Therapeutic effects of α-iso-cubebenol, a natural compound isolated from the Schisandra chinensis fruit, against sepsis

► α-Iso-cubebenol showed therapeutic effect against experimental sepsis. ► α-Iso-cubebenol enhanced the bactericidal effects of phagocytic cells. ► α-Iso-cubebenol reduced immune cell apoptosis. ► α-Iso-cubebenol significantly reduced the production of IL-1β in sepsis model. ► The finding suggests a novel therapeutic approach to treat polymicrobial sepsis. α-Iso-cubebenol, a natural compound isolated from the Schisandra chinensis fruit, strongly enhances survival rate in cecal ligation and puncture (CLP) challenge-induced sepsis. Mechanistically, α-iso-cubebenol markedly reduces viable bacteria in the peritoneal fluid and peripheral blood, by increasing production of superoxide anion. α-Iso-cubebenol also significantly attenuates widespread immune cell apoptosis in a mouse CLP sepsis model, and inhibits the production of proinflammatory cytokines including interleukin-1β (IL-1β) and IL-6 in CLP mice and lipopolysaccharide-stimulated splenocytes. Taken together, the results indicate that α-iso-cubebenol can reverse the progression of septic shock by triggering multiple protective downstream signaling pathways to enhance microbial killing and maintain organ function and leukocyte survival.