Online discovery of the molecular mechanism for directionally detoxification of Fuzi using real-time extractive electrospray ionization mass spectrometry

Qiu, Zi-Dong; Zhang, Xiaoping; Wei, Xu-Ya; Chingin, Konstantin; Xu, Jiaquan; Gao, Wei; Yang, Bin; Wang, Shuanglong; Tan, Ting; Liu, E‐Hu; Xu, Haiyu; Cui, Guanghong; Guo, Juan; Wang, Yanan; Shen, Ye; Zhao, Yujun; Chen, Huanwen; Lai, Chang-Jiang-Sheng; Huang, Luqi

doi:10.1016/j.jep.2021.114216

Cited by 15 publications

(13 citation statements)

References 43 publications

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“…The DESI-MSI comparison of the 42 metabolites of raw Fuzi and processed Fuzi steamed for 4.0 and 8.0 h showed that the content of highly toxic DDAs decreased dramatically, and a large part of the content of MDAs and NDAs fluctuated during steaming, which indicated a reversible process ( Figure 8 ). DDAs and MDAs were the major metabolic markers between raw and processed Fuzi steamed for 4.0 h, whereas NDAs were identified as the predominant markers of Fuzi steamed for 4.0 and 8.0 h. During 0–4.0 h of steaming, hydrolysis was conducted to convert DDAs to MDAs and then to NDAs, which are considered as the major chemical transformations based on the present results and published literature ( Liu et al, 2008 ; Chen et al, 2013 ; Qiu et al, 2021 ), and three main paths for the transformation of C 19 -ester-diterpenoid alkaloids were proposed ( Figure 9 ). Except for conventional hydrolysis and dehydration processes ( Figures 9A,B ), esterification reactions 1 and 2 in path C also indicated two important reversible processes, which explained why some of the alkaloids’ content fluctuated during steaming.…”

Section: Discussionsupporting

confidence: 63%

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Unveiling Dynamic Changes of Chemical Constituents in Raw and Processed Fuzi With Different Steaming Time Points Using Desorption Electrospray Ionization Mass Spectrometry Imaging Combined With Metabolomics

et al. 2022

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Fuzi is a famous toxic traditional herbal medicine, which has long been used for the treatment of various diseases in China and many other Asian countries because of its extraordinary pharmacological activities and high toxicity. Different processing methods to attenuate the toxicity of Fuzi are important for its safe clinical use. In this study, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with a metabolomics-combined multivariate statistical analysis approach was applied to investigate a series of Aconitum alkaloids and explore potential metabolic markers to understand the differences between raw and processed Fuzi with different steaming time points. Moreover, the selected metabolic markers were visualized by DESI-MSI, and six index alkaloids’ contents were determined through HPLC. The results indicated visible differences among raw and processed Fuzi with different steaming times, and 4.0 h is the proper time for toxicity attenuation and efficacy reservation. A total of 42 metabolic markers were identified to discriminate raw Fuzi and those steamed for 4.0 and 8.0 h, which were clearly visualized in DESI-MSI. The transformation from diester-diterpenoid alkaloids to monoester-diterpenoid alkaloids and then to non-esterified diterpene alkaloids through hydrolysis is the major toxicity attenuation process during steaming. DESI-MSI combined with metabolomics provides an efficient method to visualize the changeable rules and screen the metabolic markers of Aconitum alkaloids during steaming. The wide application of this technique could help identify markers and reveal the possible chemical transition mechanism in the “Paozhi” processes of Fuzi. It also provides an efficient and easy way to quality control and ensures the safety of Fuzi and other toxic traditional Chinese medicine.

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Section: Discussionsupporting

confidence: 63%

“…As a typical toxic traditional herbal medicine that is known for its extraordinary pharmacological activities and toxicity, Fuzi has long been used as an irreplaceable traditional herbal medicine in TCM, Kampo medicine, and homeopathy for thousands of years ( Zhou et al, 2015 ; Wu et al, 2018 ; Qiu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Unveiling Dynamic Changes of Chemical Constituents in Raw and Processed Fuzi With Different Steaming Time Points Using Desorption Electrospray Ionization Mass Spectrometry Imaging Combined With Metabolomics

et al. 2022

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“…The extraction of active ingredients is an important and necessary part of herbal pharmaceuticals, so we investigated extraction as a representative aspect of the pharmaceutical process. Aconiti Lateralis Radix Praeparata (the Chinese name is “Fuzi”) was used as our model herbal material for decoction because its pharmacological mechanism has been well-studied [ 32 , 33 ]. The diester alkaloids contained in the raw Fuzi are its main toxic components.…”

Section: Introductionmentioning

confidence: 99%

Online pharmaceutical process analysis of Chinese medicine using a miniature mass spectrometer: Extraction of active ingredients as an example

Hou

Liu

et al. 2023

Journal of Pharmaceutical Analysis

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“…The lateral root of Aconitum carmichaelii Debx (named Fuzi) is commonly used for the treatment of rheumatism, heart failure, and renal failure ( Wang et al, 2007 ; Li et al, 2017a ; Shuo et al, 2017 ; Chen et al, 2021 ). However, it often triggers aconitine poisoning events due to a narrow therapeutic window ( Singhuber et al, 2009 ; Huang et al, 2018 ; Qiu et al, 2021a ). The main active components in Fuzi are aconitines, including diester alkaloids, i.e., aconitine, mesaconitine and hypaconitine, and monoester alkaloids, i.e., benzoylaconitine, benzoylmesaconitine, and benzoylhypaconitine ( Qiu et al, 2021a ; Qiu et al, 2021b ).…”

Section: Introductionmentioning

confidence: 99%

“…However, it often triggers aconitine poisoning events due to a narrow therapeutic window ( Singhuber et al, 2009 ; Huang et al, 2018 ; Qiu et al, 2021a ). The main active components in Fuzi are aconitines, including diester alkaloids, i.e., aconitine, mesaconitine and hypaconitine, and monoester alkaloids, i.e., benzoylaconitine, benzoylmesaconitine, and benzoylhypaconitine ( Qiu et al, 2021a ; Qiu et al, 2021b ). However, the diester alkaloids are considered to be the main toxic components for the cardiac and central nervous systems.…”

Section: Introductionmentioning

confidence: 99%

Compatibility of Fuzi and Ginseng Significantly Increase the Exposure of Aconitines

et al. 2022

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The herb-pair ginseng-Fuzi (the root of Aconitum carmichaelii) is the material basis of Shenfu prescriptions and is popular in traditional Chinese medicine for the treatment of heart failure, and even shock with severe-stage of COVID-19. A narrow therapeutic window of Fuzi may cause significant regional loss of property and life in clinics. Therefore, systemic elucidation of active components is crucial to improve the safety dose window of Shenfu oral prescriptions. A high performance liquid chromatography-mass spectrometry method was developed for quantification of 10 aconitines in SD rat plasma within 9 min. The limit of detection and the limit of quantification were below 0.032 ng/ml and 0.095 ng/ml, respectively. Furthermore, a systemic comparison with their pharmacokinetic characteristics after oral administration of a safe dosage of 2 g/kg of Fuzi and ginseng-Fuzi decoction for 24 h was conducted. Eight representative diester, monoester, and non-ester aconitines and two new active components (i.e., songorine and indaconitine) were all adopted to elucidating the differences of the pharmacokinetic parameters in vivo. The compatibility of Fuzi and ginseng could significantly increase the in vivo exposure of active components. The terminal elimination half-life and the area under the concentration-time curve of mesaconitine, benzoylaconitine, benzoylmesaconitine, benzoylhypaconitine, and songorine were all increased significantly. The hypaconitine, benzoylmesaconitine, and songorine were regarded as the main active components in vivo, which gave an effective clue for the development of new Shenfu oral prescriptions.

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Online discovery of the molecular mechanism for directionally detoxification of Fuzi using real-time extractive electrospray ionization mass spectrometry

Cited by 15 publications

References 43 publications

Unveiling Dynamic Changes of Chemical Constituents in Raw and Processed Fuzi With Different Steaming Time Points Using Desorption Electrospray Ionization Mass Spectrometry Imaging Combined With Metabolomics

Unveiling Dynamic Changes of Chemical Constituents in Raw and Processed Fuzi With Different Steaming Time Points Using Desorption Electrospray Ionization Mass Spectrometry Imaging Combined With Metabolomics

Online pharmaceutical process analysis of Chinese medicine using a miniature mass spectrometer: Extraction of active ingredients as an example

Compatibility of Fuzi and Ginseng Significantly Increase the Exposure of Aconitines

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