Glycyrrhizic Acid Attenuates the Inflammatory Response After Spinal Cord Injury by Inhibiting High Mobility Group Box-1 Protein Through the p38/Jun N-Terminal Kinase Signaling Pathway

• Published in: World neurosurgery 2022-02, Vol.158, p.e856-e864
• Main Authors: Wu, Zhiwu, Wang, Zhihua, Xie, Zhiping, Zhu, Huaxin, Li, Chengcai, Xie, Shenke, Zhou, Wu, Zhang, Zhixiong, Li, Meihua
• Format: Article
• Language: English
• Subjects: Glycyrrhizic acid; HMGB1; Inflammation; MAPK signaling pathway; Spinal cord injury
• ISSN: 1878-8750; 1878-8769
• DOI: 10.1016/j.wneu.2021.11.085

Neuroinflammation is an important secondary aggravating factor in spinal cord injury (SCI). Inhibition of the inflammatory response is critical for SCI treatment. Glycyrrhizic acid (GA) is an anti-inflammatory drug, but its utility for SCI is unclear. This study aimed to evaluate the effects of GA on inflammation after SCI and the underlying mechanism. Cell counting kit-8 assays were performed to assess the viability of highly aggressively proliferating immortalized cells that had been treated with lipopolysaccharide (LPS) and/or GA. Reverse transcription quantitative polymerase chain reaction and Western blotting were performed to assess expression of high mobility group box-1 protein (HMGB1), ionized calcium binding adaptor molecule 1, and inflammatory factors in vitro and in vivo. GA (100 mg/kg) was intraperitoneally injected into rats. Anti-inflammatory effects of GA were analyzed in SCI tissues. p38/Jun N-terminal kinase signaling pathway proteins were analyzed by Western blotting. Cell counting kit-8 assay results showed that treatment with 100 ng/mL LPS for 12 hours was optimal. After LPS treatment, highly aggressively proliferating immortalized cells were activated; messenger RNA expression levels of HMGB1 and inflammatory factors were increased. GA significantly inhibited LPS-induced HMGB1 expression and inflammatory responses, as determined by reverse transcription quantitative polymerase chain reaction and Western blotting. Transfection with an HMGB1-overexpression plasmid reversed the anti-inflammatory effects of GA. In addition, intraperitoneal injection of GA (100 mg/kg) into rats for 3 days significantly reduced expression levels of HMGB1 and inflammatory factors after SCI in vivo. GA reduced phosphorylation, but not levels, of p38 and Jun N-terminal kinase proteins. GA attenuates the inflammatory response after SCI by inhibiting HMGB1 through the p38/JNK signaling pathway and thus has therapeutic potential for SCI.