title: Identification of a novel anti-inflammatory compound, α-cubebenoate from Schisandra chinensis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, 63 Beon-gil 2, Busandaehag-ro, Geumjeong-gu, Busan 609-735, Republic of Korea.
authors.forename: Saeromi
authors.initials: S
authors.lastname: Kang
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, 63 Beon-gil 2, Busandaehag-ro, Geumjeong-gu, Busan 609-735, Republic of Korea.
authors.forename: Kyoung-Pil
authors.initials: KP
authors.lastname: Lee
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, 63 Beon-gil 2, Busandaehag-ro, Geumjeong-gu, Busan 609-735, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, 63 Beon-gil 2, Busandaehag-ro, Geumjeong-gu, Busan 609-735, Republic of Korea.
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Noh
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, 63 Beon-gil 2, Busandaehag-ro, Geumjeong-gu, Busan 609-735, Republic of Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, 63 Beon-gil 2, Busandaehag-ro, Geumjeong-gu, Busan 609-735, Republic of Korea.
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.affiliation: Department of Horticultural Bioscience, College of Natural Resources & Life Science, Pusan National University, Miryang-si, Gyeongsangnam 627-706, Republic of Korea.
authors.forename: Young-Geun
authors.initials: YG
authors.lastname: Lee
authors.affiliation: Department of Horticultural Bioscience, College of Natural Resources & Life Science, Pusan National University, Miryang-si, Gyeongsangnam 627-706, Republic of Korea. Electronic address: ywchoi@pusan.ac.kr.
authors.forename: Young-Whan
authors.initials: YW
authors.lastname: Choi
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, 63 Beon-gil 2, Busandaehag-ro, Geumjeong-gu, Busan 609-735, Republic of Korea. Electronic address: imds@pusan.ac.kr.
authors.forename: Dong-Soon
authors.initials: DS
authors.lastname: Im
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005638:Fruit; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D032141:Schisandra / Q000737:chemistry*; D045789:Sesquiterpenes, Guaiane / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D045789:Sesquiterpenes, Guaiane; C000598129:alpha-cubebenoate; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: Anti-inflammation; COX-2; Macrophages; Schisandra chinensis; iNOS; α-Cubebenoate