Cornuside, by regulating the AGEs-RAGE-IκBα-ERK1/2 signaling pathway, ameliorates cognitive impairment associated with brain aging.

Anti-Alzheimer's disease (AD) drugs can only change the symptoms of cognitive impairment in a short time but cannot prevent or completely cure AD. 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-related diseases. Thus, the study aimed to explore the effects and mechanisms of Cornuside on the D-galactose (D-Gal) induced aging mice accompanied by cognitive decline. Initially, we found that Cornuside improved the learning and memory abilities of D-Gal-treated mice in behavioral experiments. Pharmacological experiments indicated that Cornuside acted on anti-oxidant and anti-inflammatory 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-derived neurotrophic factor (BDNF), and down-regulated 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 IκBα and extracellular signal-regulated kinases 1/2 (ERK1/2). These effects might be achieved through regulating the AGEs-RAGE-IκBα-ERK1/2 signaling pathway, among which, ERK1/2 might be the key protein. The study provides direct preclinical evidence for the research of Cornuside, which may become an excellent candidate drug for the treatment of aging-related AD.