Objective To optimize the preparation process parameters of Anshen Dingzhi Pills (ADP, 安神定志丸) and explore its efficacy in alleviating cognitive impairment in sleep deprived model rats. Methods Single factor experiments were conducted on the ratio of powder to honey, drying time and drying temperature. The appearance characteristics, disintegration time limit and six index components (polygalaxanthone III, 3,6′-disinapoylsucrose, ginsenoside Rb₁, β-asarone, dehydrotumulosic acid and pachymic acid) were used as comprehensive evaluation indexes. The AHP-entropy weight method combined with the Box-Behnken design-response surface method (BBD-RSM) were used to optimize the best process parameters for the preparation of ADP. The improved multi-platform water environment method was used to induce a rat model of sleep deprivation. The efficacy of ADP on sleep deprivation rats with cognitive impairment was evaluated by motor function, learning and memory performance, hippocampal histopathological changes, serum levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 and oxidative stress markers in brain tissue, such as superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA). Results The optimal preparation process parameters for ADP was determined as follows, the ratio of honey to medicinal powder of 0.316:1, drying time of 14.0 h and drying temperature of 50 ℃. Pharmacological evaluation demonstrated that the prepared ADP significantly reduced escape latency in sleep deprived rats, increased the number of platform crossings, time spent in the target quadrant, and novel object recognition index. Additionally, it markedly alleviated neuronal structural damage in the hippocampal CA1 region, decreased serum levels of inflammatory factors (TNF-α, IL-1β and IL-6) and effectively regulated the expression levels of oxidative stress (SOD, GSH and MDA) in brain tissue. Conclusion The optimized ADP preparation process is stable and has consistent quality, which can significantly improve the cognitive function and hippocampal nerve cell morphology of sleep-deprived rats, reduce the levels of inflammatory factors, alleviate oxidative stress damage, and also provide a scientific reference basis for the development of ADP preparations and clinical applications.

Anshen Dingzhi Pills  /  AHP-entropy weight method  /  Box-Behnken design-response surface methodology  /  sleep deprivation  /  cognitive impairment  /  neuroprotection  /  polygalaxanthone III  /  3,6′-disinapoylsucrose  /  ginsenoside Rb₁  /  β-asarone  /  dehydrotumulosic acid  /  pachymic acid  /  tumor necrosis factor-α  /  interleukin-1β  /  interleukin-6  /  superoxide dismutase  /  reduced glutathione  /  malondialdehyde