Luteolin and Exercise Combination Therapy Ameliorates Amyloid-β1-42 Oligomers-Induced Cognitive Impairment in AD Mice by Mediating Neuroinflammation and Autophagy

Background: Alzheimer’s disease (AD) disturbs many patients and family. However, little progress has been made in finding effective treatments. Given AD is a multifactorial disease, luteolin and exercise combination therapy may be more effective than monotherapy. Objective: To explore the therapeutic effect and underlying mechanisms of luteolin and exercise combination therapy in AD treatment. Methods: This study utilized a validated mouse model of AD by bilateral injection of amyloid-β (Aβ)1-42 oligomers into the CA1 region of the hippocampus. By combining with animal behavioral test, thioflavin T detection, immunofluorescence and western blot test, the cognitive-enhancing effects of luteolin and exercise combination therapy and the underlying mechanisms were investigated. Results: Luteolin (100 mg/kg/d) combined with exercise could significantly improve the performance of AD model mice in novel object recognition test, and the improvement was greater than that of monotherapy. Further experiments showed that luteolin and exercise alone or in combination could reverse the increase of Aβ content, the activation of astrocytes and microglia, and the decrease of the level of autophagy in hippocampus and cortex in AD model induced by Aβ1-42 oligomers. While the combination therapy involved more intact hippocampal and cortical areas, with greater degree of changes. Conclusion: Luteolin and exercise combination therapy prevented Aβ1-42 oligomers-induced cognitive impairment, possibly by decreasing neuroinflammation and enhancing autophagy. The luteolin and exercise combination therapy may be a useful therapeutic option for preventing and/or delaying the progression of memory dysfunction of AD.