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Aqueous extract of Piper betle L. leaf and Areca catechu L. nut protects against pentylenetetrazole-induced seizures and positively modulates cognitive function in adult Zebrafish

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Abstract

Piper betle L. (BL) is a popular medicinal plant in Asia. BL has been used as a traditional medicine to treat various health conditions. Areca catechu L. nut (AN) is an important traditional Chinese medicine, which has been used since antiquity. Epilepsy is a chronic neurological illness that affects millions of people. Cognitive dysfunction and abnormal behavior are the alarming co-morbidities of epilepsy. This study aims to investigate the anti-epileptic and cognitive improvement effects of Aqueous extract of Piper betle L. (AqEBL) and Aqueous extract of Areca catechu L. nut (AqEAN) against Pentylenetetrazole (PTZ) induced epilepsy associated cognitive dysfunction in adult Zebrafish (ZF). The extract was subjected to liquid chromatography coupled with tandem mass spectrometry analysis to identify its bioactive compounds. Further, molecular docking studies were carried out to understand the binding mode of various components of AqEBL and AqEAN within the active site of the gamma-aminobutyric acid receptor β3 subunit (GABAA subunit β3). The epilepsy-associated cognitive functions were assessed by behavioral studies including, seizure-score phenotype, T-maze, color recognition, and open field test; biochemical studies including brain antioxidant status and oxidative stress indices, acetylcholine esterase activity, neurotransmitters expression levels, and histopathology study in ZF model. It was evidenced in the current study that AqEBL and AqEAN have the potential to ameliorate seizure-like behavior through the GABAA receptor pathway and improve cognitive abilities. These data indicate that AqEBL and AqEAN may be potential options for epilepsy associated cognitive impairment.

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Abbreviations

AN:

Areca nut

AChE:

Acetylcholine esterase

AqEBL:

Aqueous extract of Piper betle L. leaf

AqEAN:

Aqueous extract of Areca catechu L. nut

AED:

Antiepileptic drugs

BL:

Betle leaf

CAT:

Catalase

CDE:

C Docker energy

DZP:

Diazepam

GABA:

Gamma-aminobutyric acid

GSH:

Reduced glutathione

LCMS:

Liquid chromatography-mass spectrometry

LPO:

Lipid peroxidation

LC:

Lethal concentration

NERC:

Number of entry to red chamber

PDB:

Protein data bank site

PTZ:

Pentylenetetrazole

SOD:

Superoxide dismutase

TSGC:

Time spent in green chamber

TCP:

Target chamber preference

TL:

Transfer latency

TRα2:

Thyroxine receptor α2

ZF:

Zebrafish

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  1. Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, Karnataka, 570 015, India

    Abhishek P. R. Nadig, M. Sahyadri, Seema Mehdi & K. L. Krishna

  2. Department of Dravyaguna, Government Ayurvedic Medical College and Hospital, New Sayyajirao Road, Mysuru, 570 001, India

    Suman

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APRN—Conceptualization, methodology, writing—original draft and statistical analysis. PS—Methodology and draft writing. MS—Editing and data curation. SM—Methodology. KKL—Conceptualization, methodology, draft editing, and supervision.

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Correspondence to K. L. Krishna.

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Abhishek P. R. Nadig has no conflict of interest. P. Suman has no conflict of interest. M. Sahyadri has no conflict of interest. Seema Mehdi has no conflict of interest. K. L. Krishna has no conflict of interest.

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Nadig, A.P.R., Suman, Sahyadri, M. et al. Aqueous extract of Piper betle L. leaf and Areca catechu L. nut protects against pentylenetetrazole-induced seizures and positively modulates cognitive function in adult Zebrafish. ADV TRADIT MED (ADTM) 23, 1137–1152 (2023). https://doi.org/10.1007/s13596-022-00664-0

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