Yuang Gu1  · Yu Yao1  · Qiuwen Lou1  · Xinyan Zhu1  · Ju Lan1  · Chenshu Gao1  · Shuangshuang Wu1  · Jingjia Liang1  · Cenglin Xu1  · Yi Wang1  · Heming Cheng1  · Zhong Chen1

1 Zhejiang Collaborative Innovation Center for Brain Diseases with Integrative Medicine, Zhejiang Key Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences, The First Afliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310053, China

Abstract

Epilepsy is one of the most prevalent and severe neurological disorders, and it is inadequately controlled with currently available medications. While cinnabar (mercury(II) sulfide)—a traditional Chinese medicine—has historical application in epilepsy treatment, its therapeutic efficacy and underlying mechanisms are unclear. In this study, we find that cinnabar exerts model-dependent antiseizure efficacy in mice. Specifically, it significantly attenuates acute seizures, enhances the termination of diazepam-resistant status epilepticus, and reduces spontaneous seizures in the kainic acid (KA)-induced seizure model. Conversely, no therapeutic effect was found in the maximal electroshock-, pentylenetetrazole-, or kindling-induced seizure model. Fiber photometry revealed that cinnabar normalizes KA-induced hippocampal neurotransmission imbalances by simultaneously decreasing glutamate hyperactivity and γ-aminobutyric acid hypoactivity. Furthermore, cinnabar has neuroprotective effects and alleviates comorbid anxiety-like behaviors, while showing no alterations in motor function. Our findings suggest cinnabar's potential as a therapeutic agent for seizure management, via a mechanism associated with the reversal of the hippocampal excitatory/inhibitory imbalance.

Keywords

Cinnabar; Epilepsy; Kainic acid; Anxiety

[SpringerLink]