Lin I-Chen, Wu Jin-Yi, Fang Chuan-Yin, Wang Shou-Chie, Liu Yi-Wen, Ho Shang-Tse
Department of Colon-Rectal Surgery, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 600, Taiwan.
Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi 600, Taiwan.
Evid Based Complement Alternat Med. 2023 Sep 5;2023:8264716. doi: 10.1155/2023/8264716. eCollection 2023.
Ellagic acid is a natural polyphenol compound found in pomegranates, walnuts, and many berries. It is not easily absorbed, but it could be metabolized to urolithins by the gut microbiota. Urolithin A, one of the ellagic acid metabolites, has been proved to prolong the lifespan of and increases muscle function of mice. The purpose of this current study was to analyze the absorption and metabolites of urolithin A and ellagic acid in mice and the anticancer effects of urolithin A, urolithin B, and ellagic acid in colorectal cancer cells.
Urolithin A and urolithin B were synthesized and analyzed by HPLC and NMR. A pharmacokinetic study of urolithin A was performed in mice by analyzing urolithin A and its metabolites in urines. Absorption and biotransformation of ellagic acid were also studied in mice by analyzing the plasma, liver, and feces. The cytotoxicity of urolithin A, urolithin B, and ellagic acid was assayed in SW480, SW620, HCT 116, and HT-29 cells.
Urolithin A and urolithin B were synthesized and purified to reach 98.1% and 99% purity, respectively, and the structures were identified by NMR. In urolithin A intake analysis, urolithin A was only detectable at 3 h, not at 6-24 h; it suggested that urolithin A was rapidly metabolized to some unknown metabolites. Using UPLC-MS/MS analysis, the metabolites might be urolithin A 3-O-glucuronide, urolithin A 3-sulfate, and urolithin A-sulfate glucuronide. After feeding mice with ellagic acid for consecutive 14 days, ellagic acid contents could be detected in the fecal samples, but not in plasma and liver, and urolithin A was not detected in all samples. It suggests that ellagic acid is not easily absorbed and that the biotransformation of ellagic acid to urolithin A by intestinal flora might be very low. From the cytotoxicity assay, it was found that there was anticancer effect in urolithin A and urolithin B but not in ellagic acid. In contrast, ellagic acid promoted the proliferation of SW480 and SW620 cells.
鞣花酸是一种天然多酚化合物，存在于石榴、核桃和许多浆果中。它不易被吸收，但可被肠道微生物群代谢为尿石素。尿石素A是鞣花酸的代谢产物之一，已被证明可延长小鼠寿命并增强其肌肉功能。本研究的目的是分析尿石素A和鞣花酸在小鼠体内的吸收和代谢产物，以及尿石素A、尿石素B和鞣花酸对结肠癌细胞的抗癌作用。
合成尿石素A和尿石素B，并通过高效液相色谱法（HPLC）和核磁共振（NMR）进行分析。通过分析小鼠尿液中的尿石素A及其代谢产物，对尿石素A进行药代动力学研究。还通过分析血浆、肝脏和粪便，研究了鞣花酸在小鼠体内的吸收和生物转化。在SW480、SW620、HCT 116和HT - 29细胞中检测尿石素A、尿石素B和鞣花酸的细胞毒性。
合成并纯化了尿石素A和尿石素B，纯度分别达到98.1%和99%，其结构通过核磁共振鉴定。在尿石素A摄入分析中，仅在3小时可检测到尿石素A，6 - 24小时未检测到；这表明尿石素A迅速代谢为一些未知代谢产物。使用超高效液相色谱 - 串联质谱（UPLC - MS/MS）分析，这些代谢产物可能是尿石素A 3 - O - 葡萄糖醛酸苷、尿石素A 3 - 硫酸盐和尿石素A - 硫酸盐葡萄糖醛酸苷。连续14天给小鼠喂食鞣花酸后，粪便样本中可检测到鞣花酸含量，但血浆和肝脏中未检测到，所有样本中均未检测到尿石素A。这表明鞣花酸不易被吸收，并且肠道菌群将鞣花酸生物转化为尿石素A的可能性非常低。从细胞毒性试验中发现，尿石素A和尿石素B具有抗癌作用，而鞣花酸没有。相反，鞣花酸促进了SW480和SW620细胞的增殖。
