Cymene consumption and physical activity effect in Alzheimer's disease model: an in vivo and in vitro study

Abstract

Purpose: Alzheimer's disease (AD) is one of the most important neurodegenerative diseases and accompanied by the production of free radicals and inflammatory factors. Studies have shown that p-cymene has anti-inflammatory and anti-oxidant effects. Here, the effects of this compound were investigated on a rat model of AD.

Methods: In order to create Alzheimer's rat model, bilateral injection of Amyloid β1-42 (Aβ1-42) into rats hippocampus was performed. Both therapeutic (post-AD induction) and preventive effects of p-cymene consumption with doses of 50 and 100 mg/kg were investigated. In addition, the effects of adding short-term exercise to the process were also observed. In vitro, Aβ1-42 peptide was driven toward fibril formation and effect of p-cymene was observed on the resulting fibrils.

Results: Learning and memory indices in the AD rats were significantly reduced compared to the Sham group, while p-cymene consumption with both doses, as well as performing exercise counteracted AD consequences. Moreover, increased neurogenesis and reduced amyloid plaques counts were observed in treated rats. In vitro formed fibrils of Aβ1-42 were partially disaggregated in the presence of p-cymene.

Discussion: p-Cymene could act on this AD model via antioxidant and anti-inflammatory properties as well as direct anti-fibril effect.

Conclusion: p-cymene can improve AD-related disorders including memory impairment.

Keywords: Alzheimer’s disease; Aβ1–42; Cymene; Fibril; Rat.

Fig. 1

Overall serum levels of SOD in different groups. ***: p < 0.001, with the Alzheimer’s disease group put as reference group. Please refer to the Methods section for groups’ definition

Fig. 2

Overall serum levels of MDA in different groups. ***: p < 0.001, with the Alzheimer’s disease group put as reference group. Please refer to the Methods section for groups’ definition

Fig. 3

Electron microscope analysis of Aβ42 fibrillation with and without p-cymene. TEM images of Aβ42 fibrillation process after immediate incubation (a), 2 days (b), and 4 days (c) in the absence of p-cymene. The second row indicates the four-day-old Aβ42 fibrils incubated with p-cymene 100 μM for 1 week (d) and 3 weeks (e)