The melanogenesis-inhibitory, anti-inflammatory, and chemopreventive effects of limonoids in n-hexane extract of Azadirachta indica A. Juss. (neem) seeds.
Seventeen limonoids (tetranortriterpenoids 1-17) were isolated from the n-hexane extract of Azadirachta indica (neem) seeds. The previously unidentified compound 16 was established by spectroscopy to be 17-defurano-17-oxosalannin. The effects of six compounds, 6 and 11-15, on melanogenesis in B16 melanoma cells was evaluated; 2 compounds, salannin (13) and 3-deacetylsalannin (15), exhibited marked inhibitory effects (70-74% reduction of melanin content at 25 µg/mL) with only minor cytotoxicity (79-85% of cell viability). Eleven compounds, 2, 3, 5, 6, and 9-15, were evaluated for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1.7 nmol/ear) in mice; all exhibited marked anti-inflammatory activity (ID(50) values 0.22-0.57 µmol/ear). In addition, compounds 6 and 11-16 exerted moderate inhibition (IC(50) values of 410-471 mol ratio/32 pmol TPA) of TPA-induced Epstein-Barr virus early antigen (EBV-EA) activation in Raji cells. The triacylglycerol fraction of the n-hexane extract contained oleic acid (50.2%) as the most predominant fatty acid constituent.
College of Science and Technology, Nihon University, Tokyo, Japan. akihisa@chem.cst.nihon-u.ac.jp
Toshihiro
T
Akihisa
Akitomo
A
Takahashi
Takashi
T
Kikuchi
Mio
M
Takagi
Kensuke
K
Watanabe
Makoto
M
Fukatsu
Yukiko
Y
Fujita
Norihiro
N
Banno
Harukuni
H
Tokuda
Ken
K
Yasukawa
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000956:Antigens, Viral / Q000378:metabolism; D031601:Azadirachta / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D018890:Chemoprevention; D005227:Fatty Acids / Q000032:analysis; D006586:Hexanes / Q000737:chemistry*; D036701:Limonins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry; D012639:Seeds / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate
D000893:Anti-Inflammatory Agents; D000956:Antigens, Viral; C033305:Epstein-Barr virus early antigen; D005227:Fatty Acids; D006586:Hexanes; D036701:Limonins; D008543:Melanins; D010936:Plant Extracts; C026385:n-hexane; D013755:Tetradecanoylphorbol Acetate