Isorhynchophylline alleviates learning and memory impairments induced by aluminum chloride in mice

To evaluate the effect of Isorhynchophylline (IRN) on the learning and memory impairments induced by aluminum chloride (AlCl₃) in mice.

Fifty male Balb-c mice (4-month-old) were randomly divided into five groups: control, AlCl₃ plus vehicle, AlCl₃ plus IRN (20 mg/kg), AlCl₃ plus IRN (40 mg/kg) and AlCl₃ plus donepezil (5 mg/kg). Learning and memory impairments were induced in mice by subcutaneously injecting with AlCl₃ (50 mg/kg) once a day for 8 consecutive weeks. At the same time, mice were intragastrically given vehicle or IRN (20 and 40 mg/kg) or donepezil (5 mg/kg) 30 min before each AlCl₃ injection. The spatial learning and memory function was assessed using radial arm maze. After sacrificed, the parameters of oxidative stress and cholinergic system in the brain tissues were examined with ELISA kits. Moreover, the expression of nuclear factor kappa B (NF-κB) signaling pathway was analyzed with western blotting.

The results showed that treatment with IRN could significantly ameliorate the cognitive deficits induced by AlCl₃ in mice. In addition, treatment with IRN was found to reduce the level of malondialdehyde, enhance the activities of superoxide dismutases and catalase, increase the level of glutathione, and markedly inhibit the activity of acetylcholinesterase (AChE) in the brain tissues of the AlCl₃-treated mice. Moreover, IRN significantly suppressed the phosphorylation of NF-κB p65 and IκBα in the brain tissues of AlCl₃-treated mice. However, IRN did not show significant effect on the activity of butyrylcholinesterase.

Our findings demonstrated for the first time that IRN could alleviate learning and memory impairments induced by AlCl₃ in mice. The neuroprotective effect of IRN against AlCl₃-induced AD is probably mediated, at least in part, through inhibiting the AChE activity and reducing the oxidative damage of brain tissue via suppress the NF-κB signaling pathway. These results contributed to a better understanding of the in vivo anti-AD mechanism of IRN. It was concluded that IRN could protect the learning and memory function.