Abstract
Traumatic brain injury (TBI) is a critical public health and socioeconomic problem worldwide. The herb pair Astragali Radix (AR)-Radix Angelica Sinensis (RAS) is a common prescribed herbal formula or is added to other Chinese medicine prescriptions for traumatic brain injury (TBI) treatment. However, the underlying mechanisms are unclear. In this study, we aimed to explore the active ingredients and action targets of AR-RAS based on the combined methods of network pharmacology prediction and experimental verification. Furthermore, the corresponding potential mechanisms of “multicomponents, multitargets, and multipathways” were disclosed. Methods. A network pharmacology approach including ADME (absorption, distribution, metabolism, and excretion) filter analysis, target prediction, known therapeutic targets collection, Gene Ontology (GO), pathway enrichment analysis, and network construction was used in this study. Further verification experiments were performed to reveal the therapeutic effects of AR-RAS in a rat model of TBI. Results. The comprehensive systematic approach was to successfully identify 14 bioactive ingredients in AR-RAS, while 33 potential targets hit by these ingredients related to TBI. Based on GO annotation analysis, multiple biological processes were significantly regulated by AR-RAS. In addition, 89 novel signaling pathways (P<0.05) underlying the effects of AR-RAS for TBI treatment were identified by DAVID. The neurotrophin signaling pathway was suggested as the major related pathway targeted by AR-RAS to improve axonal growth. The animal experiment confirmed that AR-RAS significantly induced tissue recovery and improved neurological deficits on the 14th day (P<0.01). Treatment with AR-RAS markedly reduced the protein and mRNA expression level of NogoA in the hippocampus of TBI rats. Conclusion. Our work illuminates the “multicompounds, multitargets, and multipathways” curative action of AR-RAS in the treatment of TBI by network pharmacology. The animal experiment verifies the effects of AR-RAS on neurological function improvement and axonal outgrowth via downregulation of NogoA expression, providing a theoretical basis for further research on treatment of TBI.
Highlights
Traumatic brain injury (TBI) is described as any traumatically induced structural injury or physiological disruption of brain function as a result of an external force
We considered Astragali Radix-Radix Angelica Sinensis (AR-Radix Angelica Sinensis (RAS)) could be used as an effective therapeutic for repairing and protecting nerve after TBI
The ingredients of both Astragali Radix (AR) and RAS were obtained from TCMSP database, which provided information on various active ingredients related to Traditional Chinese medicine (TCM) drugs and their target proteins
Summary
Traumatic brain injury (TBI) is described as any traumatically induced structural injury or physiological disruption of brain function as a result of an external force. It is an important contributing factor of morbidity and mortality in adult and pediatric population worldwide [1, 2]. Substantial evidence confirms that the annual global incidence and prevalence rate of TBI increased progressively over the past years [3]. It seriously damages people’s quality of life and results in a massive economic toll [4,5,6]. On account of the BioMed Research International fact that TBI involves complicated pathological mechanisms of multiple cellular and molecular events [13, 14], including blood-brain barrier breakdown, neuronal death, and neurodegeneration, “one-compound, one-target, and onepathway” based modern drugs have poor curative effect
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