Comparative metabolomics approach coupled with cell- and gene-based assays for species classification and anti-inflammatory bioactivity validation of Echinacea plants |
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| Authors: | Chia-Chung Hou Chun-Houh Chen Ning-Sun Yang Yi-Ping Chen Chiu-Ping Lo Sheng-Yang Wang Yin-Jing Tien Pi-Wen Tsai Lie-Fen Shyur |
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| Affiliation: | 1. Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, ROC;2. Institute of Statistical Sciences, Academia Sinica, Taipei 115, Taiwan, ROC;3. Department of Forestry, National Chung-Hsing University, Taichung 402, Taiwan, ROC;4. Institute of Statistics, National Central University, Taoyuan County 320, Taiwan, ROC;5. Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan, ROC;1. Department of Medicinal Pharmacology, Showa Pharmaceutical University, Machida, Tokyo, Japan;2. Department of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo, Japan;3. Department of Pharmacotheraputics, Showa Pharmaceutical University, Machida, Tokyo, Japan;4. Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University, Koriyama, Fukushima, Japan;5. Department of Pharmacy, Cancer Institute Hospital, Koto-Ku, Tokyo, Japan;1. Key Laboratory of Molecular Animal Nutrition and Feed Sciences, College of Animal Science, Zhejiang University, Hangzhou, 310058, PR China;2. Animal Nutrition and Human Health Laboratory, School of Life Sciences, Hunan Normal University, Changsha, 410006, PR China;3. International Medical Center, Zhejiang Provincial People''s Hospital, Hangzhou, 310014, PR China;4. Qilu Animal Health Products Co., Ltd., Jinan, 250100, PR China;1. Department of Life Sciences, Korea University, Seoul 136-701, South Korea;2. Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, South Korea;3. Samsung Genome Institute (SGI), Samsung Medical Center, Seoul 135-710, South Korea;4. Department of Animal Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul 143-701, South Korea;1. Department of Biotechnology, Pondicherry University, Kalapet, Puducherry605014, India;2. Analytical Chemistry Division, Indian Institute of Integrative Medicine (IIIM), Canal Road, Jammu-180001, India;1. Wayne State University, Institute of Environmental Health Sciences, 540 East Canfield Ave., Room 2105, Detroit, MI 48202, United States;2. 21st Century Therapeutics, Inc., 440 Burroughs, Suite 447, Detroit, MI 48202, United States;3. Henry Ford Health System, Internal Medicine, 440 Burroughs, Suite 415, Detroit, MI 48202, United States;4. Henry Ford Health System, Department of Surgery, One Ford Place, Oncology Research Laboratory, 4D, Detroit, MI 48202, United States |
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| 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 (8/9), 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. |
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