Abstract: Objective To investigate the effect of Shumian capsule (SMC) on learning and memory impairment induced by chronic sleep deprivation and to explore its underlying mechanism. Methods A chronic sleep deprivation (CSD) model was established with a modified multiple platform method (MMPM). The pentobarbital sodium sleep test, Barnes maze test, open field test (OFT), and forced swimming test (FST) were conducted for behavioral analysis. Western blot was used to detect the expression level of alpha2A-adrenergic receptor (α2A-AR), TWIK- related potassium channel 2(TREK2),and protein kinase A (PKA) catalytic subunit. Results Compared with the model group, high-dose SMC significantly reduced sleep onset latency (P＜0.05); low-, medium-, and high-dose SMC all significantly prolonged sleep time (L-SMC, M-SMC, and H-SMC groups, P＜0.001). In the Barnes maze test, after three consecutive days of training, CSD mice showed a significantly increased latency to find the target hole (P＜0.001). Treatment with medium- and high-dose SMC significantly reduced the latency, with the most pronounced effect observed in the high-dose SMC group (P＜0.001). In the open field test (OFT), the time spent in the center zone was significantly increased in CSD mice (P＜0.001), while all SMC-treated groups showed significantly reduced center zone time (L-SMC group, P＜0.05; M-SMC group, P＜0.01; H-SMC group, P＜0.001). In forced swimming test (FST), used to assess depressive-like behavior, the immobility time was significantly reduced in the high-dose SMC group compared with the model group (P＜0.001). In the prefrontal cortex of CSD mice, the protein levels of α2A-AR and TREK2 were significantly increased (P＜0.05)and SMC treatment reversed this increase. Conclusions SMC might improve learning and memory impairment by inhibiting α2A-AR/TREK2 channel-mediated hyper polarization of cortical neurons. SMC alleviates sleep disturbances and learning and memory impairments. High-dose SMC exhibits the most significant effect in improving learning and memory impairment. SMC may enhance learning and memory by modulating neuronal excitability via the inhibition of the α2A-AR/TREK2 pathway.

Key words: Shumian capsule (SMC), chronic sleep deprivation, learning and memory impairment, alpha2A-adrenergic receptor