Characterization of chemical constituents and rats metabolites of an alkaloidal extract of Alstonia scholaris leaves by liquid chromatography coupled with mass spectrometry.
Alstonia scholaris has been used in "Dai" ethnic medicine to treat chronic respiratory diseases for a long history, and the major bioactive constituents are alkaloids. An alkaloidal extract of A. scholaris leaves (AAS) has been developed into an investigational new drug, and has been approved for phase I/II clinical trials by China Food and Drug Administration. However, little is known on the chemical composition and in vivo metabolism of AAS, thus far. In this study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/qTOF-MS) method was established to characterize the chemical constituents of AAS. Samples were separated on an ACQUITY UPLC CSH column (2.1×100mm, 1.7μm) with acetonitrile and water containing 0.3% formic acid as the mobile phase. On the basis of high-accuracy mass spectral analysis, a total of 35 alkaloids were characterized from AAS, including 11 scholaricine-type, 9 vallesamine-type, 12 picrinine-type, and 3 tubotaiwine-type alkaloids. Furthermore, the metabolic pathways of 4 representative alkaloids in rats were studied. They mainly undertook hydroxylation and glucuronidation reactions. Based on the above metabolic pathways, the metabolism of AAS (10mg/kg) in rats after oral administration was studied by LC/MS. A total of 33 compounds in plasma, 40 compounds in urine, and 38 compounds in feces were characterized. The results indicated that scholaricine-type alkaloids could get into circulation more readily than the other types. This is the first systematic study on chemical profiling and metabolites identification of AAS.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Jing
J
Cao
The Third Affiliated Hospital of Kunming Medical University, Kunming 650106, Yunnan Province, China.
Hong-Mei
HM
Shen
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Qi
Q
Wang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Yi
Y
Qian
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Hong-Cheng
HC
Guo
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Kai
K
Li
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Xue
X
Qiao
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
De-An
DA
Guo
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, Yunnan Province, China. Electronic address: xdluo@kib.ac.cn.
Xiao-Dong
XD
Luo
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China. Electronic address: yemin@bjmu.edu.cn.
Min
M
Ye
D000470:Alkaloids / Q000737:chemistry*; D031051:Alstonia / Q000737:chemistry*; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D010936:Plant Extracts / Q000032:analysis*; D018515:Plant Leaves / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000470:Alkaloids; D010936:Plant Extracts
Alkaloids; Alstonia scholaris; Herbal medicine; Metabolites identification; UHPLC/qTOF-MS