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Abstract：
The neurotoxicity of Semen Strychni has been reported recently in several clinical cases. Therefore, this study was conducted to investigate the role of HMGB1 in a model of neurotoxicity induced by Semen Strychni and to assess the potential alleviating effects of glycyrrhizic acid (GA), which is associated with the regulation of HMGB1 release. Forty-eight SD rats were intraperitoneally injected with Semen Strychni extract (175 mg/kg), followed by oral administration of GA (50 mg/kg) for four days. After treatment of SS and GA, neuronal degeneration, apoptosis, and necrosis were observed via histopathological examination. Inflammatory cytokines (TNF-α and IL-1β), neurotransmitter associated enzymes (MAO and AChE), serum HMGB1, nuclear and cytoplasmic HMGB1/ph-HMGB1, and the interaction between PP2A, PKC, and HMGB1 were evaluated. The influence of the MAPK pathway was also examined. As a result, this neurotoxicity was characterized by neuronal degeneration and apoptosis, the induction of pro-inflammatory cytokines, and a reduction in neurotransmitter-metabolizing enzymes. In contrast, GA treatment significantly ameliorated the abovementioned effects and alleviated nerve injury. Furthermore, Semen Strychni promoted HMGB1 phosphorylation and its translocation between the nucleus and cytoplasm, thereby activating the NF-κB and MAPK pathways, initiating various inflammatory responses. Our experiments demonstrated that GA could partially reverse these effects. In summary, GA acid alleviated Semen Strychni-induced neurotoxicity, possibly by inhibiting HMGB1 phosphorylation and preventing its release from the cell.
摘要：
最近在一些临床病例中报道了SemenStrychni的神经毒性。因此,本研究旨在探讨HMGB1在马钱子神经毒性模型中的作用，并评估甘草酸（GA）的潜在缓解作用。这与HMGB1释放的调节有关。48只SD大鼠腹腔注射马钱子提取物（175mg/kg），然后口服GA（50mg/kg）4天。SS和GA治疗后，神经元变性，凋亡，通过组织病理学检查观察到坏死。炎性细胞因子（TNF-α和IL-1β），神经递质相关酶（MAO和AChE），血清HMGB1、核和胞浆HMGB1/ph-HMGB1与PP2A、PKC,和HMGB1进行评价。还检查了MAPK途径的影响。因此,这种神经毒性的特征是神经元变性和凋亡，促炎细胞因子的诱导，和神经递质代谢酶的减少。相比之下,GA治疗显著改善了上述效果并减轻了神经损伤。此外，Strychni促进HMGB1磷酸化及其在细胞核和细胞质之间的易位，从而激活NF-κB和MAPK通路，启动各种炎症反应。我们的实验表明，GA可以部分逆转这些影响。总之,GA酸缓解马钱子引起的神经毒性，可能通过抑制HMGB1磷酸化并阻止其从细胞中释放。
