Antidepressant-like effects of magnesium lithospermate B in a rat model of chronic unpredictable stress

Magnesium lithospermate B (MLB), an active polyphenol acid of Danshen [Radix Salviae miltiorrhizae (Labiatae)], shows neuroprotective and anti-inflammatory effects in vivo and in vitro.

We hypothesized that MLB might exert antidepressant-like effects by targeting the neuroinflammatory signals.

Sprague-Dawley rats were subjected to the chronic unpredictable stress (CUS) protocol. Rats in the control group received no CUS during the whole experiment. In the model group, rats were exposed to CUS for 7 weeks. From the beginning of the 5th week, model group rats were randomly grouped and subjected to different treatments. In the experiment, control and model group rats were intraperitoneally (i.p.) injected with saline. MLB was dissolved in saline to give a final concentration, and the rats were injected (i.p.) with 15, 30, or 60 mg/kg MLB once a day for 3 weeks.

MLB administration significantly reduced: (1) the immobility time in the forced swimming test (19 s, p < 0.05); (2) the immobility time in the tail suspension test (76.3 s, p < 0.05); (3) the corticosterone (CORT) concentrations in the serum (21.7 nmol/L, p > 0.05); (4) the pro-inflammatory cytokine levels in the serum - TNF-α (92.1 pg/ml, p < 0.05), IL-1β (86.9 pg/ml, p < 0.05), and IL-6 (93.8 pg/ml, p < 0.05); (5) pro-inflammatory cytokine levels in tissue - TNF-α (3.2 pg/mg protein, p < 0.05), IL-1β (1.5 pg/mg protein, p > 0.05), and IL-6 (6.3 pg/mg protein, p < 0.05); and (6) phospho-NF-κB (1.6, p < 0.05) and phospho-IκB-α (0.4, p < 0.05) expression in tissue.

The results suggested that MLB might exert therapeutic actions on depression-like behavior and the HPA axis hyperactivity in CUS rats, and the mechanisms underlying the antidepressant-like effects of MLB might be mediated by regulation of the expression of NF-κB and IκB-α in rats.