Xiaoxue Zhang1, Xue Wang1, Xinhua Hu2, Xiaowen Chu1, Xintong Li1, Fei Han3. 1. School of Pharmacy, Shenyang Pharmaceutical University, No.103 Wenhua Road, Shenhe District, Shenyang 110016, China. 2. School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, No.103 Wenhua road, Shenyang 110016, China. 3. School of Pharmacy, Shenyang Pharmaceutical University, No.103 Wenhua Road, Shenhe District, Shenyang 110016, China; Key Laboratory of Ministry Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshan Eastern Road, Huanggu District, Shenyang 110016, China. Electronic address: hanfei_spu@163.com.
Abstract
BACKGROUND: Rhodiola 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). PURPOSE: To assess the protective effects of RCE on cognitive deficits and clarify its therapeutic mechanisms in Aβ1-42 -induced rat models of AD. STUDY DESIGN: RCE was prepared by freeze-drying technology. Their protective effects on Aβ1-42-induced rat models of AD and the preliminary therapeutic mechanisms were studied. METHODS: The 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. RESULTS: RCE 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). CONCLUSION: Our 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.
BACKGROUND:Rhodiola 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). PURPOSE: To assess the protective effects of RCE on cognitive deficits and clarify its therapeutic mechanisms in Aβ1-42 -induced rat models of AD. STUDY DESIGN:RCE was prepared by freeze-drying technology. Their protective effects on Aβ1-42-induced rat models of AD and the preliminary therapeutic mechanisms were studied. METHODS: The 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. RESULTS:RCE 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). CONCLUSION: Our 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.