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. 2025 Aug;62(8):10707-10723.
doi: 10.1007/s12035-025-04916-3. Epub 2025 Apr 15.

Daidzin Enhances the Anticonvulsion Effects of Carbamazepine and Diazepam, Possibly Through Voltage-Gated Sodium Channels and GABAA-Dependent Pathways

Muhammad Torequl Islam  1   2   3 , Md Sakib Al Hasan  4   5 , Jannatul Ferdous  5   6   7 , Shoyaeb Ahammed  4   5 , Md Shimul Bhuia  4   5 , Salehin Sheikh  4   5 , Noshin Tasnim Yana  4   5 , Irfan Aamer Ansari  8 , Siddique Akber Ansari  9 , Md Saifuzzaman  10
Affiliations

Daidzin Enhances the Anticonvulsion Effects of Carbamazepine and Diazepam, Possibly Through Voltage-Gated Sodium Channels and GABAA-Dependent Pathways

Muhammad Torequl Islam et al. Mol Neurobiol. 2025 Aug.

Abstract

Epilepsy is a neurological disorder characterized by recurrent seizures, affecting approximately 50 million people globally. Daidzin (DZN), a naturally occurring isoflavone, has shown various pharmacological effects, including neuroprotective activities in animals. This study investigated the anticonvulsant effects of DZN with possible mechanisms of action using behavioral studies using experimental animals and in silico approaches. For this, a pentylenetetrazole (PTZ, 80 mg/kg, i.p.)-induced seizure model was applied in young broiler chicks. Treatment groups included DZN (5, 10, 20 mg/kg, p.o.), carbamazepine (CAR: 80 mg/kg, p.o.), and diazepam (DZP: 5 mg/kg, p.o.) alone and in combinations. After PTZ administration, convulsion onset, frequency, duration, and mortality rates were recorded. We also performed an in vitro study to check GABAergic activity of DZN and DZP. Additionally, molecular docking studies were performed against the GABAA receptor and voltage-gated sodium channel, along with pharmacokinetics and toxicity assessments of the test compound and the reference drugs. Results showed that DZN dose-dependently increased convulsion onset and significantly reduced convulsion frequency and duration compared to the control group (p < 0.05). The combination of DZN- 20 with CAR- 80 and DZP- 5 significantly enhanced convulsion onset and protection rates while reducing convulsion frequency and durations compared to their individual treatment groups. Both DZP and DZN also showed a concentration-dependent GABA activity inhibition capacity. DZN showed the highest binding affinities with GABAA receptor (- 7.8 kcal/mol) and voltage-gated sodium channel (- 9.1 kcal/mol) than the standard drugs. It also supported acceptable pharmacokinetic and toxicity profiles in in silico studies. Taken together, DZN exerted and enhanced the anticonvulsant effects of CAR and DZP, possibly through GABAA receptor and voltage-gated sodium channel interaction pathways.

Keywords: Anticonvulsion effect; Daidzin; GABA receptor interaction; Voltage-gated sodium channel.

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Conflict of interest statement

Declarations. Ethical Statement: This study was approved by the Animal Ethics Committee of Khulna University (KUAEC- 2023–05 - 09). No animals were euthanized or sacrificed by surgical procedure for this study. Finally, we sacrificed the animals by following the ethical considerations of the Animal Ethics Committee of Khulna University. Competing Interests: The authors declare no competing interests.

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