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Background: Traumatic brain injury (TBI) is one of the most common neurosurgical diseases which refers to brain function impairment or brain pathological changes induced by external causes. A traditional Chinese medicine, Xuefu Zhuyu Decoction (XFZYD), has been indicated to harbor therapeutic property against TBI. Transfer RNA (tRNA)-derived small RNAs i.e., tsRNAs (a group of small RNAs derived from tRNAs) are multifunctional regulatory non-coding RNAs generated under pressure and implicated in the progression of TBI.Methods: TBI model was successfully constructed by using of rats. Further using sequencing and omics to identify novel tsRNAs as drug targets for XFZYD therapy against TBI in rat hippocampus. qPCR assay was used to further verify the experimental results. GO analyzed the signaling pathways of downstream target genes of tsRNA in XFZYD regulated TBI model. qPCR was used to detect the influence of over-expressed tsRNA mimic/inhibitor on their target genes in PC12 cell.Results: Our RNA-Seq data illustrates that 11 tsRNAs were mediated by the XFZYD. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment and nicotine pharmacodynamics pathway. We also confirm that Pi4kb, Mlh3, Pcdh9, and Ppp1cb were targets genes of 2 XFZYD regulated tsRNAs in hippocampus of rat model and PC12 cells. Furthermore, biological function analysis revealing potential therapeutic effects of tsRNAs, and results found Mapk1, Gnai1 was the related genes of for XFZYD therapy against TBI.Conclusion: Our work successfully illuminates the efficiency of XFZYD for the treatment of TBI. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment and nicotine pharmacodynamics pathway in TBI rat model.

Background. Infertility affects approximately 15% of couples around the world, and male factors are accounted for 40–50%. Oligoasthenozoospermia is the most common reason for male infertility. Unfortunately, effective drug therapy is still lacking except for assisted reproductive technology (ART). Previous researchers found that Wuzi Ershen decoction (WZESD) can increase sperm count, enhance sperm vitality, and improve semen quality. However, the pharmacological mechanisms remain unclear. Methods. In this study, we screened compounds and predicted the targets of WZESD based on the TCMSP and BATMAN-TCM database combined with literature searching in the PubMed database. We obtained proteins related to oligoasthenozoospermia through GeneCards and submitted them to STRING to obtain the protein-protein interaction (PPI) network. Potential targets of WZESD were mapped to the network, and the hub targets were screened by topology. We used online platform Metascape and Enrichr for GO and KEGG enrichment analyses. AutoDock Vina was utilized for further verification of the binding mode between compounds and targets. Results. Totally, 276 bioactive compounds were obtained and targeted 681 proteins. 446 oligoasthenozoospermia disease-specific proteins were acquired, and further bioinformatics analysis found that they were mainly involved in the formation of gametes, meiosis, and sperm differentiation. Protein interaction network analysis revealed that target proteins of WZESD were associated with oligoasthenozoospermia disease-specific proteins. The 79 targets of disease-specific proteins, which were anchored by WZESD, mainly participate in the cellular response to the organic cyclic compound, regulation of the apoptotic process, nitricoxide biosynthetic and metabolic process, oxidative stress, and protein phosphorylation regulation, which are the causes for oligoasthenozoospermia. Molecular docking simulation further validated that bioactive compounds originated from WZESD with targeted proteins showed high binding efficiency. Conclusions. This study uncovers the therapeutic mechanisms of WZESD for oligoasthenozoospermia treatment from the perspective of network pharmacology and may provide a valuable reference for further experimental research studies and clinical applications.

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