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Identification of Coumarins from the Fruit of Citrus hystrix DC as Inhibitors of Nitric Oxide Generation in Mouse Macrophage RAW 264.7 Cells

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Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Iwade-Uchita, Wakayama 649-6493, Japan; Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan; Department of Citriculture, Fruit Tree Research Station, Okitsu, Shimizu, Shizuoka 424-0292, Japan; Faculty of Pharmacy, Meijo University, Tempaku, Nagoya 468-8503, Japan; and Environmental Science Unit, Central Laboratory and Greenhouse Complex, Kasetsart University, Nakorn-Pathom, Thailand
Cite this: J. Agric. Food Chem. 1999, 47, 1, 333–339
Publication Date (Web):December 10, 1998
https://doi.org/10.1021/jf980523e
Copyright © 1999 American Chemical Society

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    Abstract

    Three known coumarins have been isolated from Citrus hystrix DC as inhibitors of both lipopolysaccharide (LPS) and interferon-γ (IFN-γ)-induced nitric oxide (NO) generation in RAW 264.7 cells. The inhibitory activity of bergamottin (IC50 = 14 μM) was comparable to that of N-(iminoethyl)-l-ornithine (l-NIO) (IC50 = 7.9 μM), whereas oxypeucedanin and 5-[(6‘,7‘-dihydroxy-3‘,7‘-dimethyl-2-octenyl)oxy]psoralen, structurally different from bergamottin only in their side-chain moieties, were notably less active. Using 21 coumarins, we structurally classified various types of coumarins into groups A−C:  (A) bearing an isoprenyl (IP) or a geranyl (GR) group, highly active; (B) bearing an IP group cyclized to a coumarin ring, moderately active; (C) bearing an IP group modified with hydroxyl group(s) and/or having other functional groups except for the IP, completely inactive. Cellular uptake studies suggested that coumarins in group C are inactive because of poor permeability to the cell membrane.

    Keywords: Citrus hystrix DC; psoralen; coumarin; nitric oxide; RAW 264.7 cells; structure−activity relationships

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     Kinki University.

     Kyoto University.

    §

     Fruit Tree Research Station.

     Meijo University.

     Kasetsart University.

    *

     Author to whom correspondence should be addressed (telephone +81-75-753-6281; fax +81-75-753-6284; e-mail [email protected]).

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    10. Ning An, Tao Yang, Xiao-Xia Zhang, Mei-xia Xu. Bergamottin alleviates LPS-induced acute lung injury by inducing SIRT1 and suppressing NF-κB. Innate Immunity 2021, 27 (7-8) , 543-552. https://doi.org/10.1177/17534259211062553
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    16. Ewelina Kozioł, Fatma Sezer Senol Deniz, Ilkay Erdogan Orhan, Laurence Marcourt, Barbara Budzyńska, Jean-Luc Wolfender, Alexander D. Crawford, Krystyna Skalicka-Woźniak. High-performance counter-current chromatography isolation and initial neuroactivity characterization of furanocoumarin derivatives from Peucedanum alsaticum L (Apiaceae). Phytomedicine 2019, 54 , 259-264. https://doi.org/10.1016/j.phymed.2018.10.030
    17. Serena Fiorito, Francesco Epifano, Francesca Preziuso, Vito Alessandro Taddeo, Salvatore Genovese. Biomolecular Targets of Oxyprenylated Phenylpropanoids and Polyketides. 2019, 143-205. https://doi.org/10.1007/978-3-030-01099-7_2
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    19. Saisakun Kidarn, Chalermpong Saenjum, Darunee Hongwiset, Ampai Phrutivorapongkul, . Furanocoumarins from Kaffir lime and their inhibitory effects on inflammatory mediator production. Cogent Chemistry 2018, 4 (1) , 1529259. https://doi.org/10.1080/23312009.2018.1529259
    20. Soek Sin Teh, Gwendoline Cheng Lian Ee, Siau Hui Mah. Evaluation of nitric oxide inhibition effect in LPS-stimulated RAW 264.7 macrophages by phytochemical constituents from Mesua beccariana, Mesua congestiflora, and Mesua ferrea. Medicinal Chemistry Research 2017, 26 (12) , 3240-3246. https://doi.org/10.1007/s00044-017-2017-4
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    30. T. K. Lim. Citrus hystrix. 2012, 634-643. https://doi.org/10.1007/978-94-007-4053-2_76
    31. Yoshiaki Miyake, Masanori Hiramitsu. Isolation and extraction of antimicrobial substances against oral bacteria from lemon peel. Journal of Food Science and Technology 2011, 48 (5) , 635-639. https://doi.org/10.1007/s13197-011-0330-3
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    36. Toshifumi Hirata, Misato Fujii, Kazuhiro Akita, Noriyuki Yanaka, Kaori Ogawa, Masanori Kuroyanagi, Daiki Hongo. Identification and physiological evaluation of the components from Citrus fruits as potential drugs for anti-corpulence and anticancer. Bioorganic & Medicinal Chemistry 2009, 17 (1) , 25-28. https://doi.org/10.1016/j.bmc.2008.11.039
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    41. So Young Kang, Young Choong Kim. Neuroprotective coumarins from the root ofAngelica gigas: Structure-activity relationships. Archives of Pharmacal Research 2007, 30 (11) , 1368-1373. https://doi.org/10.1007/BF02977358
    42. Marellapudi S. Ramachandra, Gottumukkala V. Subbaraju. Short Synthesis of 3‐Prenylcoumarins by an Unusual Prenylation. Synthetic Communications 2006, 36 (24) , 3723-3727. https://doi.org/10.1080/10916460600946154
    43. T. Wegener, H. Wagner. The active components and the pharmacological multi-target principle of STW 5 (Iberogast®). Phytomedicine 2006, 13 , 20-35. https://doi.org/10.1016/j.phymed.2006.07.001
    44. N. Hutadilok-Towatana, P. Chaiyamutti, K. Panthong, W. Mahabusarakam, V. Rukachaisirikul. Antioxidative and Free Radical Scavenging Activities of Some Plants Used in Thai Folk Medicine. Pharmaceutical Biology 2006, 44 (3) , 221-228. https://doi.org/10.1080/13880200600685592
    45. Oliver Kayser, K Noel Masihi, Albrecht F Kiderlen. Natural products and synthetic compounds as immunomodulators. Expert Review of Anti-infective Therapy 2003, 1 (2) , 319-335. https://doi.org/10.1586/14787210.1.2.319
    46. So Young Kang, Ki Yong Lee, Mi Jung Park, Young Chul Kim, George J Markelonis, Tae H Oh, Young Choong Kim. Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice. Neurobiology of Learning and Memory 2003, 79 (1) , 11-18. https://doi.org/10.1016/S1074-7427(02)00007-2
    47. Ching-Chiung Wang, Jing-Erh Lai, Lih-Geeng Chen, Kun-Ying Yen, Ling-Ling Yang. Inducible nitric oxide synthase inhibitors of Chinese herbs. Part 2: Naturally occurring furanocoumarins. Bioorganic & Medicinal Chemistry 2000, 8 (12) , 2701-2707. https://doi.org/10.1016/S0968-0896(00)00200-5
    48. Akira Murakami, Keiji Wada, Naomi Ueda, Keiko Sasaki, Masanobu Haga, Wataru Kuki, Yasuo Takahashi, Hiroshi Yonei, Koichi Koshimizu, Hajime Ohigashi. In Vitro Absorption and Metabolism of a Citrus Chemopreventive Agent, Auraptene, and Its Modifying Effects on Xenobiotic Enzyme Activities in Mouse Livers. Nutrition and Cancer 2000, 36 (2) , 191-199. https://doi.org/10.1207/S15327914NC3602_8
    49. Akira Murakami, Guanxin Gao, Mitsuo Omura, Masamichi Yano, Chihiro Ito, Hiroshi Furukawa, Daisuke Takahashi, Koichi Koshimizu, Hajime Ohigashi. 1,1-Dimethylallylcoumarins potently supress both lipopolysaccharide- and interferon-γ-induced nitric oxide generation in mouse macrophage RAW 264.7 cells. Bioorganic & Medicinal Chemistry Letters 2000, 10 (1) , 59-62. https://doi.org/10.1016/S0960-894X(99)00578-8

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