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对盲肠内容物的代谢组学分析揭示了与苦苣菜总黄酮对雄性溃疡性结肠炎C57BL/6小鼠治疗作用相关的重要代谢物。

The metabolomics analysis of cecal contents elucidates significant metabolites involved in the therapeutic effects of total flavonoids derived from Sonchus arvensis L. in male C57BL/6 mice with ulcerative colitis.

作者信息

Chang Naidan, Wang Shihe, Hou Shenghua, Sui Yilei, He Jing, Ren Yachao, Chen Guoyou, Bu Chunlei

机构信息

Harbin Medical University 163319, China.

Daqing Oilfield Genaral Hospital, Daqing, 163319, China.

出版信息

Heliyon. 2024 Jun 16;10(12):e32790. doi: 10.1016/j.heliyon.2024.e32790. eCollection 2024 Jun 30.

Abstract

Ulcerative colitis (UC), an inflammatory disease affecting the colon and rectal mucosa, is characterized by chronic and heterogeneous behavior of unknown origin. The primary cause of UC is chronic inflammation, which is closely linked to the development of colorectal cancer. Sonchus arvensis L. (SAL), a plant consumed worldwide for its nutritional and medicinal properties, holds significance in this context. In this study, we employed the total flavone in SAL as a treatment for male C57BL/6 mice with UC. The cecal contents metabolic profile of C57BL/6 mice in different groups, including UC (group ML; n = 5), UC treated with aspirin (group AN; n = 5), UC treated with the total flavone in SAL (group FE; n = 5), and healthy male C57BL/6 mice (group CL; n = 5), was examined using UHPLC-Triple-TOF-MS. Through the identification of variations in key metabolites associated with UC and the exploration of their underlying biological mechanisms, our understanding of the pathological processes underlying this condition has been enhanced. This study identified a total of seventy-three metabolites that have a significant impact on UC. Notably, the composition of total flavone in SAL, a medication used for UC treatment, differs from that of aspirin due to the presence of four distinct metabolites (13,14-Dihydro-15-keto-PGE2, Prostaglandin I2 (PGI2), (20R,22R)-20,22-dihydroxycholesterol, and PS (18:1(9Z)/0:0)). These metabolites possess unique characteristics that set them apart. Moreover, the study identified a total of eleven pathways that were significantly enriched in mice with UC, including Aminoacyl-tRNA biosynthesis, Valine, leucine and isoleucine biosynthesis, Linoleic acid metabolism, PPAR signaling pathway, mTOR signaling pathway, Valine, leucine and isoleucine degradation, Lysine degradation, VEGF signaling pathway, Melanogenesis, Endocrine and other factor-regulated calcium reabsorption, and Cocaine addiction. These findings contribute to a better understanding of the metabolic variations in UC following total flavonoids of SAL therapy and provide valuable insights for the treatment of UC.Keywords: Ulcerative colitis; Total flavonoids of Sonchus arvensis L.; Key metabolites; Metabonomics; Cecal contents of male C57BL/6 mice.

摘要

溃疡性结肠炎(UC)是一种影响结肠和直肠黏膜的炎症性疾病,其特征为病因不明的慢性和异质性表现。UC的主要病因是慢性炎症,这与结直肠癌的发生密切相关。苣荬菜(SAL)是一种因其营养和药用特性而在全球范围内被食用的植物,在这方面具有重要意义。在本研究中,我们使用苣荬菜中的总黄酮对患有UC的雄性C57BL/6小鼠进行治疗。使用超高效液相色谱-三重四极杆飞行时间质谱(UHPLC-Triple-TOF-MS)检测了不同组C57BL/6小鼠的盲肠内容物代谢谱,包括UC组(ML组;n = 5)、用阿司匹林治疗的UC组(AN组;n = 5)、用苣荬菜总黄酮治疗的UC组(FE组;n = 5)以及健康雄性C57BL/6小鼠组(CL组;n = 5)。通过识别与UC相关的关键代谢物变化并探索其潜在生物学机制,我们对该疾病的病理过程有了更深入的了解。本研究共鉴定出73种对UC有显著影响的代谢物。值得注意的是,用于UC治疗的药物苣荬菜总黄酮的成分与阿司匹林不同,因为存在四种不同的代谢物(13,14-二氢-15-酮-PGE2、前列腺素I2(PGI2)、(20R,22R)-20,22-二羟基胆固醇和PS(18:1(9Z)/0:0))。这些代谢物具有独特的特征。此外,该研究共鉴定出11条在UC小鼠中显著富集的通路,包括氨酰-tRNA生物合成、缬氨酸、亮氨酸和异亮氨酸生物合成、亚油酸代谢、PPAR信号通路、mTOR信号通路、缬氨酸、亮氨酸和异亮氨酸降解、赖氨酸降解、VEGF信号通路、黑色素生成、内分泌及其他因子调节的钙重吸收和可卡因成瘾。这些发现有助于更好地理解苣荬菜总黄酮治疗后UC的代谢变化,并为UC的治疗提供有价值的见解。关键词:溃疡性结肠炎;苣荬菜总黄酮;关键代谢物;代谢组学;雄性C57BL/6小鼠盲肠内容物

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa6/11239596/cdc41acbf96c/ga1.jpg

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