In vitro 12(S)-HETE inhibitory activities of naphthoquinones isolated from the root bark of Euclea racemosa ssp. schimperi.
Platelet 12-lipoxygenase is believed to play a role in cancer and other pathological conditions, such as psoriasis, atherosclerosis and arthritis. The inhibition of 12-LOX is a potential therapeutic approach in the treatment of tumor metastasis. The extracts of Euclea racemosa Murr. ssp. schimperi (A. DC.) F. White (Ebenaceae) obtained by maceration and naphthoquinones isolated from the dichloromethane extract have been investigated for their 12(S)-HETE inhibitory activity using human platelets. At 100 microg/ml, the dichloromethane extract inhibited the formation of 12(S)-HETE by 88.7% and compounds 7-methyljuglone (2), isodiospyrin (3), neodiospyrin (4) and mamegakinone (5), isolated from this extract, exhibited significant activities with IC(50) values ranging from 4 to 58 microg/ml (22.2-155.7 microM). Of these the most abundant compound, 7-methyljuglone displayed a potent inhibitory activity with an IC(50) value of 4.18 microg/ml (22.2 microM), which was comparable to the positive control baicalein with an IC(50) value of 5 microg/ml (18.5 microM). In contrast, 4(S)-shinanolone (1), the reduced form of compound 2, did not show any significant inhibitory activity even at a concentration of 60 microg/ml.
Wube
Abraham Abebe
AA
Department of Pharmacognosy, Institute of Pharmaceutical Sciences, Karl-Franzens University Graz, Universitaetsplatz 4/1, A-8010 Graz, Austria.
Streit
Bernhard
B
Gibbons
Simon
S
Asres
Kaleab
K
Bucar
Franz
F
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000037:antagonists & inhibitors*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D031262:Ebenaceae / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D009362:Neoplasm Metastasis / Q000517:prevention & control; D018517:Plant Roots / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid