Zeng Xuan, Su Weiwei, Zheng Yuying, He Yudong, He Yan, Rao Hongyu, Peng Wei, Yao Hongliang
Guangdong Engineering and Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Front Pharmacol. 2019 Jan 28;10:34. doi: 10.3389/fphar.2019.00034. eCollection 2019.
Aging is an inevitable biological process characterized by the loss of functional capacity and associated with changes in all phases of pharmacokinetic processes. Naringin, a dietary flavanone glycoside, has been proved to be beneficial for the treatment of multiple age-associated chronic diseases. To date, the pharmacokinetic processes of naringin in aged individuals are still unknown. Thus, a rapid resolution liquid chromatography tandem triple quadrupole mass spectrometry (RRLC-QQQ-MS/MS) method was established for the determination of naringin and its metabolite naringenin in rat plasma, urine, feces, and tissue homogenate. The pharmacokinetic parameters were calculated and a higher exposure of naringin and naringenin were observed in aged rats. Naringin and naringenin were mostly distributed in gastrointestinal tract, liver, kidney, lung, and trachea. Furthermore, a total of 39 flavonoid metabolites (mainly glucuronides and sulfates) and 46 microbial-derived phenolic catabolites were screened with ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). Naringenin, hippuric acid, and 3-(4'-hydroxyphenyl)propionic acid were predominated metabolites. This study systemically investigated the pharmacokinetics, tissue distribution, metabolism, and excretion of naringin in aged rats, revealing age- and gender-related changes in the behavior of naringin. These results would be helpful for the interpretation of pharmacokinetics and pharmacodynamics of naringin in aged population.
衰老乃不可避免之生物学过程，其特征为功能能力丧失，且与药代动力学过程各阶段之变化相关。柚皮苷，一种膳食黄烷酮糖苷，已被证明对治疗多种与年龄相关之慢性疾病有益。迄 今为止，柚皮苷在老年个体中的药代动力学过程仍不为人知。因此，建立了一种快速液相色谱串联三重四极杆质谱法（RRLC - QQQ - MS/MS），用于测定大鼠血浆、尿液、粪便及组织匀浆中的柚皮苷及其代谢产物柚皮素。计算了药代动力学参数，并观察到老年大鼠中柚皮苷和柚皮素的暴露量更高。柚皮苷和柚皮素主要分布于胃肠道、肝脏、肾脏、肺和气管。此外，用超快速液相色谱 - 四极杆 - 飞行时间串联质谱法（UFLC - Q - TOF - MS/MS）筛选出了总共39种黄酮类代谢产物（主要为葡萄糖醛酸苷和硫酸盐）和46种微生物衍生的酚类分解代谢产物。柚皮素、马尿酸和3 -（4'-羟基苯基）丙酸为主要代谢产物。本研究系统地研究了柚皮苷在老年大鼠中的药代动力学、组织分布、代谢和排泄，揭示了柚皮苷行为中与年龄和性别相关的变化。这些结果将有助于解释柚皮苷在老年人群中的药代动力学和药效学。
