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

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 (GABA_A 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 GABA_A 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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