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In Vivo Evaluation of Self-assembled nano-Saikosaponin-a for Epilepsy Treatment

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Abstract

Saikosaponin-a (SSa) exhibits antiepileptic effects. However, its poor water solubility and inability to pass through the blood–brain barrier greatly limit its clinical development and application. In this study, SSa-loaded Methoxy poly (ethylene glycol)-poly(ε-caprolactone) (MePEG-SSa-PCL) NPs were successfully prepared and characterized. Our objective was to further investigate the effect of this composite on acute seizure in mice. First, we confirmed the particle size and surface potential of the composite (51.00 ± 0.25 nm and − 33.77 ± 2.04 mV, respectively). Further, we compared the effects of various MePEG-SSa-PCL doses (low, medium, and high) with those of free SSa, valproic acid (VPA - positive control), and saline only (model group) on acute seizure using three different acute epilepsy mouse models. We observed that compared with the model group, the three MePEG-SSa-PCL treatments showed significantly lowered seizure frequency in mice belonging to the maximum electroconvulsive model group. In the pentylenetetrazol and kainic acid (KA) acute epilepsy models, MePEG-SSa-PCL increased both clonic and convulsion latency periods and shortened convulsion duration more effectively than equivalent SSa-only doses. Furthermore, hematoxylin–eosin and Nissl staining revealed considerably less neuronal damage in the hippocampal CA3 area of KA mice in the SSa, VPA, and three MePEG-SSa-PCL groups relative to mice in the model group. Hippocampal gamma-aminobutyric acid-A (GABA-A) receptor and cleaved caspase-3 expression levels in KA mice were significantly higher and lower, respectively, in the three MePEG-SSa-PCL treatment groups than in the model group. Thus, MePEG-SSa-PCL exhibited a more potent antiepileptic effect than SSa in acute mouse epilepsy models and could alleviate neuronal damage in the hippocampus following epileptic seizures, possibly via GABA-A receptor expression upregulation.

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Data Availability

The raw data supporting the conclusions of this study will be made available by the authors, without undue reservation.

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Funding

This work was supported by the National Natural Science Foundation of China (grant number 82074265), the National Natural Science Foundation of China (grant number 81873158),the National Science Foundation of Guangdong Province, China (grant number 2020A1515010324),the National Science Foundation of Guangdong Province, China(grant number 2021A1515011505), the National Science Foundation of Guangdong Province, China(grant number 2022A1515011719), and Construction Fund of Key Disciplines of Traditional Chinese Medicine in Guangdong, China (grant number G622299957).

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  1. Xueqi Liu, Yunyan Zhao and Xiaoshan Liang contributed equally to this work.

Authors and Affiliations

  1. Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Xueqi Liu, Xiaoshan Liang, Yuewen Ding, Ping Huang & Wei Xie

  2. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China

    Xueqi Liu, Xiaoshan Liang, Yuewen Ding, Jiao Hu, Ning Deng, Yiting Zhao & Wei Xie

  3. Department of Critical Care Medicine, The Afflliated Traditional Chinese Medicine Hospital of Guangzhou Medical University, Guangzhou, 510130, China

    Yunyan Zhao

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Contributions

Xueqi Liu, Yunyan Zhao, and Xiaoshan Liang contributed equally to this work. Wei Xie, Yunyan Zhao, and Xueqi Liu conceived and designed the experiments and revised the manuscript; Especially, Yunyan Zhao provided constructive suggestions for the revision of the manuscript and help importantly to revise the manuscript; Xiaoshan Liang, Xueqi Liu, and Yuewen Ding performed the experiments; Jiao Hu, Ning Deng, Yiting Zhao, and Ping Huang assisted in some of the experimental work; Xiaoshan Liang and Yunyan Zhao analyzed data; The first draft of the manuscript was written by Xueqi Liu, and all authors commented on previous versions of the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Wei Xie.

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Liu, X., Zhao, Y., Liang, X. et al. In Vivo Evaluation of Self-assembled nano-Saikosaponin-a for Epilepsy Treatment. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00851-7

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