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Bioactive terpenoids from Euonymus verrucosus var. pauciflorus showing NO inhibitory activities
Institution:1. State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People’s Republic of China;2. Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi 832003, People’s Republic of China;3. School of Medicine, Nankai University, Tianjin 300071, People’s Republic of China;4. Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea;5. College of Chemistry and Environmental Sciences, Laboratory of Xinjiang Native Medicinal and Edible Plant Resources Chemistry, Kashgar University, Kashgar 844000, People''s Republic of China;6. Kansei Fukushi Research Institute, Tohoku Fukushi University, Sendai 989-3201, Japan;1. The Medical University of Silesia, School of Pharmacy with the Division of Laboratory Medicine, Department of Organic Chemistry, Jagiellońska 4, 41-200 Sosnowiec, Poland;2. The Medical University of Silesia, School of Pharmacy with the Division of Laboratory Medicine, Department of Cell Biology, Jedno?ci 8, 41-200 Sosnowiec, Poland;3. Faculty of Mathematics and Natural Sciences, Cardinal Stefan Wyszyński University, K. Wóycickiego 1/3, 01-938 Warszawa, Poland;4. A.M. Butlerov Institute of Chemistry, Kazan Federal University, Kremlevskaya ul. 18, Kazan 420008, Russia;1. IACYS-Unidad de Química Verde y Desarrollo Sostenible, Departamento de Química Orgánica e Inorgánica, Facultad de Ciencias, Universidad de Extremadura, 06006 Badajoz, Spain;2. Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom;3. BioLab Instituto Universitario de Bio-Orgánica Antonio González (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, 38206 La Laguna, Tenerife, Spain;4. Centro de Investigación Biomédica en Red. Bioingeniería, Biomateriales y Nanomedicina CIBER-BBN, Badajoz, Spain;1. Department of Food Science and Biotechnology, Dongguk University-Seoul, Ilsandong-gu, Goyang-si, Gyenggi-do 410820, Republic of Korea;2. Department of Chemistry, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad 500 085, India;3. Shroff S.R. Rotary Institute of Chemical Technology, Valia 393 135, India;1. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China;2. Xiangya Hospital of Central South University, Changsha 410008, PR China;3. School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, PR China;1. School of Chemistry, College of Science, University of Tehran, Tehran, Iran;2. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran;3. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran;4. Department of Medicinal Chemistry, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran;5. Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran;6. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;1. Hokkaido University of Science, Faculty of Pharmaceutical Sciences, 4-1, 7-jo 15-choume, Maeda, Teine-ku, Sapporo, 006-8590, Japan;2. Showa Pharmaceutical University, 3-3165, Higashi Tamagawa Gakuen, Machida, Tokyo, 194-8543, Japan;3. Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599-7568, USA;4. Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, 40402, Taiwan;5. Tsukuba Division, Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, Health and Nutrition, 1-2, Hachimandai, Tsukuba, Ibaraki, 305-0843, Japan
Abstract:In our continuous search for new nitric oxide (NO) inhibitory compounds as potential anti-inflammatory agents or lead compounds for inflammatory diseases, the chemical constituents of Euonymus verrucosus var. pauciflorus were investigated, leading to the isolation of eleven terpenoids including six new diterpenoids, designated as euonymupenes A–F. The structures were elucidated on the basis of NMR and ECD data analysis. Euonymupenes A, C, and F feature rare labdane-type norditerpenoid skeletons. The NO inhibitory effects were evaluated and all of the isolates were found to inhibit lipopolysaccharide (LPS)-induced NO production in murine microglial BV-2 cells. Western blotting analysis indicated that the most active compound (5) can regulate iNOS (inducible nitric oxide synthase) expression. The further molecular docking studies exhibited the affinities of bioactive compounds with iNOS.
Keywords:Celastraceae  NO inhibitory activities  Norditerpenoids  iNOS
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