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

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

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

Influence of Bacopa monnieri in suppressing the arthritis induced by MSU crystal in Wistar albino female rats: Through biochemical and histopathological approach

Gouty arthritis is caused due to the accumulation of uric acid crystals in joints which is the by-product of purinemetabolism in our body. The elevated level of uric acid in the blood is known as hyperuricemia that may resultsin deposition and inflammation of joints. This research experiment has examined the protective effect of Bacopamonnieri, an herb against the monosodium urate crystal-induced gouty arthritis in female Wistar albino rats. The ratswere divided into four groups with six rats in each group. Group-I was normal control rats, group-II rats were inducedwith monosodium urate crystal, group-III was administrated with B. monnieri in monosodium urate crystal-inducedrats, and group-IV was administrated with indomethacin in monosodium urate crystal-induced rats. The rats wereexamined for liver enzyme markers, antioxidant assays, and paw histopathology. The results of B. monnieri werecompared with that of standard drug indomethacin. The symptoms of arthritis, such as the elevation of paw volume,increased liver enzyme markers, decreased antioxidant enzymes, and histopathological changes, were found to bereversed to the normal level by the treatment with B. monnieri which is due to its anti-inflammatory properties. Asconclusion, B. monnieri has shown its anti-arthritic properties against gouty arthritis.

Bacopa monnieri extract improves novel object recognition, cell proliferation, neuroblast differentiation, brain-derived neurotrophic factor, and phosphorylation of cAMP response element-binding protein in the dentate gyrus / 한국실험동물학회지

Bacopa monnieri is a medicinal plant with a long history of use in Ayurveda, especially in the treatment of poor memory and cognitive deficits. In the present study, we hypothesized that Bacopa monnieri extract (BME) can improve memory via increased cell proliferation and neuroblast differentiation in the dentate gyrus. BME was administered to 7-week-old mice once a day for 4 weeks and a novel object recognition memory test was performed. Thereafter, the mice were euthanized followed by immunohistochemistry analysis for Ki67, doublecortin (DCX), and phosphorylated cAMP response element-binding protein (CREB), and western blot analysis of brain-derived neurotrophic factor (BDNF). BME-treated mice showed moderate increases in the exploration of new objects when compared with that of familiar objects, leading to a significant higher discrimination index compared with vehicle-treated mice. Ki67 and DCX immunohistochemistry showed a facilitation of cell proliferation and neuroblast differentiation following the administration of BME in the dentate gyrus. In addition, administration of BME significantly elevated the BDNF protein expression in the hippocampal dentate gyrus, and increased CREB phosphorylation in the dentate gyrus. These data suggest that BME improves novel object recognition by increasing the cell proliferation and neuroblast differentiation in the dentate gyrus, and this may be closely related to elevated levels of BDNF and CREB phosphorylation in the dentate gyrus.

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

OBJECTIVE: The 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. METHODS: We 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). RESULTS: Exposure 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. CONCLUSION: These 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.

Bacopa monnieri extracts prevent hydrogen peroxide-induced oxidative damage in a cellular model of neuroblastoma IMR32 cells / 中国天然药物

Neurodegenerative diseases are the consequences of imbalance between the production of oxidative stress and its nullification by cellular defense mechanisms. Hydrogen peroxide (HO), a precursor of deleterious reactive oxygen species, elicits oxidative stress, resulting in severe brain injuries. Bacopa monnieri is well known for its nerve relaxing and memory enhancing properties. The present study was designed to evaluate the protective effects of extracts from Bacopa monnieri against HO induced oxidative stress using a cellular model, neuroblastoma IMR32 cell line. The protective potential of methanolic, ethanolic, and water extracts of B. monnieri (BM-MEx, BM-EEx, and BM-WEx) was evaluated using MTT assay. Although, all the B. monnieri extracts were found to protect cells against HO-mediated stress but BM-MEx showed significantly greater protection. UPLC analysis of BM-MEx revealed various polyphenols, including quercetin, catechin, umbelliferone, and caffeic acid predominance. Further, BM-MEx was found to possess considerable greater neuroprotective potential in comparison to the standard polyphenols such as quercetin, catechin, umbelliferone, and caffeic acid. The levels of antioxidant enzymes were significantly elevated after the pretreatment of BM-MEx and quercetin. The expression levels of oxidative stress markers, such as NF200, HSP70, and mortalin, were significantly alleviated after the pretreatment of BM-MEx as shown by immunofluorescence and RT-PCR. In conclusion, the present study demonstrated the protective effects of BM-MEx, suggesting that it could be a candidate for the development of neuropathological therapeutics.

Research progress on chemical constituents from Bacopa monnieri and their pharmacological activities / 中草药

The revelant literatures about chemical constituents from the plant Bacopa monnieri and their pharmacological activities were consulted and summarized. The plant contains major chemical compounds including triterpenoids and their glycosides, flavonoids, phenylethanoid glycosides and sterols. It has the impact on central nervous system, cardiovascular system, digestive system, respiratory system and endocrine system, in addition to anti-inflammatory, analgesic, anti-oxidation, hypoglycemic, antitumor, anti-microbial and liver and kidney protection and other pharmacological activities. This paper reviewed the chemical compositions and pharmacological activities, and provided a scientific basis for further research and development of the plant.

Effect of herb-drug interactions of Bacopa monnieri Linn. (Brahmi) formulation on the pharmacokinetics of amitriptyline in rats

ABSTRACT Interactions between herbs and drugs may increase or decrease the pharmacological or toxicological effects of either component. Experimental data on the pharmacokinetic interactions between herbal products and drugs are limited. This study attempted to investigate the effect of Bacopa monnieri Linn. (Brahmi) formulation on the pharmacokinetics of amitriptyline in rats. In this study, rats were randomly divided into two groups (n = 6 each) which were served as a control (amitriptyline alone) and treatment group (amitriptyline with B. monnieri), respectively. Rats in the treatment group received B. monnieri (31 mg/kg/day) whereas the control group received normal saline by oral gavage for seven days before a single intragastric administration of 25 mg/kg amitriptyline. Plasma concentrations of amitriptyline were measured up to 24 h after its administration by a developed and validated high-performance liquid chromatography method. Pretreatment with B. monnieri produced a significant increase in the maximum plasma concentration (Cmax), area under the curve (AUC0-t) and elimination half-life (t1/2) of amitriptyline by 16.8%, 26.5%, and 15.5%, respectively, compared to amitriptyline alone. Moreover, oral clearance and volume of distribution (Vss) were decreased by 26.2% and 15.5% respectively. This study concluded that B.monnieri significantly enhanced the oral bioavailability of amitriptyline in rats.

Endophytic fungi found in association with Bacopa monnieri as potential producers of industrial enzymes and antimicrobial bioactive compounds

This study aimed to screen the endophytic fungal species of ethano-medicinal plant Bacopa monnieri (L.) Pennell for their ability to produce antimicrobial substances against Bacillus subtilis, Pseudomonas aeroginosa, Salmonella typhimurium, Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Candida albicans. Endophytes were also screened for their ability to produce amylase, cellulase, protease and lipase to evaluate their ecological role within the host plant. Twenty-six endophytes were isolated and seventeen were identified. All the isolated endophytes exhibited amylolytic activity. Lipolytic, cellulolytic, proteolytic activity was shown by 98, 28 and 31% isolates, respectively. Similarly, all the endophytes (100%) exhibited significant antimicrobial activity against K. pneumonia, while seventeen endophytes (89.5%) were active against S. aureus. Fourteen endophytes (78.9%) showed significant antimicrobial activity against B. subtilis and C. albicans. Eleven (57.8%), nine (50%), four (21%) endophytes were active against S. typhimurium, E. coli and P. aeruginosa, respectively.

Modulation of Na+/K+, Mg2+ and Ca2+ ATPase activity in different regions of rat brain during rotenone induced parkinson's disease and protective role of bacopa monnieri.

Bacopa monnieri (BM; Family: Scrophulariaceae), also referred as Brahmi or Jalbrahmi has been used for centuries in Ayurvedic system of medicine as a brain tonic, memory enhancer, revitaliser of sensory organs, anti-anxiety, cardio-tonic, diuretic, antidepressant and anticonvulsant agent, and the pharmacological actions are mainly attributed to the saponin compounds present in the alcoholic extract of the plant. The present study was carried out with a specific aim to examine the neuroprotective effect of Bacopa monnieri during Rotenone (RT) induced Parkinson’s disease (PD) with particular reference to Na+/K+, Mg2+ and Ca2+ -ATPase activities in different regions of rat brain. In the experiment conducted rats were divided into four groups of six in each group, group 1 received Saline water (1 ml/kg), group 2 received RT (2.5 mg/kg) through i.p. route administration for 60 days to induce PD. The third group received BM extract (180 mg/kg/day) for 20 days orally before induction of PD and group 4 received Levodopa (LD) (10 mg/kg/day) orally which is referred as drug control. The levels of Na+/K+, Mg2+ and Ca2+ -ATPase activities were measured. Na+/K+, Mg2+ and Ca2+ -ATPase activities were significantly depleted in different brain regions of rat during RT induced PD when compared to control rats. Treatment with BM and LD caused significant elevation in the activity levels of Na+/K+, Mg2+ and Ca2+ -ATPase in different brain regions of rats when compared to induced PD rats. Our results suggest the ability of BM extract to modulate Na+/K+, Mg2+ and Ca2+ - ATPase activities in different brain regions of RT induced rodent model of PD and thus offers effective management in the treatment of PD.

Add-on effect of Brahmi in the management of schizophrenia.

Brahmi (Bacopa monnieri), an Ayurvedic herb has primarily been used to enhance cognitive ability, memory and learning skills. We present a case study of schizophrenia in which add-on Brahmi extracts 500 mg/day for a period of one month resulted in reduction in psychopathology without any treatment-emergent adverse effect. Although preliminary, our case study suggests therapeutic efficacy of add-on Brahmi in schizophrenia, thus opening up a new dimension of its role in alternative medicines.

Development of Sequence Characterized Amplified Region (SCAR) Marker for the Authentication of Bacopa monnieri (L.) Wettst.

Aims: To develop Sequence Characterized Amplified Region (SCAR) marker for identification of Bacopa monnieri (L.) Wettst. Study design: Molecular biology tools for authentic identification of Bacopa monnieri. Methodology: RAPD-based SCAR marker was developed to identify Bacopa monnieri from its adulterant candidates namely Centella asiatica, Eclipta alba and Malva rotundifolia. 50 random primers were used for initial screening of different accessions of Bacopa monnieri, Eclipta alba and Malva rotundifolia. A putative 589 bp marker specific to Bacopa monnieri was identified using RAPD technique. This RAPD-amplicon was then sequenced and cloned. Based on the information of cloned sequences a pair of SCAR primers was designed. SCAR primers were then used for authentication of DNA samples of Bacopa monnieri and its adulterants. Market samples of Bacopa monnieri and Centella asiatica collected under the name of Brahmi was put to test with these primers. Results: Out of 50 random primers, only 14 primers were able to amplify the above plants. A 589 bp polymorphic band obtained with OPAA-3 primer which was specific to Bacopa monnieri accessions and not found in other adulterant candidates was selected. This band was eluted, cloned and further sequenced. A pair of SCAR primers (Bac F & Bac R) between 406 bp of 589 bp sequence of RAPD amplicon was designed. A single, bright, distinct band was obtained in Bacopa monnieri and not in the adulterants. Further validation was also done in the market samples. Conclusion: In essence, the study was to develop a RAPD-based SCAR marker for authentication of Bacopa monnieri. The SCAR marker was found to be useful for preventing the adulteration of other plants in Brahmi and also for screening of crude drug samples intended for export and domestic uses.

Evaluation of Analgesic, Antidiarrhoeal and Cytotoxic Activities of Ethanolic Extract of Bacopa monnieri (L).

Aims: The crude ethanolic leaf extract of Bacopa monnieri (L) Penn. (family: Scrophulariaceae) was evaluated for its possible phytochemical nature (group determination of plant constituent) and selected pharmacological activities (analgesic, antidiarrhoeal and cytotoxic activity) growing in Bangladesh. Methodology: The antinociceptive activity was evaluated by acetic acid induced writhing model, antidiarrhoeal activity by castor oil induced diarrheal method and cytotoxicity by brine shrimp lethality bioassay. Results: Phytochemical analysis of the ethanolic extract of B. monnieri indicated the presence of reducing sugar, tannins, steroid, alkaloid, saponin and gum types of compounds. The ethanolic extract of B. monnieri has effect on acetic acid induced writhing in mice. At the dose of 250 mg/kg and 500 mg/kg of body weight, the extract produced 36.69% and 59.17% writhing inhibition in test animals respectively. The results were statistically significant (p <0.01 and p <0.001) and was comparable to the standard drug Diclofenac Na, which showed 72.78% at a dose of 25 mg/kg weight. The ethanolic extract of B. monnieri has effect on castor oil induced diarrhea in mice. The result showed that the extract decreased the mean number of defecation which were 35.42 % and 47.92 % (p <0.001) at the doses of 250mg/kg and 500mg/kg respectively. The latent period for the extract treated group was increased (p <0.01) as compared to control group. The ethanolic of extract of B. monnieri showed significant toxicity to the brine shrimp nauplii. The concentrations of crude extract for 50% mortality (LC50) and 90% mortality (LC90) were 40 μg/mL and 150 μg/mL respectively. Conclusion: Therefore, the obtained results tend to suggest the antinociceptive, antidiarrhoeal and cytotoxic activities of crude ethanolic extract of Bacopa monnieri leaves and thus provide the scientific basis for the traditional uses of this plant part as a remedy for pain and diarrhoea.

Antibacterial efficacy of Bacopa monnieri leaf extracts against pathogenic bacteria.

Background: Bacopa monnieri (Linn) Pennell (Scrophulariaceae) is widely distributed in tropical regions of Asia, and used in the treatment of cough or as an antiseptic. The traditional use of this plant suggests its possible antibacterial properties, but its efficacy has not been examined yet. Objective: Evaluate the antibacterial efficacy against pathogenic bacteria using the disk diffusion method. Materials and methods: Five different concentrations (500 μg, 1, 2, 5, 10, and 15 mg/mL) of crude leaf extracts of Bacopa monnieri (L.) Pennell were tested for antibacterial efficacy against seven Gram-positive and 11 Gramnegative bacteria. The sensitivity of plant fractions was tested using the disk diffusion method. Results: Maximum activity was revealed by ethyl acetate and methanol extracts, followed by aqueous, benzene, and petrol extracts. Phyto-chemical analysis of the plant leaf showed the presence of alkaloids, flavonoids, and saponins. Conclusion: This plant may be effective for treatment of different pathogenic diseases.

Prophylactic treatment with Bacopa monnieri leaf powder mitigates paraquat- induced oxidative perturbations and lethality in Drosophila melanogaster.

Environmental exposure to the oxidant-producing herbicide, paraquat (PQ) (1, 1’-dimethyl-4, 4’-bipyridinium dichloride) has long been implicated as a risk factor in Parkinson’s disease (PD). PQ-induced oxidative stress has been exploited as a model to screen putative neuroprotective compounds employing Drosophila. In the present study, we investigated the prophylactic efficacy of Bacopa monnieri (BM) against PQ-induced oxidative stress, mitochondrial dysfunctions and lethality. Exposure of adult male flies (Oregon K) to PQ alone (40 mM in 5% sucrose) resulted in 50% mortality at 48 h. Prophylaxis (7 days) with BM extract (0.1%) offered significant protection (40%) against PQ-induced mortality. Further, oxidative impairments and mitochondrial dysfunctions were monitored among Drosophila exposed to PQ (20, 40 mM) for 24 h. Significant induction of oxidative stress was observed in terms of enhanced malondialdehyde and hydroperoxide levels, and elevated activities of antioxidant enzymes (catalase and SOD). Mitochondrial dysfunctions included of significant reduction in the activities of succinate dehydrogenase (23%), complex I-III (26%), and complex II-III (30%) enzymes. Interestingly, prophylaxis with BM extract prevented the oxidative stress induction by PQ and restored the activity of ETC complexes, suggesting clearly its specific effect on the mitochondria. While the precise mechanism of action of BM needs further investigations, it may be related to its ability to enhance antioxidant defences and thus mitigate PQ-induced oxidative stress in Drosophila.

Assessment of the effect of Bacopa monnieri (L.) Wettst. extract on the labeling of blood elements with technetium-99m and on the morphology of red blood cells / Avaliação do efeito do extrato de Bacopa monnieri (L.) Wettst. na marcação de elementos sanguíneos com tecnécio-99m e na morfologia de células vermelhas do sangue

Bacopa monnieri (L.) Wettst. (BM), a traditional Ayurvedic medicine, used for centuries as a memory enhancing, anti-inflammatory, antipyretic, sedative and antiepileptic agent. BM extract have been extensively investigated by several authors for their neuropharmacological effects. In nuclear medicine, red blood cells (RBC) labeled with technetium-99m (99mTc) have several clinical applications. However, data have demonstrated that synthetic or natural drugs could modify the labeling of RBC with 99mTc. As Bacopa monnieri is extensively used in medicine, we evaluated its influence on the labeling of RBC and plasma proteins using technetium-99m (99mTc). This labeling procedure depends on a reducing agent and usually stannous chloride is used. Blood was incubated with BM extracts. Stannous chloride solution and 99mTc were added. Blood was centrifuged and plasma (P) and blood cells (BC) were isolated. Samples of P or BC were also precipitated, centrifuged and insoluble fraction (IF) and soluble fraction (SF) were separated. The percentage of radioactivity ( percentATI) in BC, IF-BC and IF-P were calculated. The percentATI significantly decreased on BC from 95.53±0.45 to 35.41±0.44, on IF-P from 80.20±1.16 to 7.40±0.69 and on IF-BC from 73.31±1.76 to 21.26±1.40. The morphology study of RBC revealed important morphological alterations due to treatment with BM extracts. We suggest that the BM extract effect could be explained by an inhibition of the stannous and pertechnetate ions or oxidation of the stannous ion or by damages induced in the plasma membrane.

Bacopa monnieri (L.) Wettst. (BM), uma planta tradicional da medicina ayurvédica, é usada por séculos para problemas de memória, antiinflamatória, antitérmica, sedativa e como agente anti-epiléptico. O extrato BM têm sido extensivamente investigada por diversos autores por seus efeitos neurofarmacológicas. Na medicina nuclear, os glóbulos vermelhos (RBC) marcados com tecnécio-99m (99mTc) tem várias aplicações clínicas. Entretanto, os dados demonstraram que drogas sintéticas ou naturais podem modificar a marcação de hemácias com 99mTc. Como Bacopa monnieri é amplamente utilizado em medicina, foi avaliada a sua influência na marcação de hemácias e proteínas plasmáticas com tecnécio-99m (99mTc). Este procedimento de marcação depende de um agente redutor e normalmente o cloreto estanoso é usado. Sangue foi incubado com os extratos BM. Solução de cloreto estanoso e 99mTc foram adicionados. O sangue foi centrifugado e o plasma (P) e células sangüíneas (CS) foram isolados. Amostras de P ou BC também foram precipitadas, centrifugadas e fração insolúvel (FI) e fração solúvel (FS) foram separadas. A porcentagem de radioatividade ( por centoATI) em BC, IF-BC e SE-P foram calculados. A As por cento ATI diminuiu significativamente em BC de 95,53±0,45-35,41±0,44, no IF-P de 80,20±1,16 para 7,40±0,69 e no IF-BC em 73,31±1,76-21,26±1,40. O estudo da morfologia de hemácias revelou alterações morfológicas importantes devido a tratamentos com extratos BM. Sugere-se que a ação do extrato BM poderia ser explicada por uma inibição dos íons estanoso e pertecnetato ou oxidação do íon estanoso ou por danos na membrana plasmática.

Effect of bavistin on in vitro plant conversion from encapsulated uninodal microcuttings of micropropagated Bacopa monnieri (L.) - An ayurvedic herb.

A reliable and reproducible protocol for contamination free plant recovery system from alginated encapsulated uninodal microcuttings of micropropagated Bacopa monnieri L.have been developed after storage at 18oC for 45 days. Node segments excised from freshly micropropagated plants were encapsulated as single explant beads with 3.0 % sodium alginate and 80 mM CaCl2 2 H2O. To find out the optimal concentration of fungicide bavistin for efficient plant recovery, different concentrations of bavistin (1.0 - 15 mg l-1) were incorporated in to the encapsulation medium. 3.0 mg l-1 bavistin showed no reduction in plant conversion and generated maximum number of shoots (45.6 ± 1.69) at high frequency with out any contamination after storage up to 45 days at 18oC. At high concentrations (13 and 15 mg l-1), rupturing of calcium alginate coats after 8 - 9 days and gradual decline in the number of shoots indicates the toxic effect of bavistin on plant conversion. Encapsulated node cuttings stored up to 45 days regenerated shoots (5.2) and multiple shoots (45.6) in MS basal and hormone medium respectively. Maximum shoot length (8.2 ± 0.37 cm) was observed from encapsulsted node cuttings incorporated with 3.0 mg l-1 bavistin on MS basal medium. 90 % of the recovered plantlets were hardened off and successfully established in soil.