Glycyrrhiza uralensis Fisch. and its active components mitigate Semen Strychni-induced neurotoxicity through regulating high mobility group box 1 (HMGB1) translocation
Glycyrrhiza uralensis Fisch. and its active components mitigate Semen Strychni-induced neurotoxicity through regulating high mobility group box 1 (HMGB1) translocation
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DOI：
10.1016/j.biopha.2022.112884
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发表时间：
2022-03-28
影响因子：
7.5
通讯作者：
Fang, Pingfei
中科院分区：
文献类型：
--
作者：
Duan, Xiaoyu;Wen, Jing;Fang, Pingfei
马钱子因其抗炎和抗伤害特性而在中国长期以来被用于治疗类风湿性关节炎、面部麻痹和重症肌无力。然而马钱子致命的神经毒性限制了其更广泛的临床应用。为了研究马钱子引起的急性毒性和甘草的解毒作用，我们评估了大鼠的炎症、氧化应激和高迁移率族蛋白1（HMGB1）的易位。结果表明，马钱子提取物（STR）治疗后大鼠海马出现明显的氧化应激和炎症。甘草提取物 (LE) 及其三种活性单体 - 甘草酸 (GA)、甘草素 (LIQ)、异甘草素 (ISL) 显示出减轻 STR 诱导的神经毒性的潜力。 STR处理后细胞质和血清中的HMGB1水平以及两个下游受体RAGE和TLR4的水平显着升高。通过使用LE和单体，HMGB1的核质转运和释放受到抑制。此外，与STR组相比，解毒组HMGB1和TLR4之间的结合减弱。综上所述，这些研究结果表明，甘草及其活性成分部分通过 HMGB1 相关途径减轻了马钱子引起的急性神经毒性。
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.