Saikogenin F From Bupleurum smithii Ameliorates Learning and Memory Impairment via Antiinflammation Effect in an Alzheimer's Disease Mouse Model

Alzheimer's disease (AD) is the most common neurodegenerative disease associated with aging. Bupleurum smithii Wolff. is a Chinese folk medicine used to reduce fever and inflammation. Regarding the key role of neuroinflammation in AD pathogenesis, it was speculated that B. smithii may be the source of compounds that treat AD through anti-inflammatory effects. This study aimed to investigate the effects of saikogenin F, a natural active ingredient from B. smithii, on cognition impairment and neuroinflammation in AD mice induced by amyloid beta (A beta). The AD mice model was established by intracerebroventricular (i.c.v.) injection of A beta, and different doses of saikogenin F (10, 20, and 40 mg/kg) were intragastrically administrated once daily. Results of behavioral experiments, including the novel object recognition (NOR) test, Y-maze test, and Morris water maze (MWZ) test, showed that saikogenin F could ameliorate A beta-induced cognition impairment in AD mice. Enzyme linked immunosorbent assay (ELISA) results showed that tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and reactive oxygen species (ROS) levels in hippocampal tissue increased after A beta injection, while saikogenin F could significantly reduce the concentrations of these inflammatory factors. Western blotting results revealed that the A beta-induced reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits protein expression in mice hippocampus was remarkably downregulated by saikogenin F. Results of Iba-1 immunohistochemical staining showed that saikogenin F could effectively inhibit A beta-induced activation of microglia in vivo. These results suggested that saikogenin F could relieve A beta-induced cognitive impairment via inhibiting neuroinflammation and microglial activation. These effects may be achieved by inhibiting the expression of the NADPH oxidase subunits gp91phox and p47phox.