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

Abstract 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.