Figure 5: A potential PKM2 inhibitor shikonin protects mice from lethal endotoxemia and sepsis.

(a) Mice (n=20 per group) were injected with a single dose of shikonin (8 mg kg⁻¹), followed 30 min later by an infusion of endotoxin (LPS, 5 mg kg⁻¹, i.p.), and were then re-treated with shikonin 12 and 24 h later. The Kaplan–Meyer method was used to compare the differences in survival rates between groups (*P<0.05). (b–e) In parallel experiments, the PKM2 activity in peritoneal macrophages (b) and serum levels of lactate (c), IL-1β (d) and HMGB1 (e) at indicated time points were measured (n=3–5 animals per group, values are mean±s.e.m., *P<0.05 by analysis of variance (ANOVA) LSD test). (f) The CLP technique was used to induce intra-abdominal sepsis in mice (n=20 per group). Repeated administration of shikonin (8 mg kg⁻¹) at 24, 48 and 72 h after CLP significantly increased survival, as compared with vehicle group (*P<0.05), as measured by Kaplan–Meyer test. (g–i) In parallel, the PKM2 activity in peritoneal macrophages (g) and serum levels of lactate (h) and HMGB1 (i) at indicated time points were measured (n=3–5 animals per group, values are mean±s.e.m., *P<0.05 by ANOVA LSD test).