Cui Xiaofang, Zhang Shengmei, He Ling, Duan Huizhu, Xie Yujun, Pei Xiangping, Yan Yan, Du Chenhui
School of Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan 030619, China.
Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China.
Int J Mol Sci. 2025 Apr 24;26(9):4011. doi: 10.3390/ijms26094011.
Ziziphi Spinosae Semen saponins (ZSSS) show sedative-hypnotic activity but have very low bioavailability, potentially due to their conversion into bioactive metabolites by gut microbiota. In this study, the biotransformation of ZSSS by gut microbiota from healthy humans and patients with insomnia in vitro was analyzed. A total of 21 prototype compounds and 49 metabolites were identified using UHPLC-Q-Orbitrap-MS. Deglycosylation, deoxygenation, dehydration, and deacylation were detected in both healthy individuals and insomniacs. However, oxidation and hydrogenation were uniquely observed in insomniacs. ZSSS can enhance beneficial bacteria, such as , , and ZSSS can promote the synthesis of short-chain fatty acids (SCFAs), especially acetic acid, propionic acid, and butyric acid. Furthermore, it was found that the sedative-hypnotic activity of ZSSS was enhanced after biotransformation, as determined by a sodium pentobarbital-induced sleeping test (SPST), open-field behavior test (OFBT), and molecular docking experiment (MDE). These results collectively offer valuable insight into the mechanism of action of ZSSS.
酸枣仁皂苷（ZSSS）具有镇静催眠活性，但生物利用度极低，这可能是由于它们被肠道微生物群转化为生物活性代谢物所致。在本研究中，分析了健康人和失眠患者的肠道微生物群对ZSSS的体外生物转化。使用UHPLC-Q-Orbitrap-MS共鉴定出21种原型化合物和49种代谢物。在健康个体和失眠症患者中均检测到去糖基化、脱氧、脱水和脱酰化反应。然而，氧化和氢化反应仅在失眠症患者中观察到。ZSSS可以增强有益菌，如[具体有益菌名称缺失]、[具体有益菌名称缺失]和[具体有益菌名称缺失]。ZSSS可以促进短链脂肪酸（SCFA）的合成，尤其是乙酸、丙酸和丁酸。此外，通过戊巴比妥钠诱导睡眠试验（SPST）、旷场行为试验（OFBT）和分子对接实验（MDE）确定，发现ZSSS在生物转化后其镇静催眠活性增强。这些结果共同为ZSSS的作用机制提供了有价值的见解。
