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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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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.

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Data Availability

The datasets used and/or analysis during the current study are available from the corresponding author on reasonable request.

Abbreviations

BM3:

Bacoside A

BM4:

Bacopaside I

BM3NP:

Bacoside A nanoparticle

BM4NP:

Bacopaside I nanoparticle

DLS:

Dynamic Light Scattering

EEG:

Electroencephalogram

EMG:

Electromyography

FTIR:

Fourier-Transform Infrared Spectroscopy

HPTLC:

High Performance Thin Layer Chromatography

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

NREM:

Non-Rapid Eye Movement

REM:

Rapid Eye Movement

S-W:

Sleep-wakefulness

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Acknowledgements

We acknowledge the Kerala State Council for Science, Technology and Environment, Government of Kerala, India and Indian Council Medical Research for funding.

Funding

We acknowledge Kerala State Council for Science, Technology and Environment, Government of Kerala (Grant no. 17/2017/KSCSTE dated 11–04-2017) and Indian Council for Medical Research (ICMR), Government of India (Grant no. 45/35/2018-Nan/BMS dated 16/05/2018) for funding.

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Authors and Affiliations

  1. Phytochemistry and Phytopharmacology Division, KSCSTE-Jawaharlal Nehru Tropical Botanic Garden and Research Institute, Pacha-Palode, Thiruvananthapuram, 695562, Kerala, India

    Vini C. Sekhar, Sabulal Baby & Gayathri Viswanathan

  2. University of Kerala, Thiruvananthapuram, 695034, Kerala, India

    Vini C. Sekhar

  3. Division of Sleep Research, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, India

    Kamalesh K. Gulia

  4. Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682022, Kerala, India

    Ayswaria Deepti & P. S. Baby Chakrapani

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  1. Vini C. Sekhar
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  2. Kamalesh K. Gulia
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Contributions

Vini C. Sekhar: Conceptualization, Methodology, Formal analysis, Writing—original draft, Writing—review & editing. Kamalesh K Gulia: In vivo experimentation and sleep analysis, Manuscript writing and review. Ayswaria Deepti: Methodology, Formal analysis, Manuscript writing and review. Baby Chakrapani PS: Methodology, Formal analysis, Manuscript writing and review. Sabulal Baby: Conceptualization, Project administration, Funding acquisition, Writing—review & editing. Gayathri Viswanathan: Conceptualization, Methodology, Formal analysis, Project administration, Funding acquisition, Writing—original draft, Writing—review & editing.

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Correspondence to Gayathri Viswanathan.

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The study was approved by the Institutional Animal Ethics Committee of Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram (SCT/ABS/IAEC-107/11 dated 02/12/2020), Kerala, India.

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C. Sekhar, V., Gulia, K.K., Deepti, A. et al. Protection by Nano-Encapsulated Bacoside A and Bacopaside I in Seizure Alleviation and Improvement in Sleep- In Vitro and In Vivo Evidences. Mol Neurobiol 61, 3296–3313 (2024). https://doi.org/10.1007/s12035-023-03741-w

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