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Neuroprotective effect of Berberine Nanoparticles Against Seizures in Pentylenetetrazole Induced Kindling Model of Epileptogenesis: Role of Anti-Oxidative, Anti-Inflammatory, and Anti-Apoptotic Mechanisms

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Abstract

There is an unmet need to develop alternative therapeutic strategies to not only restrain seizures but also to alleviate the underlying pathologies and sequelae. Berberine (BBR), an isoquinoline alkaloid, has shown promising effect in the kindling model of epileptogenesis, but due to the poor oral bioavailability its clinical application is limited. So, the present study was designed to study the neuroprotective effect of BBR nanoparticles (enhanced bioavailability as compared to BBR) against seizures in pentylenetetrazole (PTZ) induced kindling model of epileptogenesis. Kindling model was established in male Wistar rats by intraperitoneal (i.p.) administration of PTZ (30 mg/kg) on every alternate day till the animal became fully kindled or till 6 weeks. Three doses of BBR (50, 100, and 200 mg/kg) and nano-BBR (25, 50, 100 mg/kg) were studied for seizure score, percentage of animal kindled, histopathological score, oxidative stress, inflammation, and apoptosis in PTZ treated rats by conducting cytokines, gene expression and protein expression analysis. BBR nanoparticles showed significant effect on the seizure score and percentage of animal kindled, histopathological score, neurobehavioral parameters (Forced swim test, Rotarod), oxidative (MDA, SOD, GSH, GPx) and inflammatory (IL-1beta, TNF-alpha) parameters, apoptotic parameters (Bax and iNOS), and gene (Nrf2, NQO1, HO1) and protein expression (Nrf2) as compared to both PTZ and BBR. BBR nanoparticles showed neuroprotective effect in PTZ induced kindling model of epileptogenesis and proves to be a promising antiepileptogenic therapy for the patients who are at high risk of developing seizures.

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Acknowledgements

The authors acknowledge the technical assistance provided by Senior Technician Mr. P.J. Thomas and Mr. Sunil Sharma. Also, we acknowledge Mr. Anil Kumar (Ph.D Student) for his assistance in making the graphical abstract.

Funding

This research was supported by a research fellowship provided to the student from Indian Council of Medical Research (ICMR), New Delhi, India. Indian Council of Medical Research

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Authors and Affiliations

  1. Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), 4Th Floor, Research Block B, Chandigarh, 160012, India

    Lekha Saha, Puja Kumari, Kajal Rawat, Vipasha Gautam, Arushi Sandhu, Neha Singh & Amitava Chakrabarti

  2. Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education & Research (PGIMER), 2Nd Floor, Research Block B, Chandigarh, 160012, India

    Alka Bhatia

  3. Department of Biophysics, Post Graduate Institute of Medical Education & Research (PGIMER), 5Th Floor, Research Block B, Chandigarh, 160012, India

    Shalmoli Bhattacharya

  4. Department of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, 160014, Chandigarh, India

    V. R. Sinha

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  1. Lekha Saha
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Contributions

Lekha Saha and Puja kumari : Protocol writing, Performing experiments, Data collections and analysis, Manuscript writing and final editing. Kajal Rawat, Vipasha Gautam, Neha Singh and Arushi Sandhu: Performing experiments, Manuscript writing and editing. Alka Bhatia, V R Sinha and Amitava Chakrabarti: Data Analysis,Manuscript writing and editing.

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Saha, L., Kumari, P., Rawat, K. et al. Neuroprotective effect of Berberine Nanoparticles Against Seizures in Pentylenetetrazole Induced Kindling Model of Epileptogenesis: Role of Anti-Oxidative, Anti-Inflammatory, and Anti-Apoptotic Mechanisms. Neurochem Res 48, 3055–3072 (2023). https://doi.org/10.1007/s11064-023-03967-z

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