Berberine Alleviates Kainic Acid-Induced Acute Epileptic Seizures in Mice via Reshaping Gut Microbiota-Associated Lipid Metabolism

Abstract

Background

Berberine (BBR) has been reported to mitigate epileptic seizures. However, the potential mechanism of its anti-seizure effect remains uncharacterized.

Aims

This study aimed to investigate the protective effect of BBR on acute epileptic seizures induced by kainic acid (KA) in mice and further explore its mechanism of action in the aspect of analysis of gut microbiota.

Materials and Methods

The protective effect of BBR against acute epileptic seizures was assessed via Racine score and Nissl training. Alterations of gut microbiota and metabolites in seizure mice after BBR treatment were analyzed through 16S sequencing and lipidomics, respectively.

Results

Our results showed that the BBR remarkably alleviated acute epileptic seizures and hippocampal neuron damage in KA-induced mice. The analysis of gut microbiota indicated that BBR reduced the acute epileptic seizures in KA-induced mice by increasing the abundance of Bacteroidetes and Alloprevotella, regulating short-chain fatty acids (SCFAs). Results of lipidomics also identified 21 candidate metabolites in the colon and hippocampus possibly involved in the protective effect of BBR against acute seizures.

Conclusion

These findings suggest that BBR exerts neuroprotection against KA-induced epileptic seizures through remodeling gut microbiota-associated lipid metabolism in the colon and hippocampus. BBR may serve as a valuable candidate drug for curing patients with epilepsy.