RESUMO
Purpose: Zhixiao Tang (ZXT), a traditional Chinese compound prescription, has been used clinically to treat pneumonia in China. However, the underlying mechanism of ZXT treatment in pneumonia is still unclear. The present study aimed to reveal the potential mechanism of ZXT in pneumonia using a strategy combining metabolomics and network pharmacology. Methods: Initially, the chemical compositions were identified by UPLC-QE-Orbitrap-MS, while the prediction of potential signal pathways was performed through network pharmacology. To assess the anti-inflammatory properties of ZXT in the context of pneumonia, models of 16HBE cells induced by LPS and zebrafish induced by CuSO4 were established to measure levels of inflammatory markers and apoptosis. Subsequently, the differential changes of endogenous metabolites in cells caused by ZXT were examined using metabolomics technology, and the molecular docking analysis of key targets was carried out using Autodock Vina software. Ultimately, the validation of the primary pathways and targets was conducted through quantitative RT-PCR and Western blot techniques. Results: A total of 75 compounds were identified through UPLC-QE-Orbitrap-MS analyses. Network pharmacological analysis shows that it plays an anti-inflammatory role in C-type lectin receptor signaling pathway. After ZXT intervention, the inflammatory factors and apoptosis in cells were significantly reduced. Metabonomics analysis showed that 18 metabolites changed significantly. Four key genes were identified, which exhibited partial compatibility with the findings of network pharmacology. Molecular docking analysis confirmed the substantial affinity of the primary targets for ZXT. Furthermore, ZXT exerted a suppressive effect on neutrophil migration, down-regulated the expression of pro-inflammatory cytokine genes, and inhibited the up-regulation of the Dectin-1/SYK/NF-κB signaling pathway. In vivo cell experiments also yielded consistent experimental outcomes. Conclusion: This study enhances comprehension of the pharmacological mechanism underlying ZXT's efficacy in pneumonia treatment, thereby establishing a scholarly basis for future research and clinical utilization of ZXT in pneumonia management.
RESUMO
Testicular dysfunction is distinguished by a deficiency in testosterone levels, which can be attributed to the occurrence of oxidative stress injury in Leydig cells. The empirical prescription known as Bushen Zhuanggu Tang, developed by a highly experienced traditional Chinese medicine practitioner with six decades of clinical expertize, aligns with the traditional Chinese medicine principle of "kidney governing bone". Researchers have demonstrated that the administration of BSZGT can effectively enhance testosterone production. The objective of this study is to investigate the potential anti-testicular dysfunction effects of BSZGT and elucidate its underlying mechanism in an in vitro setting. Specifically, the impact of oxidative stress induced by H2O2 on the activity and testosterone levels of Leydig cells (TM3) was examined. Furthermore, the utilization of UPLC-QE-Qrbitrap-MS enabled the identification of the involvement of BSZGT in various metabolic pathways, including arginine biosynthesis, amino acyl-tRNA biosynthesis, Alanine, aspartate and glutamine metabolism, and Citrate Cycle, through the modulation of 25 distinct metabolites. Additionally, a network pharmacological analysis was conducted to investigate the pivotal protein targets associated with the therapeutic effects of BSZGT. The findings demonstrate the identification of six key proteins (CYP19A1, CYP1B1, ALOX5, ARG1, XDH, and MPO) that play a significant role in augmenting testicular function through their involvement in the ovarian steroid production pathway. In summary, our study presents a comprehensive research methodology that combines cell metabonomics and network pharmacology to enhance the discovery of new therapeutic agents for TD.