Tetrahydrocurcumin ameliorates depression-like behaviors in chronic restraint stress mice by modulating neuroinflammation and neurotrophic balance

objectivesTo investigate whether tetrahydrocurcumin (THC) ameliorates depression-like behaviors in mice by modulating neuroinflammation and neurotrophic balance

methodsA mouse model of depression was established using chronic restraint stress (CRS). The mice were treated with THC (2.5, 5, or 10 mg/k) or sertraline (10 mg/kg) on a daily basis for 21 consecutive days. Anxiety- and depression-like behaviors of the mice were assessed using open field, elevated plus maze, tail suspension, and forced swimming tests. Serum levels and hippocampal expression levels of SIRT1, p-NF-κB/NF-κB, inflammatory factors (TNF-α and iNOS), and neurotrophic factors (BDNF, GDNF, and TGF-β1) were measured using ELISA, Western blotting, or immunohistochemistry. The expression levels of hippocampal CA3 microglial activation marker (Iba1) and silent information regulator 1 (SIRT1) were analyzed using immunofluorescence staining. In the

resultsTHC treatment significantly alleviated CRS-induced anxiety- and depression-like behaviors and increased body weight gain of the mice. THC obviously reduced serum and hippocampal levels of TNF-α and iNOS, increased the expression levels of SIRT1, BDNF, GDNF, and TGF-β1, and inhibited NF‑κB activation in the hippocampus. The THC-treated mice showed significantly reduced Iba1 expression and Iba1

conclusionsTHC produces significant antidepressant-like effects in CRS mice likely by activating SIRT1 to suppress NF‑κB-mediated neuroinflammation and restore neurotrophic factor expressions. These findings highlight the SIRT1/NF-κB pathway as a key mechanism mediating the therapeutic effect of THC against depression.