Objective: To evaluate whether Panax notoginseng flower extract (PNF) can alleviate depression-like behavior caused by chronic unpredictable mild stress (CUMS) in mice and to explore its relations to neuroinflammation.
Materials and Methods: C57BL/6J mice were subjected to CUMS for 7 weeks to induce depressive-like behaviors. Then PNF 1.7 or 3.4 g/kg was administered via intragastric gavage once a day for 4 consecutive weeks. After behavioral assessment, the systemic inflammation and neuroinflammation were investigated by detecting inflammatory factors in serum and brain with enzyme-linked immunosorbent assay (ELISA). The serum levels of adrenocorticotropic hormone (ACTH) and glucocorticoids (GC) were also determined. The activation of microglia and astrocyte was investigated by immunohistochemistry. The chemical components in PNF were analyzed with Ultra-high performance liquid chromatography/MS (UPLC/MS). 
Results: PNF 1.7 and 3.4 g/kg treatment alleviated depressive behavior in CUMS mice in various behavioral studies. In both serum and brain, PNF treatment significantly counteracted the CUMS-induced enhancement of typical pro-inflammatory factors, Tumor Necrosis Factor alpha (TNF-α), Interleukin-1β (IL-1β), and IL-6 and counteracted the CUMS-induced decrease of anti-inflammatory factorIL-10. Treatment with PNF also attenuated the CUMS-induced serum ACTH and GC elevation. Immunohistochemical analysis revealed that PNF treatment significantly reduced the number of ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) positive cells in the brains of CUMS mice, indicating an inhibition of microglial and astrocytic activation. UPLC/MS study suggest that ginsenoside Rh1 is the main ginsenoside in the extract.
Conclusion: PNF ameliorates CUMS-induced depression-like behaviors in mice, which may be mainly related to reducing neuroinflammation in the brain.