著者

Toshihiro Akihisa Taisuke Noto Akitomo Takahashi Yukiko Fujita Norihiro Banno Harukuni Tokuda Kazuo Koike Takashi Suzuki Ken Yasukawa Yumiko Kimura

出版者

Japan Oil Chemists' Society

雑誌

Journal of Oleo Science (ISSN:13458957)

巻号頁・発行日

vol.58, no.11, pp.581-594, 2009 (Released:2009-10-20)

参考文献数

35

被引用文献数

52 69

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Thirty-one nortriterpenoids, including 28 limonoids (1-28) and 3 degraded limonoids (29-31), and one diterpenoid (32), were isolated from the seed extract of Azadirachta indica (neem). Among these, six were new compounds and their structures were established to be 15-hydroxyazadiradione (3), 7-benzoyl-17-hydroxynimbocinol (5), 23-deoxyazadironolide (12), limocin E (13), 23-epilimocin E (14), and 7α-acetoxy-3-oxoisocopala-1,13-dien-15-oic acid (32). Upon evaluation of compounds 1-32 on the melanogenesis in the B16 melanoma cells, five compounds, 20, 26, 27, 29, and 31, exhibited marked inhibitory effect (74-91% reduction of melanin content at 25 μg/mL) with no or almost no toxicity to the cells. Seven compounds, 1, 6, 9, 10, 18, 20, and 26, on evaluation for their inhibitory effect against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 μg/ear) in mice, exhibited, except for compound 26, marked anti-inflammatory activity (ID50 values 0.09-0.26 mg/ear). In addition, all of the 32 compounds exhibited moderate or potent inhibitory effects (IC50 values of 230-501 mol ratio/32 pmol TPA) against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA. Furthermore, on evaluation of azadirachtin B (21) for its anti-tumor-initiating activity on the two-stage carcinogenesis of mouse skin tumor induced by peroxynitrite (ONOO-; PN) as an initiator and TPA as a promoter, this exhibited marked inhibitory activity.