title: Comparative metabolomics approach coupled with cell- and gene-based assays for species classification and anti-inflammatory bioactivity validation of Echinacea plants.
abstract: Echinacea preparations were the top-selling herbal supplements or medicines in the past decade; however, there is still frequent misidentification or substitution of the Echinacea plant species in the commercial Echinacea products with not well chemically defined compositions in a specific preparation. In this report, a comparative metabolomics study, integrating supercritical fluid extraction, gas chromatography/mass spectrometry and data mining, demonstrates that the three most used medicinal Echinacea species, Echinacea purpurea, E. pallida, and E. angustifolia, can be easily classified by the distribution and relative content of metabolites. A mitogen-induced murine skin inflammation study suggested that alkamides were the active anti-inflammatory components present in Echinacea plants. Mixed alkamides and the major component, dodeca-2E,4E,8Z,10Z(E)-tetraenoic acid isobutylamides, were then isolated from E. purpurea root extracts for further bioactivity elucidation. In macrophages, the alkamides significantly inhibited cyclooxygenase 2 (COX-2) activity and the lipopolysaccharide-induced expression of COX-2, inducible nitric oxide synthase and specific cytokines or chemokines [i.e., TNF-α, interleukin (IL)-1α, IL-6, MCP-1, MIP-1β] but elevated heme oxygenase-1 protein expression. Cichoric acid, however, exhibited little or no effect. The results of high-performance liquid chromatography/electron spray ionization/mass spectrometry metabolite profiling of alkamides and phenolic compounds in E. purpurea roots showed that specific phytocompound (i.e., alkamides, cichoric acid and rutin) contents were subject to change under certain post-harvest or abiotic treatment. This study provides new insight in using the emerging metabolomics approach coupled with bioactivity assays for medicinal/nutritional plant species classification, quality control and the identification of novel botanical agents for inflammatory disorders.
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, ROC.
authors.forename: Chia-Chung
authors.initials: CC
authors.lastname: Hou
authors.forename: Chun-Houh
authors.initials: CH
authors.lastname: Chen
authors.forename: Ning-Sun
authors.initials: NS
authors.lastname: Yang
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Chen
authors.forename: Chiu-Ping
authors.initials: CP
authors.lastname: Lo
authors.forename: Sheng-Yang
authors.initials: SY
authors.lastname: Wang
authors.forename: Yin-Jing
authors.initials: YJ
authors.lastname: Tien
authors.forename: Pi-Wen
authors.initials: PW
authors.lastname: Tsai
authors.forename: Lie-Fen
authors.initials: LF
authors.lastname: Shyur
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000032:analysis* / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D020900:Echinacea / Q000737:chemistry / Q000145:classification*; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics*; D018517:Plant Roots / Q000737:chemistry; D053284:Polyunsaturated Alkamides / Q000737:chemistry / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2