Melanogenesis inhibitory, anti-inflammatory, and chemopreventive effects of limonoids from the seeds of Azadirachta indicia A. Juss. (neem).

Abstract

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 7alpha-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 microg/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 microg/ear) in mice, exhibited, except for compound 26, marked anti-inflammatory activity (ID(50) values 0.09-0.26 mg/ear). In addition, all of the 32 compounds exhibited moderate or potent inhibitory effects (IC(50) 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.

• Authors: Toshihiro Akihisa, Taisuke Noto, Akitomo Takahashi, Yukiko Fujita, Norihiro Banno, Harukuni Tokuda, Kazuo Koike, Takashi Suzuki, Ken Yasukawa, Yumiko Kimura
• Journal: Journal of oleo science (J Oleo Sci) Vol. 58 Issue 11 Pg. 581-94 ( 2009) ISSN: 1347-3352 [Electronic] Japan
• PMID: 19844073 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antineoplastic Agents, Phytogenic
• Limonins
• Melanins
• Plant Extracts

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemistry, isolation & purification, therapeutic use)
• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, therapeutic use)
• Azadirachta (chemistry, physiology)
• Drug Screening Assays, Antitumor (methods)
• Limonins (chemistry, isolation & purification, therapeutic use)
• Magnetic Resonance Spectroscopy
• Melanins (antagonists & inhibitors, biosynthesis)
• Melanoma, Experimental (metabolism, prevention & control)
• Mice
• Plant Extracts (chemistry, isolation & purification, therapeutic use)
• Seeds
• Tumor Cells, Cultured