HMGB1 inhibitor glycyrrhizin inhibited 3-NP–induced upregulation of p-JNK and caspase-3 and death of striatal neurons <i>in vivo</i>.

<p>To study the effects of HMGB1 inhibition on phosphorylation of JNK, caspase-3 cleavage, and death of striatal neurons, striatal tissues were isolated from rats intrastriatally infused with glycyrrhizin (200 nmol) 1 h prior to 3-NP (300 nmol) infusion for an additional 24 h. (A-B) Glycyrrhizin inhibited 3-NP–induced increases in levels of p-JNK, LC3, SQSTM1, and cleaved caspase-3. (C) Cell death was identified by cresyl violet staining on brain sections from control and 3-NP–treated rats. Representative micrographs were taken in the center of the area injected with drugs (adjacent to needle tracks). (a and d) Vehicle treatment (CONT); (b and e) 3-NP treatment; (c and f) 3-NP + glycyrrhizin (Gly) treatment. Scale bars = 500 μm (a–c); 100 μm (d-f). (D) Quantitative analysis of the effects of glycyrrhizin on striatal lesions induced by 3-NP. Densities of protein bands were analyzed with an image analyzer (Sigma Scan Pro 5) and normalized to the loading control (β-actin). Bars represent mean ± SE; n = 3 samples per group. Groups were compared by ANOVA followed by the Dunnet’s post hoc test before data conversion. All panels, **p <0.01 vs control. ##p <0.01 vs. 3-NP alone.