Cang-Ai Volatile Oil Mitigates Lipopolysaccharide-Induced Depressive-Like Behaviour in Mice by Modulating the Microglial BDNF/CREB Signaling Pathway

Depression is a severe mental disorder with evidence suggesting that microglial modulation can play a crucial role in elevating brain-derived neurotrophic factor (BDNF) level in hippocampus. Previous studies highlight that Cang-ai volatile oil (CAVO) exhibits antidepressant effects by inhibiting microglial activation and neuroinflammation while upregulating BDNF expression. This study aimed to investigate CAVO's antidepressant effects through modulating microglial phenotypic polarization and the BDNF/cAMP response element binding protein (CREB) pathway. Results showed that in a Lipopolysaccharide (LPS)-induced depression model, CAVO increased the animals' body weight (BW) and alleviated depressive-like behaviors. CAVO reduced the number of Iba1 and CD16/32 co-localized cells and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), while increasing IL-4, IL-10, and BDNF levels. In LPS-activated BV2 cells, CAVO reversed the elevated release of pro-inflammatory cytokines and enhanced anti-inflammatory factors, demonstrating a dose-dependent response. Additionally, CAVO treatment significantly elevated CD163 expression while reducing CD86 expression, with the most prominent effects observed at the higher CAVO dose, indicating the potential of CAVO to modulate microglial polarization from an M1 pro-inflammatory state towards an M2 anti-inflammatory phenotype. Western blot analysis confirmed that CAVO elevated BDNF, AKT, and p-CREB while reducing ERK1/2 expression in both mouse and BV2 cells. The findings support the therapeutic potential of CAVO in depression treatment through modulation of inflammatory responses and enhancement of BDNF synthesis via the BDNF/CREB pathway in microglia.