A comprehensive quality evaluation of Fuzi and its processed product through integration of UPLC-QTOF/MS combined MS/MS-based mass spectral molecular networking with multivariate statistical analysis and HPLC-MS/MS
A comprehensive quality evaluation of Fuzi and its processed product through integration of UPLC-QTOF/MS combined MS/MS-based mass spectral molecular networking with multivariate statistical analysis and HPLC-MS/MS
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DOI：
10.1016/j.jep.2020.113455
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发表时间：
2021-02-10
影响因子：
5.4
通讯作者：
Zhang, Weidong
中科院分区：
文献类型：
--
作者：
Lei, Huibo;Zhang, Yuhao;Zhang, Weidong
民族药理学相关性：附子（学名：FZ），为菊科植物紫菀的侧根或子根。（毛茛科），是一种有争议的传统中药，在中国、日本、韩国和印度等许多国家广泛分布和应用。FZ可用于治疗风湿热、风湿病、关节痛、晕厥、虚脱、支气管哮喘、某些内分泌疾病等多种疾病，但由于其明显的高毒理学风险，其质量控制和评价具有挑战性，并且根据相关安全法规，仅允许其加工产品用于临床。因此，有必要对熔凝区的整体化学成分以及熔凝区在加工前后的动态变化进行分析。解决原料和加工产品的化学物质变化是降低毒性的一种方法。研究目的：本文分析了FZ的整体化学成分，评价了生FZ与加工FZ的差异，采用定性和定量分析方法，从化学成分的角度，对影响炮制FZ减毒效果的可能因素进行了解释。方法：基于超高效液相色谱-四极杆飞行时间质谱联用的多重数据采集与处理新策略（UPLC-QTOF/MS）方法，结合全球天然产物社会分子网络（GNPS）和多元统计分析，为系统鉴定FZ的化学成分，全面研究FZ的化学鉴别标志物，用醋和蜂蜜从其原料中加工而成。结合定性分析结果，采用高效液相色谱-三重四极杆质谱联用技术（HPLC-MS/MS）对其中8种化学标志化合物和4种毒性成分进行了定量分析。77个化学标记物也检测到之间的原料和加工FZ。用正交偏最小二乘判别分析（OPLS-DA）对化学标记的鉴别结果进行了验证。定量结果表明，炮制后12种重要成分的含量均有所下降，尤其是二酯型二萜生物碱（DDAs）。结论：炮制后FZ的毒性降低与其化学成分的变化密切相关。本研究建立的FZ质量综合评价方法，为中药化学成分的定性、鉴别及中药材生、炮制品化学标志物的差异性研究提供了一种有效、快速的方法。
Ethnopharmacological relevance: Aconiti Lateralis Radix Praeparata (the Chinese name is Fuzi, FZ), the lateral or daughter root of Aconitum carmichaelii Debx. (Ranunculaceae), is a controversial traditional Chinese medicine (TCM) that is universally distributed and applied in many countries, such as China, Japan, Korea, and India. FZ can be used to treat various diseases, including rheumatic fever, rheumatism, painful joints, syncope, collapse, bronchial asthma, some endocrinal disorders, etc. However, quality control and assessment of FZ are challenging due to its obvious and high toxicological risks, and only its processed products are allowed to be used clinically according to the relative safety regulations. Consequently, it is necessary to analyze the whole chemical composition and the dynamic changes of FZ before and after processing. Addressing the changes in the chemical substance of raw and processed products is a way to reduce toxicity.Aim of the study: In this article, the whole chemical composition of FZ is analyzed, the differences between raw and processed FZ are evaluated, and possible factors that influence the reduced toxicity of processed FZ are explained from the perspective of its chemical composition using qualitative and quantitative analysis methods.Materials and methods: A novel strategy of multiple data collection and processing based on ultra-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) method in the positive ion mode, together with Global Natural Product Social Molecular Networking (GNPS) and multivariate statistical analysis, was established to systematically identify the chemical constituents of FZ and comprehensively investigate the chemical markers that can be used to differentiate FZ processed with vinegar and honey from its raw product. Combined with the qualitative analysis results, 12 components, including 8 chemical marker compounds and 4 toxicity components, were quantitatively analyzed by using high-performance liquid chromatography equipped with triple-quadrupole mass spectrometry (HPLC-MS/MS).Results: Using the molecular networking (MN) analysis method, a total of 145 compounds were identified, of which 13 were identified using reference compounds. Seventy seven chemical markers were also detected between raw and processed FZ. The identification results of the chemical markers were also verified by orthogonal partial least squares discriminant analysis (OPLS-DA). The quantitative results indicated that the contents of 12 important components all decreased, especially diester-diterpenoid alkaloids (DDAs), after processing.Conclusion: The decrease of toxicity of FZ after processing is closely related to the changes in its chemical composition. The method developed in this study is a comprehensive analysis technique for quality assessment of FZ, and this study provides a useful and quick strategy to characterize chemical compounds of TCM and explore the different chemical markers between raw and processed Chinese herbal medicine.