目的 探究蒙药疗齿草Odontites vulgaris‎总提取物（total extraction of O. vulgaris，TOT）的化学成分及其对热性病大鼠的物质能量代谢、肝组织代谢轮廓及差异代谢物的影响，以阐明TOT的寒热药性归属及药性发挥的作用机制。方法 使用超高效液相色谱系统联用质谱仪（liquid chromatography-mass spectrometry，LC-MS）对TOT进行化学成分鉴定并采用紫外-可见分光光度计法测定其总黄酮的含量；采用ig左甲状腺素钠片及sc干酵母诱导热性病大鼠模型，ig给予大鼠TOT；酶联免疫法测定大鼠物质能量代谢相关酶指标；采用LC-MS技术对左甲状腺素纳片诱导的热性病大鼠肝组织进行非靶向代谢组学分析，探究TOT对其差异代谢物的影响及代谢通路，阐释差异代谢物的生物学意义并探讨TOT药性的归属。结果 通过LC-MS鉴定出29个成分，包括14个黄酮类，3个苯丙素类，3个苯乙醇苷类，2个萜类，2个脂肪酸类，1个生物碱类，4个其他类化合物，TOT中总黄酮质量分数为14.73 mg/g。TOT能显著降低左甲状腺素钠片诱导的热性病模型大鼠肝组织糖原磷酸化酶（glycogen phosphorylase，PYGL）、腺苷三磷酸（adenosine triphosphate，ATP）等7个酶活性（P＜0.05），并能显著降低干酵母诱导的热性病模型大鼠肝组织腺苷酸激酶（adenylate kinase，ADK）等4个酶活性（P＜0.05）。非靶向肝组织代谢组学结果显示，对照组与热性病模型组中有14个差异代谢物在TOT给药后出现回调，主要为甘油磷脂、嘌呤等代谢物，富集分析结果显示TOT主要影响甘油磷脂代谢、嘌呤代谢、谷胱甘肽代谢等多条代谢通路。结论 TOT可降低左甲状腺素钠片及干酵母诱导的热性病模型大鼠的物质能量代谢发挥寒性作用。

Objective To investigated the effects of total extraction of Odontites vulgaris (TOT) on material and energy metabolism, liver tissue metabolism, and differential metabolites in rats with heat diseases, in order to clarify the mechanism of TOT’s action and its attribution to the cold and heat properties.Methods Chemical composition of TOT were measured by ultra-high performance liquid chromatography (HPLC) combined with mass spectrometer (LC-MS), and the total flavonoid content were measured by UV-VIS spectrophotometer. To treat rats with heat disease, TOT was administered by gavage after ig levothyroxine sodium tablets and sc yeast were used. Rat enzyme indices of material and energy metabolism were measured using enzyme linked immunoassays. Non-targeted metabolomic analysis of liver tissue of rats with febrile disease induced by levothyroxine sodium tablets was performed by LC-MS to explore the effect of TOT on its differential metabolites and metabolic pathways, elucidate the biological significance of differential metabolites, and explore the attribution of TOT’s medicinal properties.Results A total of 29 components were identified using LC-MS, including 14 flavonoids, three phenylpropanoids, three phenylethanol glycosides, two terpenoids, two fatty acids, one alkaloid, and four other components. The content of total flavonoids in TOT was 14.73 mg/g. TOT significantly reduced the activity levels of seven enzymes, including liver glycogen phosphorylase (PYGL) and adenosine triphosphate (ATP), in the liver tissue of rats with heat disease induced by levothyroxine sodium tablets (P < 0.05). It also notably decreased the activity levels of four enzymes, including adenylate kinase (ADK), in the liver tissue of rats with febrile disease induced by dry yeast (P < 0.05). The non-targeted metabolomics analysis of liver tissue revealed that 14 different metabolites in both the normal and heat disease model groups exhibited reversed levels following TOT administration, predominantly involving glycerophospholipids, purines, and other metabolites. Enrichment analysis indicated that TOT primarily impacted several metabolic pathways including glycerophospholipid metabolism, purine metabolism, and glutathione metabolism. Conclusion TOT reduces the material and energy metabolism in rats with heat disease induced by levothyroxine sodium tablets and dry yeast.

R285.5

国家自然科学基金项目（82060784，82260836）;内蒙古自治区自然科学基金项目（2023MS08029）;内蒙古自治区高等学校“青年科技英才支持项目”（NJYT24079）;内蒙古自治区中医药（蒙医药）中青年领军人才培育项目（2022-[RC001]）;内蒙古自治区高等学校创新团队发展计划项目（NMGIRT2326）;内蒙古自治区科技计划项目—黄芪有机生态种植溯源体系的建设与推广（2020GG0144）