Metabolites identification and multi-component pharmacokinetics of ergostane and lanostane triterpenoids in the anticancer mushroom Antrodia cinnamomea.
Antrodia cinnamomea is a precious medicinal mushroom popularly used for adjuvant cancer therapy in Taiwan. Its major bioactive constituents are ergostane and lanostane triterpenoids. Although clinical trials for A. cinnamomea have been recently initiated, its metabolism remains unclear. The present study aims to elucidate the metabolism and pharmacokinetics of A. cinnamomea in rats. After oral administration of an ethanol extract, 18 triterpenoids and 8 biotransformed metabolites were detected in rats plasma by UHPLC/qTOF-MS. Four of the metabolites were prepared by semi-synthesis and fully identified by NMR, while the others were tentatively characterized by comparing with the metabolites of single compounds (antcins B, C, H and K). Furthermore, a multi-component pharmacokinetic study of A. cinnamomea was carried out to monitor the plasma concentrations of 14 triterpenoids (ergostanes 1-3, 5-8, 14-16; lanostanes 9, 10, 17, 19) and 2 metabolites (M5, M6) by LC/MS/MS in rats after oral administration of the ethanol extract (1.0 g/kg). The results showed that ergostanes and Δ(7,9(11)) lanostanes, but not Δ(8) lanostanes, could get into circulation. The low-polarity ergostanes (antcins B and C) undertook hydrogenation (C-3 or C-7 carbonyl groups) or hydroxylation to produce polar metabolites. High-polarity ergostanes (antcins H and K) and Δ(7,9(11)) lanostanes were metabolically stable. We also discovered that ergostanes and lanostanes showed remarkably different pharmacokinetic patterns. The ergostanes were generally absorbed and eliminated rapidly, whereas the lanostanes remained in the plasma at a low concentration for a relatively long time. The results indicate that high-polarity ergostanes are the major plasma-exposed components of A. cinnamomea, and may play an important role in its therapeutic effects.
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.
Qi
Q
Wang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Shuai
S
Ji
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Yun
Y
Huang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Ke-di
KD
Liu
Agilent Technologies, 3 Wangjing North Road, Beijing 100102, China.
Zheng-xiang
ZX
Zhang
Agilent Technologies, 3 Wangjing North Road, Beijing 100102, China.
Tao
T
Bo
Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung 41349, Taiwan.
Yew-min
YM
Tzeng
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 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
D000363:Agaricales / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D055491:Antrodia / Q000737:chemistry* / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D010936:Plant Extracts / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013624:Taiwan; D053719:Tandem Mass Spectrometry / Q000379:methods; D013729:Terpenes / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D014315:Triterpenes / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D010936:Plant Extracts; D013729:Terpenes; D014315:Triterpenes; C015190:ergostane; D004875:Ergosterol
Antrodia cinnamomea; Ergostane; Lanostane; Metabolites identification; Multi-component pharmacokinetics; Triterpenoids