Neuroprotective effects of a Rhodiola crenulata extract on amyloid-β peptides (Aβ1-42) -induced cognitive deficits in rat models of Alzheimer's disease

Abstract

BackgroundRhodiola crenulata has been wildly used as a healthy food, antidepressant and antifatigue for many years in China. Recent studies suggested that Rhodiola crenulata extract (RCE) has cognitive protective effects in the treatment of Alzheimer's disease (AD). PurposeTo assess the protective effects of RCE on cognitive deficits and clarify its therapeutic mechanisms in Aβ1-42 -induced rat models of AD. Study designRCE was prepared by freeze-drying technology. Their protective effects on Aβ1-42-induced rat models of AD and the preliminary therapeutic mechanisms were studied. MethodsThe Y maze test and Morris water maze (MWM) test were conducted to evaluate the learning and memory abilities of the rats. Subsequently, biochemical assays, hematoxylin-eosin staining, immunohistochemistry and Western blotting were performed to elucidate the mechanisms. ResultsRCE significantly increased the spontaneous alternation (F (6, 111) = 8.165, p < 0.001), prolonged the swimming time (F (6, 111) = 20.143, p < 0.001) and decreased the escape latency in rat models of AD. In addition, RCE significantly increased the acetylcholine (Ach) level and the choline acetyl transferase (ChAT) activity (F (6, 34) = 6.033, p < 0.001; F (6, 34) = 6.958, p < 0.001, respectively), repaired the damage of hippocampus neurons and prevented Aβ formation in the hippocampus in Aβ1-42 injected rats. Moreover, RCE increased the superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) level in cortex of Aβ1-42 injected rats (F (6, 34) = 5.097, p < 0.01; F (6, 34) = 2.907, p < 0.05, respectively), significantly reduced the expressions of p-tau (ser396) and induced the expressions of p-GSK3β (ser9) in hippocampus (F (6, 34) = 15.297, p < 0.001; F (6, 34) = 9.652, p < 0.001, respectively). ConclusionOur findings demonstrated that RCE significantly alleviated the learning and memory deficits in the Aβ1-42-induced rat models of AD. The mechanisms involved its protection effects against cholinergic system deficiency, oxidative stress damage and GSK3β activation. RCE may be a potential therapeutic medicine with multi-targets to prevent the progression of cognitive deterioration in AD.