective herbs have been reported in Ayurveda. Brahmi, Bacopa monnieri is a nootropic ayurvedic herb known to be effective in neurological disorders from ancient times. Numerous approaches including natural and synthetic compounds have been applied against Alzheimer's disease. Amyloid-β and Tau are the hallmarks proteins of several neuronal dysfunctions resulting in Alzheimer's disease. Tau is a microtubule-associated protein known to be involved in progression of Alzheimer's disease. The generation of reaction oxygen species, increased neuroinflammation and neurotoxicity are the major physiological dysfunctions associated with Tau aggregates, which leads to dementia and behavioural deficits. Bacoside A, Bacoside B, Bacosaponins, Betulinic acid, etc; are the bioactive component of Brahmi belonging to various chemical families. Each chemical component known have its significant role in neuroprotection. The neuroprotective properties of Brahmi and its bioactive components including reduction of ROS, neuroinflammation, aggregation inhibition of Amyloid-β and improvement of cognitive and learning behaviour. Here on basis of earlier studies we hypothesize the inhibitory role of Brahmi against Tau-mediated toxicity. The overall studies have concluded that Brahmi can be used as a lead formulation for treatment of Alzheimer's disease and other neurological disorders., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A major goal in the discovery of bioactive natural products is to rapidly identify active compound(s) and dereplicate known molecules from complex biological extracts. The conventional bioassay-guided fractionation process can be time consuming and often requires multi-step procedures. Herein, we apply a metabolomic strategy merging multivariate data analysis and multi-informative molecular maps to rapidly prioritize bioactive molecules directly from crude plant extracts. The strategy was applied to 59 extracts of three Bacopa species ( B. monnieri , B. caroliniana and B. floribunda ), which were profiled by UHPLC-HRMS 2 and screened for anti-lipid peroxidation activity. Using this approach, six lipid peroxidation inhibitors 1 ‒ 6 of three Bacopa spp. were discovered, three of them being new compounds: monnieraside IV ( 4 ), monnieraside V ( 5 ) and monnieraside VI ( 6 ). The results demonstrate that this combined approach could efficiently guide the discovery of new bioactive natural products. Furthermore, the approach allowed to evidence that main semi-quantitative changes in composition linked to the anti-lipid peroxidation activity were also correlated to seasonal effects notably for B. monnieri ., Competing Interests: The authors declare no conflict of interest.

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.

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Highly bioavailable plant phospholipid complex that can reverse aluminum maltolate (AlM)-induced toxicity is not yet reported. Hence, the present study was planned to investigate the impact of oxidative stress and apoptotic changes provoked by Al and ameliorative role of Bacopa phospholipid complex (BPC) in albino rats. The levels of antioxidant enzymes such as superoxide dismutase (SOD), catalase activity (CAT), glutathione peroxidase (GPx), and thiobarbituric acid-reactive substance (TBA-RS) were measured and immunohistochemistry analysis of apoptotic markers, Bax and Bcl-2, was done from the four brain regions such as the hippocampus, cerebral cortex, cerebellum, and medulla oblongata. The levels of antioxidant enzymes and apoptotic markers that were decreased on AlM induction showed a significant increase in their levels, almost as observed in the control, when treated with BPC and Bm. Our results indicate that both BPC and Bm showed a therapeutic effect against AlM toxicity; however, it was found that the therapeutic potential of BPC was more pronounced than Bm against AlM-induced neurotoxicity.

Evidence has revealed a high degree of comorbidity of excessive alcohol intake and abstinence anxiety-like behavior. The ethanolic extracts of Bacopa monnieri (BME) are used in Indian traditional medicines for the management of alcoholic disorders. However, the underlying mechanism(s) associated with the influence of BME on alcohol abstinence-induced anxiety-like behavior have not been adequately addressed. Therefore, the present study was planned to examine the beneficial effects of BME in alcohol abstinence-induced anxiety-like behavior and the underlying mechanism of action subsequent to long-term voluntary drinking of alcohol. For the assessment of the effects of BME, Wistar rats were exposed to voluntary ingestion of 4.5%, 7.5% and 9% v/v alcohol for 15 days. The doses (100, 200, and 500 mg/kg) of BME and diazepam (2 mg/kg) were administered via gavage for three consecutive days in the alcohol abstinence period on the days 16, 17, and 18. The behavioral studies were conducted employing the elevated plus maze test (EPM), and light-dark test on day 18 to determine the effects of BME and diazepam in the ethanol abstinence-induced anxiety-like behavior. Alcohol biomarkers like ALT, AST, ALP, GGT, and MCV were estimated using commercially available kits. The expression of Gabra1, Gabra2, Gabra3, Gabra4, Gabra5 genes of the GABA A receptors subunits in the hippocampus as well as amygdala were also examined by reverse-transcription quantitative polymerase chain reaction. The HPLC analysis demonstrated that BME contained 9.9% bacoside-A as a major component. The results revealed that alcohol abstinence group depicted a reduction in the time spent on the open arms, numbers of entries in the open as well as closed arms in EPM test and similarly decrease in latency to the dark chamber, time spent in light chamber and numbers of transitions in LDT. Further, BME at the doses of 200 mg/kg and 500 mg/kg alleviated anxiety-like behavior which was escalated during alcohol abstinence. However, BME (100 mg/kg) exhibited insignificant protection against alcohol abstinence-induced syndrome. The escalated levels of alcohol-intake biomarkers were also reversed by BME at the dose of 200 mg/kg and 500 mg/kg. The down-regulation of Gabra1, Gabra4, and Gabra5 gene expression following alcohol abstinence were also reversed with a higher dose of BME (200 and 500 mg/kg) treatment. These results show that BME abrogates anxiety-like behavior by modulating alcohol markers and Gabra1, Gabra4, Gabra5 gene expression of GABA A receptor signaling pathway in rats., (Copyright © 2019. Published by Elsevier Masson SAS.)

Plant based lead compounds have been historically incredible as a source of therapeutic agents for various complex disorders including Alzheimer's disease (AD). AD is one of the leading neurodegenerative disorder in which the underlying risk factors remain largely unclear and presently, there is no disease modifying treatment available. Despite its potential, to date only few compounds have entered for clinical trials. Herein, we described the identification of plant based lead compounds for treatment of AD through an integrative approach of pharmacokinetics and structure bioinformatics approach. In particular we performed screening of lead compounds from 3 traditional medicinal plants namely Withania somnifera, Bacopa monnieri and Morus alba, which are known to have potential for treatment of neurodegenerative disease. We retrieved a total of 210 plant based compounds of which 21 compounds were screened based on their pharmacokinetic properties. Further, Docking study against 7 known AD associated targets were carried out to identify the binding sites and direct interacting residues. In addition we investigate the stable and reliable binding mechanism of top such plant compounds against 3 targets through molecular docking followed by Molecular Dynamic(MD) simulation. The results obtained in the study revealed that 3 drug compounds namely Morusin (MRSN), Withanone (WTHN) and 27-Hydroxywithanolide B (HWTHN) were identified as putative lead compounds against mono amine oxidase (MAOB), Beta-secretase 1(BACE1) and phosphodiesterase 4D., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Bacopa monnieri, commonly known as Brahmi, has been extensively used as a neuromedicine for various disorders such as anxiety, depression and memory loss. Chemical characterization studies revealed the major active constituents of the herb as the triterpenoid saponins, bacosides. Bacoside A, the vital neuroprotective constituent, is composed of four constituents viz., bacoside A3, bacopaside II, jujubogenin isomer of bacopasaponin C (bacopaside X) and bacopasaponin C. B. monnieri extracts as well as bacosides successfully establish a healthy antioxidant environment in various tissues especially in the liver and brain. Free radical scavenging, suppression of lipid peroxidation and activation of antioxidant enzymes by bacosides help to attain a physiological state of minimized oxidative stress. The molecular basis of neuroprotective activity of bacosides is attributed to the regulation of mRNA translation and surface expression of neuroreceptors such as AMPAR, NMDAR and GABAR in the various parts of the brain. Bioavailability as well as binding of neuroprotective agents (such as bacosides) to these receptors is controlled by the Blood Brain Barrier (BBB). However, nano conversion of these drug candidates easily resolves the BBB restriction and carries a promising role in future therapies. This review summarizes the neuroprotective functions of B. monnieri extracts as well as its active compounds (bacoside A, bacopaside I) and the molecular mechanisms responsible for these pharmacological activities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Medicinal plants may prove useful in developing plant-based strategies for regulation of male fertility. The present review describes the antifertility potential of certain medicinal plants, viz. Azadirachta indica, Curcuma longa, Allamanda cathartica and Bacopa monnieri in Parkes (P) male mice. The results suggested that treatment with the aqueous extracts of these plants caused reversible suppression of spermatogenesis and fertility in P mice and that there were no signs of detectable toxicity in treated mice. Further research needs to be done to develop plant-based strategies for control of male fertility., Competing Interests: None

In the present study, engineered lactoferrin (Lf)-conjugated pH and redox-sensitive polymersomes derived from the triblock copolymer polyethylene glycol-S-S-polylactic acid-polycaprolactone (PEG-S-S-PLA-PCL-OH) have been used to deliver bacosides to the brain. Bacosides are classified as triterpenoid saponins and are used in Indian Ayurveda for reversal of amnesia; however, no study has extensively demonstrated their efficacy as a nano-formulation in an animal model. The polymer was synthesized by ring opening polymerization of lactide and ε-caprolactone. The nanoparticles obtained by nanoprecipitation showed a core-shell morphology, with an average size of 110 nm, by transmission electron microscopy (TEM). The colloidal stability, hemocompatibility and cytocompatibility of the polymersomes proved their biocompatibility. pH and disulfide linkages in the polymeric chain accelerated the disintegration of the polymersomes at pH 6.6 and at pH 6.6 with glutathione (GSH) in comparison to pH 7.4, supporting their degradation behavior. Supermagnetic iron oxide nanoparticles (SPIONs, 74.99 μg mg-1 polymer) encapsulated into the polymersomes demonstrated their uptake in a mouse model by MRI. Furthermore, bacosides encapsulated in the polymersomes (10% loading) showed significant memory loss reversal in chemically induced amnesic mice, supported by the gene expression profiles of Arc, BDNF and CREB as well as by histopathology.