Cynanchum bungei Decne-derived extracellular vesicles alleviate cognitive impairment and pathological damage in Alzheimer’s disease

IntroductionCynanchum bungei Decne (CB) is known for its therapeutic benefits for neurodegenerative conditions as anti-inflammatory, antioxidant, and barrier significantly limits their potential advantages. Given the ability of crossing the barrier with minimal toxicity, extracellular vesicles derived from CB (CB-EVs) were utilized as an innovative approach to mitigate Alzheimer’s disease (AD).MethodsCB-EVs were isolated using gradient ultracentrifugation and identified via TEM imaging, nanoparticle tracking analysis, marker identification, and in vivo imaging system. Ten-month-old triple transgenic AD (3xTg-AD) mice received intravenous administration of CB-EVs at doses of 10 or 20 mg/kg every 3 days for the cognitive and pathological assessments. The human APP Swedish mutation transgenic SH-SY5Y cells were constructed as Aβ-induced neural damage model, and different concentrations of CB-EVs were added into medium to analyze its roles on cell viability, transcriptome changes, oxidative stress, and mitochondrial damage.ResultsCB-EVs exhibited standard morphological and molecular traits, accumulating in the cerebral cortex and hippocampus. Two months of CB-EVs treatment alleviated cognitive impairments, diminished Aβ plaque, reduced Tau protein hyperphosphorylation, and lessened neuronal loss in 3xTg-AD mice. In transgenic SH-SY5Y cells, CB-EVs improved cell viability, enhanced superoxide dismutase activity, downregulated oxidative stress related NUPR1 and CHOP expression, decreased reactive oxygen species, lipid peroxidation, and malondialdehyde levels, reduced mitochondrial damage.ConclusionThese results demonstrated that CB-EVs could protect neurons from oxidative stress, attenuate cognitive impairment and pathological damage in AD.