The dual functions of Ziziphi spinosae semen as medicine and food: origins, cross-domain applications, antidepressant metabolites, and pharmacological mechanisms

Depression, a serious mental illness prevalent globally, exhibits a strong clinical heterogeneity. Existing chemical drug treatments have significant limitations, necessitating the development of safe and effective new intervention strategies. Ziziphi Spinosae Semen , included in the first group of medicinal botanical drugs in China’s “dual functions of medicine and food” database, combines traditional sedative effects with modern pharmacological activities, demonstrating unique potential for the prevention and treatment of depression. This article systematically reviews literature from databases such as PubMed, Web of Science, Google Scholar, CNKI, and Wanfang Data. It elucidates the significance of its “dual functions of medicine and food” by tracing its journey from traditional use in prescriptions to modern food and health applications. The review focuses on summarizing its four major categories of antidepressant bioactive metabolites and deeply analyzes its multi-dimensional synergistic mechanisms of action. These include regulating monoamine neurotransmitter homeostasis, repairing hypothalamic-pituitary-adrenal axis hyperfunction, upregulating brain-derived neurotrophic factor expression, and inhibiting neuroinflammatory responses. This synthesis aims to provide new insights and a scientific basis for developing novel antidepressant drugs or functional dietary supplements based on the “dual functions of medicine and food” concept.