Protective effects of Dendrobium nobile Lindl. alkaloids in a novel mouse model of Alzheimer's disease with chronic cerebral hypoperfusion

Background Increasing numbers of studies indicate that the pathophysiological progression of Alzheimer's disease (AD) could be accelerated by chronic cerebral hypoperfusion (CCH). These findings suggest that cerebrovascular dysfunction may induce cognitive impairment in AD by expediting neurodegeneration. Dendrobium nobile Lindl. alkaloids (DNLA), the primary active components of Dendrobium nobile Lindl., have been shown to enhance cognitive function and exhibit neuroprotective effects in AD animal models. Objective However, the impact of DNLA on AD with CCH is still elusive. Methods In this study, we explored the therapeutic potential and underlying mechanisms of DNLA using a novel AD plus CCH mouse model. Results Our results demonstrate that DNLA significantly improved cerebral blood flow, attenuated motor and cognitive decline, reduced amyloid-β deposition, mitigated neuroinflammation, and alleviated neural oxidative stress in 12-month-old AD mice with CCH. Conclusions Our study suggests that DNLA exerts multiple neuroprotective effects, effectively preserving motor and cognitive function in AD with CCH mice of 12 months. Thus, DNLA represents a promising therapeutic candidate for the prevention and treatment of AD plus CCH.