Effect of Bacopa monniera Extract on Methylmercury-Induced Behavioral and Histopathological Changes in Rats

Methylmercury (MeHg) is a well-recognized environmental contaminant with established health risk to human beings by fish and marine mammal consumption. Bacopa monniera (BM) is a perennial herb and is used as a nerve tonic in Ayurveda, a traditional medicine system in India. This study was aimed to evaluate the effect of B. monniera extract (BME) on MeHg-induced toxicity in rat cerebellum. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with BME (40 mg/kg, orally) 1 h prior to the administration of MeHg for 21 days. After treatment period, MeHg exposure significantly decreases the body weight and also caused the following behavioral changes. Decrease tail flick response, longer immobility time, significant decrease in motor activity, and spatial short-term memory. BME pretreatment reverted the behavioral changes to normal. MeHg exposure decreases the DNA and RNA content in cerebellum and also caused some pathological changes in cerebellum. Pretreatment with BME restored all the changes to near normal. These findings suggest that BME has a potent efficacy to alleviate MeHg-induced toxicity in rat cerebellum.     

In vitro evaluation of Bacopa monniera on anti-Helicobacter pylori activity and accumulation of prostaglandins.

Bacopa monniera is an Indian tratidional medicine widely used to improve intellectual functions. Earlier, we had reported the prophylactic and curative effects of standardized extract of Bacopa monniera (BME) in various gastric ulcer models. The effect was due to augmentation of the defensive mucosal factors like increase in mucin secretion, life span of mucosal cells and gastric antioxidant effect rather than on the offensive acid-pepsin secretion. The present study includes evaluation of standardized BME (bacoside A content--35.5 +/- 0.9) on other contributing factors towards ulcerogenesis. BME in the dose of 1000 microg/ml showed anti-Helicobacter pylori activity in vitrol and in the dose of 10 microg/ml increased in vitro of prostanoids (PGE and PGI2) in human colonic mucosal incubates. It may be concluded that these factors may contribute to antiulcerogenic activity of BME.     

Prophylactic and curative effects of Bacopa monniera in gastric ulcer models

Bacopa monniera Wettst. (BM, syn. Herpestis monniera L; Scrophulariaceae), is an Ayurvedic drug used as a rasayana. Its fresh juice was earlier reported to have significant antiulcerogenic activity. In continuation, methanolic extract of BM (BME) standardized to bacoside-A content (percentage-38.0 ± 0.9), when given in the dose of 10–50 mg/kg, twice daily for 5 days, showed dose-dependent anti-ulcerogenic on various gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. BME in the dose of 20 mg/kg, given for 10 days, twice daily showed healing effects against 50% acetic acid-induced gastric ulcers. Further work was done to investigate the possible mechanisms of its action by studying its effect on various mucosal offensive acid-pepsin secretion and defensive factors like mucin secretion, mucosal cell shedding, cell proliferation and antioxidant activity in rats. BME 20 mg/kg showed no effect on acid-pepsin secretion, increased mucin secretion, while it decreased cell shedding with no effect on cell proliferation. BME showed significant antioxidant effect per se and in stressed animals. Thus, the gastric prophylactic and curative effects of BME may be due to its predominant effect on mucosal defensive factors.     

Effect of Grape Seed Proanthocyanidin Extracts on Methylmercury-Induced Neurotoxicity in Rats

As a highly toxic environmental pollutant, methylmercury (MeHg) can cause neurotoxicity in animals and humans. Considering the antioxidant property of grape seed proanthocyanidin extracts (GSPE), this study was aimed to evaluate the effect of GSPE on MeHg-induced neurotoxicity in rats. Rats were exposed to MeHg by intraperitoneal injection (4, 12 μmol/kg, respectively) and GSPE was administered by gavage (250 mg/kg) 2 h later. After a 4-week treatment, phosphate-activated glutaminase, glutamine synthetase, glutathione peroxidase and superoxide dismutase activities, glutamate, glutamine, malondialdehyde and glutathione contents in cerebral cortex were measured. Reactive oxygen species (ROS) and apoptosis were also estimated in cells. The results showed that the MeHg-induced neurotoxicity was significantly attenuated. GSPE significantly decreased the production of ROS, counteracted oxidative damage and increased the antioxidants and antioxidant enzymes activities in rats prior to MeHg exposure. Moreover, the effects on the rate of apoptotic cells and the disturbance of glutamate homeostasis were correspondingly modulated. These observations highlighted the potential of GSPE in offering protection against MeHg-induced neurotoxicity.     

Effect of Bacopa monniera on liver and kidney toxicity in chronic use of opioids

In the present study, we investigated the protective effect of Bacopa monniera, an indigenous Ayurvedic medicinal plant in India, against morphine-induced liver and kidney toxicity in rats. Morphine intoxicated rats received 10-160 mg/kg body weight of morphine hydrochloride intraperitoneally for 21 days. Bacopa monniera Extract (BME) pretreated rats were administered with BME (40 mg/kg) orally once a day 2 h before the injection of morphine for 21 days. Pretreatment with BME has shown to possess a significant protective effect against morphine-induced liver and kidney functions in terms of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, lactate dehydrogenases and gamma-glutamyl transferase activities and urea, creatinine and uric acid level respectively. Histopathological changes of liver and kidney were also in accordance with the biochemical findings. The results of this study indicate that Bacopa monniera extract exerted a protection against morphine-induced liver and kidney toxicity.     

<Emphasis Type="Italic">Bacopa monnieri</Emphasis> Extract Offsets Rotenone-Induced Cytotoxicity in Dopaminergic Cells and Oxidative Impairments in Mice Brain

Bacopa monnieri (BM), an ayurvedic medicinal herb is widely known for its memory enhancing ability and improvement of brain function. In this study, we tested the hypothesis that BM extract (BME) could offset neurotoxicant-induced oxidative dysfunctions in developing brain in a rotenone (ROT) mouse model. Pretreatment of dopaminergic (N27 cell lines) cells with BME exhibited significant cytoprotective effect as evidenced by the attenuation of ROT-induced oxidative stress and cell death. Further, the neuroprotective efficacy of BME was assessed in prepubertal mice administered ROT (i.p. 1.0 mg/kg b.w./day) for 7 days. BME treatment significantly offset ROT-induced oxidative damage in striatum (St) and other brain regions as evident by the normalized levels of oxidative markers (malondialdehyde, ROS levels, and hydroperoxides) and restoration of depleted GSH levels. Further, BME effectively normalized the protein carbonyl content in all brain regions suggesting its ability to prevent protein oxidation. Furthermore, BME treatment restored the activity levels of cytosolic antioxidant enzymes, neurotransmitter function, and dopamine levels in St. Based on our findings, we hypothesize that the neuroprotective effects of BM extract may be at least in part related to its ability to enhance reduced glutathione and antioxidant defenses in brain regions. It is suggested that BM may be effectively exploited as a prophylactic/therapeutic adjuvant for neurodegenerative disorders involving oxidative stress.     

Pretreatment with Bacopa monnieri extract offsets 3-nitropropionic acid induced mitochondrial oxidative stress and dysfunctions in the striatum of prepubertal mouse brain

The present investigation was designed to determine the efficacy of Bacopa monnieri (Brahmi; BM) to offset 3-nitropropionic acid (3-NPA) induced oxidative stress and mitochondrial dysfunction in dopaminergic (N27) cells and prepubertal mouse brain. Pretreatment of N27 cells with BM ethanolic extract (BME) significantly attenuated 3-NPA-induced cytotoxicity. Further, we determined the degree of oxidative stress induction, redox status, enzymic antioxidants, and protein oxidation in the striatal mitochondria of mice given BME prophylaxis followed by 3-NPA challenge. While 3-NPA-induced marked oxidative stress in the mitochondria of the striatum, BME prophylaxis markedly prevented 3-NPA-induced oxidative dysfunctions and depletion of reduced glutathione and thiol levels. The activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase, thioredoxin reductase), Na(+),K(+)-ATPase, and citric acid cycle enzymes in the striatum discernible among 3-NPA mice were significantly restored with BME prophylaxis. Interestingly, BME offered protection against 3-NPA-induced mitochondrial dysfunctions as evidenced by the restoration of the activities of ETC enzymes (NADH:ubiquinone oxidoreductase, NADH:cytochrome c reductase, succinate-ubiquinone oxidoreductase, and cytochrome c oxidase) and mitochondrial viability. We hypothesize that the neuroprotective effects of BME may be wholly or in part related to its propensity to scavenge free radicals, maintain redox status, and upregulate antioxidant machinery in striatal mitochondria.     

Antidepressant activity of standardized extract of Bacopa monniera in experimental models of depression in rats.

Bacopa monniera Wettst. (syn. Herpestis monniera L.; Scrophulariaceae) is a commonly used Ayurvedic drug for mental disorders. The standardized extract was reported earlier to have significant anti-oxidant effect, anxiolytic activity and improve memory retention in Alzheimer's disease. Presently, the standardized methanolic extract of Bacopa monniera (bacoside A - 38.0+/-0.9) was investigated for potential antidepressant activity in rodent models of depression. The effect was compared with the standard antidepressant drug imipramine (15 mg/kg, ip). The extract when given in the dose of 20 and 40 mg/kg, orally once daily for 5 days was found to have significant antidepressant activity in forced swim and learned helplessness models of depression and was comparable to that of imipramine.     

Participation of microRNA 124-CREB pathway: a parallel memory enhancing mechanism of standardised extract of Bacopa monniera (BESEB CDRI-08)

Bacosides, the effective component of standardised leaf extract of Bacopa monniera (BESEB CDRI-08) has been reported to have memory enhancing effect. Our previous reports suggested that BESEB CDRI-08 (BME) improves memory in postnatal rats by enhancing serotonin [5-hydroxytryptamine (5-HT)] metabolism, its transportation and subsequently activates 5-HT(3A) receptor during hippocampus-dependent learning. In this study, we examine whether the up-regulated 5-HT(3A) receptor activity by BME modulate microRNA 124-CREB pathway to enhance synaptic plasticity. Wistar rat pups received single dose of vehicle solution (0.5?% gum acacia?+?0.9?% saline)/BME (80?mg/kg)/mCPBG (10?mg/kg)/BME?+?mCPBG during the postnatal days (PND) 15-29. On PND 30, individuals were trained at brightness discrimination task and 24?h later, they were tested on the task. The BME treated group exhibited significantly lower percentage of errors during retention than acquisition. In addition, pre-miR-124 expression in hippocampus was significantly down-regulated in the BME and mCPBG?+?BME treated groups combined with a significant increase in the plasticity related genes, cAMP response element-binding protein, its phosphorylation and postsynaptic density protein 95. Our results suggest that this may be one of the mechanisms of bacosides present in BME for the memory enhancement.     

Prophylactic and curative effects of Bacopa monniera in gastric ulcer models.

Bacopa monniera Wettst. (BM, syn. Herpestis monniera L; Scrophulariaceae), is an Ayurvedic drug used as a rasayana. Its fresh juice was earlier reported to have significant antiulcerogenic activity. In continuation, methanolic extract of BM (BME) standardized to bacoside-A content (percentage-38.0 ± 0.9), when given in the dose of 10–50 mg/kg, twice daily for 5 days, showed dose-dependent anti-ulcerogenic on various gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. BME in the dose of 20 mg/kg, given for 10 days, twice daily showed healing effects against 50% acetic acid-induced gastric ulcers. Further work was done to investigate the possible mechanisms of its action by studying its effect on various mucosal offensive acid-pepsin secretion and defensive factors like mucin secretion, mucosal cell shedding, cell proliferation and antioxidant activity in rats. BME 20 mg/kg showed no effect on acid-pepsin secretion, increased mucin secretion, while it decreased cell shedding with no effect on cell proliferation. BME showed significant antioxidant effect per se and in stressed animals. Thus, the gastric prophylactic and curative effects of BME may be due to its predominant effect on mucosal defensive factors.     

Excess Manganese-Induced Apoptosis in Chicken Cerebrums and Embryonic Neurocytes

Methyl mercury (MeHg) is a developmental neurotoxin that causes irreversible cognitive damage in offspring of gestationally exposed mothers. Currently, no preventive drugs are established against MeHg developmental neurotoxicity. The neuroprotective effect of gestational administration of a flavanoid against in utero toxicity of MeHg is not explored much. Hence, the present study validated the effect of a bioactive flavanoid, fisetin, on MeHg developmental neurotoxicity outcomes in rat offspring at postnatal weaning age. Pregnant Wistar rats were simultaneously given MeHg (1.5 mg/kg b.w.) and two doses of fisetin (10 and 50 mg/kg b.w. in two separate groups) orally from gestational day (GD) 5 till parturition. Accordingly, after parturition, on postnatal day (PND) 24, weaning F₁ generation rats were studied for motor and cognitive behavioural changes. Biochemical and histopathological changes were also studied in the cerebral cortex, cerebellum and hippocampus on PND 25. Administration of fisetin during pregnancy prevented behavioural impairment due to transplacental MeHg exposure in weaning rats. Fisetin decreased the levels of oxidative stress markers, increased enzymatic and non-enzymatic antioxidant levels and increased the activity of membrane-bound ATPases and cholinergic function in F₁ generation rats. In light microscopic studies, fisetin treatment protected the specific offspring brain regions from significant morphological aberrations. Between the two doses of fisetin studied, 10 mg/kg b.w. was found to be more satisfactory and effective than 50 mg/kg b.w. The present study shows that intake of fisetin during pregnancy in rats ameliorated in utero MeHg exposure-induced neurotoxicity outcomes in postnatal weaning F₁ generation rats.     

Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats

Free radicals mediated oxidative stress has been implicated in the pathogenesis of smoking-related diseases and antioxidant nutrients are reported to prevent the oxidative damage induced by smoking. Therefore, the present study was conducted to evaluate the antioxidant role of bacoside A (triterpenoid saponin isolated from Bacopa monniera) against chronic cigarette smoking induced oxidative damage in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with bacoside A (10 mg/kg b.w./day, p.o.). Antioxidant status of the brain was assessed from the levels of reduced glutathione, vitamin C, vitamin E, and vitamin A and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The levels of copper, iron, zinc and selenium in brain and serum ceruloplasmin activity were also measured. Oxidative stress was evident from the diminished levels of both enzymatic and non-enzymatic antioxidants. Alterations in the levels of trace elements with accumulation of copper and iron, and depletion of zinc and selenium were also observed. Bacoside A administration improved the antioxidant status and maintained the levels of trace elements. These results suggest that chronic cigarette smoke exposure enhances oxidative stress, thereby disturbing the tissue defense system and bacoside A protects the brain from the oxidative damage through its antioxidant potential.     

假马齿苋的生物活性及其临床研究

假马齿苋(Bacopa monniera,BM)具有提高记忆,镇静,抗癫痫和抗炎,镇痛,退烧,强心等生物活性。假马齿苋皂苷(bacosides)是主要的益智活性成分。     

Protective effects of glutathione and cysteine on the methylmercury-induced striatal dopamine release in vivo

The possible protective effects of glutathione (GSH), cysteine (CYS) and methionine (MET) on the Methylmercury (MeHg)-induced dopamine (DA) release from rat striatum were investigated using in vivo microdialysis coupled to HPLC with electrochemical detection. Intrastriatal infusion of MeHg 400 microM increased extracellular DA levels to 1941 +/- 199% in terms of basal levels. Infusion of MeHg 400 microM in GSH 400 microM pretreated animals, only increased striatal DA levels to 465 +/- 104%, in terms of basal levels, this increase being 76% lower than induced by MeHg alone. Conversely, the infusion of MeHg 400 microM after infusion of GSH 400 microM increased DA levels to 1019 +/- 96% in terms of basal levels, this increase being 47.5% lower than that observed in MeHg non-pretreated animals. The infusion of MeHg 400 microM in CYS 400 microM -pretreated animals, increased striatal DA levels to 740 +/- 149%, in terms of basal levels, this increase being 62% lower than that induced by MeHg in non-pretreated animals. The infusion of MeHg 400 microM in MET 400 microM pretreated animals increased striatal DA levels to 2011 +/- 230% in terms of basal, an increase that was not significantly different from that produced by MeHg 400 muM alone. In summary, the administration of compounds containing free -SH groups prevented the MeHg-induced DA release from rat striatum, probably due to the binding of MeHg to -SH groups. This would result in a lower metal availability to interact with -SH membrane proteins groups, which would decrease MeHg ability to interact with DA transporter.     

Safety evaluation of BacoMind in healthy volunteers: a phase I study.

BacoMind is an enriched phytochemical composition of Bacopa monniera (B. monniera), a common medicinal plant used in the traditional systems of medicine as a memory-enhancing agent. BacoMind was standardized with reference to bioactive compounds and was evaluated for short-term safety and tolerability in healthy adult volunteers. The study plan employed randomized, open label, dose escalation design. Each of 23 participants were orally given one single capsule of BacoMind daily for 30 days, i.e., 300 mg for first 15 days and 450 mg for next 15 days. Detailed examination of clinical, hematological, biochemical and electrocardiographic parameters done in pre and post-treatment periods did not indicate any untoward effects in any of the treated volunteers. Mild adverse events related to gastrointestinal system were observed in the trial, which subsided spontaneously. BacoMind was found to meet the safety criteria at the dose administered for the given duration of trial period in healthy adult volunteers.     

Bacopa monniera Linn. extract modulates antioxidant and marker enzyme status in fibrosarcoma bearing rats

Antioxidative property and tumor inhibitive property of B. monniera (20mg/kg body wt, sc) was examined in 3-methylcholanthrene induced fibrosarcoma rats. Antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and the levels of glutathione (GSH) and the rate of lipid peroxidation (LPO) in the liver and kidney tissues were assessed. A significant increase was noted for the rate of LPO with a corresponding decrease in the antioxidant enzyme status in fibrosarcoma bearing rats. In fibrosarcoma bearing rats, the tumor markers like lactate dehydrogenase (LDH), creatine kinase (CK), alanine transaminase (ALT), aspartate transaminase (AST) and sialic acid (SA) were increased in the serum. Treatment with B. monniera extract significantly increased the antioxidant enzyme status, inhibited lipid peroxidation and reduced the tumor markers. It can be concluded that B.monniera extract promotes the antioxidant status, reduces the rate of lipid peroxidation and the markers of tumor progression in the fibrosarcoma bearing rats.     

Alcoholic Extract of Bacopa monniera Linn. Protects Against 6-Hydroxydopamine-Induced Changes in Behavioral and Biochemical Aspects: A Pilot Study

Parkinson's disease is one of the commonest neurodegenerative diseases, and oxidative stress has been evidenced to play a vital role in its causation. In this study, we evaluated whether alcoholic extract of Bacopa monniera (AEBM), an antioxidant and memory enhancer can slow the neuronal injury in a 6-OHDA-rat model of Parkinson's. Rats were treated with 20 and 40?mg/kg bodyweight of AEBM for 3?weeks. On Day 21, 2?μl of 6-OHDA (12?μg in 0.01?% in ascorbic acid-saline) was infused into the right striatum, while the control group received 2?μl of vehicle. Three weeks after the 6-OHDA injection, the rats were tested for neurobehavioral activity (rotarod, locomotor activity, grip test, forced swim test, radial arm maze) and were killed after 6?weeks for the estimation of lipid peroxidation, reduced glutathione (GSH) content, activities of glutathione-S-transferase, glutathione reductase, glutathione peroxidase, superoxide dismutase (SOD), and catalase (CAT). The deficits in behavioral activity due to 6-OHDA lesioning were significantly and dose dependently restored by AEBM. Lesioning was followed by an increased lipid peroxidation and significant depletion of reduced GSH content in the substantia nigra, which was prevented with AEBM pretreatment. The activities of GSH-dependent enzymes, CAT and SOD in striatum were reduced significantly by lesioning, which were restored significantly and dose dependently by AEBM. This study indicates that the extract of B.?monniera might be helpful in attenuating 6-OHDA-induced lesioning in rats.     

Nitric oxide-related toxicity in cultured astrocytes: effect of Bacopa monniera

There is growing evidence that high concentrations of nitric oxide (NO), generated by activated astrocytes, might be involved in a variety of neurodegenerative diseases, such as Alzheimer's disease, ischemia and epilepsy. It has recently been suggested that glial cells may produce NO under superoxide radical stimulation by enzyme-independent mechanism. This suggests that also natural antioxidants may have therapeutical relevance in neurodegenerative diseases. Studies of Bhattacharya et al. have evidenced that Bacopa monniera (BM) (family Scrophulariaceae), an Ayurvedic medicinal plant clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative, is able to reduce the memory-dysfunction in rat models of Alzheimer's disease, but the molecular mechanisms of this action are yet to be determined. In the present study, we examined the effect of a methanolic extract of BM on toxicity induced by the nitric oxide donor, S-nitroso-N-acetyl-penicillamine (SNAP), in culture of purified rat astrocytes. Our results indicate that, after 18 h of treatment, SNAP induced an increase in the production of reactive species, but did not induce the rupture of cellular membrane. Conversely, this NO donor induced a fragmentation of genomic DNA compared to control astrocytes. The extract of BM inhibited the formation of reactive species and DNA damage in a dose dependent manner. This data supports the traditional use of BM and indicates that this medicinal plant has a therapeutic potential in treatment or prevention of neurological diseases.     

Evaluation of Memory Enhancing Clinically Available Standardized Extract of Bacopa monniera on P-Glycoprotein and Cytochrome P450 3A in Sprague-Dawley Rats

Bacopa monniera is a traditional Ayurvedic herbal medicine used to treat various mental ailments from ancient times. Recently, chemically standardized alcoholic extract of Bacopa monniera (BM) has been developed and currently available as over the counter herbal remedy for memory enhancement in children and adults. However, the consumption of herbal drugs has been reported to alter the expression of drug metabolizing enzymes and membrane transporters. Present study in male Sprague-Dawley rat was performed to evaluate the effect of memory enhancing standardized extract of BM on hepatic and intestinal cytochrome P450 3A and P-glycoprotein expression and activity. The BM (31 mg/kg/day) was orally administered for one week in BM pre-treated group while the control group received the same amount of vehicle for the same time period. The BM treatment decreased the cytochrome P450 3A (CYP3A) mediated testosterone 6β-hydroxylation activity of the liver and intestine by 2 and 1.5 fold, respectively compared to vehicle treated control. Similarly pretreatment with BM extract decreased the expression of intestinal P-glycoprotein (Pgp) as confirmed by Western blot analysis but did not alter the expression of hepatic Pgp. To investigate whether this BM pretreatment mediated decrease in activity of CYP3A and Pgp would account for the alteration of respective substrate or not, pharmacokinetic study with carbamazepine and digoxin was performed in BM pre-treated rats and vehicle treated rats. Carbamazepine and digoxin were used as CYP3A and Pgp probe drugs, respectively. Significant increase in AUC and Cmax of carbamazepine (4 and 1.8 fold) and digoxin (1.3 and 1.2 fold), respectively following the BM pre-treatment confirmed the down regulation of CYP3A and Pgp.