The anxiolytic effect of koumine on a predatory sound stress-induced anxiety model and its associated molecular mechanisms

Koumine is the most abundant alkaloid extracted from Gelsemium elegans Benth.. Preliminary studies by our research group have shown that koumine has significant anxiolytic effect, but this needs to be further confirmed.To investigate the potential anxiolytic effect of koumine on predatory sound (PS) stress-induced anxiety models and preliminarily explore its therapeutic targets and molecular mechanisms.The anxiolytic effect of koumine in an animal model of acute PS stress-induced anxiety were determined. Then, neurosteroids levels in the main brain regions involved in anxiety disorders, as well as plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels, were determinated. Finally, to clarify the effect of koumine on translocator protein 18 kDa (TSPO), the affinity between koumine and TSPO was evaluated by surface plasmon resonance (SPR) technology.Koumine treatment mitigated anxiety-like behavior following acute PS stress in the open field test and elevated plus maze test. PS exposure significantly decreased progesterone and allopregnanolone levels in the PFC, Hip, and Amy and increased ACTH and CORT levels in plasma, and koumine administration significantly reversed these effects. Finally, the reliable SPR results showed that the KD of koumine with TSPO was 155.33 ± 11.0 μM, indicating that koumine is a human TSPO high-affinity ligand that has an affinity comparable to typical TSPO ligands.Our results show that koumine has obvious anxiolytic effect in the PS-induced anxiety model. Targeting TSPO-neurosteroids-HPA axis may be an important mechanism by which koumine exerts its anxiolytic effect.