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Zanthoxylum bungeanum  Maxim (Rutaceae), a popular condiment and dietetic herbal medicine, has been used traditionally in the treatment of forgetfulness, as recorded in  Shen Nong's Herbal Medicine , an old Chinese medicine book. To explore effects and potential mechanisms of it, extracts of  Z. bungeanum  through water (WEZ), volatile oil (VOZ), petroleum ether (PEZ), and methylene chloride (MCZ) were used to treat the memory loss induced in D-galactose-induced aging mice. The impaired memory was significantly alleviated after WEZ and VOZ extract treatment. WEZ and VOZ extracts also prevented D-galactose-induced hippocampal neuron damage. In addition, WEZ and VOZ extracts upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), which suggests that the effects of WEZ and VOZ extracts on oxidative stress and apoptosis might be involved in the cognitive dysfunctions. Furthermore, WEZ and VOZ extracts enhanced the activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), which suggests that  Z. bungeanum  has an appreciable therapeutic effect on learning and memory disabilities, and its mechanism may be related to activate PI3K/Akt signaling pathway. Collectively, our study suggested that  Z. bungeanum  extracts are promising agents for prevention of aging-related cognitive dysfunction and neurological deficits.

Bungeanum Improves Cognitive Dysfunction and Neurological Deficits in D-Galactose-Induced Aging Mice via Activating PI3K/Akt/Nrf2 Signaling Pathway