Deciphering the metabolic profile and anti-colorectal cancer mechanism of Capilliposide A using ultra performance liquid chromatography mass spectrometry combined with non-targeted metabolomics studies

化学 代谢组学 代谢物 结直肠癌 药理学 代谢组 代谢途径 液相色谱-质谱法 鞘脂 尿 癌症 新陈代谢 生物化学 内科学 色谱法 质谱法 医学
作者
Wei Li,Xiaoyong Zhang,Feng Yue,Haote Han,Jinhong Cai,Huan Zhao,Shouxin Li,Jingkui Tian,Wei Zhu
出处
期刊:Journal of Pharmaceutical and Biomedical Analysis [Elsevier]
卷期号:234: 115548-115548 被引量:1
标识
DOI:10.1016/j.jpba.2023.115548
摘要

Colorectal cancer is a highly prevalent malignancy that threatens human health worldwide. Despite the availability of chemotherapy as a primary treatment option, individuals with CRC undergoing frequent chemotherapy are susceptible to developing drug resistance, which can result in poor treatment outcomes. Consequently, there is an urgent need to discover new bioactive compounds for the treatment of CRC. Capilliposide A is a triterpenoid saponin that is extracted from Lysimachia capillipes Hemsl. Although it has been reported that LC-A exhibits good bioactivity, its metabolic profile and potential mechanism underlying its anti-CRC effects remain unknown. In this study, the metabolic products of LC-A in rat plasma, feces, and urine were identified using an LC-MS platform. In addition, LC-MS-based metabolomics was employed to investigate the mechanism of LC-A against CRC. The results showed that LC-A significantly inhibited CRC cell proliferation, attenuated tumor growth, and alleviated metabolic abnormalities in CRC-bearing mice. Furthermore, the levels of p-cresol sulfate and phenylacetylglycine in CRC model plasma decreased, with an increment in sphingosine 1-phosphate, D-tryptophan, and L-2-aminoadipic acid. These metabolite levels can be reversed by LC-A treatment. These metabolite alterations were related to the sphingolipid and amino acid metabolic pathways, demonstrating that LC-A anti-CRC effects were regulated through the modulation of underlying metabolism. Additionally, seven metabolites of LC-A were characterized in rat feces, plasma, and urine. This study offers a scientific foundation for elucidating the metabolism of LC-A and its treatment of colorectal cancer.
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