Isoacteoside alleviates LPS-induced depressive-like behaviors in mice by inhibiting neuroinflammation through regulating microglial polarization and oxidative stress

Recent studies have demonstrated a close association between neuroinflammation and depression. Isoacteoside (ISO) has recently been reported to exhibit anti-inflammatory properties. However, the effects of ISO on neuroinflammation-induced depression and its underlying mechanisms have not been fully elucidated. This study aimed to investigate the mechanism of ISO on neuroinflammation-induced depression from both in vivo and in vitro aspects. In the in vivo experiments, lipopolysaccharide (LPS) was used to induce depressive-like behavior in adult male C57BL/6J mice, which were subsequently detected using the open field test (OFT), forced swim test (FST), and tail suspension test (TST). Quantitative real-time polymerase chain reaction (qPCR) and western blot were employed to measure the expression of inflammatory and polarization markers, as well as related proteins. Immunofluorescence staining was used to detect the expression of glial cell markers. For the in vitro experiments, BV2 and SH-SY5Y cells were selected and treated with LPS for subsequent analysis. The results indicated that mice treated with LPS exhibited depressive-like behaviors, accompanied by significant levels of neuroinflammation and oxidative stress, all of which were effectively reduced by ISO treatment. Furthermore, ISO facilitated the normalization of microglial polarization from the M1 to M2 phenotype, reduced the expression of ionized calcium-binding adaptor 1 (Iba1) and glial fibrillary acidic protein (GFAP), and modulated the CREB/BDNF signaling pathway. These findings suggest that ISO has an ameliorative effect on LPS-induced depressive-like behavior in mice, which may be achieved by attenuating neuroinflammation and oxidative stress as well as modulating the phenotype of microglia.