Protection by Nano-Encapsulated Bacoside A and Bacopaside I in Seizure Alleviation and Improvement in Sleep- In Vitro and In Vivo Evidences
Therapeutic options to contain seizures, a transitional stage of many neuropathologies, are limited due to the blood–brain barrier (BBB). Herbal nanoparticle formulations can be employed to enhance seizure prognosis. Bacoside A (BM3) and bacopaside I (BM4) were isolated from Bacopa monnieri and synt...
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| creator | C. Sekhar, Vini Gulia, Kamalesh K. Deepti, Ayswaria Chakrapani, P. S. Baby Baby, Sabulal Viswanathan, Gayathri |
| description | Therapeutic options to contain seizures, a transitional stage of many neuropathologies, are limited due to the blood–brain barrier (BBB). Herbal nanoparticle formulations can be employed to enhance seizure prognosis. Bacoside A (BM3) and bacopaside I (BM4) were isolated from
Bacopa monnieri
and synthesized as nanoparticles (BM3NP and BM4NP, respectively) for an effective delivery system to alleviate seizures and associated conditions. After physicochemical characterization, cell viability was assessed on mouse neuronal stem cells (mNSC) and neuroblastoma cells (N2a). Thereafter, anti-seizure effects, mitochondrial membrane potential (MMP), apoptosis, immunostaining and epileptic marker mRNA expression were determined in vitro. The seizure-induced changes in the cortical electroencephalogram (EEG), electromyography (EMG), Non-Rapid Eye Movement (NREM) and Rapid Eye Movement (REM) sleep were monitored in vivo in a kainic acid (KA)-induced rat seizure model. The sizes of BM3NPs and BM4NPs were 165.5 nm and 689.6 nm, respectively. They were biocompatible and also aided in neuroplasticity in mNSC. BM3NPs and BM4NPs depicted more than 50% cell viability in N2a cells, with IC50 values of 1609 and 2962 µg/mL, respectively. Similarly, these nanoparticles reduced the cytotoxicity of N2a cells upon KA treatment. Nanoparticles decreased the expression of epileptic markers like fractalkine, HMGB1, FOXO3a and pro-inflammatory cytokines (
P
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| doi_str_mv | 10.1007/s12035-023-03741-w |
| format | Article |
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Bacopa monnieri
and synthesized as nanoparticles (BM3NP and BM4NP, respectively) for an effective delivery system to alleviate seizures and associated conditions. After physicochemical characterization, cell viability was assessed on mouse neuronal stem cells (mNSC) and neuroblastoma cells (N2a). Thereafter, anti-seizure effects, mitochondrial membrane potential (MMP), apoptosis, immunostaining and epileptic marker mRNA expression were determined in vitro. The seizure-induced changes in the cortical electroencephalogram (EEG), electromyography (EMG), Non-Rapid Eye Movement (NREM) and Rapid Eye Movement (REM) sleep were monitored in vivo in a kainic acid (KA)-induced rat seizure model. The sizes of BM3NPs and BM4NPs were 165.5 nm and 689.6 nm, respectively. They were biocompatible and also aided in neuroplasticity in mNSC. BM3NPs and BM4NPs depicted more than 50% cell viability in N2a cells, with IC50 values of 1609 and 2962 µg/mL, respectively. Similarly, these nanoparticles reduced the cytotoxicity of N2a cells upon KA treatment. Nanoparticles decreased the expression of epileptic markers like fractalkine, HMGB1, FOXO3a and pro-inflammatory cytokines (
P
< 0.05). They protected neurons from apoptosis and restored MMP. After administration of BM3NPs and BM4NPs, KA-treated rats attained a significant reduction in the epileptic spikes, sleep latency and an increase in NREM sleep duration. Results indicate the potential of BM3NPs and BM4NPs in neutralizing the KA-induced excitotoxic seizures in neurons.
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Bacopa monnieri
and synthesized as nanoparticles (BM3NP and BM4NP, respectively) for an effective delivery system to alleviate seizures and associated conditions. After physicochemical characterization, cell viability was assessed on mouse neuronal stem cells (mNSC) and neuroblastoma cells (N2a). Thereafter, anti-seizure effects, mitochondrial membrane potential (MMP), apoptosis, immunostaining and epileptic marker mRNA expression were determined in vitro. The seizure-induced changes in the cortical electroencephalogram (EEG), electromyography (EMG), Non-Rapid Eye Movement (NREM) and Rapid Eye Movement (REM) sleep were monitored in vivo in a kainic acid (KA)-induced rat seizure model. The sizes of BM3NPs and BM4NPs were 165.5 nm and 689.6 nm, respectively. They were biocompatible and also aided in neuroplasticity in mNSC. BM3NPs and BM4NPs depicted more than 50% cell viability in N2a cells, with IC50 values of 1609 and 2962 µg/mL, respectively. Similarly, these nanoparticles reduced the cytotoxicity of N2a cells upon KA treatment. Nanoparticles decreased the expression of epileptic markers like fractalkine, HMGB1, FOXO3a and pro-inflammatory cytokines (
P
< 0.05). They protected neurons from apoptosis and restored MMP. After administration of BM3NPs and BM4NPs, KA-treated rats attained a significant reduction in the epileptic spikes, sleep latency and an increase in NREM sleep duration. Results indicate the potential of BM3NPs and BM4NPs in neutralizing the KA-induced excitotoxic seizures in neurons.
Graphical Abstract</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood-brain barrier</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cell viability</subject><subject>Convulsions & seizures</subject><subject>Cytotoxicity</subject><subject>EEG</subject><subject>Electroencephalography</subject><subject>Electromyography</subject><subject>Epilepsy</subject><subject>Excitotoxicity</subject><subject>Eye movements</subject><subject>FOXO3 protein</subject><subject>Fractalkine</subject><subject>Gene expression</subject><subject>HMGB1 protein</subject><subject>Inflammation</subject><subject>Kainic acid</subject><subject>Kainic Acid - toxicity</subject><subject>Latency</subject><subject>Male</subject><subject>Membrane potential</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mice</subject><subject>Nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>Neural stem cells</subject><subject>Neurobiology</subject><subject>Neuroblastoma</subject><subject>Neuroblasts</subject><subject>Neurology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neuroplasticity</subject><subject>Neurosciences</subject><subject>NREM sleep</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>REM sleep</subject><subject>Saponins - pharmacology</subject><subject>Seizures</subject><subject>Seizures - drug therapy</subject><subject>Sleep - drug effects</subject><subject>Triterpenes - pharmacology</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EokvhD3BAlrhwMfgjju1jqRZYqWor8XG1HGeCUiV2sJOtyl_on8a7KSBx4GSN55l3RnoQesnoW0apepcZp0ISygWhQlWM3D5CGyalIYxp_hhtqDaCqLrSJ-hZzjeUcs6oeopOhDJaGak36P46xRn83MeAmzt86UIk2-DdlJfBzdDi987H3LeAz7ALazm548cO9wF_hv7nkkp3GGDfu2POgduNU4p7GCHMR2wAmAjeBfytn1NckUOxj3i7L2nBQ36OnnRuyPDi4T1FXz9sv5x_IhdXH3fnZxfECyVn4mVTUVM3BqDVUivgsu081bQDp7SjslaSC9HQzjvfVJV3natZ66Qw0lQaxCl6s-aWE38skGc79tnDMLgAccmWa8N5bYyoC_r6H_QmLimU66ygUggpKFeF4ivlU8w5QWen1I8u3VlG7UGVXVXZosoeVdnbMvTqIXppRmj_jPx2UwCxArm0wndIf3f_J_YXGKyfqA</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>C. Sekhar, Vini</creator><creator>Gulia, Kamalesh K.</creator><creator>Deepti, Ayswaria</creator><creator>Chakrapani, P. S. 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Sekhar, Vini ; Gulia, Kamalesh K. ; Deepti, Ayswaria ; Chakrapani, P. S. Baby ; Baby, Sabulal ; Viswanathan, Gayathri</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-c5b4096b9eed8587e25dfc080fea78a05675233b0fcacb44cafa61da5395948e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blood-brain barrier</topic><topic>Cell Biology</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Cell viability</topic><topic>Convulsions & seizures</topic><topic>Cytotoxicity</topic><topic>EEG</topic><topic>Electroencephalography</topic><topic>Electromyography</topic><topic>Epilepsy</topic><topic>Excitotoxicity</topic><topic>Eye movements</topic><topic>FOXO3 protein</topic><topic>Fractalkine</topic><topic>Gene expression</topic><topic>HMGB1 protein</topic><topic>Inflammation</topic><topic>Kainic acid</topic><topic>Kainic Acid - toxicity</topic><topic>Latency</topic><topic>Male</topic><topic>Membrane potential</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Mice</topic><topic>Nanoparticles</topic><topic>Nanoparticles - chemistry</topic><topic>Neural stem cells</topic><topic>Neurobiology</topic><topic>Neuroblastoma</topic><topic>Neuroblasts</topic><topic>Neurology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neuroplasticity</topic><topic>Neurosciences</topic><topic>NREM sleep</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>REM sleep</topic><topic>Saponins - pharmacology</topic><topic>Seizures</topic><topic>Seizures - drug therapy</topic><topic>Sleep - drug effects</topic><topic>Triterpenes - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>C. 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Baby</au><au>Baby, Sabulal</au><au>Viswanathan, Gayathri</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protection by Nano-Encapsulated Bacoside A and Bacopaside I in Seizure Alleviation and Improvement in Sleep- In Vitro and In Vivo Evidences</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>61</volume><issue>6</issue><spage>3296</spage><epage>3313</epage><pages>3296-3313</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>Therapeutic options to contain seizures, a transitional stage of many neuropathologies, are limited due to the blood–brain barrier (BBB). Herbal nanoparticle formulations can be employed to enhance seizure prognosis. Bacoside A (BM3) and bacopaside I (BM4) were isolated from
Bacopa monnieri
and synthesized as nanoparticles (BM3NP and BM4NP, respectively) for an effective delivery system to alleviate seizures and associated conditions. After physicochemical characterization, cell viability was assessed on mouse neuronal stem cells (mNSC) and neuroblastoma cells (N2a). Thereafter, anti-seizure effects, mitochondrial membrane potential (MMP), apoptosis, immunostaining and epileptic marker mRNA expression were determined in vitro. The seizure-induced changes in the cortical electroencephalogram (EEG), electromyography (EMG), Non-Rapid Eye Movement (NREM) and Rapid Eye Movement (REM) sleep were monitored in vivo in a kainic acid (KA)-induced rat seizure model. The sizes of BM3NPs and BM4NPs were 165.5 nm and 689.6 nm, respectively. They were biocompatible and also aided in neuroplasticity in mNSC. BM3NPs and BM4NPs depicted more than 50% cell viability in N2a cells, with IC50 values of 1609 and 2962 µg/mL, respectively. Similarly, these nanoparticles reduced the cytotoxicity of N2a cells upon KA treatment. Nanoparticles decreased the expression of epileptic markers like fractalkine, HMGB1, FOXO3a and pro-inflammatory cytokines (
P
< 0.05). They protected neurons from apoptosis and restored MMP. After administration of BM3NPs and BM4NPs, KA-treated rats attained a significant reduction in the epileptic spikes, sleep latency and an increase in NREM sleep duration. Results indicate the potential of BM3NPs and BM4NPs in neutralizing the KA-induced excitotoxic seizures in neurons.
Graphical Abstract</abstract><cop>New York</cop><pub>Springer US</pub><pmid>37987958</pmid><doi>10.1007/s12035-023-03741-w</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0001-7159-6911</orcidid><orcidid>https://orcid.org/0000-0002-2253-2644</orcidid><orcidid>https://orcid.org/0000-0003-3757-8132</orcidid><orcidid>https://orcid.org/0000-0002-4337-9431</orcidid><orcidid>https://orcid.org/0000-0001-8439-6724</orcidid><orcidid>https://orcid.org/0000-0002-6760-7187</orcidid></addata></record> |
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| subjects | Animals Apoptosis Apoptosis - drug effects Biomedical and Life Sciences Biomedicine Blood-brain barrier Cell Biology Cell Line, Tumor Cell Survival - drug effects Cell viability Convulsions & seizures Cytotoxicity EEG Electroencephalography Electromyography Epilepsy Excitotoxicity Eye movements FOXO3 protein Fractalkine Gene expression HMGB1 protein Inflammation Kainic acid Kainic Acid - toxicity Latency Male Membrane potential Membrane Potential, Mitochondrial - drug effects Mice Nanoparticles Nanoparticles - chemistry Neural stem cells Neurobiology Neuroblastoma Neuroblasts Neurology Neurons - drug effects Neurons - metabolism Neuroplasticity Neurosciences NREM sleep Rats Rats, Sprague-Dawley REM sleep Saponins - pharmacology Seizures Seizures - drug therapy Sleep - drug effects Triterpenes - pharmacology |
| title | Protection by Nano-Encapsulated Bacoside A and Bacopaside I in Seizure Alleviation and Improvement in Sleep- In Vitro and In Vivo Evidences |
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