2,3,5,4′-Tetrahydroxystilbene-2-O-beta-D-glucoside Reverses Stress-Induced Depression via Inflammatory and Oxidative Stress Pathways

Major depressive disorder (MDD) is a chronic mental disease that adversely affects human mood and cognition. Many first-line antidepressant drugs have high rates of partial responsiveness or nonresponsiveness with side effects, and finding more effective drugs for the treatment of depression is therefore urgently needed. THSG, a main active compound of the traditional Chinese herb Polygonum multiflorum, reportedly acts as a neuroprotective agent. This study aimed to illustrate whether THSG prevents depressive-like behaviors induced by chronic restraint stress (CRS) in an MDD mouse model. Our results demonstrated that the peripheral administration of different THSG doses (10 mg/kg, 20 mg/kg, and 40 mg/kg) reversed the depressive-like behaviors in CRS mice as measured by the tail suspension test, forced swimming test, and open-field test. Further analyses suggested that THSG treatment reduced oxidative stress in both the central and peripheral nervous systems of CRS mice. In addition, heightened inflammatory responses, demonstrated by the increased expression of proinflammatory factors (TNF-α, IL-1β, and IL-6), in hippocampal and prefrontal cortex tissues of CRS mice were inhibited by THSG administration. THSG also restored the diminished Akt signaling pathway in the brains of CRS mice. Moreover, our data suggest increased astrocyte proliferation and neurogenesis in the hippocampus of CRS mice after THSG treatment. Taken together, our results demonstrated an antidepressant effect of THSG in a mouse model of MDD for the first time, and oxidative stress and inflammatory pathways were determined to play roles in this effect.