Research progress on the mechanism of antidepressant effect of salidroside

Current pharmacological interventions for depression, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), noradrenergic and specific serotonergic antidepressants (NaSSAs), tricyclic and tetracyclic antidepressants, and monoamine oxidase inhibitors (MAOIs), are often constrained by side effects, such as gastrointestinal disturbances, headaches, dizziness, and sexual dysfunction, as well as variable therapeutic efficacy and delayed onset of action. In recent years, increasing interest has been directed toward identifying novel antidepressant agents derived from traditional Chinese herbal medicines, with a growing body of preclinical studies supporting their potential utility. Salidroside (SAL), traditionally used to invigorate qi and enhance blood circulation, has demonstrated promising antidepressant properties. Accumulating evidence suggests that its therapeutic effects may involve multiple molecular mechanisms, including upregulation of the SIRT1/PGC-1α signaling pathway to stimulate hippocampal neurogenesis, suppression of NLRP3 inflammasome-mediated pyroptosis via the P2X7/NF-κB/NLRP3 axis, downregulation of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), inhibition of microglial activation, enhancement of monoaminergic neurotransmission, and attenuation of lipopolysaccharide (LPS)-induced neuroinflammation. This review aims to comprehensively summarize the pharmacological activities and underlying molecular mechanisms of SAL in the context of antidepressant therapy.