Anti-inflammatory and chemopreventive effects of triterpene cinnamates and acetates from shea fat.
Four triterpene acetates, alpha-amyrin acetate (1a), beta-amyrin acetate (2a), lupeol acetate (3a), and butyrospermol acetate (4a), and four triterpene cinnamates, alpha-amyrin cinnamate (1c), beta-amyrin cinnamate (2c), lupeol cinnamate (3c), and butyrospermol cinnamate (4c), were isolated from the kernel fat (n-hexane extract) of the shea tree (Vitellaria paradoxa; Sapotaceae). Upon evaluation of these eight triterpene esters for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, all of the compounds tested exhibited marked anti-inflammatory activity, with ID50 values in the range of 0.15-0.75 micromol/ear, and among which compound 3c showed the highest activity with ID(50) of 0.15 micromol/ear. Compound 3c (10 mg/kg) further exhibited anti-inflammatory activity on rat hind paw edema induced by carrageenan, with the percentage of inflammation at 1, 3, and 5 h of 35.4, 41.5, and 45.5%, respectively. The eight triterpene esters were then evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) in Raji cells as a primary screening test for inhibitors of tumor promoters. All the compounds showed moderate inhibitory effects. Furthermore, compound 3c exhibited inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz [a] anthracene (DMBA) as an initiator and TPA as a promoter. The biological activities of triterpene acetate and cinnamate esters, together with the exceptionally high levels of these triterpenes in shea fat, indicate that shea nuts and shea fat (shea butter) constitute a significant source of anti-inflammatory and anti-tumor promoting compounds.
Akihisa
Toshihiro
T
College of Science and Technology, Nihon University, 1-8 Kanda Surugadai, Chiyoda-ku, Tokyo 1001-8308, Japan. akihisa@chem.cst.nihon-u.ac.jp
Kojima
Nobuo
N
Kikuchi
Takashi
T
Yasukawa
Ken
K
Tokuda
Harukuni
H
T Masters
Eliot
E
Manosroi
Aranya
A
Manosroi
Jiradej
J
D015127:9,10-Dimethyl-1,2-benzanthracene; D000085:Acetates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000956:Antigens, Viral / Q000097:blood / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D002351:Carrageenan; D045744:Cell Line, Tumor; D002934:Cinnamates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D029632:Sapotaceae / Q000737:chemistry*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*
D000085:Acetates; D000893:Anti-Inflammatory Agents; D000956:Antigens, Viral; D000972:Antineoplastic Agents, Phytogenic; D002934:Cinnamates; C033305:Epstein-Barr virus early antigen; D014315:Triterpenes; D015127:9,10-Dimethyl-1,2-benzanthracene; D002351:Carrageenan; D013755:Tetradecanoylphorbol Acetate