Bacopa Monnieri Extract Research Articles

Effect of Bacopa monnieri extracts on storage quality of chicken nuggets at refrigeration temperature (4 ± 1°C)

PurposeThe purpose of this paper was to explore the antioxidant and antimicrobial properties of locally available herbs, namely, Bacopa monnieri in enhancing the shelf life of chicken nuggets.Design/methodology/approachMeat products are highly vulnerable to spoilage due to their excessive fats and protein content. Therefore, chicken nuggets incorporated with 1, 2 and 3 per cent Bacopa monnieri extracts and control chicken nuggets, were studied to explore the potency of this locally available herb on oxidative stability and storage quality of chicken nuggets on the 0,7th,14th and the 21st day at the refrigerated storage (4 ± 1°C).FindingsExtracts of Bacopa monnieri were prepared and optimally incorporated in the chicken nuggets. Chicken nuggets prepared with 2 per cent of Bacopa monnieri were adjudged as the best among all based on sensory attributes. Extracts of Bacopa monnieri-incorporated nuggets were safe for consumption until 21 days of refrigerated storage (4 ± 1°C), based upon the power of hydrogen (pH), free fatty acid (FFA), thiobarbituric acid reactive substances (TBARS), microbiological profile and sensory evaluation of the chicken nuggets.Practical implicationsTwo per cent of Bacopa monnieri extracts’ incorporation in the chicken nuggets successfully improved the oxidative stability and storage quality of chicken nuggets and, therefore, can be commercially exploited.Social implicationsThe Bacopa monnieri herb is commonly available in the Jammu region of Jammu and Kashmir state in the Indian Republic; hence, it can be used in its extract form in meat products, to make the products function with enhanced shelf life.Originality/valueThe addition of 2 per cent extracts of Bacopa monnieri in the chicken nuggets successfully improved the oxidative stability and its storage quality during the refrigerated (4 ± 1°C) storage. Therefore, it can be commercially exploited to improve the storage quality for longer duration of the meat food without adversely affecting the sensory quality of the products.

Modulation of carcinogenicity and mutagenicity by herbal medicinal plant Bacopa monnieri extract in swiss albino mice

In the present investigation the topical application of single dose of DMBA followed by croton oil induced the skin papillomas in all the animals by the 15th week. Cumulative number of Papillomas and tumor yields were recorded as 28, and 4.6 respectively. Whereas the animals which received Bacopa monnieri extract additionally at the dose of 200 mg/kg body weight, the cumulative number of Papillomas, tumor yields were recorded as 18 and 3.0 respectively and these were observed to be significantly lower than DMBA+Croton oil group. In another experiment, B16F10 melanoma propagated by subcutaneous injection of 106 melanoma cells on the dorsal skin of C57BL mice. The tumour growth and tumor volume of cyclophosphamide treated by subcutaneous route at single dose of 300 mg/kg body weight, 30 min. after tumor cell inoculation the tumors size was significantly reduced and inhibited the tumors growth by 46.74 %. Whereas when cyclophosphamide was given at single dose and Bacopa monniere extract was given for 21 days by oral route, the tumor size was further reduced and tumor growth was inhibited by 50.71%. However Bacopa monniera ext. alone treatment (200 mg/kg oral 21 days) the tumour volume was also reduced and tumor growth was inhibited by 27.27 %. It seems that Bacopa monnieri extract in combination with cyclophosphamide has significantly prevented the tumour volume as compared to control. In antimutagenicity studies Bacopa monnieri administered i.p. at the dose dependent manner have inhibited micronucleus formation and chromosomal aberrations induced by known mutagen in Bone marrow cells of Swiss albino mice. It is therefore concluded that Bacopa monnieri extract has anticarcinogenic and antimutagenic activity in the above test systems.

Exploring the Cytotoxic Potential of Triterpenoids-enriched Fraction of Bacopa monnieri by Implementing In vitro, In vivo, and In silico Approaches.

Background:Bacopa monnieri (BM) is a herbaceous plant traditionally used from time immemorial in Ayurvedic and folklore medicines. We hypothesized that the extract of the whole plant might contain numerous molecules with having antitumor activities that could be very effective in killing of human cancer cells.Objectives:This work investigated anticancer activity of bioactive fraction of BM.Materials and Methods:The hydroalcoholic extract of BM was fractionated with different solvent, namely, hexane, dichloromethane (DCM), acetone, methanol, and water. The in vitro anticancer activity was performed against various Human Cancer Cell lines, namely, Colon (HT29, Colo320, and Caco2), Lung (A549), Cervix (HeLa, SiHa), and Breast (MCF-7, MDAMB-231). Further, DCM fraction was evaluated in vivo for anticancer activity against Ehrlich ascites carcinoma (EAC) tumor-bearing mice since it showed the best cytotoxicity at 72 h (IC50 41.0–60.0 µg/mL). The metabolic fingerprinting of these extract were carried out using high-performance thin-layer chromatography along with quantification of bacoside A, bacoside B, cucurbitacin B, cucurbitacin E, and bittulinic acid.Results:Oral administration of DCM fraction at a dose of 40 mg/kg rendered prominent reduction of tumor regression parameters such as tumor weight, packed cell volume, tumor volume and viable tumor cell count as compared to the untreated mice of the EAC control group. The anticancer activity of DCM fraction may be due to the presence of large amount of bacoside A, B and cucurbitacins. The molecular docking studies of major metabolites with targeted proteins predicted the anticancer activity of DCM fraction which was in support of in vivo activity.Conclusion:The in vitro, in vivo, analytical and in silico studies on DCM fraction of Bacopa monieri has proved its great potential for development of anticancer phytopharmaceuticals.SUMMARY A new HPTLC method has been developed and validated for the qualitative and quantitative analysis of bacoside A, B, cucurbitacin B, D, E and bittulinic acid in Bacopa monnieri extract. Enrichment of active anticancer metabolites was done by polarity based fractionations of hydroalcoholic extract of Bacopa. DCM fraction of a hydroalcoholic extract of Bacopa showed anticancer potential against human cancer cell line (IC50 41.0-60.0 µg/mL) and in EAC treated mice (at a dose of 40 mg/kg body weight). The anticancer activity of Bacopa may be due to the presence of bacosides and cucurbitacin and it was confirmed by in silico screening. Abbreviations used: DBM: DCM fraction of Bacopa monnieri; DCM: Dichloromethane; EAC: Ehrlich ascites carcinoma; HCT: Hematocrit; HGB: Hemoglobin; HPTLC: High performance thin layer chromatography; ICH: International council for Harmonisation; LOD: Limit of detection; LOQ: Limit of quantification; LYM: Lymphocytes; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular haemoglobin concentration (MCHC); MCV: Mean corpuscular volume; MTT: 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PLT: Platelet; RBC: Red blood cell; RDW: Red blood cell distribution width; RSD: Relative standard deviation; WBC: White blood cells.

Bacoside A Induces Tumor Cell Death in Human Glioblastoma Cell Lines through Catastrophic Macropinocytosis

Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumor with an extremely poor prognosis. Recent evidences have shown that the “biomechanical imbalances” induced in GBM patient-derived glioblastoma cells (GC) and in vivo via the administration of synthetic small molecules, may effectively inhibit disease progression and prolong survival of GBM animal models. This novel concept associated with de novo anti-GBM drug development has however suffered obstacles in adequate clinical utility due to the appearance of unrelated toxicity in the prolonged therapeutic windows. Here, we took a “drug repurposing approach” to trigger similar physico-chemical disturbances in the GBM tumor cells, wherein, the candidate therapeutic agent has been previously well established for its neuro-protective roles, safety, efficacy, prolonged tolerance and excellent brain bioavailability in human subjects and mouse models. In this study, we show that the extracts of an Indian traditional medicinal plant Bacopa monnieri (BM) and its bioactive component Bacoside A can generate dosage associated tumor specific disturbances in the hydrostatic pressure balance of the cell via a mechanism involving excessive phosphorylation of calcium/calmodulin-dependent protein kinase IIA (CaMKIIA/CaMK2A) enzyme that is further involved in the release of calcium from the smooth endoplasmic reticular networks. High intracellular calcium stimulated massive macropinocytotic extracellular fluid intake causing cell hypertrophy in the initial stages, excessive macropinosome enlargement and fluid accumulation associated organellar congestion, cell swelling, cell rounding and membrane rupture of glioblastoma cells; with all these events culminating into a non-apoptotic, physical non-homeostasis associated glioblastoma tumor cell death. These results identify glioblastoma tumor cells to be a specific target of the tested herbal medicine and therefore can be exploited as a safe anti-GBM therapeutic.

Reversion of BDNF, Akt and CREB in Hippocampus of Chronic Unpredictable Stress Induced Rats: Effects of Phytochemical, Bacopa Monnieri.

ObjectiveThe aims of the present study were to explore the behavioural effects and to understand the possible mode of action of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced depressive model and the biochemical alterations such as brain derived neurotrophic factor (BDNF), Akt, cyclic-AMP response element binding (CREB) protein level in the hippocampus of rats.MethodsWe examined the effects of chronic administration of BME on CUS exposed rats for 28 days. Behavioural changes were assessed by sucrose consumption and open field test to assess the effect of BME on CUS-induced depression. The mechanisms underlying antidepressant like action of BME was further evaluated by measuring levels of BDNF, Akt, and CREB in the hippocampus of rat brain and compared with the standard tricyclic antidepressant drug imipramine (20 mg/kg body weight).ResultsExposure to CUS for 28 days produced depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity including decreased BDNF, Akt and CREB levels in the hippocampus. Daily administration of BME at a dose of (80 mg/kg body weight) significantly reverses the behavioral alteration and restored the normal level of BDNF, total and phospho-Akt, total and phospho CREB in the hippocampus of CUS induced rats as compared to vehicle treated control rats.ConclusionThese findings suggest that BME ameliorates CUS induced behavioural depression in rats and that can be used as a potent therapeutic agent in treating depressive like behavior.

Renoprotective effect of Bacopa monnieri via inhibition of advanced glycation end products and oxidative stress in STZ-nicotinamide-induced diabetic nephropathy

Hyperglycemia and oxidative stress are involved in the development of diabetic nephropathy (DN). This study was designed to evaluate the effect of alcohol and hydroalcohol extract of Bacopa monnieri and stigmasterol isolated from B. monnieri in the treatment of DN. Diabetes was induced in male wistar rats by streptozotocin (65 mg/kg i.p.) 15 min after nicotinamide (230 mg/kg, i.p.) administration. After 30 days, the rats were treated with different doses of extracts (100, 200, and 400 mg/kg) and stigmasterol (5 and 10 mg/kg) for 45 days to analyze their nephroprotective effect and produced significant attenuation in the serum glucose level, uric acid, creatinine, and lipid levels. Moreover, there is improvement in the level of superoxide dismutase (SOD), glutathione (GSH), and decrease in lipid peroxidation in terms of TBARS. The formation of AGEs in kidneys was also significantly reduced. These findings suggest that B. monnieri and its isolate (stigmasterol) might inhibit the progression of DN.

Neuroprotective, Neurotrophic and Anti-oxidative Role of Bacopa monnieri on CUS Induced Model of Depression in Rat.

Major depression is a life threatening neuropsychiatric disorder that produces mental illness and major cause of morbidity. The present study was conducted to evaluate the neuroprotective, neurotrophic and antioxidant potential of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced behavioral depression in rats. Behavioral tests were carried out for investigation of antidepressant like effects of BME, and potential mechanism was assessed by determining neurotrophin level and hippocampal neurogenesis. Depressive-like behavior was assessed by shuttle-box escape test, forced swim test and tail suspension test. Effect of BME on hypothalamic-pituitary-adrenal (HPA) axis was evaluated by measuring the plasma level of adrenocorticotropic hormone (ACTH) and corticosterone. The expression of brain derived neurotrophic factor (BDNF), neuronal marker doublecortin (DCX) in the hippocampus were measured and hippocampal neurogenesis was investigated by 5-bromo-2-deoxyuridine/neuronal nuclei (BrdU/NeuN). In addition, effects of BME on oxidative stress markers were also measured in the hippocampus of CUS exposed rats. The results indicated that BME significantly able to attenuate the depressive-like behaviors, normalized the levels of ACTH, corticosterone, and up-regulate the expression of BDNF, DCX and BrdU/NeuN in CUS induced rats compared to BME treated rats. It is also found that BME significantly increased the activity of antioxidant enzymes on CUS induced rats. These findings revealed that BME exerted neuroprotective effects possibly by promoting hippocampal neurogenesis with elevation of BDNF level and antioxidant defense against oxidative stress.

Acute and chronic toxicities of Bacopa monnieri extract in Sprague-Dawley rats

BackgroundBacopa monnieri is a medicinal plant which has long been used in Ayurvedic medicines to augment brain function and to improve memory. The purpose of our study was to identify and evaluate possible toxic effects of B. monnieri extract in rats by assessing hematological, biochemical, and histopathological parameters.MethodsAcute oral toxicity of Bacopa monnieri extract was studied in female rats by giving a single orally administered dose at a level of 5,000 mg/kg. The rats were monitored for toxic signs for 14 days. In the chronic toxicity test, groups of both female and male rats were given daily oral doses of B. monnieri extract at dose levels of either 30, 60, 300 or 1,500 mg/kg for 270 days. The behavior and health of the animals was then monitored. At the end of the observation period, the body and organ weights of the rats in each group were measured. Blood was collected and necropsy was performed to evaluate their hematology, blood clinical chemistry, and microanatomy.ResultsThe acute toxicity test found no significant differences between the experimental and the control group rats. In the chronic toxicity test, animal behavior and health of the experimental groups were normal, just as in the control rats. All values of other parameters assessed remained within the normal range.ConclusionA single oral administration of B. monnieri extract at the dose of 5,000 mg/kg did not cause any serious undesirable effects. B. monnieri extract at doses of 30, 60, 300 and 1,500 mg/kg given for 270 days did not produce any toxicity in rats.

Effect of standardized extract of Bacopa monnieri (CDRI-08) on testicular functions in adult male mice

Ethnopharmacological relevanceBacopa monnieri (BM) has been used in India since the time of Rig-Veda for augmentation of learning, memory, brain health etc. Aim of the studyThe memory augmenting effect of BM is well documented. CDRI-08 is a standardized extract of Bacopa monnieri, but its effect on the male reproductive health has not been investigated. Therefore, the aim of the present study was to examine the effect of CDRI-08 administration on the male reproductive organs with special emphasis on testis in adult mice. Materials and methodsCDRI-08, containing at least 55% bacosides (the major constituent of BM), was investigated for its effect on testicular functions in adult Parkes (P) mice. A suspension of CDRI-08 was orally administered in doses of 40 and 80mgkg−1 body weight day−1 for 28 days and various male reproductive end points were evaluated. ResultsCompared to control, CDRI-08 treatment caused a significant increase (p<0.05) in spermatogenic cell density (germinal epithelial height: control, 55.03±4.22 vs 40mg, 67.15±2.65 and 80mg, 69.93±3.76; and tubular diameter: control, 206.55±2.62 vs 80mg, 253.23±12.19), PCNA index (control, 59.85±2.09 vs 40mg, 82.17±1.56 and 80mg, 84.05±3.51) and in steroidogenic indices in the testis, and in sperm viability (control, 0.67±0.010 vs 80mg, 0.80±0.04) in cauda epididymidis of the treated mice. On the other hand, however, the same treatment caused a significant decrease (p<0.05) in abnormal sperm morphology (control, 21.72±1.06 vs 40mg, 10.63±1.50 and 80mg, 15.86±0.87) in cauda epididymidis, and in lipid peroxidation level in testis of the treated mice compared to controls. ConclusionThe results suggest that treatment with CDRI-08 extract improves sperm quality, and spermatogenic cell density and steroidogenic indices in the testis of P mice.

LC-ESI-QTOF-MS based screening and identification of isomeric jujubogenin and pseudojujubogenin aglycones in Bacopa monnieri extract

Bacopa monnieri (L.) Wettst. (Scrophulariaceae) is an Ayurvedic medicinal plant used as a memory enhancer. Its major chemical constituents are Bacopa saponins consisting of jujubogenin and pseudojujubogenin glycosides. These two aglycones are isomers different at the positions of prenyl substitution i.e., at C-23 for jujubogenin and at C-22 for pseudojujubogenin. In this study, we demonstrate the rapid and comprehensive characterization of saponin glycosides in B. monnieri using liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometer (LC-ESI-QTOF-MS). This shows that ESI-QTOF-MS in positive-ion mode, jujubogenin and pseudojujubogenin glycosides could be discriminated by the peak abundance ratio of m/z 455 [Aglycone+H-H2O]+ to m/z of 473 [Aglycone+H]+. Furthermore, the sequence of sugar moieties can be observed. In a similar manner, the isomeric saponins; deoxyjujubogenin and deoxypseudojujubogenin glycosides can be distinguished using the m/z 437[Aglycone+H-H2O]+ and m/z 455[Aglycone+H]+ peak ratio. Use of the negative-ion mode with MS/MS fragmentation can provide information about the type of sugar linked to the aglycone i.e., at m/z 633 (aglycone+glucose) or at m/z 603 (aglycone+arabinose). With our method, 62 chemical constituents in B. monnieri including saponin glycosides, flavonoids, and alkaloids were identified. This is the first systematic study in structural characterization on isomeric saponins and other metabolites in B. monnieri using ESI-QTOF-MS.

Possible Involvement of Standardized Bacopa monniera Extract (CDRI-08) in Epigenetic Regulation of reelin and Brain-Derived Neurotrophic Factor to Enhance Memory.

Bacopa monniera extract (CDRI-08; BME) has been known to improve learning and memory, and understanding the molecular mechanisms may help to know its specificity. We investigated whether the BME treatment alters the methylation status of reelin and brain-derived neurotropic factor (BDNF) to enhance the memory through the interaction of N-methyl-D-aspartate receptor (NMDAR) with synaptic proteins. Rat pups were subjected to novel object recognition test following daily oral administration of BME (80 mg/kg) in 0.5% gum acacia (per-orally, p.o.; PND 15–29)/three doses of 5-azacytidine (5-azaC; 3.2 mg/kg) in 0.9% saline (intraperitoneally, i.p.) on PND-30. After the behavioral test, methylation status of reelin, BDNF and activation of NMDAR, and its interactions with synaptic proteins were tested. Rat pups treated with BME/5-azaC showed higher discrimination towards novel objects than with old objects during testing. Further, we observed an elevated level of unmethylated DNA in reelin and BDNF promoter region. Up-regulated reelin along with the splice variant of apolipoprotein E receptor 2 (ApoER 2, ex 19) form a cluster and activate NMDAR through disabled adopter protein-1 (DAB1) to enhance BDNF. Observed results suggest that BME regulate reelin epigenetically, which might enhance NMDAR interactions with synaptic proteins and induction of BDNF. These changes may be linked with improved novel object recognition memory.

Standardized Bacopa monnieri extract ameliorates acute paraquat-induced oxidative stress, and neurotoxicity in prepubertal mice brain

Objectives: Bacopa monnieri (BM), an ayurvedic medicinal plant, has attracted considerable interest owing to its diverse neuropharmacological properties. Epidemiological studies have shown significant correlation between paraquat (PQ) exposure and increased risk for Parkinson's disease in humans. In this study, we examined the propensity of standardized extract of BM to attenuate acute PQ-induced oxidative stress, mitochondrial dysfunctions, and neurotoxicity in the different brain regions of prepubertal mice.Methods: To test this hypothesis, prepubertal mice provided orally with standardized BM extract (200 mg/kg body weight/day for 4 weeks) were challenged with an acute dose (15 mg/kg body weight, intraperitoneally) of PQ after 3 hours of last dose of extract. Mice were sacrificed after 48 hours of PQ injection, and different brain regions were isolated and subjected to biochemical determinations/quantification of central monoamine (dopamine, DA) levels (by high-performance liquid chromatography).Results: Oral supplementation of BM for 4 weeks resulted in significant reduction in the basal levels of oxidative markers such as reactive oxygen species (ROS), malondialdehyde (MDA), and hydroperoxides (HP) in various brain regions. PQ at the administered dose elicited marked oxidative stress within 48 hours in various brain regions of mice. However, BM prophylaxis significantly improved oxidative homeostasis by restoring PQ-induced ROS, MDA, and HP levels and also by attenuating mitochondrial dysfunction. Interestingly, BM supplementation restored the activities of cholinergic enzymes along with the restoration of striatal DA levels among the PQ-treated mice.Discussion: Based on these findings, we infer that BM prophylaxis renders the brain resistant to PQ-mediated oxidative perturbations and thus may be better exploited as a preventive approach to protect against oxidative-mediated neuronal dysfunctions.

Analysis of bacopaside I in biomatrices using liquid chromatography-tandem mass spectrometry: Pharmacokinetics and brain distribution in Swiss-albino mice

Bacopaside I (BP-I) is the major pseudojujubogenin glycoside of Bacopa monniera (BM) extract which has been widely used as a nerve tonic to improve the memory and intellect of human beings from ancient times. A selective and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the quantification of BP-I in mouse plasma and brain homogenate has been developed and validated. All biosamples were processed by liquid-liquid extraction and chromatographed on C18- reversed phase column using mobile phase consisting of ammonium acetate (10mM, pH 4) – acetonitrile (10:90, v/v) at a flow rate of 0.5mL/min. The detection was performed in negative electrospray ionization mode and the precursor/product ion transitions of BP-I and internal standard (IS) hydrochlorothiazide were quantified in multiple reaction monitoring (MRM) using QTRAP-5500 MS/MS. The linearity was established over the concentration range of 0.5–2000ng/mL (r2>0.990), with lower limit of quantification (LLOQ) of 0.5ng/mL in both plasma and brain matrix. Within- and between-run precision and accuracy were well within the acceptable limits of variation. Consistent and reproducible recovery (>70%) was obtained with insignificant matrix effect for BP-I and IS. The method fulfilled US Food and Drug Administration (USFDA) guidelines for bioanalytical method validation in terms of selectivity, sensitivity, linearity, accuracy, precision, matrix effect, dilution integrity, carry-over effect and stability. Further, the method was successfully applied to execute the plasma pharmacokinetics and brain distribution of BP-I in Swiss-albino mice following intravenous administration at a dose of 5mg/kg.

Bacopaside I ameliorates cognitive impairment in APP/PS1 mice via immune-mediated clearance of β-amyloid.

Standardized extracts of Bacopa monniera (BME) have been shown to exert a neuroprotective effect against mental diseases, such as depression, anxiety and Alzheimer's disease (AD), in chronic administration studies. However, its mechanism of action has remained unclear. In this study, we evaluated the therapeutic effect of Bacopaside I (BS-I), a major triterpenoid saponin of BME, on the cognitive impairment and neuropathology in APP/PS1 transgenic mice and explored the possible mechanism from a biological systems perspective. We found that BS-I treatment significantly ameliorated learning deficits, improved long-term spatial memory, and reduced plaque load in APP/PS1 mice. We constructed BS-I's therapeutic effect network by mapping the nodes onto the protein-protein interaction (PPI) network constructed according to their functional categories based on genomic and proteomic data. Because many of the top enrichment categories related to the processes of the immune system and phagocytosis were detected, we proposed that BS-I promotes amyloid clearance via the induction of a suitable degree of innate immune stimulation and phagocytosis. Our research may help to clarify the neuroprotective effect of BME and indicated that natural saponins target the immune system, which may offer new research avenues to discover novel treatments for AD.

Beneficial effects of Bacopa monnieri extract on opioid induced toxicity.

The present study examined the hepatotoxicity and nephrotoxicity of morphine and illicit street heroin and their amelioration by a standardized methanolic extract of Bacopa monnieri (L.) (mBME) in rats. Morphine or street heroin was administered at a dose of 20 mg/kg for 14 and 21 days. mBME (40 mg/kg) or ascorbic acid (50 mg/kg) was administered two hours before morphine or street heroin. High performance liquid chromatography (HPLC) was used for the standardization of bacoside-A major components in mBME. The antioxidant potential of mBME was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Administration of morphine and street heroin resulted in marked elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine. Histopathological changes induced by morphine and street heroin after 14 days were of reversible nature while treatment for 21 days was associated with irreversible changes. Pretreatment with mBME or ascorbic acid restored the elevation of serum ALT, AST and creatinine and protected liver and kidneys from the toxicological influence of morphine and street heroin. HPLC analysis showed that mBME contained bacoside-A major components i.e. bacoside-A3 (37.5 μg/mg), bacopaside-II (4.62 μg/mg) and bacopasaponin-C (1.91 μg/mg). The EC50 for the DPPH free radical scavenging assay revealed that mBME possessed strong antioxidant potential. These results concluded that as compared to morphine, street heroin was associated with severe biochemical and histopathological changes in the liver and kidneys. Bacopa monnieri having strong antioxidant potential may provide a beneficial herbal remedy for the efficient management of opioid related hepatotoxicity and nephrotoxicity.

Innovation and Validation of Neuropsychopharmacological Testing Methods for the Assessment of Memory, Attention and Cognition in Human Participants

To meet the challenges of time searching for the new method for neuropsychopharmacology is still an ongoing process. In this experiment, we proposed and validated three neuropsychopharmacological testing methods, which are Matching Capacity (MC), Dissimilarity Identification (DI) and Sense Making (SM) tests for the estimation of memory, attention and cognition respectively in healthy aged human participants. The purpose of this experiment was to generate more effective testing methods for the determination of memory, attention and cognition in human. To endorse proposed methods a randomized double blind placebo controlled clinical trial was conducted among healthy aged human participants between the period of December 2015 and February 2016. The experiment was conducted at Gazipur Sadar, Gazipur-1703, Dhaka, Bangladesh and the experiment center was the Department of Pharmacy, Southeast University, Dhaka-1213, Bangladesh. In this experiment, 60 healthy male participants between the age of 42 to 50 years were selected and divided into 4 groups with 15 participants in each by simple randomization process. Ginkgo biloba standardized extract’s capsule (Giloba?) and Bacopa monnieri standardized extract’s syrup (Monera?) were used as standard. Psyllium seed husk (i.e., seed of the Plantago ovata) was incorporated in the hard gelatin capsule shell (size 0) to prepare capsule and used as a placebo control of the capsule (PCC). Excipients of oral liquid preparation of vitamin were used to prepare syrup and used as a placebo control of the syrup (PCS). The treatment procedure for group 1 was Ginkgo biloba standardized extract’s capsule (120 mg/capsule), 3 times daily for 21 days; group 2 was treated with Bacopa monnieri standardized extract’s syrup (1.21 g/5 ml), 2 teaspoonfuls, 3 times daily for 21 days. Psyllium seed husk’s capsule and excipients of oral liquid vitamin’s syrup were used as placebo control (PC) for group 3 and group 4 and administered in the similar manner of group 1 and group 2, respectively. Administration of Ginkgo biloba (GB) and Bacopa monnieri (BM) standardized extracts for successive days significantly increased the memory, attention and cognition of the participants with respect to PC groups. In the MC test, treatment with GB extract markedly (P < 0.05) increased the memory of the participants on 21st day with respect to PCC group. On the other hand administration of BM extract remarkably (P < 0.01) increased the memory of the participants on 14th day in comparison with PCS group. For DI test, administration of GB extract noticeably (P < 0.01, P < 0.05) increased the attention of the participants on 14th and 21st day as compared to that of PCC group. Conversely BM extract significantly (P < 0.05, P < 0.01) increased the attention of the participants on 7th, 14th and 21st day with regard to PCS group. In the SM test, administration of GB extract noticeably (P < 0.05) increased the cognition of the participants on 7th and 21st day in comparison with PCC group. BM extract administration considerably (P < 0.01) increased cognition of the participants on 14th and 21st day related to the PCS groups. The experiment demonstrates that MC, DI and SM tests clearly exposed the memory, attention and cognition enhancing activity of the GB and BM standardized extracts in healthful aged human participants respectively. Therefore, the proposed method can be used for the fortitude of memory, attention and cognition in human and will generate a landmark in the sphere of neuroscience.

Psychophysiological Effects of a Combination of Sideritis and Bacopa Extract (memoLoges&amp;lt;sup&amp;gt;&amp;#174;&amp;lt;/sup&amp;gt;) in 32 Subjects Suffering from Mild Cognitive Impairment. A Double-Blind, Randomized, Placebo-Controlled, 2-Armed Study with Parallel Design

Mild cognitive impairment (MCI) can be regarded as a non-demented transitional stage during the development of Alzheimer’s disease. Early recognition of this stage might increase the chance of prevention by early treatment. Within a pilot study, two plant-derived preparations and mixtures thereof were tested successfully in subjects suffering from MCI. A combination of Sideritis scardica and Bacopa monnieri extract (memoLoges®) was chosen now for a repetitive dosing during 4 weeks. Thirty-two subjects aged 50 to 80 years and suffering from MCI (having a DemTect questionnaire score between 8 and 13) were recruited for intake of 2 capsules of the preparation per day. Quantitative EEG recording during relaxation and concomitant performance of three 5 minutes lasting psychometric tests (d2-concentration test, arithmetic calculation test and memory test) was achieved at the first day and one day after the last repetitive intake. Seventeen channels of EEG and one channel EOG (for artefact rejection) were recorded. After frequency analysis (FFT) current source density was calculated as reported earlier. One, two and three hours after intake of the herbal extract or placebo the whole procedure was repeated. Brain imaging was achieved by conversion of numerical values of spectral EEG power into spectral colors and additive color mixture according to RGB as used in TV settings. Intake of memoLoges® induced a trend of improvement of performance in psychometric testing (all three tests). During relaxation quantitative assessment of EEG data revealed attenuation of delta and theta spectral power in frontal brain as likewise reported in the presence of the Alzheimer drug rivastigmine, bringing the spectrum back to “normality”. During mental work memoLoges® induced statistically significant increases of beta power. Since MCI subjects produce less beta power in comparison to healthy subjects, this increase must likewise be seen as a positive effect pointing to a healthier spectrum.

Evidence for the involvement of the monoaminergic system in the antidepressant-like activity of methanolic extract of Bacopa monnieri in albino mice

Background: Depression is a common illness worldwide, with an estimated 121 million people affected. The efficacy of currently available drugs for treating depression often lack consistency and many of them exert undesirable side effects. This emphasises on the need for newer drugs for the treatment of major depression.Methods: The present study evaluated the antidepressant-like activity of methanolic extract of Bacopa monnieri in mouse forced swimming test (FST) and tail suspension test (TST), which are predictive models of antidepressant activity. An attempt was also made to understand the involvement of the monoaminergic system and the opioid system in Bacopas’ antidepressant activity. Albino mice were treated with vehicle, fluoxetine (20 mg/kg), or Bacopa monnieri (20, 40, 80, and 120 mg/kg) orally and evaluated in FST and TST. The actophotometer performance was also examined after different treatments. For understanding the mechanisms, different receptor antagonists were used.Results: Bacopa monnieri produced a significant reduction in the duration of immobility, with better activity at 80 mg/kg dose. Furthermore, the antidepressant-like action produced by Bacopa monnieri was abolished by the pre-treatment of mice with p-chlorophenylalanine (100 mg/kg, i.p., a serotonin synthesis inhibitor), pindolol (10 mg/kg, i.p., a β-adrenoceptor blocker/5HT1A/1B receptor antagonist, ketanserin (5 mg/kg, i.p., a 5HT2A/2B receptor antagonist), prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), and yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), but not with ondansetron (1 mg/kg, i.p., a 5HT3 receptor antagonist) and naloxone (1 mg/kg, i.p., an opioid receptor antagonist).Conclusions: These findings suggest that the antidepressant-like effect produced by Bacopa monnieri may be mediated through an interaction with the serotonergic and noradrenergic nervous system. The antidepressant doses of Bacopa monnieri had no effect on the locomotor activity of mice.

Efficacy of Standardized Extract of Bacopa monnieri (Bacognize®) on Cognitive Functions of Medical Students: A Six-Week, Randomized Placebo-Controlled Trial.

Rationale. Bacopa monnieri, popularly known as Brahmi, has been traditionally used in Ayurveda since ages for its memory enhancing properties. However, data on placebo-controlled trial of Bacopa monnieri on intellectual sample is scarce. Hence this study was planned to evaluate the effect of Bacopa monnieri on memory of medical students for six weeks. Objective. To evaluate the efficacy of Bacopa monnieri on memory of medical students with six weeks' administration. Method and Material. This was a randomized double blind placebo-controlled noncrossover, parallel trial. Sixty medical students of either gender from second year of medical school, third term, regular batch, were enrolled from Government Medical College, Nagpur, India. Baseline biochemical and memory tests were done. The participants were randomly divided in two groups to receive either 150 mg of standardized extract of Bacopa monnieri (Bacognize) or matching placebo twice daily for six weeks. All baseline investigations were repeated at the end of the trial. Students were followed up for 15 days after the intervention. Results. Statistically significant improvement was seen in the tests relating to the cognitive functions with use of Bacopa monnieri. Blood biochemistry also showed a significant increase in serum calcium levels (still within normal range).

Cognition Enhancing and Neuromodulatory Propensity of Bacopa monniera Extract Against Scopolamine Induced Cognitive Impairments in Rat Hippocampus

Cognition-enhancing activity of Bacopa monniera extract (BME) was evaluated against scopolamine-induced amnesic rats by novel object recognition test (NOR), elevated plus maze (EPM) and Morris water maze (MWM) tests. Scopolamine (2mg/kg body wt, i.p.) was used to induce amnesia in rats. Piracetam (200mg/kg body wt, i.p.) was used as positive control. BME at three different dosages (i.e., 10, 20 and 40mg/kg body wt.) improved the impairment induced by scopolamine by increasing the discrimination index of NOR and by decreasing the transfer latency of EPM and escape latency of MWM tests. Our results further elucidate that BME administration has normalized the neurotransmitters (acetylcholine, glutamate, 5-hydroxytryptamine, dopamine, 3,4 dihydroxyphenylacetic acid, norepinephrine) levels that were altered by scopolamine administration in hippocampus of rat brain. BME administration also ameliorated scopolamine effect by down-regulating AChE and up-regulating BDNF, muscarinic M1 receptor and CREB expression in brain hippocampus confirms the potent neuroprotective role and these results are in corroboration with the earlier in vitro studies. BME administration showed significant protection against scopolamine-induced toxicity by restoring the levels of antioxidant and lipid peroxidation. These results indicate that, cognition-enhancing and neuromodulatory propensity of BME is through modulating the expression of AChE, BDNF, MUS-1, CREB and also by altering the levels of neurotransmitters in hippocampus of rat brain.