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Background Short-term memory impairment is a neurodegenerative disease associated with oxidative stress. Bryophyllum pinnatum (Lam.) Oken of the family Crassulaceae is traditionally used in the treatment of diseases, such as cough, wounds, and kidney diseases. This study evaluates the effect of the aqueous extract of B. pinnatum (AEBP) leaves on acetylcholinesterase activity in carbon tetrachloride (CCl4)-induced short-term memory impairment in rats. Methods Thirty male Wistar albino rats were used in this study and were divided into six groups (n=5). Group I served as control, group II rats were induced with CCl4, while groups III–V animals were pretreated with silymarin (25 mg/kg body weight), 25 and 50 mg/kg body weight AEBP leaves, respectively, once daily by oral gavage for 14 days prior to a single intraperitoneal injection of CCl4. Animals in group VI received 50 mg/kg body weight AEBP only by oral gavage. Results Administration of carbon tetrachloride significantly increased (p<0.05) spontaneous alternation and locomotor function in rats when compared with the control group. Also, the levels of acetylcholinesterase, adenosine deaminase, and malondialdehyde were increased in CCl4-administered rats, with reduction in both enzymatic and nonenzymatic antioxidant levels. However, pretreatment of rats with AEBP leaves, at tested doses, prevented these changes. Conclusions The increased antioxidant status and the inhibition of acetylcholinesterase activity show that AEBP leaves improve learning memory and stabilizes memory impairment caused by CCl4.

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