Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.
School of Life Science and Technology, Shanxi University, Taiyuan, China.
Food Funct. 2020 Sep 23;11(9):8259-8272. doi: 10.1039/d0fo01375g.
Homology of medicine and food-zizyphi spinosi semen (ZSS) exhibits abundant pharmacological activities, such as sedation, hypnosis and anti-depression. In the present study, the water soluble polyphenols extracted from ZSS via the acid digestion method were named ZSSP, and exhibited significant anti-colorectal cancer (CRC) activity, characterized by restraining cell proliferation, promoting cell apoptosis and increasing chemo-sensitivity of CRC cells. The potential of ZSSP in vivo was further evaluated in an AOM/DSS-induced colitis-associated carcinogenesis (CAC) mouse model. Intriguingly, ZSSP diminished the number and volume of CAC polyps in mice in a dose-dependent manner, and effectively limited the damage of mice organs induced by AOM/DSS. The immunohistochemistry result showed that the elevated CRC early markers in CAC mice, such as COX-II, EMR1, and Ki67, were potently prevented by the ZSSP treatment. Further, the component in ZSSP with the anti-CRC activity was identified as spinosin by the macroporous resin of SP207 and RP-HPLC-MS/MS. Interestingly, during the extraction process, sodium ions were introduced forming spinosin·Na+, which had better water solubility and more remarkable anti-CRC activity than the spinosin. This study provides a new pharmacological property of spinosin derived from ZSS, inhibiting the growth of human CRC cells and colitis-associated CRC in mice, which indicates its potential use as a natural agent against CRC.
药食同源-酸枣仁（ZSS）具有丰富的药理活性，如镇静、催眠和抗抑郁作用。本研究采用酸消化法从 ZSS 中提取出水溶性多酚，命名为 ZSSP，具有显著的抗结直肠癌（CRC）活性，表现为抑制细胞增殖、促进细胞凋亡和增加 CRC 细胞的化疗敏感性。进一步在 AOM/DSS 诱导的结肠炎相关癌变（CAC）小鼠模型中评估了 ZSSP 的体内潜力。有趣的是，ZSSP 以剂量依赖的方式减少了小鼠 CAC 息肉的数量和体积，并有效限制了 AOM/DSS 引起的小鼠器官损伤。免疫组化结果表明，ZSSP 治疗可显著抑制 CAC 小鼠中升高的 CRC 早期标志物，如 COX-II、EMR1 和 Ki67。此外，通过大孔树脂 SP207 和 RP-HPLC-MS/MS 鉴定出 ZSSP 中具有抗 CRC 活性的成分是斯皮诺辛。有趣的是，在提取过程中引入了钠离子，形成了斯皮诺辛·Na+，其水溶性更好，抗 CRC 活性比斯皮诺辛更显著。本研究提供了 ZSS 衍生的斯皮诺辛的新药理特性，抑制了人 CRC 细胞和小鼠结肠炎相关 CRC 的生长，表明其可能作为天然 CRC 治疗药物的潜在用途。
