Clausena Harmandiana Root Extract Improved Amyloid-β Induced Cognitive Impairments in Rats By Reducing Aβ1-42 Protein Levels and Neuroinflammation

Abstract

Background: Neuroinflammation caused by amyloid‐β (Aβ) is associated with Alzheimer’s disease (AD) pathogenesis. In AD, Aβ accumulation can activate the surrounding microglia which followed by the synthesis and release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), results in cognitive impairments. Clausena harmandiana (CH) is an herb in the Rutaceae family and has been used in folk medicine for the treatment of illness such as stomachache and headache, and as a health tonic. It is interesting that CH root extract (CHRE) exhibits various anti-inflammatory and other pharmacological activities, but there has not been any study in Alzheimer's disease-like animal models.Objectives: This study aimed to investigate the effects of CHRE on Aβ1-42-induced cognitive impairments, increased Aβ1-42 protein levels and neuroinflammation. Methods: Forty-eight adult male Sprague-Dawley rats (250-300 g) were randomly divided into 6 groups (n=8). The rats were given 0.5% sodium carboxymethylcellulose, Celebrex® (10 mg/kg BW) or CHRE (125, 250, and 500 mg/kg BW) and not given any treatment by oral gavage for 35 days. On day 21, all treated rats were injected with aggregated Aβ1-42 at a concentration of 1 µg/µl into both lateral ventricles (1 µl/side), while untreated rats were injected with sterilized normal saline. Ten days later, their recognition memory was assessed using the novel object recognition test. At the end of the experiment, all rats were euthanized by an overdose of thiopental sodium (120 mg/kg BW) and transcardial perfusion with 0.9% normal saline solution, to observe Aβ1-42 protein levels and the expression of inflammatory markers (CD11b-positive microglia, IL-1β, and TNFα) in the cerebral cortex and hippocampus.Results: The results indicated that pretreatment with CHRE at all doses improved impairment of short- and long-term recognition memory. In addition, CHRE significantly decreased Aβ1-42 protein levels and the expression of inflammatory markers in both brain regions as well as pretreatment with Celebrex®.Conclusions: This suggests that CHRE has a potential therapeutic effect against Aβ1-42-induced cognitive impairments by reducing Aβ1-42 protein levels and neuroinflammation.