The mechanism of Zizyphi Spinosae Semen in relieving benzodiazepine dependence based on the strategy of

Xinbo Shi; Changle Liu; Zhongxing Song; Zhishu Tang; Hongbo XU; Guolong LI; Chen Sun; Hongbo Liu; Jiaxin Chen

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The mechanism of Zizyphi Spinosae Semen in relieving benzodiazepine dependence based on the strategy of "enhancing efficacy and reducing toxicity"

VernacularTitle:基于“增效减毒”策略探究酸枣仁缓解苯二氮类药物依赖性的作用机制
Author: Xinbo SHI ¹ ; Changle LIU ¹ ; Zhongxing SONG ¹ ; Zhishu TANG ^{1
,

2} ; Hongbo XU ¹ ; Guolong LI ¹ ; Chen SUN ¹ ; Hongbo LIU ¹ ; Jiaxin CHEN ¹
Author Information

1. Shaanxi University of Chinese Medicine, Co-construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi & Education Ministry, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Xianyang 712083
2. Graduate School, Chinese Academy of Chinese Medical Sciences, Beijing 100700, China
Publication Type:Journal Article
Keywords: network pharmacology; Zizyphi Spinosae Semen; benzodiazepine dependence; molecular docking; molecular dynamics simulation
From: Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):828-836
CountryChina
Language:Chinese
Abstract: 【Objective】 To investigate the active ingredients of Zizyphi Spinosae Semen (ZSS) in relieving benzodiazepine (BDZ) dependence and its molecular mechanism based on the integrated Traditional Chinese Medicine and chemical drugs idea of "enhancing effect and reducing toxicity" via the approach of network pharmacology and the technique of molecular dynamics simulation. 【Methods】 First, literature search was undertaken to find the main components of ZSS. Then, the major effective constituents of ZSS in relieving BDZ dependence and its target of action were explored on the basis of network pharmacology and molecular docking. Finally, the relationship between core components of ZSS and key proteins was further verified through the technique of molecular dynamics simulation. 【Results】 After literature search, a total of 24 chemical components in ZSS were found to act on 731 targets. Through establishing the network of "ingredients-targets-pathways" , topology analysis was performed to obtain nine core components such as linoleic acid, palmitic acid, oleic acid, tetradecanoic acid, spinosin, oleanolic acid and jujuboside A, as well as five key targets including AR, PTGS2, PPARG, RXRA and CYP19A1. Bioinformation enrichment analysis was made to obtain critical pathways such as calcium signaling pathway, cAMP signaling pathway, IL-17 signaling pathway and TNF signaling pathway. The results of molecular docking revealed that there was a good combination between core components of ZSS and key targets, and it was mainly dominated by hydrogen bonding. Furthermore, the molecular dynamics simulation experiments indicated that the combinations between jujuboside A and RXRA, oleanolic acid and RXRA, spinosin and PPARG were stable, and these three active ingredients played an important role in improving BDZ dependence. 【Conclusion】 The active components in ZSS may exert multi-target and multi-pathway intervention effects on BDZ dependence by means of processes such as immunoregulation, anti-anxiety, and anti-insomnia.