Identification of a novel anti-inflammatory compound, α-cubebenoate from Schisandra chinensis

• Published in: Journal of ethnopharmacology 2014-04, Vol.153 (1), p.242-249
• Main Authors: Kang, Saeromi, Lee, Kyoung-Pil, Park, Soo-Jin, Noh, Dae-Young, Kim, Jung-Min, Moon, Hyung Ryong, Lee, Young-Geun, Choi, Young-Whan, Im, Dong-Soon
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammation; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Blotting, Western; COX-2; Cyclooxygenase 2 - metabolism; Dinoprostone - metabolism; Dose-Response Relationship, Drug; Fruit; iNOS; Lipopolysaccharides - pharmacology; Macrophages; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - metabolism; Male; Mice; Mice, Inbred C57BL; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; RNA, Messenger - metabolism; Schisandra - chemistry; Schisandra chinensis; Sesquiterpenes, Guaiane - administration & dosage; Sesquiterpenes, Guaiane - isolation & purification; Sesquiterpenes, Guaiane - pharmacology; α-Cubebenoate
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2014.02.027

Extracts of Schisandra chinensis have been used as an anti-fatigue and tonic agent. Because chronic fatigue syndrome is related to inflammatory and oxidative stress, we assessed whether Schisandra chinensis has anti-inflammatory constituents and studied the effect of a novel α-cubebenoate isolated from Schisandra chinensis. α-Cubebenoate was isolated from an extract of Schisandra chinensis fruits. The inductions of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) by lipopolysaccharide (LPS) were quantified by RT-PCR and Western blotting in mouse peritoneal macrophages. Nitric oxide (NO) and prostaglandin E2 (PGE2) were also measured in the media by Griess reagent and EIA method. A mouse model of LPS-induced peritonitis was used to test the in vivo efficacy of α-cubebenoate. α-Cubebenoate (5–10μg/ml) inhibited the inductions of iNOS and COX-2 in mouse peritoneal macrophages at the mRNA and protein levels. LPS-induced productions of NO and PGE2 were inhibited by α-cubebenoate (5–10μg/ml). In addition, α-cubebenoate inhibited the LPS-induced activation of JNK, but not those of ERK and p38 MAPK in mouse peritoneal macrophages. Furthermore, in the LPS-induced in vivo peritonitis model, α-cubebenoate (1mg/kg) strongly inhibited the accumulation of polymorph nuclear lymphocytes in the peritoneal cavity. α-Cubebenoate inhibited LPS-induced expression of iNOS and COX-2 in a concentration-dependent manner, thereby suppressing productions of NO and PGE2 in vitro in peritoneal macrophages. α-Cubebenoate also inhibited LPS-induced accumulation of polymorph nuclear lymphocytes in LPS-induced peritonitis model in vivo. α-Cubebenoate may act as an anti-fatigue constituent of Schisandra chinensis through anti-inflammation and could be of therapeutic use as a treatment for inflammatory diseases. [Display omitted]