FIXED OIL OF NIGELLA-SATIVA AND DERIVED THYMOQUINONE INHIBIT EICOSANOID GENERATION IN LEUKOCYTES AND MEMBRANE LIPID-PEROXIDATION

Samples of the expressed fixed oil from different sources of Nigella s ativa seeds were examined by thin-layer and gas chromatography for con tent of fixed oils and thymoquinone, and these substances were tested as possible inhibitors of eicosanoid generation and membrane lipid per oxidation. The crude fixed oil and pure thymoquinone both inhibited th e cyclooxygenase and 5-lipoxygenase pathways of arachidonate metabolis m in rat peritoneal leukocytes stimulated with calcium ionophore A2318 7, as shown by dose-dependent inhibition of thromboxane B-2 and leukot riene B-4, respectively. Thymoquinone was very potent, with approximat e IC50 values against 5-lipoxygenase and cyclo-oxygenase of <1 mu g/ml and 3.5 mu g/ml, respectively. Both substances also inhibited non-enz ymatic peroxidation in ox brain phospholipid liposomes, but thymoquino ne was about ten times more potent. However, the inhibition of eicosan oid generation and lipid peroxidation by the fixed oil of N. sativa is greater than is expected from its content of thymoquinone (ca. 0.2% w /v), and it is possible that other components such as the unusual C20: 2 unsaturated fatty acids may contribute also to its anti-eicosanoid a nd antioxidant activity. These pharmacological properties of the oil s upport the traditional use of N. sativa and its derived products as a treatment for rheumatism and related inflammatory diseases.