Danshen extract (Salvia miltiorrhiza Bunge) attenuate spinal cord injury in a rat model: A metabolomic approach for the mechanism study

Abstract Backgroud Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. To date, SCI treatment is still a significant challenge in clinic and research around the world. Danshen (dried roots and rhizomes of Salvia miltiorrhiza ), a commonly used Chinese medicinal herb, has been attracting attention in SCI treatment. Purpose Aim of this study was to evaluate the potential beneficial effects of danshen extract in a SCI rat model, as well as investigate possible mechanism of action and potential biomarkers. Methods Here, a rat SCI model was established with weight-drop method, and danshen extract was administered by oral gavage (12.5 g/kg). Recovery of motor function and histomorphological changes were evaluated by Basso, Beattie and Bresnahan score and hematoxylin-eosin staining, respectively. In addition, neurofilament 200 (NF-H), brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP) and CD11b expressions were assayed by immunofluorescence and western blot analysis. Furthermore, a metabolomics analysis based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was conducted. Results The results demonstrated that danshen extract could significantly ameliorated histopathology changes and improved recovery of motor function after SCI. Moreover, NF-H, BDNF and CD11b expression were progressively increased until 4 weeks post-injury after administrated danshen extract. Furthermore, a good separation was observed among different groups using OPLS-DA. Trajectory analysis showed the gradual shift from position of model group toward normal group with increasing time after administration of danshen extract. Meanwhile, 51 significantly altered metabolites were identified, while metabolic pathway analysis suggested that 6 metabolic pathways were disturbed by the altered metabolites. Conclusion In summary, this study provides an overview of neuroprotective effects and investigates possible mechanism of danshen extract in SCI treatment. However, further research is needed to uncover its regulatory mechanisms more clearly.