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Anticonvulsant potential of Grewia tiliaefolia in pentylenetetrazole induced epilepsy: insights from in vivo and in silico studies

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Abstract

Epilepsy, a chronic neurological condition, impacts millions of individuals globally and remains a significant contributor to both illness and mortality. Available antiepileptic drugs have serious side effects which warrants to explore different medicinal plants used for the management of epilepsy reported in Traditional Indian Medicinal System (TIMS). Therefore, we explored the antiepileptic potential of the Grewia tiliaefolia (Tiliaeceae) which is known for its neuroprotective properties. Aerial parts of G. tiliaefolia were subjected to extraction with increasing order of polarity viz. hexane, chloroform and methanol. Antioxidant potential of hexane, chloroform and methanol extracts of G. tiliaefolia was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay, total antioxidant capacity (TAC) assay, reducing power assay (RPA) and DNA nicking assay. Additionally, quantitative antioxidant assays were also conducted to quantify total phenolic (TPC) and total flavonoid content (TFC). As revealed by in vitro assays, methanol extract was found to contain more phenolic content. Hence, the methanol extract was further explored for its anticonvulsant potential in pentylenetetrazole (PTZ) induced acute seizures in mice. The methanol extract (400 mg/kg) significantly increased the latency to occurrence of myoclonic jerks and generalized tonic clonic seizures (GTCS). Additionally, it also reduced duration and seizure severity score associated with GTCS. The Grewia tiliaefolia methanol extract was further screened by Ultra High-Performance Liquid Chromatography (UHPLC) for presence of polyphenolic compounds, among which gallic acid and kaempferol were present in higher amount and were further analysed by in silico study to predict their possible binding sites and type of interactions these compounds show with gamma amino butyric acid (GABA) receptor and glutamate α amino-3- hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu-AMPA) receptor. It was revealed that gallic acid and kaempferol had shown agonistic interaction for GABA receptor and antagonistic interaction for Glu-AMPA receptor. We concluded that G. tiliaefolia showed anticonvulsant potential possibly because of gallic acid and kaempferol possibly mediated through GABA and Glu-AMPA receptor.

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Data availability

The datasets used or analyzed during the current study will be available from the corresponding author on reasonable request.

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Acknowledgements

Authors are very grateful to Guru Nanak Dev University for providing the necessary facilities for conducting research work.

Funding

Authors are thankful to Indian Council of Medical Research (ICMR-SRF) for fellowship to Ms. Ankita Rajput.

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Authors and Affiliations

  1. Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, India

    Ankita Rajput, Palvi Sharma, Sharabjit Singh & Saroj Arora

  2. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India

    Nitish Kumar, Hasandeep Singh, Preet Mohinder Singh Bedi, Balbir Singh & Sarabjit Kaur

  3. Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, 77807, USA

    Tanveer Singh

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  1. Ankita Rajput
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  2. Palvi Sharma
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  3. Nitish Kumar
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  4. Hasandeep Singh
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  10. Sarabjit Kaur
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Contributions

Ankita Rajput performed the experiment and wrote the original manuscript; Palvi Sharma, Nitish Kumar and Sharabjit Singh helped in the experiment work; Hasandeep Singh guided in the experiment work and edited the original manuscript writing; Tanveer Singh guided for the in vivo PTZ experiment; Gave suggestion and edited manuscript. Sarabjit Kaur and Saroj Arora perceived the idea and gave suggestions in the manuscript.

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Correspondence to Saroj Arora or Sarabjit Kaur.

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Studies were conducted as per the protocol approved by the institutional animal ethical committee (IAEC) of Guru Nanak Dev University, India with protocol number 226/CPCSEA-2019/30.

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Rajput, A., Sharma, P., Kumar, N. et al. Anticonvulsant potential of Grewia tiliaefolia in pentylenetetrazole induced epilepsy: insights from in vivo and in silico studies. Metab Brain Dis 38, 2355–2367 (2023). https://doi.org/10.1007/s11011-023-01252-0

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