Posttraumatic stress disorder (PTSD) is a serious stress disorder that occurs in individuals who have experienced major traumatic events. The underlying pathological mechanisms of PTSD are complex, and the related predisposing factors are still not fully understood. In this study, label-free quantitative proteomics and untargeted metabolomics were used to comprehensively characterize changes in a PTSD mice model. Differential expression analysis showed that 12 metabolites and 27 proteins were significantly differentially expressed between the two groups. Bioinformatics analysis revealed that the differentiated proteins were mostly enriched in: small molecule binding, transporter activity, extracellular region, extracellular space, endopeptidase activity, zymogen activation, hydrolase activity, proteolysis, peptidase activity, sodium channel regulator activity. The differentially expressed metabolites were mainly enriched in Pyrimidine metabolism, D-Glutamine and D-glutamate metabolism, Alanine, aspartate and glutamate metabolism, Arginine biosynthesis, Glutathione metabolism, Arginine, and proline metabolism. These results expand the existing understanding of the molecular basis of the pathogenesis and progression of PTSD, and also suggest a new direction for potential therapeutic targets of PTSD. Therefore, the combination of urine proteomics and metabolomics explores a new approach for the study of the underlying pathological mechanisms of PTSD.
Sesquiterpene pyridine alkaloids are a large group of highly oxygenated sesquiterpenoids, which are characterized by a macrocyclic dilactone skeleton containing 2-(carboxyalkyl) nicotinic acid and dihydro-β-agarofuran sesquiterpenoid, and are believed to be the active and less toxic components of Tripterygium. In this study, 55 sesquiterpene pyridine alkaloids from Tripterygium were subjected to identification of pharmacophore characteristics and potential targets analysis. Our results revealed that the greatest structural difference of these compounds was in the pyridine ring and the pharmacophore model-5 (Pm-05) was the best model that consisted of three features including hydrogen bond acceptor (HBA), hydrogen bond donor (HBD), and hydrophobic (HY), especially hydrophobic group located in the pyridine ring. It was proposed that 2-(carboxyalkyl) nicotinic acid part possessing a pyridine ring system was not only a pharmacologically active center but also a core of structural diversity of alkaloids from Tripterygium wilfordii. Furthermore, sesquiterpene pyridine alkaloids from Tripterygium were predicted to target multiple proteins and pathways and possibly played essential roles in the cure of Alzheimer’s disease, breast cancer, Chagas disease, and nonalcoholic fatty liver disease (NAFLD). They also had other pharmacological effects, depending on the binding interactions between pyridine rings of these compounds and active cavities of the target genes platelet-activating factor receptor (PTAFR), cannabinoid receptor 1 (CNR1), cannabinoid receptor 1 (CNR2), squalene synthase (FDFT1), and heat shock protein HSP 90-alpha (HSP90AA1). Taken together, the results of this present study indicated that sesquiterpene pyridine alkaloids from Tripterygium are promising candidates that exhibit potential for development as medicine sources and need to be promoted.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.