Abstract： Objective To study the effects of Leonurine on learning and memory abilities of mice with Alzheimer's disease(AD)induced by oral gavage of aluminum chloride(AlCl3)and the underlying mechanism.Methods Sixty C57BL/6 mice were randomly assigned into blank control group,AlCl3 model group,piracetam positive control group,and high-dose,medium-dose and low-dose Leonurine groups.The AD mouse model was made by gavage of AlCl3,and daily oral gavage of piracetam and Leonurine was applied in corresponding groups.After 50 days of modeling,water maze test was used to detect the learning and memory abilities of AD mice.Malondialdehyde(MDA),superoxide dismutase(SOD),total antioxidant capacity(T-AOC)and glutathione peroxidase(GSH-Px)in brain tissues were detected.The expression levels of tumor necrosis factor alpha(TNF-α),interleukin 6(IL-6)and IL-1β in brain tissues were determined.The hematoxylin and eosin(H&E)staining of brain sections was performed to observe the effect of Leonurine on pathological injury of AD mice.Results Leonurine could significantly reduce escape latency(P＜0.05)and crossing times(P＜0.05).Leonurine could significantly reduce the damage of neurons and inhibit the loss of neurons.Furthermore,Leonurine significantly decreased MDA content in brain tissue(P＜0.01),and increased SOD,GSH-Px and T-AOC activities(P＜0.01).The expression levels of TNF-α,IL-6 and IL-1β in brain tissue were significantly inhibited by Leonurine treatment(P＜0.01).In addition,Leonurine upregulated protein levels of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in brain tissue of AD mice dose-dependently.Conclusion Leonurine can improve the learning and memory abilities of AD mice by enhancing anti-oxidative stress in the brain by activating the Nrf2/HO-l pathway.