Cuminaldehyde Improves Seizures by Reducing the Expression of Tnf-Α, Inos, Nnos, and Oxidative Stress in the Hippocampus Publisher Pubmed



Asgharzadeh N ; Eshragh P ; Aminikhoei H ; Jivad N ; Khavasi AA ; Mardani M ; Abedi HA ; Bijad E ; Shahrani Korrani D ; Shahrani Korrani M ; Shahrani Korrani M
Source: Journal of Psychiatric Research Published:2026

Abstract

Introduction and objective: Neuroinflammation is a significant contributor to seizure occurrence. This study examines the anticonvulsant effects of cuminaldehyde. Materials and methods: Forty-eight NMRI mice weighing 25–30 grams and 2 months old were obtained from the Pasteur Institute of Tehran and divided into six groups: Control group (Normal saline 10 ml/kg), Saline group (Normal saline 10 ml/kg + pentylenetetrazol 90 mg/kg), Cuminaldehyde 12.5 group (Cuminaldehyde 12.5 mg/kg + pentylenetetrazol 90 mg/kg), Cuminaldehyde 25 group (Cuminaldehyde 25 mg/kg + pentylenetetrazol 90 mg/kg), Cuminaldehyde 50 group (Cuminaldehyde 50 mg/kg + pentylenetetrazol 90 mg/kg), Diazepam group (Diazepam 3 mg/kg + pentylenetetrazol 90 mg/kg). Treatments were administered for seven consecutive days. On the eighth day, seizures were induced in all groups except the control group. One hour after the final dose of cuminaldehyde, pentylenetetrazol (90 mg/kg) was administered via intravenous injection. The latency to seizure onset was recorded.On the ninth day, the mice were anesthetized using ketamine (100 mg/kg) and xylazine (10 mg/kg). Blood samples were collected, and the brains were removed. The serum and hippocampus were separated and stored at −80 °C until further analysis. Nitrite levels, total antioxidant capacity, and malondialdehyde levels in serum and hippocampus were measured. The expression levels of TNF-α, iNOS, and nNOS genes in the hippocampus were analyzed using real-time RT-PCR. Results: Seizure induction in the saline group significantly increased nitrite and malondialdehyde levels and decreased hippocampal antioxidant capacity (p < 0.001). Cuminaldehyde and diazepam prolonged seizure onset latency (p < 0.001), with diazepam showing greater efficacy than the 12.5 mg/kg and 25 mg/kg cuminaldehyde groups. Cuminaldehyde improved hippocampal antioxidant capacity, lowered nitrite and malondialdehyde levels (p < 0.001), and reduced TNF-α, iNOS, and nNOS gene expression compared to the saline group (p < 0.001). Conclusion: Cuminaldehyde delays seizure onset by enhancing antioxidant defenses, mitigating oxidative stress, and downregulating TNF-α, iNOS, and nNOS gene expression in the hippocampus, demonstrating potential as an anticonvulsant. © 2025 Elsevier B.V., All rights reserved.