Pharmacological evidence for curcumin neuroprotective effects against lead-stimulated neurodegeneration: possible role of Akt/GSK3 signaling pathway

Document Type: Research article

Authors

1 Department of Veterinary and Biomedical Science University of Minnesota, USA.

2 Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

3 Department of Organic Chemistry, Faculty of Pharmaceutical Chemistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

4 Department of Organic Chemistry, Faculty of Pharmaceutical Chemistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.

5 Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.

6 School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

7 Department of Animal science, Qaemshahr Branch, Islamic Azad University, Mazandaran, Iran

Abstract

One of the main herbal compounds with neuroprotective effects is curcumin. Lead poisoning cause neurodegeneration effect, however, its mechanism is unclear. The present study assesses the role of Akt/GSK3 signaling pathway in mediating the neuroprotective actions of curcumin against lead-stimulated neurodegeneration. Sixty, adult male, rats were divided in to: Group 1 and 2 received normal saline and drinking water containing 0.075% of lead acetate. Groups 3, 4, 5 and 6 were treated simultaneously with lead acetate (0.075% in drinking water) and I.P. injection of curcumin (10, 20, 40 and 60 mg/kg).Morris water maze (MWM) was used to estimate cognitive activity, Hippocampal oxidative, anti-oxidant, inflammatory and apoptotic factors and also protein kinase B (Akt) and glycogen synthase kinase 3(GSK3) protein levels were studied. We found that lead poisoning disturbed the learning and memory and simultaneous treatment with curcumin reduced the lead -stimulated cognition disorders. Furthermore, treatment with lead acetate triggered an increase in lipid peroxidation and levels of interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), oxidized form of glutathione (GSSG), Bax, GSK3 (total and phosphorylated) while decreasing the reduced form of glutathione (GSH), Bcl-2, and Akt3 (total and phosphorylated) in the hippocampus. Lead also decreased the action of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) in the hippocampus. Conversely, several doses of curcumin attenuated lead-stimulated apoptosis, oxidative stress, and inflammation; whereas increasing Akt (both forms) and reducing GSK3 (both forms) levels. Consequently, curcumin through the mediation of Akt/GSK3 signaling pathway promotes neuroprotection against lead-stimulated neurodegeneration.

Graphical Abstract

Pharmacological evidence for curcumin neuroprotective effects against lead-stimulated neurodegeneration: possible role of Akt/GSK3 signaling pathway

Keywords