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

BackgroundIncreasing 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. <i>Dendrobium nobile</i> Lindl. alkaloids (DNLA), the primary active components of <i>Dendrobium nobile</i> Lindl., have been shown to enhance cognitive function and exhibit neuroprotective effects in AD animal models.ObjectiveHowever, the impact of DNLA on AD with CCH is still elusive.MethodsIn this study, we explored the therapeutic potential and underlying mechanisms of DNLA using a novel AD plus CCH mouse model.ResultsOur 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.ConclusionsOur 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.