Schaftoside Reduces Depression- and Anxiogenic-like Behaviors in Mice Depression Models

Background: Major depressive disorder is a common mental health issue characterized by persistently low mood and high morbidity and mortality. The major pathophysiology is neuroinflammation, as evidenced by elevated cytokine levels. Patients often fail to achieve full remission with the use of currently available antidepressants, prompting the search for new treatment options. Schaftoside (SS), a flavonoid found in traditional Chinese herbs, has both antioxidant and anti-inflammatory properties. However, its antidepressant effects are poorly understood. Methods: Male C57BL/6 mice underwent chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS) treatment to induce depression- and anxiety-like behaviors. SS was administered at 40, 80, and 160 mg/kg for 28 days. The effect on depression-like behaviors was assessed using behavioral assays, and ELISA was used to measure pro-inflammatory cytokines in the serum and hippocampus. Results: SS significantly decreased immobility in the forced swim and tail suspension tests, increased sucrose preference in the sucrose preference test, and reduced feeding latency in the novelty-suppressed feeding test. These findings indicate improved depression and anxiety-like behaviors. ELISA showed that SS lowered interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha levels in the serum and hippocampus of CUMS mice. Conclusions: Our study indicates that SS has antidepressant and anxiolytic effects, possibly through neuroinflammatory processes, making it a promising therapeutic candidate for depression, and thus deserves further investigation into its mechanisms and clinical efficacy.