• Zhiwu Wu, Zhihua Wang, Zhiping Xie, Huaxin Zhu, Chengcai Li, Shenke Xie, Wu Zhou, Zhixiong Zhang, and Meihua Li.
• Department of Neurosurgery and Jiangxi Key Laboratory of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
• World Neurosurg. 2022 Feb 1; 158: e856-e864.

BackgroundNeuroinflammation 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.MethodsCell 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.ResultsCell 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.ConclusionsGA attenuates the inflammatory response after SCI by inhibiting HMGB1 through the p38/JNK signaling pathway and thus has therapeutic potential for SCI.Copyright © 2021. Published by Elsevier Inc.

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