Chicory, renowned for its multifaceted benefits, houses two vital coumarins, esculetin and esculin, both instrumental in reducing uric acid. This study emphasizes the metabolic pathways of esculetin and esculin under both standard and hyperuricemia conditions. Hyperuricemia was induced in Sprague–Dawley rats using oxonic acid potassium salt (300 mg·kg⁻¹) and a 10% fructose water regimen over 21 days. Leveraging the ultra-high-performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high resolution mass spectrometry, we analyzed the fragmentation behaviors of esculetin and esculin in rat bio-samples. Post oral-intake of esculetin or esculin, a notable dip in serum uric acid levels was observed in hyperuricemia rats. The investigation unveiled 24 esculetin metabolites and 14 for esculin. The metabolic pathways of both compounds were hydrolysis, hydroxylation, hydrogenation, dehydroxylation, glucuronidation, sulfation, and methylation. Interestingly, certain metabolites presented variations between standard and hyperuricemia rats, indicating that elevated levels of uric acid may affect enzyme activity linked to these metabolic reactions. This is the first systematic study on comparison of metabolic profiles of esculetin and esculin in both normal and hyperuricemia states, which was helpful to enrich our understanding of the complicated structure–activity relationships between esculin and esculetin and shed light to their action mechanism.

中文翻译：

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使用超高效液相色谱结合四极杆轨道阱高分辨率质谱法对高尿酸血症大鼠中菊苣中的七叶亭和七叶亭进行体内全面代谢分析


菊苣以其多方面的功效而闻名，含有两种重要的香豆素：七叶亭和七叶苷，两者都有助于降低尿酸。本研究强调了七叶亭和七叶苷在标准和高尿酸血症条件下的代谢途径。使用含氧酸钾盐(300 mg·kg ^-1 )和10%果糖水疗法在21天内诱导Sprague-Dawley大鼠高尿酸血症。利用超高效液相色谱-Q Exactive 混合四极杆轨道阱高分辨率质谱仪，我们分析了大鼠生物样品中七叶亭和七叶苷的裂解行为。口服七叶亭或七叶甙后，在高尿酸血症大鼠中观察到血清尿酸水平显着下降。该调查揭示了 24 种七叶亭代谢物和 14 种七叶亭代谢物。两种化合物的代谢途径为水解、羟基化、氢化、脱羟基、葡萄糖醛酸化、硫酸化和甲基化。有趣的是，某些代谢物在标准和高尿酸血症大鼠之间存在差异，表明尿酸水平升高可能会影响与这些代谢反应相关的酶活性。这是首次对七叶碱和七叶碱在正常和高尿酸血症状态下的代谢谱进行比较的系统研究，有助于丰富我们对七叶碱和七叶碱之间复杂的构效关系的理解，并揭示其作用机制。