Metabolomics study on Fuzi and its processed products using ultra-performance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry coupled with pattern recognition analysis
Metabolomics study on Fuzi and its processed products using ultra-performance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry coupled with pattern recognition analysis
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DOI：
10.1039/c1an15833c
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发表时间：
2012-01-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Xijun
中科院分区：
文献类型：
--
作者：
Sun, Hui;Ni, Bei;Wang, Xijun
广布于亚洲及北美洲的乌藨子，其侧根名为“附子”，用于缓解关节疼痛及治疗风湿性疾病已有两千多年的历史。然而，它的治疗范围非常窄，尽管有毒理学风险，但其使用量仍然非常高。传统的中药炮制方法（泡治）是去除乌头中主要由乌头碱、中乌头碱和次乌头碱等双酯型二萜生物碱（DDAs）组成的有毒生物碱的必要手段。它们可以通过泡汁分解成毒性较小或无毒的衍生物，在解毒中起着重要作用。附子炮制品主要集中在炎附子、黑顺片和白附片三大剂型，为保证临床用药安全性和降低毒性而备受青睐。附子及其炮制品的代谢组学特征差异尚不完全清楚。因此，本文采用超高效液相色谱/电喷雾电离高分辨质谱（UPLC-Q-TOF-HDMS）结合模式识别方法，对附子及其炮制品的代谢物组进行了研究。主成分分析表明附子及其炮制品在代谢过程中存在差异。附子样品和三种制剂中检测到19种代谢物生物标志物发生显着变化。根据已鉴定的代谢产物，探讨了炮枝干扰代谢途径的潜在调控机制。本研究证明，基于UPLC-Q-TOF-HDMS的代谢组学分析有助于通过泡制技术研究附子的代谢，并为进一步全面了解附子炮制品的药理活性和潜在毒性提供有用信息。
The lateral root of Aconitum carmichaelii Debx is named "Fuzi" which is widely distributed across Asia and North America and has been used to relieve joint pain and treat rheumatic diseases for over two thousand years. However, it has very narrow therapeutic ranges and despite the toxicological risk, its usage remains very high. A traditional Chinese processing approach (Paozhi, detoxifying measure) is necessary to remove the poisonous Aconitum alkaloids mainly deriving from the diester diterpene alkaloids (DDAs) including aconitine, mesaconitine and hypaconitine. They can be decomposed into less or non-toxic derivatives through Paozhi that plays an essential role in detoxification. Processed Fuzi is mainly focused on the three main forms of Yanfuzi (YFZ), Heishunpian (HSP) and Baifupian (BFP) which are highly desirable in order to guarantee the clinical safety and their low toxicity in decoctions. The difference in metabolomic characters between Fuzi and its processed preparations is still completely unclear. Therefore, this paper was designed to investigate a comprehensive metabolome of Fuzi and its processed products by ultra-performance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry (UPLC-Q-TOF-HDMS) combined with pattern recognition methods. The difference in metabolic profiles between Fuzi and its processed preparations was well observed by the principal component analysis (PCA) of the MS spectra. Significant changes of 19 metabolite biomarkers were detected in the Fuzi samples and three preparations. The underlying regulations of Paozhi-perturbed metabolic pathways were also discussed according to the identified metabolites. The present study proves that UPLC-Q-TOF-HDMS based metabolomic analysis greatly contributes to the investigation of Fuzi metabolism through Paozhi techniques, and provides useful information to further comprehensively understand the pharmacological activity and potential toxicity of processed Fuzi in a clinical environment.