Exploring potential mechanism of ciwujia tablets for insomnia by UPLC-Q-TOF-MS/MS, network pharmacology, and experimental validation

Abstract

Insomnia, whether chronic or intermittent, is a common central nervous system disease. Ciwujia Tablet (CWT) is a well-known traditional Chinese medicine (TCM) made from the extract of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. This medication is commonly used for treating insomnia in China, but the lack of in-depth research focused on the chemical ingredients of CWT creates a gap in knowledge regarding its effective constituents against insomnia. Considering that the therapeutic material basis, targets, and pathways related to this drug have not been fully investigated by scholars in the field, the focus of this study is on identifying the chemical ingredients or structural characteristics of CWT by the UPLC-Q-TOF-MS/MS technique. Besides, concepts of network pharmacology were also used to investigate the targets and pathways of CWT. An insomnia rat model was established by intraperitoneal injection of p-chlorophenylalanine, and the results were verified through various experiments. A total of 46 ingredients were identified in CWT, such as eleutheroside B, eleutheroside E, isofraxidin, and chlorogenic acid. Among them, 17 ingredients with good solubility, favorable gastrointestinal absorption, and high bioavailability were selected for network pharmacological analysis. It was concluded that CWT participated in the regulation of neurotransmitter levels, modulation of ion transport, neurotransmitter receptor activity, synaptic transmission, dopaminergic transmission and other essential processes. Results from the animal experiments showed that CWT can increase the content of inhibitory neurotransmitters 5-HT and GABA in the brain, reduce the synthesis of excitatory escalating transmitters DA and NE, shorten the sleep latency and prolong the sleep duration of insomnia rats. Furthermore, CWT could significantly alleviate the symptoms of insomnia in model rats. Identifying the chemical ingredients of CWT in this experiment is of great significance for exploring its potential curative effects, which provides a solid basis for further understanding the therapeutic value of this medication.

Qualitative and quantitative analysis of chemical constituents in goupi plaster prepared by various extraction methods using UPLC-Q-Exactive-MS and UPLC-MS/MS

“…The secondary cracking fragment ions include m/z 115 [M-H-H 2 O] + , m/z 105 [M-H-CO] + , m/z 103 [M-H–H 2 O–C] + , m/z 91 [M-H–H 2 O–2C] + . Combined with the fragmentation law of mass spectrometry and literature reference [ 38 ]. It is inferred that the compound is cinnamaldehyde.…”

Integrated Transcriptomic and Metabolomic Analyses Reveal the Effects of Grafting on Special Metabolites of Acanthopanax senticosus Leaves

“…[ 1 , 2 , 3 , 4 ]. These health properties are due to the presence of various positive health-promoting components in the leaves, such as triterpenoids, phenylpropanoids, flavonoids, polysaccharides, lignans and other individual compounds such as chlorogenic acid, quercetin, syringin, and isofraxidin [ 5 , 6 , 7 , 8 ]. The metabolites syringin and isofraxidin are active medicinal ingredients extracted from A. senticosus , produced through the phenylpropanoid biosynthesis pathway and used in Chinese Pharmacopoeia to determine the quality of the traditional Chinese herb A. senticosus .…”

Evaluation of the pharmacological effects and exploration of the mechanism of traditional Chinese medicine preparation Ciwujia tablets in treating insomnia based on ethology, energy metabolism, and urine metabolomic approaches

“…Research shows that CWT mainly contains eleutheroside B, eleutheroside E, isofraxidin, eleutheroside C, ciwujiatone, and chlorogenic acid, as well as other chemical components, especially eleutheroside B, eleutheroside E and isofraxidin can be used as characteristic components of CWT to evaluate their quality. ( Liu et al, 2022 ). It has been demonstrated that E. senticosus extract can be used in the treatment of neurodegenerative diseases.…”