α-Iso-cubebene, a natural compound isolated from Schisandra chinensis fruit, has therapeutic benefit against polymicrobial sepsis

α-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. α-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-α, interleukin (IL)-1β, and IL-6 in CLP mice and lipopolysaccharide-stimulated splenocytes. The results indicate that α-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.