Zhou Huixian, Huang Xinxin, Tan Ting, Luo Yun
National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China.
Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China.
Rapid Commun Mass Spectrom. 2023 Sep 30;37(18):e9607. doi: 10.1002/rcm.9607.
The flower of Citrus aurantium L. var. amara Engl. (FCAVA), an edible tea and herbal medicine with anti-obesity effect, has attracted great attention in China. The structural elucidation of chemical components in FCAVA has been realized in our previous work. It is well known that metabolic profiling provided a structural basis to discover potential anti-obesity ingredients in FCAVA. Nevertheless, there are no reports about in vivo metabolic profiles of FCAVA. Therefore, it is necessary to comprehensively identify in vivo substances of FCAVA.
The identification of in vivo substances of FCAVA remains a challenge due to the strong interference of complex chemical components, biological matrices and metabolite isomers. In this work, ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) analysis with a data mining strategy was established and applied for the metabolic profiling of FCAVA in rats. The data mining strategy, including diagnostic product ions and neutral loss filtering, improved structural elucidation of xenobiotics in rats after oral administration of FCAVA.
A total of 228 xenobiotics, including 80 prototypes (10 unambiguous confirmed with reference standards) and 148 metabolites, were tentatively characterized in rat plasma, urine and fecal samples. Among them, 35 xenobiotics were found in plasma, 124 in urine and 156 in feces. The main biotransformation pathway of FCAVA metabolism was deglycosylation, methylation, glucuronidation and sulfation. The main compounds absorbed into the blood were neohesperidin and naringin, which have been reported to show significant anti-obesity effect.
Collectively, this present study would be conducive to the discovery of active ingredients of FCAVA for the treatment of obesity and the development of quality control of FCAVA.
酸橙花（FCAVA）是一种具有抗肥胖作用的可食用茶和草药，在中国备受关注。我们之前的工作已经实现了对FCAVA中化学成分的结构解析。众所周知，代谢谱为发现FCAVA中潜在的抗肥胖成分提供了结构基础。然而，目前尚无关于FCAVA体内代谢谱的报道。因此，有必要全面鉴定FCAVA的体内物质。
由于复杂的化学成分、生物基质和代谢物异构体的强烈干扰，FCAVA体内物质的鉴定仍然是一个挑战。在这项工作中，建立了一种结合数据挖掘策略的超高效液相色谱-四极杆飞行时间串联质谱（UHPLC-QTOF-MS/MS）分析方法，并将其应用于大鼠体内FCAVA的代谢谱分析。该数据挖掘策略，包括诊断性产物离子和中性丢失过滤，改进了口服FCAVA后大鼠体内外源性物质的结构解析。
在大鼠血浆、尿液和粪便样本中初步鉴定出总共228种外源性物质，包括80种原型（其中10种经参考标准明确确认）和148种代谢物。其中，在血浆中发现35种外源性物质，尿液中发现124种，粪便中发现156种。FCAVA代谢的主要生物转化途径是去糖基化、甲基化、葡萄糖醛酸化和硫酸化。吸收进入血液的主要化合物是新橙皮苷和柚皮苷，据报道它们具有显著的抗肥胖作用。
总的来说，本研究将有助于发现FCAVA治疗肥胖的活性成分以及FCAVA质量控制的发展。
