Online discovery of the molecular mechanism for directionally detoxification of Fuzi using real-time extractive electrospray ionization mass spectrometry
| Autor: | Haiyu Xu, Yujun Zhao, Luqi Huang, Yanan Wang, E-Hu Liu, Wei Gao, Jiaquan Xu, Chang-Jiang-Sheng Lai, Guanghong Cui, Juan Guo, Xu-Ya Wei, Ye Shen, Huanwen Chen, Konstantin Chingin, Shuang-Long Wang, Ting Tan, Xiaoping Zhang, Bin Yang, Qiu Zidong |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Spectrometry
Mass Electrospray Ionization Painful joints Mass spectrometry Aconitum carmichaelii 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alkaloids Detoxification Drug Discovery Aconitine Aconitum 030304 developmental biology Pharmacology 0303 health sciences biology Fatty Acids Extractive electrospray ionization Reproducibility of Results biology.organism_classification Combinatorial chemistry chemistry 030220 oncology & carcinogenesis Molecular mechanism Diterpenes Drugs Chinese Herbal |
| Zdroj: | Journal of ethnopharmacology. 277 |
| ISSN: | 1872-7573 |
| Popis: | Ethnopharmacological relevance Aconitum carmichaelii Debeaux, a famous traditional medicinal herb for collapse, rheumatic fever, and painful joints, always raises global concerns about its fatal toxicity from toxic alkaloids when improperly processed. Therefore, it is urgent to clarify the internal molecular mechanism of processing detoxification on Aconitum and develop simple and reliable approaches for clinical application, which is also of great significance to the rational medicinal use of Aconitum. Aim of the study The study aimed at developing a complete molecular mechanism exploration strategy in complex medicinal herb decocting system, clarifying the internal molecular mechanism of processing detoxification on Aconitum, and exploring valid approaches for detoxification. Materials and methods Aconiti Lateralis Radix Praeparata (Fuzi) was selected as the model for exploring the complex Aconitum detoxification mechanism using an advanced online real-time platform based on extractive electrospray ionization mass spectrometry. The methods realized the sensitive capture of dynamic trace intermediates, accurate qualitative and quantitative analysis, and real-time and long-term monitoring of multi-components with satisfactory accuracy and resistance to complex matrices. Results Components in the complex Aconitum decocting system were real-timely characterized and fat meat was discovered and verified to directionally detoxify Aconitum while reserving the therapy effect. More importantly, the dynamic detoxification mechanism in the chemically complex Aconitum decoction was molecularly profiled. A novel reaction pathway based on nucleophilic substitution reaction mechanism was proposed. As confirmed by the theoretic calculations at DFT B3LYP/6-31G (d) levels, fatty acids (e.g., palmitic acid) acted as a green, cheap, and high-performance catalyst and promote the decomposition of toxic diester alkaloids to non-toxic and active benzoyl-monoester alkaloids through the discovered mechanism. Conclusion The study exposed a novel detoxification molecular mechanism of Aconitum and provided an effective method for the safe use of Aconitum, which could effectively guide the development of traditional processing technology and compatibility regulation of the toxic herb and had great value to the modernization and standardization development of traditional medicine. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect