A comparative study of curcuminoids to measure their effect on inflammatory and apoptotic gene expression in an Aβ plus ibotenic acid-infused rat model of Alzheimer's disease

Brain Res. 2011;1400:1-18

 

Alzheimer's disease (AD) is the most common form of dementia affecting the elderly. Even though several studies have demonstrated the pathogenic mechanism of AD, identification of proper drug targets based on such mechanisms has not been very successful. Moreover, current therapeutic options available are limited. Alzheimer's disease is also called as a chronic inflammatory disease, as deposition of neurotoxin plaques and tangles results in inflammatory stress. Moreover, several study reports have shown that inflammation and apoptotic stress are the leading processes that are responsible for the devastating state of AD brain.

Several plant-based products, including turmeric have shown their potential usefulness in AD, acting through multiple pathways. Especially, Curcuminoids, a mixture of three chemical compounds (Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin), and important constituent of turmeric, have been found to be effective against AD, acting through multiple mechanisms.

 

Objective:

To explore the effect of a curcuminoid mixture and its individual components on inflammatory and apoptotic genes expression in AD using an Aβ+ibotenic acid-infused rat model.

 

Study Design:

  • SD rats (180-250 g) were injected with amyloid beta (1–40) and ibotenic acid combination in hippocampal region to produce the AD model
  • The animals were treated post-operative day 2 with either compounds or saline and studied the effect of the compounds over a short duration (5 days treatment) and over a long duration (20 days treatment)
  • At the end of the study, hippocampus and frontal cortex (for RNA extraction) were isolated from animals’ brain after sacrificing
  • RT-PCR method was adopted to study the expression of different genes after treatment with drugs

 

Results and Discussion:

  • Demethoxycurcumin (10 mg/kg and 30 mg/kg) significantly decreased hippocampal IL-1β levels when evaluated after short duration treatment compared with the neurotoxin treated group
  • Expression of glial fibrillary acidic protein (GFAP) was also decreased in curcuminoid mixture and demethoxycurcumin treatment groups after 5 days of treatment
  • In 20 days treatment study, curcuminoid mixture and bisdemethoxycurcumin effectively decreased caspase-3 level in the hippocampus
  • Hippocampal FasL level was significantly decreased by the curcuminoid mixture at 30 mg/kg after 5 days as well as 20 days of treatment
  • In case of Fas receptor levels, each compound was effective after 20 days in reducing its levels in the hippocampus

 

Conclusion:

Curcuminoids, along with each constituent in the mixture played a significant role, via different pathways, in the attenuation of Aβ-induced apoptotic and inflammatory features, which clearly indicated their potential beneficial role in treating AD.

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