LAUSR

20 (S)-protopanaxadiol (PPD) possesses a variety of biological activities, including antioxidant, antifatigue and anti-inflammatory properties. This study was aimed to investigate the antidepressant-like effects of PPD and potential mechanisms in rats exposed to chronic unpredictable mild stress (CUMS) model. Results showed that chronic treatment with PPD for 14 days ameliorated depressive-like behaviour, as indicated by the increase in sucrose preference in the sucrose preference test and decrease in immobility in the forced swim test and tail suspension test. In addition, PPD decreased the elevated levels of CORT and proinflammatory cytokines (IL-6, IL-1β and TNF-α) in the serum and neurotransmitters (5-HT and NE) in the hippocampus and PFC induced by CUMS. PPD suppressed the microglial activation in the DG induced by CUMS. Furthermore, our results suggested that rats treated with PPD displayed decreased iNOS, COX2, cleaved-caspase3, cleaved-caspase9, Bax, Bcl-2, and ac-p65 levels and increased Sirt1 levels in the hippocampus. In conclusion, this study indicated that PPD exerts promising antidepressant-like effects in CUMS rats that are mediated in part through alterations in the dysfunction of the HPA axis, the normalization of the levels of neurotransmitters, and the suppression of neuronal apoptosis and neuroinflammation, possibly through the regulation of the SIRT1/NF-kB signalling pathway.