Overall, for the first time, this study reports that W. somnifera ameliorates AD-related pathology, including downregulated NCX3 and cognitive impairment in the 5xFAD mouse model, establishing W. somnifera as a promising candidate to benefit a model with brain integrity challenged by forced amyloidosis created via expression of a mutant human APP transgene. Here, SLC8A3 is linked to Alzheimer disease.