PMID- 38399454 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240227 IS - 1424-8247 (Print) IS - 1424-8247 (Electronic) IS - 1424-8247 (Linking) VI - 17 IP - 2 DP - 2024 Feb 12 TI - Integrated UPLC/Q-TOF-MS/MS Analysis and Network Pharmacology to Reveal the Neuroprotective Mechanisms and Potential Pharmacological Ingredients of Aurantii Fructus Immaturus and Aurantii Fructus. LID - 10.3390/ph17020239 [doi] LID - 239 AB - Aurantii Fructus (AF) and Aurantii Fructus Immaturus (AFI) have been used for thousands of years as traditional Chinese medicine (TCM) with sedative effects. Modern studies have shown that Citrus plants also have protective effects on the nervous system. However, the effective substances and mechanisms of action in Citrus TCMs still remain unclear. In order to explore the pharmacodynamic profiles of identified substances and the action mechanism of these herbs, a comprehensive approach combining ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS) analysis and network pharmacology was employed. Firstly, UNIFI 2.1.1 software was used to identify the chemical characteristics of AF and AFI. Secondly, the SwissTargetPrediction database was used to predict the targets of chemical components in AF and AFI. Targets for neuroprotection were also collected from GeneCards: The Human Gene Database (GeneCards-Human Genes|Gene Database|Gene Search). The networks between targets and compounds or diseases were then constructed using Cytoscape 3.9.1. Finally, the Annotation, Visualization and Integrated Discovery Database (DAVID) (DAVID Functional Annotation Bioinformatics Microarray Analysis) was used for GO and pathway enrichment analysis. The results showed that 50 of 188 compounds in AF and AFI may have neuroprotective biological activities. These activities are associated with the regulatory effects of related components on 146 important signaling pathways, derived from the KEGG (KEGG: Kyoto Encyclopedia of Genes and Genomes), such as neurodegeneration (hsa05022), the Alzheimer's disease pathway (hsa05010), the NF-kappa B signaling pathway (hsa04064), the hypoxia-inducible factor (HIF)-1 signaling pathway (hsa04066), apoptosis (hsa04210), the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance signaling pathway (hsa01521), and others, by targeting 108 proteins, including xanthine dehydrogenase (XDH), glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B), and glucose-6-phosphate dehydrogenase (G6PD), among others. These targets are thought to be related to inflammation, neural function and cell growth. FAU - Qiu, Mingyang AU - Qiu M AUID- ORCID: 0000-0002-5254-5489 AD - National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200100, China. AD - College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Zhang, Jianqing AU - Zhang J AD - National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200100, China. FAU - Wei, Wenlong AU - Wei W AD - National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200100, China. FAU - Zhang, Yan AU - Zhang Y AD - National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200100, China. AD - College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Li, Mengmeng AU - Li M AD - National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200100, China. AD - College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Bai, Yuxin AU - Bai Y AD - National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200100, China. AD - College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Wang, Hanze AU - Wang H AUID- ORCID: 0000-0002-2447-170X AD - National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200100, China. AD - College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China. FAU - Meng, Qian AU - Meng Q AD - National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200100, China. FAU - Guo, De-An AU - Guo DA AD - National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200100, China. AD - College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China. LA - eng PT - Journal Article DEP - 20240212 PL - Switzerland TA - Pharmaceuticals (Basel) JT - Pharmaceuticals (Basel, Switzerland) JID - 101238453 PMC - PMC10892462 OTO - NOTNLM OT - Aurantii Fructus OT - Aurantii Fructus Immaturus OT - UPLC/Q-TOF-MS/MS OT - network pharmacology OT - neuroprotection COIS- The authors declare that they have no competing financial interests associated with this work. EDAT- 2024/02/24 11:44 MHDA- 2024/02/24 11:45 PMCR- 2024/02/12 CRDT- 2024/02/24 01:19 PHST- 2023/12/19 00:00 [received] PHST- 2024/01/24 00:00 [revised] PHST- 2024/02/01 00:00 [accepted] PHST- 2024/02/24 11:45 [medline] PHST- 2024/02/24 11:44 [pubmed] PHST- 2024/02/24 01:19 [entrez] PHST- 2024/02/12 00:00 [pmc-release] AID - ph17020239 [pii] AID - pharmaceuticals-17-00239 [pii] AID - 10.3390/ph17020239 [doi] PST - epublish SO - Pharmaceuticals (Basel). 2024 Feb 12;17(2):239. doi: 10.3390/ph17020239.