An integrated strategy of UPLC-Q-TOF-MS analysis, network pharmacology, and molecular docking to explore the chemical constituents and mechanism of Zixue Powder against febrile seizures
Lingling Song,
Jian Xu,
Yanqiong Shi,
Hemiao Zhao,
Min Zhang,
Yuefei Wang,
Ying Cui,
Xin Chai
Affiliations
Lingling Song
National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
Jian Xu
National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
Yanqiong Shi
Department of Pharmacy, Xuhui District Central Hospital, Shanghai, 200031, China
Hemiao Zhao
National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
Min Zhang
National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China
Yuefei Wang
National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China
Ying Cui
National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China; Corresponding author. National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
Xin Chai
National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China; Corresponding author. National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Febrile seizures (FS) are the most common type of seizures for children. As a commonly used representative cold formula for resuscitation, Zixue Powder (ZP) has shown great efficacy for the treatment of FS in clinic, while its active ingredients and underlying mechanism remain largely unclear. This study aimed to preliminarily elucidate the material basis of ZP and the potential mechanism for the treatment of FS through ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), network pharmacology, and molecular docking. UPLC-Q-TOF-MS was firstly applied to characterize the ingredients in ZP, followed by network pharmacology to explore the potential bioactive ingredients and pathways of ZP against FS. Furthermore, molecular docking technique was employed to verify the binding affinity between the screened active ingredients and targets. As a result, 75 ingredients were identified, containing flavonoids, chromogenic ketones, triterpenes and their saponins, organic acids, etc. Through the current study, we focused on 13 potential active ingredients and 14 key potential anti-FS targets of ZP, such as IL6, STAT3, TNF, and MMP9. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that inflammatory response, EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, and neuroactive ligand-receptor interaction were the main anti-FS signaling pathways. Licochalcones A and B, 26-deoxycimicifugoside, and hederagenin were screened as the main potential active ingredients by molecular docking. In conclusion, this study provides an effective in-depth investigation of the chemical composition, potential bioactive components, and possible anti-FS mechanism of ZP, which lays the foundation for pharmacodynamic studies and clinical applications of ZP.
