Flavonoids ameliorate aluminum chloride-induced learning and memory impairments via suppression of apoptosis and oxidative stress in rats

Abstract

The study was to investigate the effects of flavonoids (rutin, puerarin, and silymarin) on learning and memory function in rats exposed to aluminum chloride (AlCl3). Wistar rats were administered flavonoids at a dose of 100 mg/(kg·bw)/day or 200 mg/(kg·bw)/day after exposed to 281.40 mg/(kg·bw)/day AlCl3·6H2O. The results of Morris water maze suggested that rutin and puerarin increased the frequency of crossing the platform and swimming time spent in the target quadrant of AlCl3-induced rats significantly. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay indicated that three flavonoids could alleviate apoptosis of hippocampal neurons induced by AlCl3. Real time-PCR and western blot suggested that rutin, puerarin and 100 mg/(kg·bw)/day silymarin could decrease the AlCl3-induced high expression of Bcl-2 associated X protein (Bax) mRNA and protein in hippocampus, but the expression of B cell lymphoma/leukemia-2 (Bcl-2) mRNA and protein was not significantly different among groups. Flavonoids could up regulate the low expression of autophagy related proteins (Beclin 1 (Bcl-2-interacting protein with a coiled-coil domain 1) and LC3 (microtubule-associated protein 1 light chain 3)) caused by AlCl3 exposure. Flavonoids could also adjust the change in adenosine triphosphatase, superoxide dismutase, glutathione peroxidase and malondialdehyde induced by intake of AlCl3. The results of inductively coupled plasma atomic emission spectroscopy (ICP-AES) suggested that flavonoids could effectively reduce the high Al level in brain and serum of AlCl3 exposed rats. In conclusion, three flavonoids may improve learning and memory function by inhibiting excessive apoptosis and oxidative stress in AlCl3 exposed rats.