Bulbocodin D ameliorate cognitive impairment in APP/PS1 transgenic mice by modulating amyloid-beta burden, oxidative status and neuroinflammation

Rationale Amyloid beta peptide (A beta) triggers a series of pathological events including microglial activation, oxidative stress, and inflammation-causing neuronal death and typical pathological changes in Alzheimer's disease (AD). Objectives This study aimed to investigate the therapeutic effects and mechanism of bulbocodin D for AD in vivo. Methods In this study, Morris water maze (MWM) analysis was used to detect the cognitive ability of APP/PS1 mice after gavage with bulbocodin D for 2 months. Levels of A beta 40, A beta 42, IL-1 beta, and TNF-alpha were evaluated by ELISA. A beta plaques and biomarkers of neuroinflammation were also investigated through histological analysis. Results We established that bulbocodin D significantly improved cognitive deficits in APP/PS1 transgenic mice and reduced the levels of amyloid plaque, A beta 40, and A beta 42. Bulbocodin D also reduced levels of microglial markers IbA1, GFAP, and antioxidant enzymes and reduced the products of lipid peroxidation and proinflammatory cytokines. Conclusion In summary, the present study provides preclinical evidence that oral bulbocodin D can reduce AD pathology.