Eugenol alleviates neuronal damage via inhibiting inflammatory process against pilocarpine-induced status epilepticus

Author:

Zhu Jing1,Park Soojin1,Kim Chul Hoon2,Jeong Kyoung Hoon3ORCID,Kim Won-Joo4

Affiliation:

1. Department of Neurology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

2. Department of Pharmacology, Brain Korea 21 Project, Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

3. Epilepsy Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

4. Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea

Abstract

Neuroinflammation is one of the most common pathological outcomes in various neurological diseases. A growing body of evidence suggests that neuroinflammation plays a pivotal role in the pathogenesis of epileptic seizures. Eugenol is the major phytoconstituent of essential oils extracted from several plants and possesses protective and anticonvulsant properties. However, it remains unclear whether eugenol exerts an anti-inflammatory effect to protect against severe neuronal damage induced by epileptic seizures. In this study, we investigated the anti-inflammatory action of eugenol in an experimental epilepsy model of pilocarpine-induced status epilepticus (SE). To examine the protective effect of eugenol via anti-inflammatory mechanisms, eugenol (200 mg/kg) was administrated daily for three days after pilocarpine-induced SE onset. The anti-inflammatory action of eugenol was evaluated by examining the expression of reactive gliosis, pro-inflammatory cytokines, nuclear factor-κB (NF-κB), and the nucleotide-binding domain leucine-rich repeat with a pyrin-domain containing 3 (NLRP3) inflammasome. Our results showed that eugenol reduced SE-induced apoptotic neuronal cell death, mitigated the activation of astrocytes and microglia, and attenuated the expression of interleukin-1β and tumor necrosis factor α in the hippocampus after SE onset. Furthermore, eugenol inhibited NF-κB activation and the formation of the NLRP3 inflammasome in the hippocampus after SE. These results suggest that eugenol is a potential phytoconstituent that suppresses the neuroinflammatory processes induced by epileptic seizures. Therefore, these findings provide evidence that eugenol has therapeutic potential for epileptic seizures.

Funder

National Research Foundation of Korea funded by the Ministry of Education

National Research Foundation of Korea funded by the Korea government

Publisher

Frontiers Media SA

Subject

General Biochemistry, Genetics and Molecular Biology

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