Effects of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou Seed mixture on sleep quality in pre-clinical and clinical studies

Introduction Sleep disorders negatively impact quality of life and are often associated with delayed sleep onset and poor sleep maintenance. This study evaluated the effects on sleep quality based on the traditional sedative use of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou Seed (ZJS), through preclinical tests using a fermented ZJS mixture (ZJM) and clinical trials employing ZJS extract (ZJE) and ZJM. Methods In preclinical studies, the effects of ZJM on sleep latency, total sleep time, blood melatonin levels, and urinary 6-sulfatoxymelatonin (6-SMT) levels were assessed in a mouse model. Melatonin was used as a comparator. A randomized, double-blind clinical trial was conducted with 25 participants aged 20–60 years who experienced delayed sleep latency (≥30 min) and infrequent bowel movements (<4 times per week). Sleep latency, total sleep time, and subjective sleep quality were evaluated using the Pittsburgh Sleep Quality Index (PSQI). Results In preclinical models, ZJM significantly reduced sleep latency compared to 1 mg of melatonin and showed comparable efficacy to 3 mg of melatonin, and repeated ZJM administration increased urinary 6-SMT levels. In clinical trials, both ZJE and ZJM significantly improved PSQI scores, particularly in subjective sleep quality and sleep latency components. Sleep latency decreased from 53 to 30 min in the ZJE group and from 46 to 25 min in the ZJM group. Total sleep time showed a trend toward an increase but was not statistically significant. Discussion Preclinical experiments demonstrated a statistically significant reduction in sleep onset time with ZJM compared to both control and melatonin 1 mg-treated groups. In addition, clinical trials further revealed that both ZJE and ZJM exhibited significant reductions in sleep onset time and improvements in sleep quality. Collectively, these findings suggest that ZJM holds potential efficacy in sleep induction.