Atractylenolide III ameliorates spinal cord injury in rats by modulating microglial/macrophage polarization.

BACKGROUND: Inflammatory reactions induced by spinal cord injury (SCI) are essential for recovery after SCI. Atractylenolide III (ATL-III) is a natural monomeric herbal bioactive compound that is mainly derived in Atractylodes macrocephala Koidz and has anti-inflammatory and neuroprotective effects. OBJECTIVE: Here, we speculated that ATL-III may ameliorate SCI by modulating microglial/macrophage polarization. In the present research, we focused on investigating the role of ATL-III on SCI in rats and explored the potential mechanism. METHODS: The protective and anti-inflammatory effects of ATL-III on neuronal cells were examined in a rat SCI model and lipopolysaccharide (LPS)-stimulated BV2 microglial line. The spinal cord lesion area, myelin integrity, and surviving neurons were assessed by specific staining. Locomotor function was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale, grid walk test, and footprint test. The activation and polarization of microglia/macrophages were assessed by immunohistofluorescence and flow cytometry. The expression of corresponding inflammatory factors from M1/M2 and the activation of relevant signaling pathways were assessed by Western blotting. RESULTS: ATL-III effectively improved histological and functional recovery in SCI rats. Furthermore, ATL-III promoted the transformation of M1 into M2 and attenuated the activation of microglia/macrophages, further suppressing the expression of corresponding inflammatory mediators. This effect may be partly mediated by inhibition of neuroinflammation through the NF-κB, JNK MAPK, p38 MAPK, and Akt pathways. CONCLUSION: This study reveals a novel effect of ATL-III in the regulation of microglial/macrophage polarization and provides initial evidence that ATL-III has potential therapeutic benefits in SCI rats.

Effect of morroniside on the transcriptome profiles of rat in injured spinal cords.

We have previously reported that morroniside promoted motor activity after spinal cord injury (SCI) in rats. However, the mechanism by which morroniside induces recovery of injured spinal cord (SC) remains unknown. In the current study, RNA sequencing (RNA-seq) was employed to evaluate changes of gene expressions at the transcriptional level of the injured spinal cords in morroniside-administrated rats. Principal component analysis, analysis of enriched Gene Ontology (GO), enrichment analyses Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and other bioinformatics analyses were executed to distinguish differentially expressed genes (DEGs). The results of RNA-seq confirmed the anti-inflammatory and anti-apoptotic effects of morroniside on injured SC tissues, and provided the basis for additional research of the mechanisms involving the protective effects of morroniside on SCI.