Insomnia is the most common sleep disorder marked by difficulty initiating or maintaining sleep. It affects about one-third of the general population, and reduces the quality of life, work productivity, contributes to irritability, depression, anxiety, and is common in older people. 

 

    Ziziphus Spinosa seed, also known as Suan Zao Ren (酸枣仁), is one of the most common herbs to calm the mind and reduce insomnia in traditional Chinese medicine. Its function in treating insomnia and helping with sleep had been documented for thousands of years in Chinese medical books such as the ancient Chinese Shennong's Materia Medica (神农本草经) and the Compendium of Materia Medica (本草纲目).

 

    The major pharmacological action mechanisms shared by most of the sedative herbs are to act through the neurotransmitter gamma-aminobutyric acid (GABA) or via stimulation of the GABA receptor. Preclinical research of the mechanisms has been focused on GABA because it is the main inhibitory neurotransmitter in the brain. Animal studies of single compounds from Ziziphus Spinosa reveal its sedative and anxiolytic effects function as GABA agonists (1).

 

    Ziziphus Spinosa seeds typically contain complex mixtures of phytochemicals including alkaloids, glycoside saponins, and flavonoids. Flavonoids and saponins extracted from Ziziphus Spinosa seeds caused a significant reduction of walking time and coordinated movement ability of mouse, significantly prolonged its sleeping time. Saponins had a more effective sedative and hypnotic function than flavonoids, while polysaccharides did not show a sedative and hypnotic effect (2).

 

    The ethanolic extract of Ziziphus Spinosa seeds was orally administered to mice, at 0.5, 1.0, and 2. 0 g/kg, 30 min before the behavioral evaluation in the black and white test (BWT) and elevated plus maze (EPM) (both tests for anxiety). The Ziziphus Spinosa seeds at the dosage 0.5-2.0 g/kg increased the first time entry, total changes, and times spent in the white chamber of the BWT. The Ziziphus Spinosa seeds at the dosage 0.5-1.0 g/kg increased the percentage of time spent and the percentage of arm entries in the open arms of the EPM and decreased the percentage of time spent and the percentage of arm entries in the closed arms of the EPM. Furthermore, the Ziziphus Spinosa seeds at the dosage of 1. 0 g/kg prolonged the hexobarbital-induced sleeping time in mice and decreased the locomotor activity in rats. These results suggested that Ziziphus Spinosa seeds possessed an anxiolytic effect at lower doses and sedative effect at a higher dose (3).

 

    Fang et al. reported that the water extract of Suan Zao Ren (400 and 800 mg/kg body weight.) could shorten sleep latency significantly, increase sleeping time and prolong movement convalescence time induced by sodium pentobarbital administration in mice. Aqueous extraction, not alcohol extraction, is the main prescription form of traditional Chinese medicine, so it is much more meaningful to demonstrate the hypnotic effect of Suan Zao Ren aqueous extracts (4).

 

    A randomized, cross-over clinical study was conducted on twelve human participants for the effect of Ziziphus Spinosa on sleep. After two-week run-in participants were randomized to either Ziziphus Spinosa (encapsulated granules extracted from raw seeds; 2 g daily which is equivalent to ~10 g of raw seeds) or placebo for four weeks. After a four-week wash-out, participants swapped to the other treatment for four weeks. Improvements for sleep quality measured on the Insomnia Severity Index and Pittsburgh Sleep Quality Index (PSQI) were statistically significant during the Ziziphus Spinosa treatment periods compared to placebo (p<0.05). Subjective sleep parameters measured on sleep diaries showed improvements after Ziziphus Spinosa in terms of total sleep time, sleep efficiency, and sleep onset latency, but not after placebo(5).

 

    Ziziphus Spinosa is a relatively safe sedative/hypnotic of choice for patients to manage insomnia. Laboratory animal studies of Ziziphus Spinosa extract confirm a sedative effect, though the constituents that contribute to this effect have not all been specifically identified. Semen Ziziphus Spinosa is reported to have very low toxicity when taken orally. In laboratory animals, a huge single dose of 50 g/kg body weight produced no toxic symptoms, and a daily dose of 20 g/kg for 30 days did not produce toxic reactions. Side effects have not been reported (6). Importantly, a 2-gram (~10 g raw seeds) per day dose was shown to be effective to improve sleep quality in humans (5).

 

    Sleep problems can significantly affect the daily functions of people before the sleep disorders are diagnosed. Studies have reported that patients with sleep disorders have a higher risk of developing dementia than those without sleep disorders. Therefore, developing proper treatments for sleep disorders may also provide preventive strategies for reducing the risk of dementia (7).

 

    Suan Zao Ren or Ziziphus Spinosa seed is a widely used herb for treating insomnia in China. Dose-ranging can vary depending on the ways of preparation and individual response. The pan-fried (dry, no oil) form is the common form documented in Chinese medicine. Hope that by reading the well-documented effects of Suan Zao Ren on alleviating sleep problem, you may benefit from this Chinese herb and have a restful and rejuvenating good night sleep.

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References:

 

1. Shergis, J. L., Ni, X., Sarris, J., Zhang, A. L., Guo, X., Xue, C. C., … Hugel, H. (2017). Ziziphus spinosa seeds for insomnia: A review of chemistry and psychopharmacology. Phytomedicine, 34, 38–43.

2. Jiang, J.-G., Huang, X.-J., Chen, J., & Lin, Q.-S. (2007). Comparison of the sedative and hypnotic effects of flavonoids, saponins, and polysaccharides extracted from SemenZiziphus jujube. Natural Product Research, 21(4), 310–320.

3. Peng, W.-H., Hsieh, M.-T., Lee, Y.-S., Lin, Y.-C., & Liao, J. (2000). Anxiolytic effect of seed of Ziziphus jujuba in mouse models of anxiety. Journal of Ethnopharmacology, 72(3), 435–441.

4. Fang, X. S., Hao, J. F., Zhou, H. Y., Zhu, L. X., Wang, J. H., & Song, F. Q. (2010). Pharmacological studies on the sedative-hypnotic effect of Semen Ziziphi spinosae (Suanzaoren) and Radix et Rhizoma Salviae miltiorrhizae (Danshen) extracts and the synergistic effect of their combinations. Phytomedicine, 17(1), 75–80.

5. Shergis, J. L., Hyde, A., Meaklim, H., Varma,P., Da Costa, C., Jackson, M. L. (2021). Medicinal seeds Ziziphus spinosa for insomnia: A randomized, placebo-controlled, cross-over, feasibility clinical trial. Complementary Therapies in Medicine, 57, 102657.

6. Chen, C.-J., Li, M., Wang, X., Fang, F.-F., & Ling, C.-Q. (2011). Effect of Sour Date (Semen ziziphi spinosae) Seed Extract on Treating Insomnia and Anxiety. Nuts and Seeds in Health and Disease Prevention, 1037–1043.

7. Chen, C.-J., Liu, X., Chiou, J.-S., Hang, L.-W., Li, T.-M., Tsai, F.-J., … Lin, Y.-J. (2020). Effects of Chinese herbal medicines on dementia risk in patients with sleep disorders in Taiwan. Journal of Ethnopharmacology, 113267.