title: Nitric Oxide Production-Inhibitory Activity of Limonoids from Azadirachta indica and Melia azedarach.
abstract: Seventy-three limonoids isolated from three Meliaceae plants, Azadirachta indica, A. indica var. siamensis, and Melia azedarach, or semi-synthesized from the Meliaceae limonoids, were evaluated for their inhibitory activity against nitric oxide (NO) production in mouse macrophage RAW 264.7 cells induced by lipopolysaccharide (LPS), as a primary screening test for anti-inflammatory agents. Of the compounds tested, 21 compounds exhibited inhibitory activity (IC504.6 - 58.6 μm) without any significant toxicity (IC50> 100 μm) which were more potent than l-NMMA (NO-production inhibitory activity, IC5065.6 μm; cytotoxicity, IC50> 100 μm), and among which, nine compounds, i.e., 17-hydroxy-15-methoxynimbocinol (6), ohchinin (20), 1-cis-cinnamoyl-1-decinnamoylohchinin (24), salannin (27), methyl nimbidate (32), isosalannin (55), nimbolinin D (58), mesendanin E (69), and 7-deacetylgedunin (73) exhibited potent inhibitory activity (IC504.6 - 29.3 μm). In particular, compounds 6 (IC507.3 μm), an azadirone-type limonoid, and 73 (IC504.6 μm), a gedunin-type limonoid, exhibited remarkable activity. Western blot analysis revealed that 27 and 73 reduced the expression levels of the inducible NO synthase and cyclooxygenase-2 proteins in a concentration-dependent manner. These findings suggest that limonoids of A. indica, A. indica var. siamensis, and M. azedarach, and their semi-synthetic derivatives may be effective against inflammation.
authors.affiliation: Research Institute for Science & Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.|Akihisa Medical Clinic, 1086-3 Kamo, Sanda-shi, Hyogo, 669-1311, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akihisa
authors.affiliation: College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo, 101-8308, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nishimoto
authors.affiliation: College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo, 101-8308, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Ogihara
authors.affiliation: College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo, 101-8308, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Natural Medicine Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Research Institute for Science & Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Abe
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification* / Q000494:pharmacology; D031601:Azadirachta / Q000737:chemistry*; D052246:Cyclooxygenase 2 Inhibitors; D020128:Inhibitory Concentration 50; D036701:Limonins / Q000494:pharmacology*; D031586:Melia azedarach / Q000737:chemistry*; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D036701:Limonins; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II
keywords: Inflammation; Limonoids; Meliaceae; NO Production-inhibitory activity; Terpenoids