Pharmacokinetic Study of 7 Compounds Following Oral Administration of Fructus Aurantii to Depressive Rats

Frontiers in Pharmacology

Yuxin Guo¹  Jian Wang²  Xi Huang³  Xianhua Zhang⁶  Ping Ren⁷  Wan Zheng⁷  Qiuyue Xu⁷  Linran Han⁷  Jin Liu⁸ 

[1] Clinical Pharmaceutics Room, Shenzhen Children’s Hospital, Shenzhen, China;Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States;Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China;Department of Human Anatomy, Basic Medical College of Zhengzhou University, Zhengzhou, China;Department of Pharmacy, Xiamen University Hospital, Xiamen, China;Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China;Institute of TCM-Related Comorbid Depression, Nanjing University of Chinese Medicine, Nanjing, China;Mental Health Institute, The Second Xiangya Hospital of Central South University, Changsha, China;

关键词: Fructus Aurantii;    herb;    pharmacokinetic;    LC/MS/MS;    anti-depression;   

DOI  :  10.3389/fphar.2018.00131

来源: DOAJ

【 摘 要 】

In the present study, the pharmacokinetics of multi-components (naringenin, nobiletin, meranzin hydrate, narirutin, naringin, hesperidin, and neohesperidin) were investigated in acute depressive rats following oral administration of Fructus Aurantii (Zhi-Qiao, ZQ) extract (20 g/kg). A rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established to quantitatively or qualitatively analyze the 7 absorbed ingredients in the plasma, hippocampus and cortex of acute depressive rats. Biological samples were separated on a 300SB-C18 column, and the 7 compounds were detected with sequential positive and negative ionization modes. Our results confirmed that ZQ has antidepressant effects by decreasing the immobility time. In addition, this validated method showed good linearity (r ≥ 0.9987), and the lower limits of quantification were 2.73–16.38 ng/mL for the 7 analytes. This method successfully determined the pharmacokinetics of the 7 compounds and separated two pairs of isomers in plasma of acute depressive rats following oral administration of ZQ extracts. The 7 active ingredients were also identified as marked compounds in target tissues and should be further examined in pharmacokinetic studies with acute depressive rats. So, pharmacokinetic compounds were precisely linked with the antidepressant effect of ZQ in our study. This relationship is well-understood and contributes to the application of Traditional Chinese Medicine (TCM).

【 授权许可】

Unknown