The molecular mechanism of Silexan: Neurotrophic effects via CREB activation might explain preclinical antidepressant properties

Recent clinical data indicate that Silexan, an oral Lavender oil preparation (LO), exerts safe therapeutic effects in the treatment of patients affected by general anxiety disorders and specifically patients with subtreshold anxiety. Comparing LO's effects with those of pregabalin it was demonstrated that LO can similarly inhibit the opening of voltage dependent calcium channels (VOCCs) in synaptosomes and primary hippocampal neurons at a concentration comparable to that used in clinical trials (i.e. 80 mg/d). Surprisingly, LO displayed additional effects as compared to pregabalin: specifically, it increased behavioural scores in the forced swimming test in vivo and stimulated the neurogenesis in PC12 cells in vitro. These effects, considered necessary for an effective and long-lasting antidepressant activity, are generally linked with the the activation of the cAMP response element-binding protein (CREB). In this study, we first demonstrated that LO stimulates neurogenesis by increasing levels of growth associateted proteins and increased ratio values of P-CREB vs. CREB. Next, we tried to identify the pathways involved in CREB's activation using different kinase's inhibitors. In particular, we tested the role of a series of signal molecules known to be involved in the cascade that finally leads to CREB's phosphorylation. Our results showed that kinases such as PKA, PI3K, MAPK and CaMK IV are clearly involved in the neurotrophic effects of LO. This study was supported by Schwabe