Isoliquiritigenin alleviates neuropathic pain by reducing microglia inflammation through inhibition of the ERK signaling pathway and decreasing CEBPB transcription expression

作者：Zikun Wang, Shu Jia, Xizhi Kang, Shang Chen, L. Zhang, Z. Tian, Xiao Liang, Chunyang Meng · 发表于：International Immunopharmacology · 年份：2024 · DOI：10.1016/j.intimp.2024.113536 · 被引用次数：17 · 研究领域：Pain Mechanisms and Treatments、Pharmacological Effects of Natural Compounds、Ginseng Biological Effects and Applications

BACKGROUND: Natural compounds are invaluable for their therapeutic effects in treating various diseases. Isoliquiritigenin (ISL) stands out due to its potent anti-inflammatory and antioxidative properties, offering significant therapeutic effects in many diseases. However, there is currently no existing literature on the role of ISL in neuropathic pain treatment. METHODS: We used lipopolysaccharide to stimulate BV-2 microglia in order to evaluate the inhibitory effects of ISL on neuroinflammation. Proteomics data and protein-protein interaction network analysis were used to identify differential proteins expressed in BV-2 microglia treated with ISL. This allowed for the identification of targets impacted by ISL action. Additionally, we assessed the analgesic efficacy of ISL in a mouse model of chronic constriction injury of the sciatic nerve (CCI) and investigated its inhibitory influence on pro-inflammatory cytokine production and spinal microglia activation. RESULTS: Our results indicate that ISL efficiently inhibits BV-2 microglia activation and pro-inflammatory cytokine expression. Furthermore, CEBPB has been recognized as a possible target for ISL activity. Crucially, microglia activation was successfully reduced by CEBPB knockdown. Functional recovery tests carried out later on validated that ISL works by specifically inhibiting the ERK/CEBPB signaling pathway. In vivo studies showed that giving mice ISL reduces the mechanical and thermal pain caused on by chronic contr...