title: Pharmacokinetics of 21 active components in focal cerebral ischemic rats after oral administration of the active fraction of Xiao-Xu-Ming decoction.
abstract: The Xiao-Xu-Ming decoction (XXMD) is a traditional Chinese medicine prescription that is clinically used for the treatment of stroke. The active fraction of XXMD (AF-XXMD) exhibits pharmacological effects that are similar to those of XXMD. In this study, 21 primary compounds of AF-XXMD with potential anti-ischemic-stroke activities were selected as effective candidates to perform comparisons of their pharmacokinetic differences between control and cerebral ischemic rats and to characterize their pharmacokinetic behaviors in cerebral ischemic rats. After oral administration of AF-XXMD to control and cerebral ischemic rats, plasma and brain were harvested and analyzed using liquid chromatography coupled with tandem mass spectrometry. Reverse molecular docking results indicate that 21 AF-XXMD-derived compounds exert potential neuroprotection, anti- inflammation, and vascular dilation effects via interaction with multiple targets in stroke-related pathways. The blood-brain permeability, cerebral exposure and brain region distribution of these compounds were found to change in cerebral ischemic models. Flavonoids were identified as the predominant form in plasma, whereas chromones were found to be the major form in the brain, and alkaloids possessed moderate blood-brain permeability. Collectively, the cerebral pharmacokinetic behaviors of chromones, flavonoids and alkaloids were found to change under pathological conditions. The efficacy of AF-XXMD against cerebral ischemia is relevant to the synergistic effects of these compounds in targeting different receptors and pathways. Chromones exhibit relatively high brain permeability, and their activity and mechanism warrant further investigation.
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Caihong
authors: C
authors: Wang
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Zhixin
authors: Z
authors: Jia
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Zhe
authors: Z
authors: Wang
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Ting
authors: T
authors: Hu
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Hailin
authors: H
authors: Qin
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Guanhua
authors: G
authors: Du
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: wucsh@xmu.edu.cn.
authors: Caisheng
authors: C
authors: Wu
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: zhjl@imm.ac.cn.
authors: Jinlan
authors: J
authors: Zhang
mesh_terms: D000284:Administration, Oral; D000470:Alkaloids / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics* / Q000494:pharmacology; D005419:Flavonoids / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008516:Medicine, Chinese Traditional / Q000379:methods; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000188:drug therapy; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; C548754:xiao-xu-ming
keywords: Ischemic stroke; Pharmacokinetic; Reverse molecular docking; Synergistic effect; Xiao-Xu-Ming decoction