Neuroprotective Effects of Proso Millet (Panicum miliaceum L.) Free Phenolic Extract in an Aβ_1–42-Induced Alzheimer’s Disease Mouse Model

Background

Alzheimer's Disease (AD) is a neurodegenerative condition linked with inflammation and oxidative stress of neurones. The conventional anti-inflammatory drugs showed little efficacy in reducing AD, thus new anti-AD drugs have become more important. Inhibitors of soluble Epoxide Hydrolase (sEH) have been recently reported to retain the memory function in diabetic rats, but their effectiveness in reducing memory loss in Aβ_1-42-induced AD model is not known.

Objectives

The objective of the present study was to assess the sEH inhibition potential of proso millet free phenolics (Panicum miliaceum L., PM-FP) in vitro and to compare its effect with the standard sEH inhibitor 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) Urea (TPPU) in ameliorating AD.

Materials and Methods

As AD is also linked with loss of the sense of smell, we assessed the ability of sEH inhibitors to retain the olfactory function (buried pellet food test) in AD mice as well as memory loss (Novel object recognition test, discrimination index). Further, we have also evaluated the effect of treatment on ROS production in brain.

Results

Proso Millet seeds Free Phenolics extract (PM-FP) was found to be a potent inhibitor of human sEH and mouse sEH with IC₅₀ of 6.40 and 16.38 µg/mL respectively. AD was induced in mice by intra-cerebroventricular injection of Aβ_1-42 which resulted in olfactory and memory dysfunction.

Conclusion

Proso millet and standard sEH inhibitors improved olfactory and memory function with a reduction in ROS generation in AD mice. The present study demonstrates that sEH inhibition by PM-FP is a promising approach to treat AD.