title: Anti-inflammatory activity of omphalocarpin isolated from Radix Toddaliae Asiaticae.
abstract: BACKGROUND
  Radix Toddaliae Asiaticae has long been used as a traditional ethnic Chinese medicine for the treatment of inflammation and rheumatism. In our earlier communication we have reported the anti-arthritic activity of the ethyl alcohol extract and ethyl acetate fraction from Radix Toddaliae Asiaticae. This study was to examine the anti-inflammatory activity of prenylcoumarin omphalocarpin isolated from the ethyl acetate extract with the bioassay-guided methods.
  
  
  METHODS
  Cultured macrophage RAW 264.7 cells were used for the experiments. The ability of omphalocarpin to modulate the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was evaluated. Western blot was used to detect the expression of iNOS and COX-2 and the translocation of nuclear factor kappa B (NF-κB) to the nucleus. Meanwhile, the anti-inflammatory activity of omphalocarpin in vivo was also assayed by xylene induced ear edema in mice.
  
  
  RESULTS
  It has been shown that omphalocarpin inhibited lipopolysaccharide (LPS)-stimulated NO production and pro-inflammatory mediators secretion, including TNF-α, IL-6 in a dose-dependent manner. Omphalocarpin also strongly suppressed the expression and enzymatic activity of iNOS and COX-2 and the translocation of NF-κB to the nucleus. In vivo assays omphalocarpin exhibited anti-inflammatory activity for alleviation of the ear swelling in xylene induced ear edema test.
  
  
  CONCLUSIONS
  These results obtained in vitro and in vivo showed that the anti-inflammatory mechanism of omphalocarpin might be attributed to the inhibition of pro-inflammatory mediators including nitric oxide, IL-6 and TNF-α. Omphalocarpin decreased the overproduction of NO through down-regulation of the expression and enzymatic activity of iNOS and COX-2 in LPS-stimulated macrophage, which was due to the suppression of NF-κB activation in the transcriptional level. This is the first report of the anti-inflammatory activity of omphalocarpin.
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tong
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Tu
authors.initials: T
authors.lastname: Chen
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: zpeng023@gmail.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Pi
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Hanli
authors.initials: H
authors.lastname: Ruan
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jizhou
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D020672:I-kappa B Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008516:Medicine, Chinese Traditional; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D024301:Plant Bark; D010936:Plant Extracts / Q000737:chemistry; D027821:Rutaceae; D051996:Transcription Factor RelA / Q000378:metabolism; D014992:Xylenes
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D020672:I-kappa B Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009573:Nitrites; D010936:Plant Extracts; D051996:Transcription Factor RelA; D014992:Xylenes; C000600255:omphalocarpin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: Anti-inflammatory activity; Macrophage; NF-κB; Omphalocarpin; Pro-inflammatory mediators; Toddaculin (PubChem CID: 5321960); Ulopterol (PubChem CID: 605103); Xylene-induced ear edema test