Essential oil from Ligusticum chuanxiong Hort. Alleviates lipopolysaccharide-induced neuroinflammation: Integrating network pharmacology and molecular mechanism evaluation

Ethnopharmacological relevance: Chuanxiong, the rhizome of Ligusticum chuanxiong Hort., is an ancient herbal medicine that has gained extensive popularity in alleviating migraines with satisfying therapeutic effects in China. As the major bioactive component of Chuanxiong, the essential oil also exerts a marked impact on the treatment of migraine. It is widely recognized that neuroinflammation contributes to migraine. However, it remains unknown whether Chuanxiong essential oil has anti-neuroinflammatory activity.Aim of the study: To explore the anti-neuroinflammatory properties of Chuanxiong essential oil and its molecular mechanisms by network pharmacology analysis and in vitro experiments.Materials and methods: Gas chromatography-mass spectrometry (GC-MS) was used to identify the chemical components of Chuanxiong essential oil. Public databases were used to predict possible targets, build the protein-protein interaction network (PPI), and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Moreover, cytological experiments, nitric oxide assay, enzyme-link immunosorbent assay, western blotting, and immunofluorescence assay were adopted to prove the critical signaling pathway in lipopolysaccharide (LPS)-induced BV2 cells.Results: Thirty-six compounds were identified from Chuanxiong essential oil by GC-MS, and their corresponding putative targets were predicted. The network pharmacology study identified 232 candidate targets of Chuanxiong essential oil in anti-neuroinflammation. Furthermore, Chuanxiong essential oil was found to potentially affect the C-type lectin receptor, FoxO, and NF-kappa B signaling pathways according to the KEGG analysis. Experimentally, we verified that Chuanxiong essential oil could significantly reduce the overproduction of inflammatory mediators and pro-inflammatory factors via the NF-kappa B signaling pathway. Conclusion: Chuanxiong essential oil alleviates neuroinflammation through the NF-kappa B signaling pathway, which provides a theoretical foundation for a better understanding of the clinical application of Chuanxiong essential oil in migraine treatment.