Bacopa Monnieri

BACKGROUND AND OBJECTIVES: Bacopa monnieri is a plant used in Ayurvedic medicine with traditional uses for memory and cognitive function. The objective of this study was to examine the effects of supplementation with a Bacopa monnieri extract (Bacumen®) on cognitive function, stress, and fatigue in adults with self-reported memory and attention problems. STUDY DESIGN: Two-arm, 12-week, parallel-group, randomized, double-blind, placebo-controlled trial. METHODS: Overall, 101 volunteers aged 40-70 years with self-reported memory and attention problems were supplemented with 300 mg daily of a Bacopa monnieri extract (Bacumen®) (n = 50) or a placebo (n = 51). Outcome measures included several computer and researcher-administered cognitive tasks assessing verbal learning, attention and working memory (primary outcome measures) and self-report measures assessing memory, mood, and fatigue (secondary outcome measures). Changes in blood concentrations of brain-derived neurotrophic factor, malondialdehyde, and acetylcholine esterase activity were also examined. Cognitive assessments, blood collections and self-reported questionnaires were completed in person on day 0 and week 12. Moreover, self-report questionnaires were completed online at weeks 4 and 8. Participants, researchers and the statistician were blinded until all data was collected and a blind review was completed. RESULTS: Of the 101 participants randomized, 87 participants completed the study, 47 in the placebo group and 40 in the Bacopa monnieri group. On the basis of complete data collected from 87 participants, there were no between-group differences in changes in the primary outcome measures comprising verbal learning (p = 0.391), attention (p = 0.713), and working memory (p = 0.610). However, in the Bacopa-supplemented participants, there were greater reductions in overall self-reported stress reactivity (p = 0.03); and fatigue and stress levels after exposure to a cognitive-demanding computer task (secondary outcome measures). There were no group differences in changes in blood concentrations of measured markers. Bacopa monnieri supplementation was generally well-tolerated, with no serious adverse react

INTRODUCTION: Mild cognitive impairment is the middle level of natural cognitive impairment during primary steps of dementia. There are a few studies about improving the cognitive performance and sleep quality in patients with a limited dementia. So, this study was conducted to evaluate the effects of Bacopa monnieri on cognitive performance and sleep quality of patients with mild cognitive impairment. MATERIALS AND METHODS: In this study, 62 patients with mild cognitive impairment were categorized into two groups of control and intervention. The intervention group received one pill of 160 mg Bacopa monnieri extract in 2 months, and the control group received a pill containing starch powder. The cognitive impairment and sleep quality was assessed using a questionnaire containing demographic information, Montreal Cognitive Assessment, and the Pittsburg Sleep Quality Index in three time-points of before the study, one months after the intervention and 2 months after the intervention (the end of study). RESULTS: The results showed no statistically significant difference between two groups in all three time-points in overall cognitive performance score and its 6 parameters (P > 0.05). While in the field of attention at the end of the first month (P = 0.033) and the end of the second month (P = 0.004), it was significant difference between the study groups. Also, in the field of verbal fluency at the end of the second month, this difference was significant (P = 0.003). The cognitive performance overall score showed no significant difference between two groups in first (P = 0.939) and second time-points (P = 0.661), although it was significant at third time-point (P = 0.029). There was no statistically significant difference between two groups in all time-points for sleep quality overall score (P > 0.05). CONCLUSION: The results showed that Bacopa monnieri can improve the cognitive performance overall score and some of its parameters, but it had no effect on sleep quality.

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. could be of interest in the control of symptoms of Parkinson's disease, but clinical evidence of its efficacy is lacking. This clinical trial assessed the effects of an extract of B. monnieri on parameters that are related to Parkinson's diseases. Twenty volunteers with Parkinson's disease were recruited for a primary, interventional, controlled, parallel, double-blind clinical study. The volunteers were assigned to treatment with either a commercial B. monnieri extract (225 or 450 mg/day) or placebo. The Parkinson's Disease Quality-of-Life (PDQL) questionnaire was applied, and motor activity was assessed before treatment and 30, 60, and 90 days after treatment with the B. monnieri extract or placebo. Characteristics such as age, body weight, and height were also collected. No differences in parkinsonian and systemic symptoms, emotional function, or social function were observed between. The delta percent (Δ%) showed time-dependent improvements in emotional function with B. monnieri treatment at the daily dose of 450 mg. A strong correlation was found between quality of life and motor outcomes at baseline and 30 days of treatment with B. monnieri, and a moderate correlation for 60 and 90 days of treatment with B. monnieri when compared with baseline time. A moderate correlation was found between motor outcomes and Hoehn and Yahr stages at baseline. Our results suggest that B. monnieri extract can improve emotional function in Parkinson's disease patients, but further clinical trials are needed to confirm this possibility.

The current study investigated the efficacy of extract of Bacopa monnieri (BM; CDRI 08®) in reducing levels of inattention and hyperactivity in young children. BM has demonstrated improvements in cognitive outcomes in adults, yet little research is available on its effects in younger populations. A 14-week randomized, double-blind, placebo-controlled clinical trial, with placebo run-in and run-out phases, investigated the effects of BM on behavioural, cognitive, mood, and sleep effects in male children aged 6 to 14 years against placebo. One-hundred and twelve participants were recruited into the trial, with 93 datasets available for analysis. No significant behavioural differences were noted between treatment groups. Cognitive outcomes indicated decreased error-making in children taking CDRI 08® (p = .04) and increased speed of reaction time in those taking placebo (p = .04) at study end. Improvements in cognitive flexibility (p = .01), executive functioning (p = .04), interpersonal problems (p = .02), and sleep routine (p = .04) were noted in those consuming CDRI 08® over placebo. CDRI 08® did not improve behavioural outcomes, but may have cognitive, mood and sleep benefits in children aged 6 to 14 years. Further study is required to support the findings presented here. © 2022 John Wiley & Sons Ltd.

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.

Temozolomide (TMZ) is the primary chemotherapeutic agent for glioblastoma multiforme (GBM), but its effectiveness is limited by resistance, recurrence, and toxicity. Combining natural compounds with TMZ is a promising approach to overcome these challenges. Bacoside-A, a brain tonic derived from Bacopa monnieri with proven anticancer properties, was evaluated for its chemotherapeutic potential in U87MG cells. Our study demonstrates that the combination of Bacoside-A and TMZ significantly enhanced intracellular TMZ accumulation and promoted ROS-mediated apoptosis through Ca2+ influx, mitochondrial membrane depolarization, and subsequent cell death by Apoptosis. Additionally, inhibition of EGFR-driven MAPK signalling and suppression of NF-κB nuclear translocation were observed, highlighting modulation of key survival pathways. These findings suggest that Bacoside-A potentiates TMZ efficacy while enabling dose reduction, thereby minimizing toxicity. Overall, this combinatorial approach provides mechanistic insights and a potential therapeutic strategy for improving GBM treatment outcomes.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and high resistance to chemotherapy. Doxorubicin is commonly used, but its efficacy is limited by variable sensitivity and resistance. Bacopaside II, a saponin compound, has shown anti-cancer potential. This study evaluates the effects of doxorubicin and bacopaside II, both individually and in combination, across TNBC subtypes to explore mechanisms of resistance and enhanced drug efficacy. METHODS: The growth-inhibitory effects of doxorubicin and bacopaside II were assessed in four TNBC cell lines. IC50 values were determined using dose-response assays, and doxorubicin accumulation was measured via spectral flow cytometry. ATP-binding cassette (ABC) transporter expression (ABCB1, ABCC1, ABCC3, and ABCG2) was analyzed for correlations with drug sensitivity. In silico docking assessed the binding affinity of bacopaside II to ABC transporters. A 3D culture model simulated drug-resistant TNBC, and combination effects were evaluated with live-cell imaging. RESULTS: Doxorubicin sensitivity varied across TNBC molecular subtypes, correlating to intracellular accumulation. Bacopaside II inhibited growth across subtypes, inducing apoptosis in sensitive cells and necrosis in resistant cells. Bacopaside II increased doxorubicin accumulation, independent of P-glycoprotein (ABCB1), possibly through interactions with other ABC transporters. In drug-resistant 3D cultures, bacopaside II maintained efficacy and enhanced doxorubicin accumulation, counteracting ABC transporter-mediated resistance. The doxorubicin and bacopaside II combination showed synergistic growth inhibition. CONCLUSIONS: Bacopaside II enhances doxorubicin efficacy in TNBC by increasing drug accumulation and overcoming ABC transporter-mediated resistance, suggesting its potential as an adjuvant in TNBC treatment. These findings support further investigation of bacopaside II, particularly for resistant TNBC subtypes.

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.

Bacopaside (bac) I and II are triterpene saponins purified from the medicinal herb Bacopa monnieri. Previously, we showed that bac II reduced endothelial cell migration and tube formation and induced apoptosis in colorectal cancer cell lines. The aim of the current study was to examine the effects of treatment with combined doses of bac I and bac II using four cell lines representative of the breast cancer subtypes: triple negative (MDA-MB-231), estrogen receptor positive (T47D and MCF7) and human epidermal growth factor receptor 2 (HER2) positive (BT-474). Drug treatment outcome measures included cell viability, proliferation, cell cycle, apoptosis, migration, and invasion assays. Relationships were analysed by one- and two-way analysis of variance with Bonferroni post-hoc analysis. Combined doses of bac I and bac II, each below their half maximal inhibitory concentration (IC50), were synergistic and reduced the viability and proliferation of the four breast cancer cell lines. Cell loss occurred at the highest dose combinations and was associated with G2/M arrest and apoptosis. Migration in the scratch wound assay was significantly reduced at apoptosis-inducing combinations, but also at non-cytotoxic combinations, for MDA-MB-231 and T47D (p < 0.0001) and BT-474 (p = 0.0003). Non-cytotoxic combinations also significantly reduced spheroid invasion of MDA-MB-231 cells by up to 97% (p < 0.0001). Combining bac I and II below their IC50 reduced the viability, proliferation, and migration and invasiveness of breast cancer cell lines, suggesting synergy between bac I and II.

Bacopa monnieri and the constituents of this plant, especially bacosides, possess various neuropharmacological properties. Like drugs, some herbal extracts and the constituents of their extracts alter cytochrome P450 (CYP) enzymes, causing potential herb-drug interactions. The effects of Bacopa monnieri standardized extract and the bacosides from the extract on five major CYP isoforms in vitro were analyzed using a luminescent CYP recombinant human enzyme assay. B. monnieri extract exhibited non-competitive inhibition of CYP2C19 (IC50/Ki = 23.67/9.5 µg/mL), CYP2C9 (36.49/12.5 µg/mL), CYP1A2 (52.20/25.1 µg/mL); competitive inhibition of CYP3A4 (83.95/14.5 µg/mL) and weak inhibition of CYP2D6 (IC50 = 2061.50 µg/mL). However, the bacosides showed negligible inhibition of the same isoforms. B. monnieri, which is orally administered, has a higher concentration in the gut than the liver; therefore, this herb could exhibit stronger inhibition of intestinal CYPs than hepatic CYPs. At an estimated gut concentration of 600 µg/mL (based on a daily dosage of 300 mg/day), B. monnieri reduced the catalytic activities of CYP3A4, CYP2C9 and CYP2C19 to less than 10% compared to the total activity (without inhibitor = 100%). These findings suggest that B. monnieri extract could contribute to herb-drug interactions when orally co-administered with drugs metabolized by CYP1A2, CYP3A4, CYP2C9 and CYP2C19.

BACKGROUND: Growing cognitive health interest fuels 8.3% market growth. Bacopa monnieri Wettst. (Brahmi) and Ginkgo biloba L. (Ginkgo) are among the most studied natural nootropics, but their effects have not been directly compared. This study aimed to evaluate and compare their efficacy in healthy adults using a network meta-analysis. METHODS: We searched PubMed, EMBASE, Cochrane CENTRAL, and EBSCO Open Dissertations in November 2024. Randomized controlled trials (RCTs) on healthy adults receiving Brahmi or Ginkgo extracts and reported cognitive outcomes were included. Risk of bias was assessed using the Cochrane Risk of Bias version 2. Cognitive outcomes were analyzed using standardized mean differences (SMDs) with 95% confidence intervals (CI) under a random-effects model. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA). RESULTS: Twenty-nine RCTs (n = 2107) were included. High-dose Brahmi (≥600 mg/day) significantly improved working memory compared to low-dose Brahmi (300 to <600 mg/day), high-dose Ginkgo (≥240 mg/day), low-dose Ginkgo (60 to <240 mg/day), and placebo, with SMDs (95% CI) of 1.84 (1.05-2.64), 1.94 (1.10-2.77), 2.04 (1.24-2.84), and 2.03 (1.28-2.78), respectively. A SUCRA of 100% further supports the strong efficacy of high-dose Brahmi. It also demonstrated significantly greater benefits for short-term memory. For delayed memory, low-dose Brahmi outperformed both low-dose Ginkgo and placebo. No significant differences were observed in sustained attention, selective attention, or processing speed. CONCLUSION: Brahmi, particularly in high-dose formulations, shows promise as a cognitive enhancer compared to Ginkgo in healthy adults. However, the lack of direct comparisons may limit the strength of this evidence. OTHER: The authors are grateful for financial support from The Royal Golden Jubilee Ph.D. Program (RGJ-Ph.D. Program), Thailand Research Fund (TRF) (N41A670299). This study is registered with PROSPERO (CRD420251034900).

The incidence of cognitive disorders is rising, and medications to address cognitive impairments are limited. Phytochemical compounds have had some success in improving cognitive outcomes in preclinical studies. However, the evidence surrounding the implementation of these compounds routinely in (1) improving cognition in healthy individuals or (2) as prophylaxis and treatment against the cognitive sequelae of neurological insult has not been collated. To address this, the evidence base surrounding the impact of phytochemical agents on cognitive function in healthy individuals was reviewed. Web of Science, PubMed, PsycNET, and AYUSH Research Portal were systematically searched for double-blind and single-blind randomized controlled trials assessing the efficacy of Curcuma longa, Bacopa monnieri, Ocimum tenuiflorum, Camellia sinensis, Centella asiatica, Ganoderma lingzhi, and Rosmarinus officinalis on cognitive function. Seven studies met inclusion. These examined the impact of B. monnieri, O. tenuiflorum, or C. sinensis. There was no benefit of B. monnieri or C. sinensis on processing speed, attention, working memory, language, psychomotor function, or overall cognitive performance. O. tenuiflorum improved reaction times on an executive function task. Further, more methodologically robust trials of longer duration are recommended to investigate the efficacy of phytochemical supplementation for cognition. © The Author(s) 2026. Published by Oxford University Press on behalf of the CINP.

OBJECTIVE: This review aims to assess the efficacy and safety of different supplements, such as L-theanine, caffeine, Ginkgo biloba L., and Bacopa monnieri for improving ADHD symptoms, to determine the most effective supplement and provide insight for medical practice. METHODS: International databases (PubMed/MEDLINE and Scopus) were searched for English-language RCTs, open-label studies, and cross-sectional studies. RESULTS: Studies on L-theanine, caffeine, Ginkgo biloba L., and Bacopa monnieri have shown various effects on ADHD symptoms. L-theanine improved sleep efficiency but not other sleep parameters. Caffeine showed no significant benefits, although its combination with L-theanine may enhance attention. Bacopa monnieri consistently improved inattention, hyperactivity, and memory, whereas Ginkgo biloba L. reduced ADHD symptoms, particularly inattention, but was less effective than methylphenidate. CONCLUSIONS: The evidence revealed the potential use of supplements as complementary ADHD treatments under clinical guidance. The limited effect of supplements cannot replace the well-documented efficacy of stimulants for ADHD treatment. Additional studies are needed to ascertain the most effective dosages and the safety of these supplements as adjunctive treatments for ADHD.

Schizophrenia is a psychotic disorder affecting approximately 0.32% of the global population. Despite advancements in pharmacological treatments, many patients with schizophrenia continue to experience significant impairments, and approximately one-third of these patients do not respond to antipsychotic drugs. However, various studies have demonstrated the potential benefits of herbs in managing schizophrenia due to the diverse biological activities of phytochemicals, including neuroprotective activity, anti-oxidant potential, modulation of neurotransmission, and anti-inflammatory activity. Bacopa monnieri (Brahmi) is a widely studied herb used in the treatment of the central nervous system. This study conducted a systematic review to determine the effectiveness of Brahmi in managing schizophrenia. PubMed, Scopus, Web of Science, and Cochrane databases were searched between February and March, 2024. A total of 103 articles were found, with only 9 studies meeting the eligibility criteria. Data analysis was done by using themes. The review found that Brahmi could reverse positive, negative, and cognitive symptoms of schizophrenia. It does this by changing the glutamatergic pathway and GABAergic transmission, lowering MDA levels, raising GSH levels, slowing down the activity of acetylcholinesterase (AchE), and maintaining the density of neurones. It is recommended that additional research elucidating the effects of Brahmi in other models of schizophrenia and the possible mechanisms of action be conducted.

166. Altern Ther Health Med. 2024 Sep;30(9):54-64. Therapeutic Evaluation of Unani Medicine, Including Single Drugs and Polyherbal Formulations with Special Reference to Neurodegenerative Disorders. Imran S, Ahmad W, Saltanat S. ETHNOPHARMACOLOGICAL RELEVANCE: Unani remedies are considered safe and can be utilized as a healthcare resource due to the adverse effects of conventional pharmaceuticals. For instance, Donepezil, used to treat alzhemier's disease exerts many adverse effects such as dizziness, vertigo, dryness of mouth. Similarly, Memantine used to slow the neurotoxicity involved in alzhemier's disease also exerts adverse effects like vomiting, tremors and sleep disturbance. Over sixty percent of drugs are derived from synthetic basis, highlighting the potential benefits of natural Unani treatments as a safer alternative. Neurodegenerative disorders are illnesses characterized by structural and functional deterioration due to abnormal protein aggregation, resulting in inflammation and oxidative stress in the central nervous system. In unani system of medicine all current brain ailments, including alzheimer's disease, parkinson's disease, mania, anxiety, melancholia and others are classified under the general category of neurodegenerative disorders Their pathogenic variables and soociated symptoms and therapeutic modalities are similar. This study focuses on evidence-based Unani herbs and polyherbal formulations for the treatment of various neurodegenerative disorders. It reveals that 43 ethnomedicinal plants can be employed to treat the symptoms of neurodegenerative disorders. The material was gathered from several sources that tabulated the specific details of individual herbs and polyherbal formulations and highlighted the importance of various phytoconstituents on neuroprotective action. The research provides in vivo and scientific evidence to support the use of ethnomedicine in treating neurodegenerative disorders. AIM OF THE STUDY: This study aims to validate the efficacy of Unani medicines, traditionally used for neurodegenerative diorders through evidence-based research. METHODS: To scan single and polyherbal formulations for neurodegenerative

BACKGROUND: Subjective cognitive impairment (SCI) substantially increases dementia risk and is often conceptualised as the preclinical asymptomatic phase of the cognitive decline continuum. Due to the lack of pharmacological interventions available to treat SCI and reduce dementia risk, and the popularity of herbal and nutritional medicines, the primary aim of this review was to investigate the efficacy on cognitive function and safety of herbal and nutritional medicines (relative to a control) for older adults with and without SCI. The secondary aims were to describe the study characteristics and assess the methodological quality of included studies. METHOD: Five databases (Cochrane, MEDLINE, CINAHL, PsycInfo, and EMBASE) were searched from database inception with weekly alerts established until review finalisation on 18 September 2022. Articles were eligible if they included the following: study population of older adults with and without SCI, herbal and nutritional medicines as an intervention, evaluated cognitive outcomes and were randomised control trials. RESULTS: Data were extracted from 21/7666 eligible full-text articles, and the risk of methodological bias was assessed (with SCI = 9/21; without SCI = 12/21). Most studies (20/21) employed parallel, randomised, placebo-controlled designs and were 12 weeks in length. Herbal supplements were widely used (17/21), namely a form of Ginkgo biloba (8/21) or Bacopa monnieri (6/21). Measures of cognition varied across studies, with 14/21 reporting improvements in at least one domain of cognitive functioning over time, in the intervention group (compared to control). A total of 14/21 studies were deemed as having an overall high methodological risk of bias, 6/21 had some concerns, and only one study (using an SCI population) was assessed as having a low risk of methodological bias. CONCLUSIONS: Overall, this review found that there is a low quality of evidence regarding the efficacy of cognitive function and safety of herbal and nutritional medicines for older adults with and without SCI, due to a high risk of bias across studies. Additionally, further work needs to be done in classifying and understanding SCI and

Substances with modulatory capabilities on certain aspects of human cognition have been revered as nootropics from the dawn of time. The plant kingdom provides most of the currently available nootropics of natural origin. Here, in this systematic review, we aim to provide state-of-the-art information regarding proven and unproven effects of plant-derived nootropics (PDNs) on human cognition in conditions of health and disease. Six independent searches, one for each neurocognitive domain (NCD), were performed in parallel using three independent scientific library databases: PubMed, Cochrane and Scopus. Only scientific studies and systematic reviews with humans published between January 2000 and November 2021 were reviewed, and 256 papers were included. Ginkgo biloba was the most relevant nootropic regarding perceptual and motor functions. Bacopa monnieri improves language, learning and memory. Withania somnifera (Ashwagandha) modulates anxiety and social-related cognitions. Caffeine enhances attention and executive functions. Together, the results from the compiled studies highlight the nootropic effects and the inconsistencies regarding PDNs that require further research.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.2021137.

Background: Dietary supplements promoted for brain health and enhanced cognitive performance are widely available. Claims made for these products are directed not only to the elderly wishing to prevent or mitigate cognitive decline, but also young healthy populations looking to boost their cognitive performance. It is unclear whether these claims made on product bottles and through advertising match the science. Objectives: To explore the evidence on the efficacy and safety of single dietary supplement ingredients frequently marketed with claims of enhanced cognitive performance among healthy adults. Design: A systematic review. Results: Nine of 54 dietary supplement ingredients identified through a scoping review met the eligibility criteria with at least 3 published studies identified per ingredient, yielding 69 unique publications. Ingredients evaluated included Bacopa monnieri, choline, creatine, omega-3 fatty acids, Ginkgo biloba, ginseng, Rhodiola rosea, tyrosine, and valerian root, all in supplement form and compared with a placebo, at various serving sizes and durations of use. Conclusions: The low level of certainty in the state of the science, coupled with not always knowing what is in a dietary supplement product, make weighing risks and benefits difficult; these data hinder the ability to develop recommendations about using such ingredients for consumers interested in boosting their cognitive performance. Whereas certain trends regarding promising serving sizes or duration for use, are pointed to in this synthesis, when combined, studies are inconsistent and imprecise, and many are methodologically flawed. Potential solutions to address research gaps are offered, for future research next steps, which is needed to strengthen the evidence and inform decisions.

INTRODUCTION: The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the stress response. Plants, herbs, spices, and plant-based nutrients may influence HPA-axis activity. OBJECTIVE: To evaluate randomised controlled, human trials assessing the effects of single plants or phytonutrients on HPA-axis related hormones. METHODS: A systematic review of PubMed, Cochrane library, and the Cumulative Index to Nursing and Allied Health Literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria comprised of human, randomised controlled studies with a control intervention examining the effects of a single herb, spice, plant, or extract on pre- and post-changes in blood, saliva, urine, or hair concentrations of cortisol, cortisone, corticotrophin-releasing hormone, or adrenocorticotropic hormone. Databases were searched from inception until October 2020. RESULTS: Fifty-two studies were identified examining the effects of ashwagandha, Korean ginseng, St John's Wort, cannabidiol, Rhodiola rosea, curcumin, cherry juice, asparagus, Jiaogulan, Black cohosh, Siberian ginseng, Bacopa monnieri, blueberries, green tea, Caralluma fimbriata, cashew apple juice, melon, American ginseng, Ginkgo biloba, grape juice, grapefruit juice, rosella, hops, mangosteen, holy basil, and pomegranate juice. Due to significant variability in study designs, the effect of phytonutrients on HPA-axis activity in humans was unclear. The most consistent finding was a morning, cortisol-lowering effect from ashwagandha supplementation. CONCLUSION: For most phytonutrients, the effects of supplementation on HPA-axis activity in humans is unclear. Before more definitive conclusions about the effects of phytonutrients on the HPA-axis can be made, further research is required.

RELEVANCE: More than 70 million people suffer epilepsy worldwide. Low availability of anti-epileptic drugs, side-effects and drug-resistant epilepsy affect the quality of life of persons with epilepsy in countries with a poorly developed health system. Herbal medicine is frequently used for this neurological condition. OBJECTIVES: The main objective was to provide a detailed analysis of Herbal Medicine used for neurological conditions related with epilepsy in Asia, Africa and Latin America. More broadly, this study aims to highlight species with assessed efficacy (cross-cultural use, pharmacological effects on models of epileptic seizures) and safety (toxicological data in laboratory) information, in order to point out species of interest for further studies. A critical assessment of models used in pharmacological evaluations was done. MATERIALS AND METHODS: The systematic search for Herbal Medicine treatments for epilepsy was performed considering all the articles published until February 2017 through three scientific databases. It was made with MeSH terms and free text defining the epilepsy seizures and plant species. We included studies carried out in Asia, Africa and Latin America. All articles reporting the use of Herbal Medicine to treat epilepsy seizures and/or their pharmacological evaluation were retained for further analysis. RESULTS: The search yielded 1886 articles, from 30 countries. Hundred and six articles published between 1982 and 2017 were included, corresponding to a total of 497 use reports for 351 plant species belonging to 106 families. Three hundred and seventy seven use reports corresponding to 264 species in ethnopharmacological surveys and 120 evaluation reports corresponding to 107 species were noted. Twenty-nine reports, for 29 species, combined both ethnopharmacological and pharmacological evaluation. Fifty eight studies originated from Africa, 35 studies from Asia and 18 from Latin America. Highest use report was noted for rhizomes of Acorus calamus L. (12 use report in 1 country) and leaves of Bacopa monnieri (L.) Wettst. (8 use report in 2 countries). Therefore these species display the highest use convergence. Regarding pharmacol