Abstract
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.
Highlights
Fuzi, the lateral root of Aconitum carmichaelii Debeaux
The filtered sample was analyzed using Agilent Technology 1260 Infinity (Agilent Technologies, Santa Clara, CA, FIGURE 6 | OPLS-DA score plots and S-plots based on raw and processed Fuzi steamed for 4.0 h (A,B) and Fuzi steamed for 4.0 and 8.0 h (C,D) from DESIMSI data
The solvent compositions are selected based on the analyte of interest and the tissue surface, which play a major role in the elution of each category of the compound (Claude et al, 2017)
Summary
The lateral root of Aconitum carmichaelii Debeaux (Fam. Ranunculaceae), primarily cultivated in Jiangyou and Butuo in Sichuan, China, has been an indispensable herb in traditional Chinese medicine (TCM) for thousands of years (Chinese Pharmacopoeia Commission, 2020). Fuzi has potent efficacy to restore from collapse, reinforce fire and Yang, and dispel cold to relieve pain (Luo et al, 2019; Chinese Pharmacopoeia Commission, 2020). It is usually combined with other herbs in formulations such as Si Ni Tang, Shen Fu Tang, and Fuzi Lizhong Wan to treat cold-damp-type illness (Singhuber et al, 2009). The studies of toxic components and their mechanisms and the proper methods to attenuate the toxicity and reserve efficacy are the primary concern of scholars
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