Salvianolic acid B alleviates depression-like behaviors by reducing neuronal injury and promoting neurogenesis in a manner associated with JAK-STAT signaling pathway inhibition

Background Depression is strongly associated with hippocampal neuroinflammation, neuronal damage and neurogenesis. Salvianolic acid B (SalB) has anti-inflammatory and neuroprotective potential, but whether its antidepressant effect is achieved by regulating the JAK-STAT signaling pathway has not been systematically studied. Methods HT22 cell injury was induced by corticosterone (CORT) and treated with SalB. The appropriate intervention dose was screened by CCK-8 assay. The degree of cell damage was detected by flow cytometry, ELISA and kit. A chronic unpredictable mild stress (CUMS) model of depression was induced, and behavioral tests were performed. Neuronal damage, microglia activation, neuronal apoptosis, neurogenesis and synaptic plasticity were detected by ELISA, immunofluorescence, immunohistochemistry, Nissl staining and Golgi-Cox staining. The activity of JAK-STAT pathway in hippocampus and cells was detected. Results HT22 cells were exposed to 10, 15, and 20 μM SalB and 200 μM CORT, respectively. SalB inhibited CORT-induced release of inflammatory factors, oxidative stress and apoptosis. In CUMS mice, SalB significantly improved depression-like behavior, inhibited excessive activation of microglia, reduced neuroinflammation and hippocampal neuronal apoptosis, protected Nissl body structure and mature neurons, promoted neurogenesis and improved dendritic spine density and synaptic protein expression. In addition, SalB also inhibited JAK-STAT signaling, and pathway activator RO8191 reversed the neuroprotective effect of SalB. Conclusion SalB exerted multiple protective effects against neuroinflammation, neuronal apoptosis and neurogenesis in a manner associated with inhibition of the JAK-STAT signaling pathway, and ultimately improved depression-like behavior.