Anti-inflammatory, anti-arthritic and analgesic activity of each herbal extract, which is extracted from Bacopa monnieriis, Cassia fistula and Phyllanthus polyphyllus, respectively. The treatment of herbal extract exhibited anti-inflammatory effect as a dose-dependent manner, from 1.25mg/kg to 12.5mg/kg, in acute inflammatory models (carrageen and egg-albumin induced rat hind paw edema). It also elicited significant anti-inflammatory activity in chronic inflammatory models (cotton pellet granuloma and Freund's adjuvant induced polyarthritis in rat). In cotton pellet granuloma test, the extract exhibited the inhibitory effect of 23 and 57% at the dose of 6.25 and 12.5 mg/kg, respectively. In Freund's adjuvant induced model, the treatment of the extract of 1.25, 6.25 and 12.5 mg/kg showed the inhibitory effect of 23, 56 and 66% at 8 days, respectively. In the acetic acid-induced model, the extract significantly reduced abdominal writhing in mice when compared to the control group, reducing the mean number of writhing from 41 ± 2 in the control group to 17 ± 3 and 15 ± 2 at the dose of 6.25 and 12.5 mg/kg. From these experiments, the extract, which was extracted from the combination of Bacopa monnieriis, Cassia fistula and Phyllanthus polyphyllus, (w/w/w = 1/2/1) is surprisingly found a significant analgesic and anti-inflammatory activity.
Animals ; Arthritis ; Bacopa* ; Cassia* ; Freund's Adjuvant ; Granuloma ; Mice ; Phyllanthus* ; Rats

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.
Animals ; Bacopa* ; Brain ; Brain-Derived Neurotrophic Factor* ; Depression ; Hippocampus* ; Imipramine ; Motor Activity ; Rats* ; Response Elements ; Sucrose

OBJECTIVEAyurvedic formulations are preferred over other formulations as well as commercialized on broad level to treat various ailments. The World Health Organization has established certain guidelines for quality control of heavy metals and pesticide residues. Bacopa monnieri, a popular herb with immunomodulator and memory-enhancing properties is the chief constituent of several Ayurvedic formulations, which include Brahmi Vati (BV), Brahmi Ghrita (BG) and Saraswat Churna (SC), etc. In view of the World Health Organization guidelines, two products of each formulation from six different manufacturers were purchased from Ayurvedic Pharmacy, Bulanala-Varanasi, India for testing heavy metal and pesticide residue.

METHODSIn the present study, all the formulations--BV, BG and SC--were selected for estimation of four heavy metals namely lead (Pb), cadmium (Cd), chromium (Cr) and nickel (Ni) by a plasma emission spectrophotometer. Organochlorine pesticidal residues were estimated for dichlorodiphenyl trichloroethane, isomers of hexachlorocyclohexane (HCH) and α-endosulfan, etc. in total 12 samples of test formulations containing Bacopa monnieri L. using gas chromatography technique.

RESULTSOut of 12 samples, Pb, Cd, Cr and Ni were present in all samples but below the permissible limit. Although atrazine, aldrin, dialdrin were in below detection limit, but other pesticides were detected in some samples as oxamyl, hexachlorocyclohexanes (α-HCH, β-HCH and γ-HCH), dichlorodiphenyl trichloroethane and dichlorodiphenyl dichloroethylene.

CONCLUSIONThe presence of heavy metals in the formulations was low to cause toxicity. However evaluation of heavy metals and pesticide residue in every batch is necessary.

Bacopa ; chemistry ; Chemistry, Pharmaceutical ; Medicine, Ayurvedic ; Metals, Heavy ; analysis ; Pesticides ; analysis

OBJECTIVE: The present study aimed to investigate whether graded doses of Bacopa Monniera (BM) extract could produce antidepressant-like effects in chronic unpredictable stress (CUS) induced depression in rats and its possible mechanism(s). METHODS: Rats were subjected to an experimental setting of CUS. The effect of BM extract treatment in CUS-induced depression was examined using behavioral tests including the sucrose consumption, open field test and shuttle box escape test. The mechanism underlying the antidepressant-like action of BM extract was examined by measuring brain-derived neurotrophic factor (BDNF) protein and mRNA expression in brain tissues of CUS-exposed rats. RESULTS: Exposure to CUS for 4 weeks caused depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity and escape latency. In addition, it was found that BDNF protein and mRNA levels in the hippocampus and frontal cortex were lower in CUS-treated rats, as compared to controls. Daily administration of the graded doses of BM extract during the 4-week period of CUS significantly suppressed behavioral changes and attenuated the CUS-induced decrease in BDNF protein and mRNA levels in the hippocampus and frontal cortex. CONCLUSION: The results suggest that BM extract alleviates depression induced by CUS. Present study also confirms that 80-120 mg/kg doses of BM extract have significantly higher antidepressant-like activity.
Animals ; Bacopa* ; Brain ; Brain-Derived Neurotrophic Factor* ; Depression* ; Hippocampus ; Models, Animal* ; Motor Activity ; Rats ; RNA, Messenger* ; Sucrose ; United Nations

OBJECTIVEBacoMind (BM) is a standardized extract of Bacopa monnieri, which belongs to the family Scrophulariaceae and is a creeping annual plant found throughout the Indian subcontinent. It has been used by Ayurvedic medicinal practitioners in India for almost 3000 years and is classified as a medharasayana, a substance which improves memory and intellect. With the widespread traditional use as well as scientific validation of Bacopa monnieri for nootropic activity, a bioactive-rich unique phytochemical composition-BacoMind was developed from B. monnieri for use as a cognition and memory enhancing agent. The present study aimed to investigate the in vitro toxicity of this formulation of BacoMind on human lymphocytes and to rule out its possible contribution to mutagenicity.

METHODSIn the present investigation the active ingredients present in BM were identified and quantified by high performance liquid chromatography (HPLC) and high performance thin-layer chromatography (HPTLC). Antioxidant and anticlastogenic properties of BM were studied in vitro with and without metabolic activation. Doses of BM were chosen on the basis of mitotic index (MI) and cytokinesis-block proliferation index (CBPI). Clastogenicity assays were performed at 31.2 microg/mL, 62.5 microg/mL, and 125 microg/mL, while the Salmonella reverse mutation assay (Ames test) was performed at doses of 61.72, 185.18, 555.55, 1666.67, and 5000.00 microg/plate.

RESULTSHPLC and HPTLC analysis of BM revealed the presence of bacoside A3, bacopaside I, bacopaside II, jujubogenin isomer of bacopasaponin C, bacosine, luteolin, apigenin, bacosine, and beta-sitosterol D glucoside. BM demonstrated significant antioxidant activity. The number of chromosomal aberrations and the frequency of micronuclei induced by BM were not statistically significant up to a dose of 62.5 microg/mL. A subsequent dose of 125 microg/mL prior to metabolic activation induced mild clastogenicity, but it was found to be biologically insignificant as this effect was not seen post metabolic activation. BM also demonstrated a dose-dependent protection against the clastogens used in this study using the above tests for clastogenicity. Maximum protection was observed in presence of metabolic activation. Moreover, BM demonstrated no mutagenic effect on the tested strains, as observed in the Ames test.

CONCLUSIONBM protected human lymphocytes against various clastogens. BM also exhibited high antioxidant activity which might be responsible for the observed protective effects against the clastogens since the used clastogens are known to induce their clastogenic effects via production of oxidative radicals.

Antimutagenic Agents ; adverse effects ; pharmacology ; Bacopa ; chemistry ; Biotransformation ; Chromatography, High Pressure Liquid ; Chromatography, Thin Layer ; Chromosome Aberrations ; Humans ; Lymphocytes ; drug effects ; Plant Extracts ; adverse effects ; pharmacology

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.
Antioxidants ; metabolism ; pharmacology ; Bacopa ; chemistry ; Cell Line ; Humans ; Hydrogen Peroxide ; Neuroblastoma ; Neurodegenerative Diseases ; metabolism ; Neuroprotective Agents ; pharmacology ; Oxidative Stress ; drug effects ; Plant Extracts ; pharmacology ; Polyphenols ; analysis ; pharmacology ; Reactive Oxygen Species ; metabolism

BACKGROUND: Glioblastoma multiforme (GBM) is a highly malignant brain tumor with a worst prognosis of less than one year despite advance treatment facilities. Among various signaling pathway genes displaying genetic modifications, aberrant expression of Notch pathway genes is frequent in GBM offering novel therapeutic targets. Herbal extracts having anticancer properties are used in adjuvant therapy that is safe and affordable as compared to chemotherapeutics. Bacopa monnieri has been used for the development of brain cells because of its neuroprotective properties. Its anticancer properties have shown to be promising in cancer treatment. METHODS: The anticancer properties of Bacoside A, an active and abundant component of Bacopa monnieri was assessed on U-87 MG cell line and its effects on expression of Notch pathway genes were studied. Cell cycle arrest and apoptosis were studied using flow cytometry. Expression of Notch pathway genes comprising of Notch receptors (notch1, notch2, notch3 and notch4), ligands (jagged1 and jagged2), a component of gamma-secretase complex (APH1A) and downstream target (HES1) were evaluated by quantitative real-time PCR. RESULTS: Bacoside A exhibited considerable cytotoxicity on U-87 MG cells inducing cell cycle arrest and apoptosis. Cell cycle analysis revealed a significant arrest of 39.21% cells in sub-G0 phase at 80 µg/mL concentration, increasing to 53.21% at a higher concentration of 100 µg/mL. The fraction of early apoptotic cells in control was low (3.48%) that increased substantially to 31.36% and 41.11% after 80 µg/mL and 100 µg/mL of Bacoside A treatment respectively. Additionally, the expression of notch1 gene decreased after exposure to Bacoside A with a fold change of 0.05, whereas HES1 gene expression was increased by 25 fold. CONCLUSION: These data indicate that Bacoside A has a possible anticancer activity that could be inducing cell cycle arrest and apoptosis through Notch pathway in GBM in vitro.
Amyloid Precursor Protein Secretases ; Apoptosis ; Bacopa ; Brain ; Brain Neoplasms ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line ; Flow Cytometry ; Gene Expression ; Glioblastoma ; Humans ; In Vitro Techniques ; Ligands ; Prognosis ; Real-Time Polymerase Chain Reaction ; Receptors, Notch

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.
Animals ; Bacopa* ; Blotting, Western ; Brain-Derived Neurotrophic Factor* ; Cell Proliferation* ; Cognition Disorders ; Cyclic AMP Response Element-Binding Protein* ; Dentate Gyrus* ; Discrimination (Psychology) ; Immunohistochemistry ; Memory ; Mice ; Neurogenesis ; Phosphorylation* ; Plants, Medicinal