Abstract：
Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotic therapy, characterized by intestinal inflammation which reduces the quality of life of patients. Xianglian Pill (XLP) has long been used to treat abdominal pain, diarrhea, bacillary dysentery and enteritis. Studies found that XLP has curative effect on AAD; however, the chemical constituents and mechanism of XLP have not been fully elucidated because of the lack of in vitro and in vivo studies. In this study, ultra-high performance liquid chromatography mass spectrometry method (UPLC-Q-Exactive-Orbitrap-HRMS) was used to examine the components of the XLP. Then, the binding between active compounds and the key targets was studied using network pharmacology and molecular docking. A comparative tissue distribution study was established for the simultaneous determination of the 10 active components in healthy and AAD mouse models. Forty-six components were characterized from XLP. According to the network pharmacology degree value, a prediction was made that encompassed 42 components and 14 core targets, which were intricately involved in crucial biological pathways, such as the AGE-RAGE signaling, cellular senescence, and MAPK signaling. Tissue distribution analysis showed that the 10 components were widely distributed in the heart, liver, spleen, lungs, kidneys, small intestine, and large intestine of mice, with varying concentrations in healthy and AAD mice. Molecular docking analysis also indicated that the active compounds in the tissue distribution could bind tightly to key targets of network pharmacological studies. This study provides a reference for further investigations of the relationships between the chemical components and pharmacological activities of XLP.
摘要：
抗生素相关性腹泻（AAD）是抗生素治疗的常见副作用，以肠道炎症为特征，降低患者的生活质量。香连丸（XLP）长期用于治疗腹痛，腹泻,细菌性痢疾和肠炎。研究发现,XLP对AAD有疗效;然而,由于缺乏体外和体内研究，XLP的化学成分和机制尚未完全阐明。在这项研究中,超高效液相色谱质谱法(UPLC-Q-Exactive-Orbitrap-HRMS)用于检测XLP的成分。然后，使用网络药理学和分子对接研究了活性化合物与关键靶标之间的结合。建立了比较组织分布研究，用于同时测定健康和AAD小鼠模型中的10种活性成分。从XLP表征了46个组分。根据网络药理学学位值，进行了一项包含42个组件和14个核心目标的预测，它们错综复杂地参与了关键的生物学途径，例如AGE-RAGE信令，细胞衰老,和MAPK信号。组织分布分析表明,这10种成分广泛分布于心脏,肝脏,脾,脾肺,肾脏，小肠,和小鼠的大肠，在健康和AAD小鼠中具有不同的浓度。分子对接分析还表明，组织分布中的活性化合物可以与网络药理学研究的关键靶标紧密结合。本研究为进一步研究XLP的化学成分与药理活性的关系提供了参考。
