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

Phytomedicine. 2019 Apr:57:331-338. doi: 10.1016/j.phymed.2018.12.042. Epub 2018 Dec 31.

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.

Keywords: Alzheimer's disease; Aβ(1-42); Cognitive deficits; Intrahippocampal injection; Rhodiola crenulata.

MeSH terms

  • Acetylcholine / metabolism
  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cognition Disorders / drug therapy
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Male
  • Malondialdehyde / metabolism
  • Memory Disorders / drug therapy
  • Neurons / drug effects
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Peptide Fragments / toxicity
  • Plants, Medicinal / chemistry
  • Rats, Sprague-Dawley
  • Rhodiola / chemistry*

Substances

  • Amyloid beta-Peptides
  • Drugs, Chinese Herbal
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Malondialdehyde
  • Acetylcholine