Bacopa monnieri (L.) Pennell, commonly known as Brahmi is an important medicinal plant traditionally used as memory enhancer and antiepileptic agent.
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Aged people are more prone to developing neurodegenerative and infectious diseases, autoimmune disorders, and cancer due to impairment of neuroendocrine-immune functions. Neuronal degeneration and immunosuppression aided by increased generation of reactive oxygen species combined with loss of antioxidant enzyme activities promote the aging process. Bacopa monnieri (brahmi), an Ayurvedic herb, and donepezil, a reversible acetylcholinesterase inhibitor, have been used to reverse cognitive dysfunctions in several neurodegenerative diseases. The aim of this study was to investigate the effects of in vitro incubation of lymphocytes from spleens of young (3-month-old), early middle-aged (8- to 9-month-old), and old (18-month-old) F344 rats with brahmi (0.001%, 0.01%, 0.05%, 0.1%, and 1%) and donepezil (5, 10, 25, 50, and 100 μg/ml) on Concanavalin (Con A)-induced proliferation of T lymphocytes and cytokine production, and the activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST)]. In addition, the effects of these compounds on the expression of intracellular signaling pathway markers (ERK, p-ERK, CREB, p-CREB, Akt and p-Akt), nitric oxide (NO) production, and the extent of lipid peroxidation were measured in the splenocytes. Age-related decline in Con A-induced proliferation of T lymphocytes was not reversed by treatment with brahmi and donepezil but donepezil alone further reduced the lymphocyte proliferation in young rats. Lower doses of brahmi treatment reversed the age-related decrease in Con A-induced IL-2 and IFN-γ production by the splenocytes while their production by splenocytes was suppressed by treatment with donepezil in the young and early middle-aged rats. An age-associated decline in the activities of SOD, CAT, GPx, and GST was evident in the lymphocytes of spleen. Brahmi enhanced CAT activity of lymphocytes in all the age groups while donepezil increased SOD activity in old rats. Both brahmi and donepezil increased GPx and GST activities in a dose-dependent manner in the lymphocytes of all age groups. There was an age-related decline in NO production and increase in the extent of lipid peroxidation in the splenocytes. Brahmi and donepezil increased NO production in the lymphocytes of early middle-aged and old rats. Brahmi reversed the age-related increase in lipid peroxidation in the splenocytes of both early-middle-aged and old rats while donepezil suppressed lipid peroxidation only in the splenocytes of old rats. The expressions of p-ERK1/2 and p-CREB in the splenocytes were elevated following treatment with brahmi and donepezil in the early middle-aged and old rats while age-related decline in p-Akt expression was reversed by treatment of lymphocytes with brahmi alone in early-middle-aged and old rats. Taken together, these results suggest that both brahmi and donepezil exert distinct age-related effects on the cell-mediated immune responses through selective modulation of antioxidant enzyme activities and intracellular targets that may influence the therapeutic efficacy of these drugs in neurodegenerative diseases.
In this study there were 55 cases of MRCT, consisting of 18 Ewing's sarcoma (EW), 10 neuroblastoma (NB), 5 non-Hodgkin's lymphoma (NHL), 6 rhabdomyosarcoma (RMS), 4 peripheral neuroectodermal tumor (PNET), 8 Wilm's tumor (WT), 2 retinoblastoma (RB) and 2 undifferentiated round cell tumor (URCT). A Leica image cytometer with Quantimet 600 software (Leica, Cambridge, U.K) was used to measure nuclear area, nuclear diameter, nuclear perimeter, nuclear convex perimeter (CP), nuclear roundness and nuclear convex area on hematoxylin and eosin-stained cytologic smears. At least 100 cells were studied in each case.
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Pancreatic adenocarcinoma is extremely rare in childhood. We report a case of metastatic pancreatic adenocarcinoma in a 13-year-old boy, revealed by jaundice.
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Patients included in this study were seriously poisoned because all developed muscarinic and nicotinic syndromes. Deep coma and respiratory failure requiring mechanical ventilation were noted in all methomyl-poisoned patients and in only 3 dichlorvos-poisoned patients. Acute pancreatitis occurred 24 to 72 hours after dosing and was characterized by painless abdominal paralytic ileus and vomiting. Clinical features and laboratory examinations were normalized by the fifth day under medical treatment. Complications such as intrapancreatic fluid collection occurred later between days 10 and 20 in 1 methomyl-poisoned patient who required secondary surgical drainage and in 1 dichlorvos-poisoned patient who was treated conservatively. Outcome was favorable in all cases.
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Nine studies met the inclusion criteria using 518 subjects. Overall quality of all included trials was low risk of bias and quality of reported information was high. Meta-analysis of 437 eligible subjects showed improved cognition by shortened Trail B test (-17.9 ms; 95% CI -24.6 to -11.2; p<0.001) and decreased choice reaction time (10.6 ms; 95% CI -12.1 to -9.2; p<0.001).
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Bacopa monniera Wettst. (syn. Herpestis monniera L.; Hindi - Brahmi) is classified in Ayurveda, the classical Indian system of medicine, as Medhyarasayana, a group of plant derived drugs used as nervine tonics to promote mental health and improve memory and intellect. Earlier experimental and clinical studies have demonstrated the memory-promoting action of the plant extracts and that of its active saponins, bacoside A and B. The present study was designed to investigate the anxiolytic activity of a standardized extract (bacoside A content 25.5 ± 0.8%) of B. monniera (BM), since the plant is used in Ayurveda in clinical conditions resembling the modern concept of anxiety disorders. The animal models used have been extensively validated as experimental models of anxiety and included the open-field, elevated plusmaze, social interaction and novelty-suppressed feeding latency tests in rats. BM was used at doses of 5, 10 and 20 mg/kg, p.o. and the results were compared with those elicited by lorazepam, a well known benzodiazepine anxiolytic, used at a dose of 0.5 mg/kg, i.p. BM produced a dose-related anxiolytic activity, qualitatively comparable to that of lorazepam, in all the test parameters. However, statistically significant results were elicited usually by the higher two doses of BM. BM did not produce any significant motor deficit, at the doses used, as was evidenced by using the rota-rod test. The findings correlate with the clinical use of the plant in Ayurveda. The advantage of B. monniera over the widely used benzodiazepine anxiolytics lies in the fact that it promotes cognition unlike the amnesic action of the latter.
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The purpose of this project was to introduce first-year medical students to electronic resources that are best suited for different types of background questions. Specific questions from a case study were presented, and the students generalized them into a "type" of question. They then identified the best e-resources for that type of question. This is their first introduction to the lifelong learning competency in the Indiana University School of Medicine competency-based curriculum.
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The present study was designed to examine the binding and signalling effects of single base and CpG dinucleotide phosphodiester (Po) oligodeoxynucleotides (ODN) on the human natural killer (NK)-like cell line (YT-INDY). Single base Po ODN composed of 20-mers of guanosine (dG20), adenosine (dA20), cytosine (dC20) or thymidine (dT20) as well as 'conventional' Po CpG ODN were examined for their ability to bind and activate YT-INDY cells. Binding by dG20 and CpG ODN to YT-INDY cells was saturable and specific. dG20 binding was competitively inhibited by homologous dG20 and heterologous CpG ODN but not by dC20 and dA20. Two different YT-INDY membrane proteins (18 and 29 kDa) were identified by ligand (Southwestern) blotting with biotinylated dG20 and CpG. The specificity of the ODN-binding protein(s) was further confirmed by ODN depletion experiments using a teleost recombinant protein orthologue [nonspecific cytotoxic cells (NCC) cationic antimicrobial protein-1 (ncamp-1)] known to bind CpG and dG20. Cell proliferation and activation studies showed that dG20 and CpG treatment of YT-INDY cells induced cellular DNA synthesis (i.e. G1 to S-phase conversion). This signalling function was accompanied in dG20-treated cells by proliferation 10 h posttreatment. Both dG20 and CpG ODN binding induced a calcium flux in YT-INDY cells within seconds of treatment. These experiments demonstrated that Po single base dG20 and CpG ODN bind to a (potential) new class of cell-surface proteins that mediate the activation of YT-INDY cells.
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Cognitive deficit observed in rats receiving PCP was mediated by NMDAR1 up-regulation in CA2/3 and DG Interestingly, receiving Brahmi before PCP administration can restore this cognitive deficit by decreasingNMDAR1 in these brain areas. Therefore, Brahmi could be a novel neuroprotective agentfor the prevention ofcognitive deficit in schizophrenia.
Bacopa monnieri (L.), popularly known as Brahmi, is a revered Ayurvedic medicinal plant used as nerve tonic since time immemorial. The present study aims to investigate the neuroprotective effect of bacosides, the active saponins of Bacopa monnieri (L.) against age associated neurodegeneration and its impact over the prevention of Senile Dementia of Alzheimer's Type (SDAT). The optimum dose of bacosides with no adverse effect was selected by screening its dose dependant activity on ageing biomarker lipofuscin and SDAT biomarker neurotransmitter acetylcholine in the aged female Wistar rat brain. The selected therapeutic dose of bacosides (200 mg/kg) was orally administered for 3 months in middle aged and aged rats and further investigated for its protective action against age associated alterations in neurotransmission system, behavioral paradigms, hippocampal neuronal loss and oxidative stress markers. The results of the present study suggest that bacosides may act as a potential therapeutic intervention in forestalling the deleterious effects of ageing and preventing the age associated pathologies like SDAT.
The results in P mice thus suggest that Brahmi treatment causes reversible suppression of spermatogenesis and fertility, without producing apparent toxic effects.
A study is reported on the effects of Brahmi (Bacopa monniera) on human memory. Seventy-six adults aged between 40 and 65 years took part in a double-blind randomized, placebo control study in which various memory functions were tested and levels of anxiety measured. There were three testing sessions: one prior to the trial, one after three months on the trial, and one six weeks after the completion of the trial. The results show a significant effect of the Brahmi on a test for the retention of new information. Follow-up tests showed that the rate of learning was unaffected, suggesting that Brahmi decreases the rate of forgetting of newly acquired information. Tasks assessing attention, verbal and visual short-term memory and the retrieval of pre-experimental knowledge were unaffected. Questionnaire measures of everyday memory function and anxiety levels were also unaffected.
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Nordihydroguaiaretic acid (NDGA), quercetin, eicosatetraynoic acid (ETYA), phenidone, and esculetin, agents known to inhibit cellular lipoxygenase (LO) activity, also inhibit human natural killer cell-mediated cytotoxicity (NK-CMC) of K562 tumor target cells (TC) in a dose-dependent fashion. Kinetic analysis demonstrated that LO inhibitors blocked an early event in the activation of the lytic mechanism but did not impair conjugate formation. LO inhibitors also did not affect subsequent chromium release, indicating that their site of inhibition was the NK cell and not the TC. The lipoxygenase products 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and leukotriene-B4 significantly enhanced NK activity, with 5-HPETE being the more effective. Other LO products tested included 15-HPETE and the hydroxy derivatives 15-hydroxyeicosatetraenoic acid (15-HETE) and 5-HETE. These LO metabolites were either without effect on NK-CMC or inhibitory, depending upon the concentration. Additionally, we examined the ability of 5-HPETE to circumvent the effects of LO inhibitors and found that, in the presence of NDGA, ETYA or quercetin, 5-HPETE significantly (p less than 0.001) restored lytic activity. Inhibitors of LTB4 and LTC4 synthesis, diethylcarbamazine and U-60,257 respectively, produced no inhibition of NK activity. In fact, U-60,257 significantly (p less than 0.05) enhanced NK-CMC. Previous studies in our laboratory, with a new technique which allows for the separation of NK cells from K562 cells, have shown that K562-treated effector cells are greater than 90% inactivated when retested against fresh K562 in the standard chromium release assay. Lipids were extracted from K562-treated, Percoll-purified LGL and evaluated by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). No significant increases were seen in the arachidonic acid-derived LO products evaluated. Thus, our studies indicate that lipoxygenation may be required in the activation of NK-CMC, possibly as a means to generate oxygen radicals which have been previously implicated in NK-CMC.
Acute pancreatitis subsequent to methomyl (Lannate) had not been reported until 2005, when Markides published the first case. In our study, we report for the first time 2 cases of acute pancreatitis complicating voluntary methomyl intoxication and compare them with 5 cases of pancreatitis subsequent to dichlorvos poisoning admitted to our toxicological unit during the same period, between July 2001 and June 2003.