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