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Thus, a more effective drug is urgently needed. Cornuside is extracted from Corni Fructus, a traditional Chinese medicine that plays an important role in treating dementia and other age\u2010related diseases. Thus, the study aimed to explore the effects and mechanisms of Cornuside on the D\u2010galactose (D\u2010Gal) induced aging mice accompanied by cognitive decline. Initially, we found that Cornuside improved the learning and memory abilities of D\u2010Gal\u2010treated mice in behavioral experiments. Pharmacological experiments indicated that Cornuside acted on anti\u2010oxidant and anti\u2010inflammatory effects. Cornuside also reversed acetylcholin esterase (AChE) activity. Meanwhile, pathology tests showed that Cornuside had a protective effect on neuron damage. Cornuside increased the expression of brain\u2010derived neurotrophic factor (BDNF), and down\u2010regulated the expression of receptor for advanced glycosylation end products (RAGE), ionized calcium binding adapter molecule 1 (Iba1), and glial fibrillary acidic protein (GFAP) respectively. Further studies claimed that Cornuside had important effects on the expression of I\u03baB\u03b1 and extracellular signal\u2010regulated kinases 1\/2 (ERK1\/2). These effects might be achieved through regulating the AGEs\u2010RAGE\u2010I\u03baB\u03b1\u2010ERK1\/2 signaling pathway, among which, ERK1\/2 might be the key protein. 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