Hydroxy-α-sanshool isolated from Zanthoxylum bungeanum attenuated learning and memory impairments in scopolamine-treated mice

Learning and memory impairments are common symptoms in dementia with neurodegenerative disorders. Occasionally, we found that Zanthoxylum bungeanum pericarps (ZBP) significantly activated the spontaneous activity of the hippocampus (HIPP) and paraHIPP (P < 0.001, uncorrected), implying the potential ability of ZBP on improving cognitive impairments. Thus, this study was aimed to investigate the improving effect of hydroxy-α-sanshool (HAS), a characteristic ingredient of ZBP, against scopolamine (1 mg/kg, i.p.) induced learning and memory deficits. HAS (5 mg/kg, p.o.) markedly reversed scopolamine-induced cognitive impairments, as indicated by the passive avoidance test and Morris water maze test (P < 0.01). Furthermore, HAS (2.5 and 5.0 mg/kg, p.o.) also dose-dependently prevented changes in hippocampal neuron morphology and apoptosis, inhibited the acetylcholinesterase (AChE) activity, increased the acetylcholine (ACh) content, and increased the protein and mRNA expression of brain-derived neurotrophic factor (BDNF) and phosphor cAMP response element-binding (p-CREB) compared with the model group (P < 0.05 & P < 0.01). These findings demonstrated that HAS attenuated scopolamine-induced cognitive impairments mainly through enhancing the activity of the cholinergic system, and increasing CREB/BDNF signalling pathway.