Glycyrrhiza uralensis Fisch. and its active components mitigate Semen Strychni-induced neurotoxicity through regulating high mobility group box 1 (HMGB1) translocation

• Published in: Biomedicine & pharmacotherapy 2022-05, Vol.149, p.112884-112884, Article 112884
• Main Authors: Duan, Xiaoyu, Wen, Jing, Zhang, Min, Wang, Chao, Xiang, Yalan, Wang, Lu, Yu, Changwei, Deng, Gongying, Yan, Miao, Zhang, Bikui, Fang, Pingfei
• Format: Article
• Language: English
• Subjects: Animals; Glycyrrhiza - chemistry; Glycyrrhiza uralensis; HMGB1; HMGB1 Protein; Inflammation; Liquorice; Neuroprotection; Neurotoxicity; Neurotoxicity Syndromes; Plant Extracts - pharmacology; Rats; Seeds; Semen Strychni; Toll-Like Receptor 4
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.112884

Semen Strychni has long been used for the treatment of rheumatoid arthritis, facioplegia and myasthenia gravis due to its anti-inflammation and anti-nociceptive properties in China. However, the fatal neurotoxicity of Semen Strychni has limited its wider clinical application. To investigate the acute toxicity induced by Semen Strychni and the detoxification of liquorice, we evaluated inflammation, oxidative stress and the translocation of high mobility group box 1 (HMGB1) in rats. As a result, there were obvious oxidative stress and inflammation in hippocampus after the Semen Strychni extracts (STR) treatment in rats. Liquorice extracts (LE) and its three active monomers – glycyrrhizic acid (GA), liquiritigenin (LIQ), isoliquiritigenin (ISL) showed the potential for mitigating STR-induced neurotoxicity. HMGB1 levels in cytoplasm and serum and the levels of two downstream receptors RAGE and TLR4 were significantly increased after STR treatment. Through using LE and the monomers, the nucleocytoplasmic transport and release of HMGB1 were inhibited. In addition, the binding between HMGB1 and TLR4 was weakened in detoxification groups comparing with the STR group. Taken together, these findings indicated that liquorice and its active components alleviated acute neurotoxicity induced by Semen Strychni partly via HMGB1-related pathway. [Display omitted] •Semen Strychni administration induced obvious pathological changes in brain.•Liquorice and its three active components ameliorated Semen Strychni-induced neuroinflammation.•Semen Strychni-induced HMGB1 release was significantly diminished by Liquorice.•Liquorice showed neuroprotective effect on Semen Strychni poisoned rats partly through HMGB1-RAGE/TLR4 signaling.