Isoalantolactone inhibits LPS-induced inflammation via NF-κB inactivation in peritoneal macrophages and improves survival in sepsis.

Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of mortality worldwide. It involves uncontrolled inflammatory response resulting in multi-organ failure and even death. Isoalantolactone (IAL), a sesquiterpene lactone, is known for its anti-cancer effects. Nevertheless, little is known about the anti-inflammatory effects of IAL, and the role of IAL in sepsis is unclear. In this study, we demonstrated that IAL decreased lipopolysaccharide (LPS)-mediated production of nitric oxide, PEG2 and cytokines (IL-6, TNF-α) in peritoneal macrophages and RAW 264.7 macrophages. Moreover, molecular mechanism studies indicated that IAL plays an anti-inflammatory role by inhibiting LPS-induced activation of NF-κB pathway in peritoneal macrophages. In vivo, IAL reduced the secretion of IL-6 and TNF-α in serum, and increased the survival rate of mice with LPS-induced sepsis. In addition, IAL attenuated the activation of NF-κB pathway in liver. Taken together, our data suggest that IAL may represent a potentially new drug candidate for the treatment of sepsis.