alpha-Iso-cubebene, a natural compound isolated from Schisandra chinensis fruit, strongly enhanced survival rate in cecal ligation and puncture (CLP) challenge-induced sepsis. The mechanism involved the marked reduction of viable bacteria in the peritoneal fluid, by virtue of increased phagocytic activity and production of hydrogen peroxide. alpha-Iso-cubebene also significantly attenuated lung inflammation and widespread immune cell apoptosis in a mouse CLP sepsis model, and inhibited the production of proinflammatory cytokines including tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 in CLP mice and lipopolysaccharide-stimulated splenocytes. The results indicate that alpha-iso-cubebene can reverse the progression of toxic shock by triggering multiple protective downstream signaling pathways to enhance microbial killing and maintain organ function and leukocyte survival. (C) 2012 Elsevier Inc. All rights reserved.